BioMed Research International: Geriatrics The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Successful Cognitive Aging: Between Functional Decline and Failure of Compensatory Mechanisms Thu, 26 Nov 2015 13:17:26 +0000 Marc Verny, Emmanuel Moyse, and Slavica Krantic Copyright © 2015 Marc Verny et al. All rights reserved. Deep Assessment: A Novel Framework for Improving the Care of People with Very Advanced Alzheimer’s Disease Tue, 24 Nov 2015 11:51:28 +0000 Best practice in understanding and caring for people with advanced Alzheimer’s disease presents extraordinary challenges. Their severe and deteriorating cognitive impairments are such that carers find progressive difficulty in authentically ascertaining and responding to interests, preferences, and needs. Deep assessment, a novel multifaceted framework drawn from research into the experiences of others with severe cognitive impairments, has potential to empower carers and other support professionals to develop an enhanced understanding of people with advanced Alzheimer’s disease and so deliver better calibrated care in attempts to maximize quality of life. Deep assessment uses a combination of techniques, namely, Behaviour State Observation, Triangulated Proxy Reporting, and Startle Reflex Modulation Measurement, to deliver a comprehensive and deep assessment of the inner states (awareness, preferences, likes, and dislikes) of people who cannot reliably self-report. This paper explains deep assessment and its current applications. It then suggests how it can be applied to people with advanced Alzheimer’s disease to develop others’ understanding of their inner states and to help improve their quality of life. An illustrative hypothetical vignette is used to amplify this framework. We discuss the potential utility and efficacy of this technique for this population and we also propose other human conditions that may benefit from research using a deep assessment approach. Gordon Lyons, Michael Arthur-Kelly, Ami Eidels, and Aimee Mavratzakis Copyright © 2015 Gordon Lyons et al. All rights reserved. Serum Levels of ApoA1 and ApoA2 Are Associated with Cognitive Status in Older Men Mon, 23 Nov 2015 17:08:01 +0000 Background. Advancing age, chronic inflammation, oxidative damage, and disorders of lipid metabolism are positively linked to the late-life cognitive impairment. Serum biomarkers may be associated with the cognitive status in older men. Methods. 440 old male subjects with different cognitive functions were recruited to investigate probable serum markers. Pearson Chi-Squared test, univariate analysis, and multivariate logistic regression analysis were performed to evaluate biomarkers which may be associated with cognitive status. Results. Levels of fundus atherosclerosis (AS) (), age (), serum biomarkers peroxidase (POD) () and interleukin-6 (IL-6) (), serum levels of high-density lipoprotein cholesterol (HDL-C) (), apolipoprotein A2 (ApoA2) (), and ApoC2 () showed significant differences. Compared to group 3, ApoA1 in group 1 (OR = 1.30, 95% CI 1.01–1.67) and group 2 (OR = 1.47, 95% CI 1.11–1.94) were higher, while ApoA2 were lower (group 1: OR = 0.43, 95% CI 0.18–1.02; group 2: OR = 0.21, 95% CI 0.08–0.54) after adjusting for control variables. Conclusion. The results demonstrated that age, AS levels, POD, IL-6, HDL-C, ApoA2, and ApoC2 were significantly related to cognitive status. Moreover, ApoA1 and ApoA2 were independently associated with cognitive impairment and late-life dementia. Cheng Ma, Jin Li, Zhijun Bao, Qingwei Ruan, and Zhuowei Yu Copyright © 2015 Cheng Ma et al. All rights reserved. Defining Multimorbidity: From English to Portuguese Using a Delphi Technique Mon, 23 Nov 2015 16:08:56 +0000 Objective. To translate the European General Practice Research Network multimorbidity definition according to Portuguese cultural and linguistic features. Methods. Similar to the process completed in several other European countries, a forward and backward translation of the English multimorbidity definition using the Delphi technique was performed in Portugal. Results. Twenty-three general practitioners (GPs)—14 males and 9 females—agreed to form the Portuguese expert panel for the Delphi process (59% acceptance rate). The Portuguese definition of multimorbidity was achieved after two Delphi rounds with a mean (SD) consensus score for final round of 8.43/9 (0.73). Conclusion. With this paper the definition of multimorbidity is now available in a new language—Portuguese. Its availability in the local language will raise Portuguese GPs’ awareness about multimorbidity and allow future national and international research. The operationalization of the definition will allow an easier identification of patients with multimorbidity. Filipe Prazeres, Luiz Miguel Santiago, and José Augusto Simões Copyright © 2015 Filipe Prazeres et al. All rights reserved. Healthy Aging and Compensation of Sentence Comprehension Auditory Deficits Tue, 27 Oct 2015 07:05:24 +0000 Objectives. To analyze the effect of aging on sentence auditory comprehension and to study the relationship between this language skill and cognitive functions (attention, working memory, and executive functions). Methods. A total of 90 healthy subjects were divided into three groups: adults (50–59 years), young-old (60–69 years), and old-old (70–80 years). Subjects were assessed using the Revised Token Test. The measures used for performance analysis were number of correct answers (accuracy) and execution time of commands on the different subtests. Results. Regarding accuracy, groups showed similar performance on the first blocks, but the young-old and old-old performed worse than adults on blocks 9 and 10. With respect to execution time, groups differed from block 2 (i.e., the groups differed for all blocks, except for block 1), with the worst performance observed in the old-old group, followed by that of the young-old group. Therefore, the elderly required more time to attain performance similar to that of adults, showing that time measurements are more sensitive for detecting the effects of age. Sentence comprehension ability is correlated with cognitive test performance, especially for global cognition and working memory tests. Conclusions. Healthy aging is characterized by the ability to compensate for difficulties in linguistic processing, which allows the elderly to maintain functional communication. Marcela Lima Silagi, Camila Maia Rabelo, Eliane Schochat, and Letícia Lessa Mansur Copyright © 2015 Marcela Lima Silagi et al. All rights reserved. Neural Processing of Emotional Prosody across the Adult Lifespan Sun, 25 Oct 2015 09:33:41 +0000 Emotion recognition deficits emerge with the increasing age, in particular, a decline in the identification of sadness. However, little is known about the age-related changes of emotion processing in sensory, affective, and executive brain areas. This functional magnetic resonance imaging (fMRI) study investigated neural correlates of auditory processing of prosody across adult lifespan. Unattended detection of emotional prosody changes was assessed in 21 young (age range: 18–35 years), 19 middle-aged (age range: 36–55 years), and 15 older (age range: 56–75 years) adults. Pseudowords uttered with neutral prosody were standards in an oddball paradigm with angry, sad, happy, and gender deviants (total 20% deviants). Changes in emotional prosody and voice gender elicited bilateral superior temporal gyri (STG) responses reflecting automatic encoding of prosody. At the right STG, responses to sad deviants decreased linearly with age, whereas happy events exhibited a nonlinear relationship. In contrast to behavioral data, no age by sex interaction emerged on the neural networks. The aging decline of emotion processing of prosodic cues emerges already at an early automatic stage of information processing at the level of the auditory cortex. However, top-down modulation may lead to an additional perceptional bias, for example, towards positive stimuli, and may depend on context factors such as the listener’s sex. Liliana Ramona Demenescu, Yutaka Kato, and Klaus Mathiak Copyright © 2015 Liliana Ramona Demenescu et al. All rights reserved. Cognitive Interventions in Older Persons: Do They Change the Functioning of the Brain? Sun, 25 Oct 2015 08:21:22 +0000 Background. Cognitive interventions for older persons that may diminish the burden of cognitive problems and could delay conversion to dementia are of great importance. The underlying mechanisms of such interventions might be psychological compensation and neuronal plasticity. This review provides an overview of the literature concerning the evidence that cognitive interventions cause brain activation changes, even in damaged neural systems. Method. A systematic search of the literature was conducted in several international databases, Medline, Embase, Cinahl, Cochrane, and Psychinfo. The methodological quality was assessed according to the guidelines of the Dutch Institute for Health Care Improvement (CBO). Results. Nineteen relevant articles were included with varied methodological quality. All studies were conducted in diverse populations from healthy elderly to patients with dementia and show changes in brain activation after intervention. Conclusions. The results thus far show that cognitive interventions cause changes in brain activation patterns. The exact interpretation of these neurobiological changes remains unclear. More study is needed to understand the extent to which cognitive interventions are effective to delay conversion to dementia. Future studies should more explicitly try to relate clinically significant improvement to changes in brain activation. Long-term follow-up data are necessary to evaluate the stability of the effects. Yindee van Os, Marjolein E. de Vugt, and Martin van Boxtel Copyright © 2015 Yindee van Os et al. All rights reserved. The Association between Cerebral White Matter Lesions and Plasma Omega-3 to Omega-6 Polyunsaturated Fatty Acids Ratio to Cognitive Impairment Development Sun, 25 Oct 2015 07:13:34 +0000 Objective. Cerebral white matter hyperintensity (WMH) with magnetic resonance imaging (MRI) has a potential for predicting cognitive impairment. Serum polyunsaturated fatty acid (PUFA) levels are important for evaluating the extent of atherosclerosis. We investigated whether abnormal PUFA levels affected WMH grading and cognitive function in patients without significant cognitive impairment. Methods. Atherosclerotic risk factors, the internal carotid artery (ICA) plaque, and serum ratios of eicosapentaenoic to arachidonic acids (EPA/AA) and docosahexaenoic to arachidonic acids (DHA/AA) were assessed in 286 patients. The relationship among these risk factors, WMH, and cognitive function was evaluated using WMH grading and the Mini-Mental State Examination (MMSE). Results. The development of WMH was associated with aging, hypertension, ICA plaques, and a low serum EPA/AA ratio (<0.38, obtained as the median value) but was not related to dyslipidemia, diabetes, smoking, and a low serum DHA/AA ratio (<0.84, obtained as the median value). In addition, the MMSE score deteriorated slightly with the progression of WMH (29.7 ± 1.0 compared to 28.4 ± 2.1, ). Conclusions. The progression of WMH was associated with a low serum EPA/AA ratio and accompanied minimal deterioration in cognitive function. Sufficient omega-3 PUFA intake may be effective in preventing the development of cognitive impairment. Michihiro Suwa, Shigeru Yamaguchi, Tsuyoshi Komori, Sachiko Kajimoto, and Masaya Kino Copyright © 2015 Michihiro Suwa et al. All rights reserved. Working Memory and Executive Function Decline across Normal Aging, Mild Cognitive Impairment, and Alzheimer’s Disease Thu, 15 Oct 2015 12:43:14 +0000 Alzheimer’s disease (AD) is a progressive neurodegenerative disease marked by deficits in episodic memory, working memory (WM), and executive function. Examples of executive dysfunction in AD include poor selective and divided attention, failed inhibition of interfering stimuli, and poor manipulation skills. Although episodic deficits during disease progression have been widely studied and are the benchmark of a probable AD diagnosis, more recent research has investigated WM and executive function decline during mild cognitive impairment (MCI), also referred to as the preclinical stage of AD. MCI is a critical period during which cognitive restructuring and neuroplasticity such as compensation still occur; therefore, cognitive therapies could have a beneficial effect on decreasing the likelihood of AD progression during MCI. Monitoring performance on working memory and executive function tasks to track cognitive function may signal progression from normal cognition to MCI to AD. The present review tracks WM decline through normal aging, MCI, and AD to highlight the behavioral and neurological differences that distinguish these three stages in an effort to guide future research on MCI diagnosis, cognitive therapy, and AD prevention. Anna-Mariya Kirova, Rebecca B. Bays, and Sarita Lagalwar Copyright © 2015 Anna-Mariya Kirova et al. All rights reserved. Trying to Put the Puzzle Together: Age and Performance Level Modulate the Neural Response to Increasing Task Load within Left Rostral Prefrontal Cortex Thu, 08 Oct 2015 06:02:40 +0000 Age-related working memory decline is associated with functional cerebral changes within prefrontal cortex (PFC). Kind and meaning of these changes are heavily discussed since they depend on performance level and task load. Hence, we investigated the effects of age, performance level, and load on spatial working memory retrieval-related brain activation in different subregions of the PFC. 19 younger (Y) and 21 older (O) adults who were further subdivided into high performers (HP) and low performers (LP) performed a modified version of the Corsi Block-Tapping test during fMRI. Brain data was analyzed by a 4 (groups: YHP, OHP, YLP, and OLP) × 3 (load levels: loads 4, 5, and 6) ANOVA. Results revealed significant group × load interaction effects within rostral dorsolateral and ventrolateral PFC. YHP showed a flexible neural upregulation with increasing load, whereas YLP reached a resource ceiling at a moderate load level. OHP showed a similar (though less intense) pattern as YHP and may have compensated age-effects at high task load. OLP showed neural inefficiency at low and no upregulation at higher load. Our findings highlight the relevance of age and performance level for load-dependent activation within rostral PFC. Results are discussed in the context of the compensation-related utilization of neural circuits hypothesis (CRUNCH) and functional PFC organization. Eva Bauer, Gebhard Sammer, and Max Toepper Copyright © 2015 Eva Bauer et al. All rights reserved. Introduction of Auricular Acupuncture in Elderly Patients Suffering from Major Depression: Protocol of a Mixed Methods Feasibility Study Sun, 12 Apr 2015 08:03:11 +0000 Background. Due to an increasing number of elderly people suffering from major depression and potential side effects of the prescribed drugs, the introduction of new therapeutic approaches is needed. Currently, in Germany, auricular acupuncture is no part of clinical care for gerontopsychiatric patients. Based on promising clinical experiences and existing evidence for treating addiction and trauma, a benefit of auricular acupuncture integrated in existing treatment programs in elderly patients may be hypothesized. Within this project auricular acupuncture according to the National Acupuncture Detoxification Association (NADA) will be integrated in the multimodal treatment regime for elderly patients with major depression in a daytime ward setting. Methods/Design. To evaluate the feasibility and acceptance a mixed method approach is used. In a day clinic, a sample of 20 psychogeriatric patients with the diagnosis of major depression will be enrolled. The patients will receive a total of nine auricular acupuncture treatments according to the standardized NADA protocol in a group setting. The therapeutic process, its organization, the experience, and the willingness of patients to participate will be evaluated by interviews with patients and the therapeutic team. Data will be analyzed qualitatively using content analysis. Additionally, quantitative outcome parameters will be measured by standardized questionnaires. Janina Geib, Monika A. Rieger, Stefanie Joos, Gerhard W. Eschweiler, Thomas Dresler, and Florian G. Metzger Copyright © 2015 Janina Geib et al. All rights reserved. Diagnostic Value of Subjective Memory Complaints Assessed with a Single Item in Dominantly Inherited Alzheimer’s Disease: Results of the DIAN Study Thu, 02 Apr 2015 12:53:14 +0000 Objective. We examined the diagnostic value of subjective memory complaints (SMCs) assessed with a single item in a large cross-sectional cohort consisting of families with autosomal dominant Alzheimer’s disease (ADAD) participating in the Dominantly Inherited Alzheimer Network (DIAN). Methods. The baseline sample of 183 mutation carriers (MCs) and 117 noncarriers (NCs) was divided according to Clinical Dementia Rating (CDR) scale into preclinical (CDR 0; MCs: ; NCs: ), early symptomatic (CDR 0.5; MCs: ; NCs: ), and dementia stage (CDR ≥ 1; MCs: ; NCs: ). These groups were subdivided by the presence or absence of SMCs. Results. At CDR 0, SMCs were present in 12.1% of MCs and 9.2% of NCs . At CDR 0.5, SMCs were present in 66.7% of MCs and 62.5% of NCs . At CDR ≥ 1, SMCs were present in 96.4% of MCs. SMCs in MCs were significantly associated with CDR, logical memory scores, Geriatric Depression Scale, education, and estimated years to onset. Conclusions. The present study shows that SMCs assessed by a single-item scale have no diagnostic value to identify preclinical ADAD in asymptomatic individuals. These results demonstrate the need of further improvement of SMC measures that should be examined in large clinical trials. Christoph Laske, Hamid R. Sohrabi, Mateusz S. Jasielec, Stephan Müller, Niklas K. Koehler, Susanne Gräber, Stefan Förster, Alexander Drzezga, Felix Mueller-Sarnowski, Adrian Danek, Mathias Jucker, Randall J. Bateman, Virginia Buckles, Andrew J. Saykin, Ralph N. Martins, John C. Morris, and Dominantly Inherited Alzheimer Network (DIAN) Copyright © 2015 Christoph Laske et al. All rights reserved. Predictors of Mortality for Nursing Home-Acquired Pneumonia: A Systematic Review Mon, 02 Mar 2015 14:47:55 +0000 Background. Current risk stratification tools, primarily used for CAP, are suboptimal in predicting nursing home acquired pneumonia (NHAP) outcome and mortality. We conducted a systematic review to evaluate current evidence on the usefulness of proposed predictors of NHAP mortality. Methods. PubMed (MEDLINE), EMBASE, and CINAHL databases were searched for articles published in English between January 1978 and January 2014. The literature search elicited a total of 666 references; 580 were excluded and 20 articles met the inclusion criteria for the final analysis. Results. More studies supported the Pneumonia Severity Index (PSI) as a superior predictor of NHAP severity. Fewer studies suggested CURB-65 and SOAR (especially for the need of ICU care) as useful predictors for NHAP mortality. There is weak evidence for biomarkers like C-reactive protein and copeptin as prognostic tools. Conclusion. The evidence supports the use of PSI as the best available indicator while CURB-65 may be an alternative prognostic indicator for NHAP mortality. Overall, due to the paucity of information, biomarkers may not be as effective in this role. Larger prospective studies are needed to establish the most effective predictor(s) or combination scheme to help clinicians in decision-making related to NHAP mortality. Naveen Dhawan, Naushira Pandya, Michael Khalili, Manuel Bautista, Anurag Duggal, Jaya Bahl, and Vineet Gupta Copyright © 2015 Naveen Dhawan et al. All rights reserved. Aging and Cardiovascular Risk Mon, 02 Mar 2015 06:52:56 +0000 Elísio Costa, Alice Santos-Silva, Constança Paúl, and Javier González Gallego Copyright © 2015 Elísio Costa et al. All rights reserved. Age-Related Impairment of Quality of Joint Motion in Vibroarthrographic Signal Analysis Mon, 23 Feb 2015 11:28:31 +0000 Aging is associated with degenerative changes in articular surfaces leading to quantitative and qualitative impairment of joint motion. Therefore, the aim of this study is to evaluate an age-related quality of the patellofemoral joint (PFJ) motion in the vibroarthrographic (VAG) signal analysis. Two hundred and twenty individuals were enrolled in this study and divided into five groups according to age. The VAG signals were collected during flexion/extension knee motion using an acceleration sensor and described using four parameters (VMS, P1, P2, and H). We observed that values of parameters VMS, P1, and P2 increase in accordance with the age, but H level decreases. The most significant differences were achieved between the youngest and the oldest participants’ groups. Moreover, we show that parameters VMS, P1, and P2 positively correlate with age, contrary to negatively associated H parameter. Our results suggest that the impairment of joint motion is a result of age-related osteoarticular degenerative changes. Dawid Bączkowicz, Edyta Majorczyk, and Krzysztof Kręcisz Copyright © 2015 Dawid Bączkowicz et al. All rights reserved. Advances in Alzheimer’s Disease: From Bench to Bedside Thu, 19 Feb 2015 07:01:45 +0000 Teng Jiang, Raymond Chuen-Chung Chang, Hanna Rosenmann, and Jin-Tai Yu Copyright © 2015 Teng Jiang et al. All rights reserved. Icariin Intervenes in Cardiac Inflammaging through Upregulation of SIRT6 Enzyme Activity and Inhibition of the NF-Kappa B Pathway Tue, 20 Jan 2015 14:33:55 +0000 The aim of the study was to investigate the effect of icariin (ICA) on cardiac aging through its effects on the SIRT6 enzyme and on the NF-κB pathway. Investigating the effect of ICA on the enzymatic activity of histone deacetylase SIRT6 revealed a concentration of 10−8 mol/L ICA had a maximum activating effect on histone deacetylase SIRT6 enzymatic activity. Western analysis showed that ICA upregulated SIRT6 protein expression and downregulated NF-κB (p65) protein expression in animal tissues and cell models. ICA upregulated the expression of SIRT6 and had an inhibitory effect on NF-κB inflammatory signaling pathways as shown by decreasing mRNA levels of the NF-κB downstream target genes TNF-α, ICAM-1, IL-2, and IL-6. Those effects were mediated directly or indirectly by SIRT6. We provided evidence that inflammaging may involve a novel link between the effects of ICA on SIRT6 (a regulator of aging) and NF-κB (a regulator of inflammation). Yang Chen, Tao Sun, Junzhen Wu, Bill Kalionis, Changcheng Zhang, Ding Yuan, Jianhua Huang, Waijiao Cai, Hong Fang, and Shijin Xia Copyright © 2015 Yang Chen et al. All rights reserved. Resveratrol as a Therapeutic Agent for Alzheimer’s Disease Wed, 26 Nov 2014 09:06:01 +0000 Alzheimer’s disease (AD) is the most common cause of dementia, but there is no effective therapy till now. The pathogenic mechanisms of AD are considerably complex, including Aβ accumulation, tau protein phosphorylation, oxidative stress, and inflammation. Exactly, resveratrol, a polyphenol in red wine and many plants, is indicated to show the neuroprotective effect on mechanisms mostly above. Recent years, there are numerous researches about resveratrol acting on AD in many models, both in vitro and in vivo. However, the effects of resveratrol are limited by its pool bioavailability; therefore researchers have been trying a variety of methods to improve the efficiency. This review summarizes the recent studies in cell cultures and animal models, mainly discusses the molecular mechanisms of the neuroprotective effects of resveratrol, and thus investigates the therapeutic potential in AD. Teng Ma, Meng-Shan Tan, Jin-Tai Yu, and Lan Tan Copyright © 2014 Teng Ma et al. All rights reserved. The Significance of Body Mass Index in Calculating the Cut-Off Points for Low Muscle Mass in the Elderly: Methodological Issues Tue, 25 Nov 2014 09:53:05 +0000 Objectives. Cut-off points (COPs) for appendicular lean mass (ALM) index, essential to define low muscle mass (LMM) in the elderly, have never been officially defined for Poland. The aim of the study was to establish them. Additionally, the significance of body mass index (BMI) for correctly defining the COPs in a young, healthy reference group was assessed. Methods. The study was composed of reference group () and the elderly group (). In all subjects, body composition was assessed by bioimpedance analysis, and ALM index was calculated. Next, COPs (kg/m2) were set up for the whole reference group and for particular subgroups with different BMIs separately. They were used to diagnose sarcopenia in the elderly. Results. COP for all young females was 5.37 (COP-F), while it was equal to 5.52 (COP-F2) when only those with a recommended BMI (18.50–24.99 kg/m2) were taken into consideration. For males, it was 7.32 and 7.29, respectively. Only 7% of elderly females had LMM based on COP-F and 15% had LMM based on COP-F2 ; for males, the percentages were 18% and 16%, respectively. Conclusions. COPs for LMM for Poland are 5.52 kg/m2 (females) and 7.29 kg/m2 (males). The reference group BMI is an important factor in establishing COPs for low muscle mass. Roma Krzymińska-Siemaszko, Natasza Czepulis, Aleksandra Suwalska, Lechoslaw B. Dworak, Anna Fryzowicz, Beata Madej-Dziechciarow, and Katarzyna Wieczorowska-Tobis Copyright © 2014 Roma Krzymińska-Siemaszko et al. All rights reserved. Heat Shock Protein 70 in Alzheimer’s Disease Thu, 06 Nov 2014 13:02:25 +0000 Alzheimer’s disease (AD) is the most common neurodegenerative disease that caused dementia which has no effective treatment. Growing evidence has demonstrated that AD is a “protein misfolding disorder” that exhibits common features of misfolded, aggregation-prone proteins and selective cell loss in the mature nervous system. Heat shock protein 70 (HSP70) attracts extensive attention worldwide, because it plays a crucial role in preventing protein misfolding and inhibiting aggregation and represents a class of proteins potentially involved in AD pathogenesis. Numerous studies have indicated that HSP70 could suppress the progression of AD with in vitro and in vivo experiments. Thus, targeting HSP70 and the related compounds might represent a promising strategy for the treatment of AD. Rui-Chun Lu, Meng-Shan Tan, Hao Wang, An-Mu Xie, Jin-Tai Yu, and Lan Tan Copyright © 2014 Rui-Chun Lu et al. All rights reserved. Heat Shock Protein 90 in Alzheimer’s Disease Mon, 13 Oct 2014 07:15:56 +0000 Alzheimer’s disease (AD) is the first most common neurodegenerative disease. Despite a large amount of research, the pathogenetic mechanism of AD has not yet been clarified. The two hallmarks of the pathology of AD are the extracellular senile plaques (SPs) of aggregated amyloid-beta (Aβ) peptide and the accumulation of the intracellular microtubule-associated protein tau into fibrillar aggregates. Heat shock proteins (HSPs) play a key role in preventing protein misfolding and aggregation, and Hsp90 can be viewed as a ubiquitous molecular chaperone potentially involved in AD pathogenesis. A role of Hsp90 regulates the activity of the transcription factor heat shock factor-1 (HSF-1), the master regulator of the heat shock response. In AD, Hsp90 inhibitors may redirect neuronal aggregate formation, and protect against protein toxicity by activation of HSF-1 and the subsequent induction of heat shock proteins, such as Hsp70. Therefore, we review here to further discuss the recent advances and challenges in targeting Hsp90 for AD therapy. Jiang-Rong Ou, Meng-Shan Tan, An-Mu Xie, Jin-Tai Yu, and Lan Tan Copyright © 2014 Jiang-Rong Ou et al. All rights reserved. Potential Cardiovascular Risk Protection of Bilirubin in End-Stage Renal Disease Patients under Hemodialysis Wed, 10 Sep 2014 00:00:00 +0000 We evaluated the potential cardiovascular risk protection of bilirubin in hemodialysis (HD) patients. An enlarged set of studies were evaluated in 191 HD patients, including hematological study, lipid profile, iron metabolism, nutritional, inflammatory markers, and dialysis adequacy. The TA duplication screening in the UDP-glucuronosyltransferase 1 A1 (UGT1A1) promoter region was also performed. The UGT1A1 genotype frequencies in HD patients were 49.2%, 42.4%, and 8.4% for 6/6, 6/7, and 7/7 genotypes, respectively. Although no difference was found in UGT1A1 genotype distribution between the three tertiles of bilirubin, significant differences were found with increasing bilirubin levels, namely, a decrease in platelet, leukocyte, and lymphocyte counts, transferrin, oxidized low-density lipoprotein (ox-LDL), ox-LDL/low-density lipoprotein cholesterol ratio, apolipoprotein (Apo) A, Apo B, and interleukin-6 serum levels and a significant increased concentration of hemoglobin, hematocrit, erythrocyte count, iron, transferrin saturation, Apo A/Apo B ratio, adiponectin, and paraoxonase 1 serum levels. After adjustment for age these results remained significant. Our data suggest that higher bilirubin levels are associated with beneficial effects in HD patients, by improving lipid profile and reducing the inflammatory grade, which might contribute to increase in iron availability. These results suggest a potential cardiovascular risk protection of bilirubin in HD patients. Maria do Sameiro-Faria, Michaela Kohlova, Sandra Ribeiro, Petronila Rocha-Pereira, Laetitia Teixeira, Henrique Nascimento, Flávio Reis, Vasco Miranda, Elsa Bronze-da-Rocha, Alexandre Quintanilha, Luís Belo, Elísio Costa, and Alice Santos-Silva Copyright © 2014 Maria do Sameiro-Faria et al. All rights reserved. Cardiovascular Risk Factor Analysis in Patients with a Recent Clinical Fracture at the Fracture Liaison Service Wed, 27 Aug 2014 07:35:06 +0000 Patients with a low bone mineral density have an increased risk of cardiovascular diseases (CVD) and venous thromboembolic events (VTE). The aim of our retrospective chart review was to investigate the prevalence of CVD, VTE, hypertension (HT), and diabetes mellitus type 2 (DM2) in patients with a recent clinical fracture visiting the Fracture Liaison Service (FLS). Out of 3057 patients aged 50–90 years, 1359 consecutive patients, who agreed and were able to visit the FLS for fracture risk evaluation, were included (71.7% women; mean age 65.2 yrs). Based on medical history, 29.9% had a history of CVD (13.7%), VTE (1.7%), HT (14.9%), and DM2 (7.1%) or a combination. Their prevalence increased with age (21% in patients aged 50–59 years to 48% in patients aged >80 years) and was higher in men than in women (36% versus 27%), but independent of bone mineral density and fracture type. Careful evaluation of medical history with respect to these risk factors should be performed in patients with a recent clinical fracture before starting treatment with medications that increase the risk of VTE or cardiovascular events, such as raloxifene, strontium ranelate, or NSAIDs. Caroline E. Wyers, Lisanne Vranken, Robert Y. van der Velde, Piet P. M. M. Geusens, Heinrich M. J. Janzing, J. Wim Morrenhof, and Joop P. W. van den Bergh Copyright © 2014 Caroline E. Wyers et al. All rights reserved. Clinical Correlates of Hachinski Ischemic Score and Vascular Factors in Cognitive Function of Elderly Tue, 26 Aug 2014 13:05:08 +0000 The aim of this study is to investigate the relationship between Hachinski ischemic score (HIS) and vascular factors as well as between HIS and the cognitive function in elderly community. Demographic characteristics, such as sex, age, education, history of drinking and smoking, family history of dementia and stroke, diabetes mellitus, hypertension, hyperlipidemia, cardiovascular disease, stroke, and dementia, were surveyed. Neurological examination was administered to every subject and HIS was checked by a neurologist. From a total of 392 participants aged 65 and over in a rural community, 348 completed the survey and were finally enrolled. Among the vascular factors, history of hypertension (), history of stroke (), family history of dementia (), and history of cardiac diseases () showed a significant relationship with HIS. In the cognitive function tests, both Korean version of the Mini-Mental State Examination and the Clinical Dementia Rating (Global and Sum of Boxes) had a significant relationship with HIS. Our study suggested HIS may have an association with some vascular factors and cognitive scales in community dwelling elderly. In this study, the HIS seemed to contribute to the evaluation of the quantity of vascular factors and to the prediction of status of cognitive function. Youn Ho Kim and Oh Dae Kwon Copyright © 2014 Youn Ho Kim and Oh Dae Kwon. All rights reserved. Microglia in Alzheimer’s Disease Thu, 14 Aug 2014 08:46:03 +0000 Alzheimer’s disease (AD) is a familiar neurodegenerative disease in the elderly. In this paper, we will review current viewpoints of microglial activation, inflammatory regulatory systems, and their relationship with AD pathology and etiology. Microglia cells are macrophage and representative of the innate immune system in brain. AD brain is marked by obvious inflammatory features, in which microglial activation is the driving force. β-amyloid protein sedimentation activates microglia cells, which causes the inflammation in AD. Microglia cells have dual roles: they provoke the release of inflammatory factors and cytotoxins leading to neuronal injuries and death; on the other hand, they have the neuroprotective effects. Through this, we hope to illustrate that the anti-inflammatory defenses of neurons can be practiced in the future strategy for recuperating the balance between the levels of inflammatory mediators and immune regulators in AD. Ying Li, Meng-Shan Tan, Teng Jiang, and Lan Tan Copyright © 2014 Ying Li et al. All rights reserved. Relating Education, Brain Structure, and Cognition: The Role of Cardiovascular Disease Risk Factors Tue, 12 Aug 2014 10:15:47 +0000 The protective effect of education on cognitive and brain health is well established. While the direct effects of individual cardiovascular disease (CVD) risk factors (i.e., hypertension, smoking, diabetes, and obesity) on cerebral structure have been investigated, little is understood about the possible interaction between the protective effect of education and the deleterious effects of CVD risk factors in predicting brain ageing and cognition. Using data from the PATH Through Life study , we investigated the protective effect of education on cerebral structure and function and tested a possible mediating role of CVD risk factors. Higher education was associated with larger regional grey/white matter volumes in the prefrontal cortex in men only. The association between education and cognition was mediated by brain volumes but only for grey matter and only in relation to information processing speed. CVD risk factors did not mediate the association between regional volumes and cognition. This study provides additional evidence in support for a protective effect of education on cerebral structures and cognition. However, it does not provide support for a mediating role of CVD risk factors in these associations. Moyra E. Mortby, Richard Burns, Andrew L. Janke, Perminder S. Sachdev, Kaarin J. Anstey, and Nicolas Cherbuin Copyright © 2014 Moyra E. Mortby et al. All rights reserved. Cardiovascular Risk Factors and Total Serum Antioxidant Capacity in Healthy Men and in Men with Coronary Heart Disease Mon, 11 Aug 2014 07:10:24 +0000 Whether the incidence of coronary heart disease (CHD) is related to a decrease in total antioxidant capacity (TAC) has not yet been completely clarified. We assessed TAC of blood serum in a group of 163 men with CHD aged 34.8–77.0 years and in 163 age-matched peers without CHD. Two spectrophotometric methods were applied to assess TAC: ferric reducing ability of serum (TAC-FRAS) and 2.2-diphenyl-1-picryl-hydrazyl (TAC-DPPH) tests. In the CHD group, multivariate analysis revealed that uric acid (UA), triglycerides, and systolic blood pressure contributed independently to the TAC-FRAS variance. TAC-DPPH was favorably predicted by UA concentration, but negatively so by current smoking and glucose levels. In men without CHD, UA was the only independent determinant of both TAC-FRAS and TAC-DPPH. Presence of CHD was not an independent predictor of TAC—observed between-group differences (higher TAC in CHD patients) disappeared after adjustment for other confounders. We conclude that UA is the main determinant of TAC of blood serum in men. TAC is not directly influenced by age or CHD but is related to several indices of overweight/obesity and laboratory measures of metabolic syndrome, especially in patients with CHD. Anna Gawron-Skarbek, Jacek Chrzczanowicz, Joanna Kostka, Dariusz Nowak, Wojciech Drygas, Anna Jegier, and Tomasz Kostka Copyright © 2014 Anna Gawron-Skarbek et al. All rights reserved. Arterial Stiffness and Cardiovascular Therapy Thu, 07 Aug 2014 06:04:57 +0000 The world population is aging and the number of old people is continuously increasing. Arterial structure and function change with age, progressively leading to arterial stiffening. Arterial stiffness is best characterized by measurement of pulse wave velocity (PWV), which is its surrogate marker. It has been shown that PWV could improve cardiovascular event prediction in models that included standard risk factors. Consequently, it might therefore enable better identification of populations at high-risk of cardiovascular morbidity and mortality. The present review is focused on a survey of different pharmacological therapeutic options for decreasing arterial stiffness. The influence of several groups of drugs is described: antihypertensive drugs (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, beta-blockers, diuretics, and nitrates), statins, peroral antidiabetics, advanced glycation end-products (AGE) cross-link breakers, anti-inflammatory drugs, endothelin-A receptor antagonists, and vasopeptidase inhibitors. All of these have shown some effect in decreasing arterial stiffness. Nevertheless, further studies are needed which should address the influence of arterial stiffness diminishment on major adverse cardiovascular and cerebrovascular events (MACCE). Miodrag Janić, Mojca Lunder, and Mišo Šabovič Copyright © 2014 Miodrag Janić et al. All rights reserved. Heat Shock Proteins at the Crossroads between Cancer and Alzheimer’s Disease Thu, 24 Jul 2014 06:37:47 +0000 Heat shock proteins 70 and heat shock proteins 90 (Hsp70/90) have been implicated in many crucial steps of carcinogenesis: stabilizing oncogenic proteins, inhibiting programmed cell death and replicative senescence, induction of tumor angiogenesis, and activation of the invasion and metastasis. Plenty of cancer related proteins have the ability of regulating the expression of Hsp70/90 through heat shock factor 1. Cancer and Alzheimer’s disease (AD) have plenty of overlapping regions in molecular genetics and cell biology associated with Hsp70/90. The Hsp70, as a protein stabilizer, has a cellular protection against neurodegeneration of the central nervous system, while Hsp90 promote neurodegenerative disorders indirectly through regulating the expression of Hsp70 and other chaperones. All these make existing anticancer drugs target Hsp70/90 which might be used in AD therapy. Hao Wang, Meng-Shan Tan, Rui-Chun Lu, Jin-Tai Yu, and Lan Tan Copyright © 2014 Hao Wang et al. All rights reserved. The Type of Fat Ingested at Breakfast Influences the Plasma Lipid Profile of Postmenopausal Women Mon, 21 Jul 2014 07:17:20 +0000 To assess whether the type of fat ingested at breakfast can modify the plasma lipid profile and other cardiovascular risk variables in postmenopausal women at risk of cardiovascular disease, a longitudinal, randomized, and crossover study was carried out with postmenopausal women at risk of CVD. They were randomly assigned to eat each type of breakfast during one month: 6 study periods (breakfast with the same composition plus butter/margarine/virgin olive oil) separated by two washout periods. On the first and last days of each study period, weight, arterial blood pressure, heart rate, and body mass index were recorded in fasting conditions and a blood sample was collected to measure plasma lipid profile. When comparing final values to baseline values, we only found out statistically significant differences on plasma lipid profiles. Butter-based breakfast increased total cholesterol and HDL, while margarine-based breakfast decreased total cholesterol and LDL and increased HDL. After the olive oil-based breakfast intake, a tendency towards a decrease of total cholesterol and LDL levels and an increase of HDL levels was observed. No statistically significant differences were observed in triglycerides levels, BMI, and arterial pressure in any breakfast type. The margarine-based breakfast was the only one which significantly increased the percentage of volunteers with optimal lipid profiles. The polyunsaturated fat at breakfast has improved the plasma lipid profile in the analyzed sample population, suggesting that PUFA-based breakfast can be advisable in women at risk of CVD. J. M. Morillas-Ruiz, J. M. Delgado-Alarcon, J. M. Rubio-Perez, and M. D. Albaladejo Oton Copyright © 2014 J. M. Morillas-Ruiz et al. All rights reserved. The Role of Oxidative Stress and Inflammation in Cardiovascular Aging Sun, 20 Jul 2014 12:24:00 +0000 Age is an independent risk factor of cardiovascular disease, even in the absence of other traditional factors. Emerging evidence in experimental animal and human models has emphasized a central role for two main mechanisms of age-related cardiovascular disease: oxidative stress and inflammation. Excess reactive oxygen species (ROS) and superoxide generated by oxidative stress and low-grade inflammation accompanying aging recapitulate age-related cardiovascular dysfunction, that is, left ventricular hypertrophy, fibrosis, and diastolic dysfunction in the heart as well as endothelial dysfunction, reduced vascular elasticity, and increased vascular stiffness. We describe the signaling involved in these two main mechanisms that include the factors NF-κB, JunD, p66Shc, and Nrf2. Potential therapeutic strategies to improve the cardiovascular function with aging are discussed, with a focus on calorie restriction, SIRT1, and resveratrol. Junzhen Wu, Shijin Xia, Bill Kalionis, Wenbin Wan, and Tao Sun Copyright © 2014 Junzhen Wu et al. All rights reserved. Serum Osteopontin Level Correlates with Carotid-Femoral Pulse Wave Velocity in Geriatric Persons Tue, 15 Jul 2014 09:35:35 +0000 Osteopontin (OPN) is involved in the regulation of vascular calcification processes. The aim of this study was to evaluate the relationship between fasting serum OPN concentration and carotid-femoral pulse wave velocity (cfPWV) in geriatric persons. Fasting blood samples were obtained from 93 geriatric persons. cfPWV were performed by SphygmoCor system. Serum OPN levels were measured using a commercially available enzyme-linked immunosorbent assay. Geriatric adults who had diabetes () or dyslipidemia () had higher cfPWV levels than those without diabetes or dyslipidemia. The univariable linear regression analysis showed that age (), waist circumference (), body mass index (), systolic blood pressure (), diastolic blood pressure (), pulse pressure (), creatinine (), and log-OPN level () were positively correlated with cfPWV levels, while the high-density lipoprotein cholesterol (HDL-cholesterol) level () and glomerular filtration rate () were negatively correlated with cfPWV levels among the geriatric adults. Multivariable forward stepwise linear regression analysis of the significant variables also showed that log-OPN (, , regression coefficient: 1.868, ) was still an independent predictor of cfPWV levels in geriatric persons. Chung-Jen Lee, Ji-Hung Wang, Yu-Chih Chen, Mei-Ling Chen, Chiu-Fen Yang, and Bang-Gee Hsu Copyright © 2014 Chung-Jen Lee et al. All rights reserved. Behavioral and Psychological Symptoms in Alzheimer’s Disease Tue, 15 Jul 2014 08:28:55 +0000 Neuropsychiatric symptoms (NPS) such as depression, apathy, aggression, and psychosis are now recognized as core features of Alzheimer’s disease (AD), and there is a general consensus that greater symptom severity is predictive of faster cognitive decline, loss of independence, and even shorter survival. Whether these symptoms result from the same pathogenic processes responsible for cognitive decline or have unique etiologies independent of AD-associated neurodegeneration is unclear. Many structural and metabolic features of the AD brain are associated with individual neuropsychiatric symptoms or symptom clusters. In addition, many genes have been identified and confirmed that are associated with symptom risk in a few cases. However, there are no single genes strongly predictive of individual neuropsychiatric syndromes, while functional and structural brain changes unique to specific symptoms may reflect variability in progression of the same pathological processes. Unfortunately, treatment success for these psychiatric symptoms may be lower when comorbid with AD, underscoring the importance of future research on their pathobiology and treatment. This review summarizes some of the most salient aspects of NPS pathogenesis. Xiao-Ling Li, Nan Hu, Meng-Shan Tan, Jin-Tai Yu, and Lan Tan Copyright © 2014 Xiao-Ling Li et al. All rights reserved. Aromatherapy: Does It Help to Relieve Pain, Depression, Anxiety, and Stress in Community-Dwelling Older Persons? Sun, 13 Jul 2014 00:00:00 +0000 To examine the effectiveness of an aromatherapy programme for older persons with chronic pain. The community-dwelling elderly people who participated in this study underwent a four-week aromatherapy programme or were assigned to the control group, which did not receive any interventions. Their levels of pain, depression, anxiety, and stress were collected at the baseline and at the postintervention assessment after the conclusion of the four-week programme. Eighty-two participants took part in the study. Forty-four participants (37 females, 7 males) were in the intervention group and 38 participants (30 females, 8 males) were in the control group. The pain scores were 4.75 (SD 2.32) on a 10-point scale for the intervention group and 5.24 (SD 2.14) for the control group before the programme. There was a slight reduction in the pain score of the intervention group. No significant differences were found in the same-group and between-group comparisons for the baseline and postintervention assessments. The depression, anxiety, and stress scores for the intervention group before the programme were 11.18 (SD 6.18), 9.64 (SD 7.05), and 12.91 (SD 7.70), respectively. A significant reduction in negative emotions was found in the intervention group (). The aromatherapy programme can be an effective tool to reduce pain, depression, anxiety, and stress levels among community-dwelling older adults. Shuk Kwan Tang and M. Y. Mimi Tse Copyright © 2014 Shuk Kwan Tang and M. Y. Mimi Tse. All rights reserved. Modulation of Circulating Macrophage Migration Inhibitory Factor in the Elderly Tue, 08 Jul 2014 11:57:38 +0000 Aging increases the risk for cardiovascular morbidity and mortality. Chronic low-grade inflammation deteriorates vascular function, increases age-related vascular stiffness, and affects hemodynamics. The proinflammatory cytokine macrophage migration inhibitory factor (MIF) is a major mediator of atherosclerosis. Plasma MIF levels are associated with arterial stiffness, a hallmark of vascular aging. Preclinical studies show that blockade of MIF leads to atherosclerotic plaque regression. Nutritional approaches provide opportunities to counteract age-related inflammation. Following a chronic dietary supplementation with the micronutrient nitrate has been demonstrated to improve vascular stiffness. Whether dietary nitrate affects circulating MIF levels is not known. In a randomized placebo-controlled, double-blinded study, elderly subjects received a dietary nitrate supplementation for 4 weeks. Dietary nitrate led to a decrease in plasma MIF levels in the elderly and to an improvement in vascular functions. This was associated with a reduction in central systolic blood pressure. Our data show that supplementation with dietary nitrate is associated with a reduction of circulating MIF levels along with an improvement in vascular function. This supports the concept of dietary approaches to modulate age-related changes of vascular functions. Christos Rammos, Ulrike B. Hendgen-Cotta, Julia Pohl, Matthias Totzeck, Peter Luedike, Volker T. Schulze, Malte Kelm, and Tienush Rassaf Copyright © 2014 Christos Rammos et al. All rights reserved. The Impact of Low Muscle Mass Definition on the Prevalence of Sarcopenia in Older Australians Thu, 03 Jul 2014 11:21:09 +0000 Background. Sarcopenia is the presence of low muscle mass and low muscle function. The aim of this study was to establish cutoffs for low muscle mass using three published methods and to compare the prevalence of sarcopenia in older Australians. Methods. Gender specific cutoffs levels were identified for low muscle mass using three different methods. Low grip strength was determined using established cutoffs of <30 kg for men and <20 kg for women to estimate the prevalence of sarcopenia. Results. Gender specific cutoffs levels for low muscle mass identified were (a) <6.89 kg/m2 for men and <4.32 kg/m2 for women, <2 standard deviation (SD) of a young reference population; (b) <7.36 kg/m2 for men and <5.81 kg/m2 for women from the lowest 20% percentile of the older group; and (c) <−2.15 for men and <−1.42 for women from the lowest 20% of the residuals of linear regressions of appendicular skeletal mass, adjusted for fat mass and height. Prevalence of sarcopenia in older (65 years and older) people by these three methods for men was 2.5%, 6.2%, and 6.4% and for women 0.3%, 9.3%, and 8.5%, respectively. Conclusions. Sarcopenia is common but consensus on the best method to confirm low muscle mass is required. Solomon Yu, Sarah Appleton, Robert Adams, Ian Chapman, Gary Wittert, Thavarajah Visvanathan, and Renuka Visvanathan Copyright © 2014 Solomon Yu et al. All rights reserved. Adiponectin, Leptin, and Chemerin in Elderly Patients with Type 2 Diabetes Mellitus: A Close Linkage with Obesity and Length of the Disease Wed, 02 Jul 2014 11:38:20 +0000 Obesity, insulin resistance, and aging are closely associated and adipokines seem to have a crucial role in their pathophysiology. We aim to study the relationship between aging and chemerin, adiponectin, and leptin levels in type 2 diabetes mellitus (T2DM). Age correlated positively with chemerin and leptin and inversely with adiponectin. Body mass index (BMI) correlated positively with leptin (in males) and chemerin and inversely with adiponectin. The patients with ≥65 years showed significantly higher leptin and chemerin and lower adiponectin levels than middle-aged (38–64 years) patients and controls . After statistical adjustment for length of disease, there was a loss of significance, between T2DM groups, for adiponectin and, in female, for leptin. In the older group, BMI correlated with adiponectin and with leptin, but not with chemerin. Adiponectin and leptin levels in elderly T2DM patients seem to be closely linked to obesity and to length of the disease. In elderly T2DM patients, chemerin concentrations are increased and seem to be independent of length of disease and BMI, suggesting that adipocyte dysfunction is enhanced with aging. The understanding of the glucose homeostasis impairment in the elderly is mandatory in order to achieve ways to improve their quality of life and longevity. Susana Coimbra, Jorge Brandão Proença, Alice Santos-Silva, and Maria João Neuparth Copyright © 2014 Susana Coimbra et al. All rights reserved. The Effects of Housing on Health and Health Risks in an Aging Population: A Qualitative Study in Rural Thailand Wed, 02 Jul 2014 06:22:54 +0000 Background. Over the last decade, Thailand has experienced an aging population, especially in rural areas. Research finds a strong, positive relationship between good quality housing and health, and this paper assesses the impact and living experience of housing of older people in rural Thailand. Methods. This was a mixed-method study, using data from observations of the physical adequacy of housing, semistructured interviews with key informants, and archival information from health records for 13 households in rural Thailand. Results. There were four main themes, each of which led to health risks for the older people: “lighting and unsafe wires,” “house design and composition,” “maintenance of the house,” and “health care equipment.” The housing was not appropriately designed to accommodate health care equipment or to fully support individual daily activities of older people. Numerous accidents occurred as a direct result of inadequate housing and the majority of houses had insufficient and unsafe lighting, floor surfaces and furniture that created health risks, and toilets or beds that were at an unsuitable height for older people. Conclusion. This paper provides an improved and an important understanding of the housing situation among older people living in rural areas in Thailand. Ratana Somrongthong, Saovalux Dullyaperadis, Anne Louise Wulff, and Paul R. Ward Copyright © 2014 Ratana Somrongthong et al. All rights reserved. Matrix Metalloproteinases and Their Multiple Roles in Alzheimer’s Disease Tue, 24 Jun 2014 08:10:45 +0000 Alzheimer’s disease (AD) is the most prevalent type of dementia. Pathological changes in the AD brain include amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs), as well as neuronal death and synaptic loss. Matrix metalloproteinases (MMPs) play an important role as inflammatory components in the pathogenesis of AD. MMP-2 might be assumed to have a protective role in AD and is the major MMP which is directly linked to Aβ in the brain. Synthesis of MMP-9 can be induced by Aβ, and the enzymes appear to exert multiple effects in AD in senile plaque homoeostasis. The proaggregatory influence on tau oligomer formation in strategic brain regions may be a potential neurotoxic side effect of MMP-9. MMP-3 levels are correlated to the duration of AD and correlate with the CSF T-tau and P-tau levels in the elderly controls. Elevated brain levels of MMP-3 might result in increased MMP-9 activity and indirectly facilitate tau aggregation. At present, the clinical utility of these proteins, particularly in plasma or serum, as potential early diagnostic biomarkers for AD remains to be established. More research is needed to understand the diverse roles of these proteases to design specific drugs and devise therapeutic strategies for AD. Xiang-Xiang Wang, Meng-Shan Tan, Jin-Tai Yu, and Lan Tan Copyright © 2014 Xiang-Xiang Wang et al. All rights reserved. Simultaneous Changes of Spatial Memory and Spine Density after Intrahippocampal Administration of Fibrillar Aβ1–42 to the Rat Brain Mon, 23 Jun 2014 08:00:29 +0000 Several animal models of Alzheimer’s disease have been used in laboratory experiments. Intrahippocampal injection of fibrillar amyloid-beta (fAβ) peptide represents one of the most frequently used models, mimicking Aβ deposits in the brain. In our experiment synthetic fAβ1–42 peptide was administered to rat hippocampus. The effect of the Aβ peptide on spatial memory and dendritic spine density was studied. The fAβ1–42-treated rats showed decreased spatial learning ability measured in Morris water maze (MWM). Simultaneously, fAβ1–42 caused a significant reduction of the dendritic spine density in the rat hippocampus CA1 region. The decrease of learning ability and the loss of spine density were in good correlation. Our results prove that both methods (MWM and dendritic spine density measurement) are suitable for studying Aβ-triggered neurodegeneration processes. Emőke Borbély, János Horváth, Szabina Furdan, Zsolt Bozsó, Botond Penke, and Lívia Fülöp Copyright © 2014 Emőke Borbély et al. All rights reserved. We Are Ageing Sun, 22 Jun 2014 07:19:00 +0000 Ageing and longevity is unquestioningly complex. Several thoughts and mechanisms of ageing such as pathways involved in oxidative stress, lipid and glucose metabolism, inflammation, DNA damage and repair, growth hormone axis and insulin-like growth factor (GH/IGF), and environmental exposure have been proposed. Also, some theories of ageing were introduced. To date, the most promising leads for longevity are caloric restriction, particularly target of rapamycin (TOR), sirtuins, hexarelin and hormetic responses. This review is an attempt to analyze the mechanisms and theories of ageing and achieving longevity. Genovefa D. Kolovou, Vana Kolovou, and Sophie Mavrogeni Copyright © 2014 Genovefa D. Kolovou et al. All rights reserved. Protective Effects of Testosterone on Presynaptic Terminals against Oligomeric -Amyloid Peptide in Primary Culture of Hippocampal Neurons Wed, 18 Jun 2014 06:50:05 +0000 Increasing lines of evidence support that testosterone may have neuroprotective effects. While observational studies reported an association between higher bioavailable testosterone or brain testosterone levels and reduced risk of Alzheimer’s disease (AD), there is limited understanding of the underlying neuroprotective mechanisms. Previous studies demonstrated that testosterone could alleviate neurotoxicity induced by -amyloid (A), but these findings mainly focused on neuronal apoptosis. Since synaptic dysfunction and degeneration are early events during the pathogenesis of AD, we aim to investigate the effects of testosterone on oligomeric A-induced synaptic changes. Our data suggested that exposure of primary cultured hippocampal neurons to oligomeric A could reduce the length of neurites and decrease the expression of presynaptic proteins including synaptophysin, synaptotagmin, and synapsin-1. A also disrupted synaptic vesicle recycling and protein folding machinery. Testosterone preserved the integrity of neurites and the expression of presynaptic proteins. It also attenuated A-induced impairment of synaptic exocytosis. By using letrozole as an aromatase antagonist, we further demonstrated that the effects of testosterone on exocytosis were unlikely to be mediated through the estrogen receptor pathway. Furthermore, we showed that testosterone could attenuate A-induced reduction of HSP70, which suggests a novel mechanism that links testosterone and its protective function on A-induced synaptic damage. Taken together, our data provide further evidence on the beneficial effects of testosterone, which may be useful for future drug development for AD. Chi-Fai Lau, Yuen-Shan Ho, Clara Hiu-Ling Hung, Suthicha Wuwongse, Chun-Hei Poon, Kin Chiu, Xifei Yang, Leung-Wing Chu, and Raymond Chuen-Chung Chang Copyright © 2014 Chi-Fai Lau et al. All rights reserved. Dipeptidyl Peptidase 10 (DPP10789): A Voltage Gated Potassium Channel Associated Protein Is Abnormally Expressed in Alzheimer’s and Other Neurodegenerative Diseases Mon, 16 Jun 2014 07:48:11 +0000 The neuropathological features associated with Alzheimer’s disease (AD) include the presence of extracellular amyloid-β peptide-containing plaques and intracellular tau positive neurofibrillary tangles and the loss of synapses and neurons in defined regions of the brain. Dipeptidyl peptidase 10 (DPP10) is a protein that facilitates Kv4 channel surface expression and neuronal excitability. This study aims to explore DPP10789 protein distribution in human brains and its contribution to the neurofibrillary pathology of AD and other tauopathies. Immunohistochemical analysis revealed predominant neuronal staining of DPP10789 in control brains, and the CA1 region of the hippocampus contained strong reactivity in the distal dendrites of the pyramidal cells. In AD brains, robust DPP10789 reactivity was detected in neurofibrillary tangles and plaque-associated dystrophic neurites, most of which colocalized with the doubly phosphorylated Ser-202/Thr-205 tau epitope. DPP10789 positive neurofibrillary tangles and plaque-associated dystrophic neurites also appeared in other neurodegenerative diseases such as frontotemporal lobar degeneration, diffuse Lewy body disease, and progressive supranuclear palsy. Occasional DPP10789 positive neurofibrillary tangles and neurites were seen in some aged control brains. Western blot analysis showed both full length and truncated DPP10789 fragments with the later increasing significantly in AD brains compared to control brains. Our results suggest that DPP10789 is involved in the pathology of AD and other neurodegenerative diseases. Tong Chen, Wei-Ping Gai, and Catherine A. Abbott Copyright © 2014 Tong Chen et al. All rights reserved. MicroRNAs Expression Profiles in Cardiovascular Diseases Thu, 12 Jun 2014 08:55:08 +0000 The current search for new markers of cardiovascular diseases (CVDs) is explained by the high morbidity and mortality still observed in developed and developing countries due to cardiovascular events. Recently, microRNAs (miRNAs or miRs) have emerged as potential new biomarkers and are small sequences of RNAs that regulate gene expression at posttranscriptional level by inhibiting translation or inducing degradation of the target mRNAs. Circulating miRNAs are involved in the regulation of signaling pathways associated to aging and can be used as novel diagnostic markers for acute and chronic diseases such as cardiovascular pathologies. This review summarizes the biogenesis, maturation, and stability of miRNAs and their use as potential biomarkers for coronary artery disease (CAD), myocardial infarction (MI), and heart failure (HF). Elsa Bronze-da-Rocha Copyright © 2014 Elsa Bronze-da-Rocha. All rights reserved. Correlation between Behavioural and Psychological Symptoms of Alzheimer Type Dementia and Plasma Homocysteine Concentration Wed, 04 Jun 2014 07:24:44 +0000 The relationship between plasma homocysteine and behavioral and psychological symptoms of dementia (BPSD) has not been specifically investigated in previous research. In this study, we compared plasma homocysteine (Hcy) among 40 Alzheimer’s disease (AD) patients with BPSD, 37 AD patients without BPSD, and 39 healthy controls. Our results evidenced that the plasma homocysteine levels in AD patients with BPSD and without BPSD were higher than healthy controls and that the plasma homocysteine concentration in AD patients with BPSD was the highest among the three groups. Significant correlation between plasma homocysteine concentration and cognitive decline and duration of dementia was observed, but there was no correlation between BPSD and cognitive dysfunction or duration of dementia. In conclusion, this study showed for the first time that BPSD were associated with plasma homocysteine concentration in Alzheimer's dementia, and the results supported that hyperhomocysteine may take part in the pathogenesis of BPSD. Zhanjie Zheng, Jindong Wang, Lei Yi, Hui Yu, Lingli Kong, Weizhen Cui, Hong Chen, and Chunxia Wang Copyright © 2014 Zhanjie Zheng et al. All rights reserved. Comparison of Two Analytical Platforms for CSF Biomarkers of Alzheimer’s Disease Thu, 29 May 2014 12:09:48 +0000 Cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) are currently being assessed with two different assays. Our objective was to study if there is a correlation between values obtained by both techniques, to compare their validity and search for conversion factor between values obtained for every protein. We compared the performances of two commonly used platforms, an enzyme-linked immunosorbent assay (ELISA) and a multiplex (xMAP) technology for measurement of CSF , total tau (T-tau), and phosphorylated tau 181 () proteins, in 30 AD patients and 28 control subjects. The relations between the variables of both techniques were evaluated using the Spearman p correlation coefficient (). Receiver operating characteristic and area under the curve (AUC) analyses were calculated for the variables of both techniques. The two assays platforms yielded different absolute values for the various analytes, always higher in ELISA. We found some correction factor between values: 2,1- to 3-fold for ; 4,1- to 4,6-fold for T-tau; and 1,4- to 1,6-fold for . In addition, those values were highly correlated (: , ; T-tau: , ; : , ) and the AUC for the variables showed very similar values. In conclusion, the results obtained with ELISA and xMAP platforms were highly correlated and its validity is very similar. Differences in absolute values point to the need for a clear description of the technique used. Moreover, we found some conversion factor between values of every protein that may be useful for transformation between both techniques. Jose Antonio Monge-Argilés, Carlos Muñoz-Ruiz, José Sánchez-Payá, Ruth Gasparini Berenguer, Maria Empar Blanco Cantó, and Carlos Leiva-Santana Copyright © 2014 Jose Antonio Monge-Argilés et al. All rights reserved. Aging and Longevity between Genetic Background and Lifestyle Intervention Tue, 27 May 2014 09:39:11 +0000 Giuseppe Passarino, Giuseppina Rose, Dina Bellizzi, Maria De Luca, and Efstathios S. Gonos Copyright © 2014 Giuseppe Passarino et al. All rights reserved. Clinical Genetics of Alzheimer’s Disease Tue, 13 May 2014 09:45:25 +0000 Alzheimer’s disease (AD) is the most common progressive neurodegenerative disease and the most common form of dementia in the elderly. It is a complex disorder with environmental and genetic components. There are two major types of AD, early onset and the more common late onset. The genetics of early-onset AD are largely understood with mutations in three different genes leading to the disease. In contrast, while susceptibility loci and alleles associated with late-onset AD have been identified using genetic association studies, the genetics of late-onset Alzheimer’s disease are not fully understood. Here we review the known genetics of early- and late-onset AD, the clinical features of EOAD according to genotypes, and the clinical implications of the genetics of AD. Zhangyu Zou, Changyun Liu, Chunhui Che, and Huapin Huang Copyright © 2014 Zhangyu Zou et al. All rights reserved. Shared Mechanisms of Neurodegeneration in Alzheimer’s Disease and Parkinson’s Disease Mon, 12 May 2014 11:24:25 +0000 Alzheimer’s disease (AD) and Parkinson’s disease (PD) have markedly different clinical and pathological features, but these two diseases are the most common neurodegenerative disorders. Previous studies have showed that there are common mechanisms in AD and PD. Several genetic studies have revealed mutations in genes associated with the risk of AD and PD. Circumstantial evidences have shown that dysregulation of brain iron homeostasis leads to abnormal iron accumulation and results in AD as well as PD. α-Synuclein and tau take part in the mechanisms of these diseases by oxidative stress and mitochondrial dysfunction. Some studies indicated that the loss of LC noradrenergic neurons may occur early in the progression of AD and PD. Nicotinic acetylcholine receptors (nAChRs) are members of the Cys-loop superfamily of pentameric ligand-gated ion channels; some evidence showed that nicotinic receptors may be associated with AD and PD. These experimental and clinical studies may provide a scientific foundation for common shared mechanisms in AD and PD. Anmu Xie, Jing Gao, Lin Xu, and Dongmei Meng Copyright © 2014 Anmu Xie et al. All rights reserved. Mitochondrial Dysfunctions in Neurodegenerative Diseases: Relevance to Alzheimer’s Disease Mon, 12 May 2014 11:17:54 +0000 Mitochondrial dysfunctions are supposed to be responsible for many neurodegenerative diseases dominating in Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD). A growing body of evidence suggests that defects in mitochondrial metabolism and particularly of electron transport chain may play a role in pathogenesis of AD. Structurally and functionally damaged mitochondria do not produce sufficient ATP and are more prominent in producing proapoptotic factors and reactive oxygen species (ROS), and this can be an early stage of several mitochondrial disorders, including neurodegenerative diseases. Mitochondrial dysfunctions may be caused by both mutations in mitochondrial or nuclear DNA that code mitochondrial components and by environmental causes. In the following review, common aspects of mitochondrial impairment concerned about neurodegenerative diseases are summarized including ROS production, impaired mitochondrial dynamics, and apoptosis. Also, damaged function of electron transport chain complexes and interactions between pathological proteins and mitochondria are described for AD particularly and marginally for PD and HD. Jana Hroudová, Namrata Singh, and Zdeněk Fišar Copyright © 2014 Jana Hroudová et al. All rights reserved. Alteration of ROS Homeostasis and Decreased Lifespan in S. cerevisiae Elicited by Deletion of the Mitochondrial Translocator FLX1 Thu, 08 May 2014 00:00:00 +0000 This paper deals with the control exerted by the mitochondrial translocator FLX1, which catalyzes the movement of the redox cofactor FAD across the mitochondrial membrane, on the efficiency of ATP production, ROS homeostasis, and lifespan of S. cerevisiae. The deletion of the FLX1 gene resulted in respiration-deficient and small-colony phenotype accompanied by a significant ATP shortage and ROS unbalance in glycerol-grown cells. Moreover, the strain showed H2O2 hypersensitivity and decreased lifespan. The impaired biochemical phenotype found in the strain might be justified by an altered expression of the flavoprotein subunit of succinate dehydrogenase, a key enzyme in bioenergetics and cell regulation. A search for possible cis-acting consensus motifs in the regulatory region upstream SDH1-ORF revealed a dozen of upstream motifs that might respond to induced metabolic changes by altering the expression of Flx1p. Among these motifs, two are present in the regulatory region of genes encoding proteins involved in flavin homeostasis. This is the first evidence that the mitochondrial flavin cofactor status is involved in controlling the lifespan of yeasts, maybe by changing the cellular succinate level. This is not the only case in which the homeostasis of redox cofactors underlies complex phenotypical behaviours, as lifespan in yeasts. Teresa Anna Giancaspero, Emilia Dipalo, Angelica Miccolis, Eckhard Boles, Michele Caselle, and Maria Barile Copyright © 2014 Teresa Anna Giancaspero et al. All rights reserved. Calorie Restriction in Mammals and Simple Model Organisms Tue, 06 May 2014 00:00:00 +0000 Calorie restriction (CR), which usually refers to a 20–40% reduction in calorie intake, can effectively prolong lifespan preventing most age-associated diseases in several species. However, recent data from both human and nonhumans point to the ratio of macronutrients rather than the caloric intake as a major regulator of both lifespan and health-span. In addition, specific components of the diet have recently been identified as regulators of some age-associated intracellular signaling pathways in simple model systems. The comprehension of the mechanisms underpinning these findings is crucial since it may increase the beneficial effects of calorie restriction making it accessible to a broader population as well. Giusi Taormina and Mario G. Mirisola Copyright © 2014 Giusi Taormina and Mario G. Mirisola. All rights reserved. The Role of Wnt Signaling in the Development of Alzheimer’s Disease: A Potential Therapeutic Target? Sun, 04 May 2014 12:58:51 +0000 Accumulating evidence supports a key role for Wnt signaling in the development of the central nervous system (CNS) during embryonic development and in the regulation of the structure and function of the adult brain. Alzheimer’s disease (AD) is the most common form of senile dementia, which is characterized by β-amyloid (Aβ) deposition in specific brain regions. However, the molecular mechanism underlying AD pathology remains elusive. Dysfunctional Wnt signaling is associated with several diseases such as epilepsy, cancer, metabolic disease, and AD. Increasing evidence suggests that downregulation of Wnt signaling, induced by Aβ, is associated with disease progression of AD. More importantly, persistent activation of Wnt signaling through Wnt ligands, or inhibition of negative regulators of Wnt signaling, such as Dickkopf-1 (DKK-1) and glycogen synthase kinase-3β (GSK-3β) that are hyperactive in the disease state, is able to protect against Aβ toxicity and ameliorate cognitive performance in AD. Together, these data suggest that Wnt signaling might be a potential therapeutic target of AD. Here, we review recent studies related to the progression of AD where Wnt signaling might be relevant and participate in the development of the disease. Then, we focus on the potential relevance of manipulating the Wnt signaling pathway for the treatment of AD. Wenbin Wan, Shijin Xia, Bill Kalionis, Lumei Liu, and Yaming Li Copyright © 2014 Wenbin Wan et al. All rights reserved. Peripheral Blood Mononuclear Cells as a Laboratory to Study Dementia in the Elderly Wed, 30 Apr 2014 10:30:50 +0000 The steady and dramatic increase in the incidence of Alzheimer’s disease (AD) and the lack of effective treatments have stimulated the search for strategies to prevent or delay its onset and/or progression. Since the diagnosis of dementia requires a number of established features that are present when the disease is fully developed, but not always in the early stages, the need for a biological marker has proven to be urgent, in terms of both diagnosis and monitoring of AD. AD has been shown to affect peripheral blood mononuclear cells (PBMCs) that are a critical component of the immune system which provide defence against infection. Although studies are continuously supplying additional data that emphasize the central role of inflammation in AD, PBMCs have not been sufficiently investigated in this context. Delineating biochemical alterations in AD blood constituents may prove valuable in identifying accessible footprints that reflect degenerative processes within the Central Nervous System (CNS). In this review, we address the role of biomarkers in AD with a focus on the notion that PBMCs may serve as a peripheral laboratory to find molecular signatures that could aid in differential diagnosis with other forms of dementia and in monitoring of disease progression. Beatrice Arosio, Claudio D'Addario, Cristina Gussago, Martina Casati, Enzo Tedone, Evelyn Ferri, Paola Nicolini, Paolo D. Rossi, Mauro Maccarrone, and Daniela Mari Copyright © 2014 Beatrice Arosio et al. All rights reserved. Erratum to “Montreal Cognitive Assessment Is Superior to Standardized Mini-Mental Status Exam in Detecting Mild Cognitive Impairment in the Middle-Aged and Elderly Patients with Type 2 Diabetes Mellitus” Mon, 28 Apr 2014 08:26:10 +0000 Kannayiram Alagiakrishnan, Nancy Zhao, Laurie Mereu, Peter A. Senior, and Ambikaipakan Senthilselvan Copyright © 2014 Kannayiram Alagiakrishnan et al. All rights reserved. The Three Genetics (Nuclear DNA, Mitochondrial DNA, and Gut Microbiome) of Longevity in Humans Considered as Metaorganisms Thu, 24 Apr 2014 10:50:49 +0000 Usually the genetics of human longevity is restricted to the nuclear genome (nDNA). However it is well known that the nDNA interacts with a physically and functionally separated genome, the mitochondrial DNA (mtDNA) that, even if limited in length and number of genes encoded, plays a major role in the ageing process. The complex interplay between nDNA/mtDNA and the environment is most likely involved in phenomena such as ageing and longevity. To this scenario we have to add another level of complexity represented by the microbiota, that is, the whole set of bacteria present in the different part of our body with their whole set of genes. In particular, several studies investigated the role of gut microbiota (GM) modifications in ageing and longevity and an age-related GM signature was found. In this view, human being must be considered as “metaorganism” and a more holistic approach is necessary to grasp the complex dynamics of the interaction between the environment and nDNA-mtDNA-GM of the host during ageing. In this review, the relationship between the three genetics and human longevity is addressed to point out that a comprehensive view will allow the researchers to properly address the complex interactions that occur during human lifespan. Paolo Garagnani, Chiara Pirazzini, Cristina Giuliani, Marco Candela, Patrizia Brigidi, Federica Sevini, Donata Luiselli, Maria Giulia Bacalini, Stefano Salvioli, Miriam Capri, Daniela Monti, Daniela Mari, Sebastiano Collino, Massimo Delledonne, Patrick Descombes, and Claudio Franceschi Copyright © 2014 Paolo Garagnani et al. All rights reserved. PTEN Mediates the Antioxidant Effect of Resveratrol at Nutritionally Relevant Concentrations Thu, 10 Apr 2014 00:00:00 +0000 Introduction. Antioxidant properties of resveratrol have been intensively studied for the last years, both in vivo and in vitro. Its bioavailability after an oral dose is very low and therefore it is very important to make sure that plasma concentrations of free resveratrol are sufficient enough to be active as antioxidant. Aims. In the present study, using nutritionally relevant concentrations of resveratrol, we aim to confirm its antioxidant capacity on reducing peroxide levels and look for the molecular pathway involved in this antioxidant effect. Methods. We used mammary gland tumor cells (MCF-7), which were pretreated with different concentrations of resveratrol for 48 h, and/or a PTEN inhibitor (bpV: bipy). Hydrogen peroxide levels were determined by fluorimetry, PTEN levels and Akt phosphorylation by Western Blotting, and mRNA expression of antioxidant genes by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Results. Resveratrol treatment for 48 h lowered peroxide levels in MCF-7, even at low nutritional concentrations (1 nM). This effect was mediated by the activation of PTEN/Akt pathway, which resulted in an upregulation of catalase and MnSOD mRNA levels. Conclusion. Resveratrol acts as an antioxidant at nutritionally relevant concentrations by inducing the expression of antioxidant enzymes, through a mechanism involving PTEN/Akt signaling pathway. Marta Inglés, Juan Gambini, M. Graça Miguel, Vicent Bonet-Costa, Kheira M. Abdelaziz, Marya El Alami, Jose Viña, and Consuelo Borrás Copyright © 2014 Marta Inglés et al. All rights reserved. Biology of Ageing and Role of Dietary Antioxidants Thu, 03 Apr 2014 11:40:13 +0000 Interest in relationship between diet and ageing is growing. Research has shown that dietary calorie restriction and some antioxidants extend lifespan in various ageing models. On the one hand, oxygen is essential to aerobic organisms because it is a final electron acceptor in mitochondria. On the other hand, oxygen is harmful because it can continuously generate reactive oxygen species (ROS), which are believed to be the factors causing ageing of an organism. To remove these ROS in cells, aerobic organisms possess an antioxidant defense system which consists of a series of enzymes, namely, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). In addition, dietary antioxidants including ascorbic acid, vitamin A, vitamin C, α-tocopherol, and plant flavonoids are also able to scavenge ROS in cells and therefore theoretically can extend the lifespan of organisms. In this connection, various antioxidants including tea catechins, theaflavins, apple polyphenols, black rice anthocyanins, and blueberry polyphenols have been shown to be capable of extending the lifespan of fruit flies. The purpose of this review is to brief the literature on modern biological theories of ageing and role of dietary antioxidants in ageing as well as underlying mechanisms by which antioxidants can prolong the lifespan with focus on fruit flies as an model. Cheng Peng, Xiaobo Wang, Jingnan Chen, Rui Jiao, Lijun Wang, Yuk Man Li, Yuanyuan Zuo, Yuwei Liu, Lin Lei, Ka Ying Ma, Yu Huang, and Zhen-Yu Chen Copyright © 2014 Cheng Peng et al. All rights reserved. Inhibitory Effects of Edaravone in β-Amyloid-Induced Neurotoxicity in Rats Wed, 02 Apr 2014 13:22:30 +0000 Amyloid protein can damage nerve cells through a variety of biological mechanisms including oxidative stress, alterations in calcium homeostasis, and proapoptosis. Edaravone, a potent free radical scavenger possessing antioxidant effects, has been proved neuroprotective effect in stroke patients. The current study aimed to investigate the effects of EDA in an Aβ-induced rat model of AD, by studying Aβ1–40-induced voltage-gated calcium channel currents in hippocampal CA1 pyramidal neurons, learning and memory behavioral tests, the number of surviving cholinergic neurons in the basal forebrain, and the acetylcholine level in the hippocampus in this rat model of AD. The results showed that the Aβ1–40-induced increase of can be inhibited by EDA in a dose-dependent manner. Treatment with EDA significantly improved Aβ1–40-induced learning and memory performance. Choline acetyltransferase positive cells in basal forebrain and acetylcholine content in the hippocampus were increased by the administration of EDA as compared with the non-EDA treated Aβ1–40 group. These results demonstrate that EDA can inhibit the neurotoxic effect of Aβ toxicity. Collectively, these findings suggest that EDA may serve as a potential complemental treatment strategy for AD. Feng He, Yan-Ping Cao, Feng-Yuan Che, Lian-Hong Yang, Song-Hua Xiao, and Jun Liu Copyright © 2014 Feng He et al. All rights reserved. Impairment in Preattentive Processing among Patients with Hypertension Revealed by Visual Mismatch Negativity Wed, 26 Mar 2014 10:12:43 +0000 Objective. Patients with hypertension show deficits in cognitive function. However, the neural mechanisms underlying the preattentive information processing in hypertensive patients are poorly understood. We seek to investigate whether hypertensive patients have impairments in preattentive information processing. Methods. We compared visual mismatch negativity (vMMN) between 15 hypertensive patients and 15 age-matched healthy controls, which was elicited by the change of visual duration randomly presented in both peripheral visual fields. In addition, the global cognitive function for all participants was assessed with Mini-Mental State Examination (MMSE). Results. The vMMN in deviant-standard comparison was observed at occipital-temporal regions. Compared with normal healthy controls, the amplitude of vMMN was significantly decreased in hypertensive patients (). Meanwhile, the vMMN peak latency was delayed in the hypertensive group (). However, the MMSE scores of patients with hypertension were not significantly different from those of controls (), and there was no significant correlation between the mean amplitude of vMMN and SBP, DBP, and MMSE in hypertensive individuals, respectively. Conclusions. These data indicate dysfunction of automatically change detection processing in patients with hypertension. Moreover, the changes of vMMN provide a more objective and reliable assessment for cognitive impairment in hypertensive patients. Cuiping Si, Changjie Ren, Peng Wang, Hetao Bian, Haiming Wang, and Zhongrui Yan Copyright © 2014 Cuiping Si et al. All rights reserved. Effect of Antioxidants Supplementation on Aging and Longevity Tue, 25 Mar 2014 13:47:38 +0000 If aging is due to or contributed by free radical reactions, as postulated by the free radical theory of aging, lifespan of organisms should be extended by administration of exogenous antioxidants. This paper reviews data on model organisms concerning the effects of exogenous antioxidants (antioxidant vitamins, lipoic acid, coenzyme Q, melatonin, resveratrol, curcumin, other polyphenols, and synthetic antioxidants including antioxidant nanoparticles) on the lifespan of model organisms. Mechanisms of effects of antioxidants, often due to indirect antioxidant action or to action not related to the antioxidant properties of the compounds administered, are discussed. The legitimacy of antioxidant supplementation in human is considered. Izabela Sadowska-Bartosz and Grzegorz Bartosz Copyright © 2014 Izabela Sadowska-Bartosz and Grzegorz Bartosz. All rights reserved. Estimating Glomerular Filtration Rate in Older People Thu, 20 Mar 2014 10:00:21 +0000 We aimed at reviewing age-related changes in kidney structure and function, methods for estimating kidney function, and impact of reduced kidney function on geriatric outcomes, as well as the reliability and applicability of equations for estimating glomerular filtration rate (eGFR) in older patients. CKD is associated with different comorbidities and adverse outcomes such as disability and premature death in older populations. Creatinine clearance and other methods for estimating kidney function are not easy to apply in older subjects. Thus, an accurate and reliable method for calculating eGFR would be highly desirable for early detection and management of CKD in this vulnerable population. Equations based on serum creatinine, age, race, and gender have been widely used. However, these equations have their own limitations, and no equation seems better than the other ones in older people. New equations specifically developed for use in older populations, especially those based on serum cystatin C, hold promises. However, further studies are needed to definitely accept them as the reference method to estimate kidney function in older patients in the clinical setting. Sabrina Garasto, Sergio Fusco, Francesco Corica, Maria Rosignuolo, Antonio Marino, Alberto Montesanto, Francesco De Rango, Marcello Maggio, Vincenzo Mari, Andrea Corsonello, and Fabrizia Lattanzio Copyright © 2014 Sabrina Garasto et al. All rights reserved. Catechol-O-methyltransferase (COMT) Genotype Affects Age-Related Changes in Plasticity in Working Memory: A Pilot Study Wed, 19 Mar 2014 07:50:48 +0000 Objectives. Recent work suggests that a genetic variation associated with increased dopamine metabolism in the prefrontal cortex (catechol-O-methyltransferase Val158Met; COMT) amplifies age-related changes in working memory performance. Research on younger adults indicates that the influence of dopamine-related genetic polymorphisms on working memory performance increases when testing the cognitive limits through training. To date, this has not been studied in older adults. Method. Here we investigate the effect of COMT genotype on plasticity in working memory in a sample of 14 younger (aged 24–30 years) and 25 older (aged 60–75 years) healthy adults. Participants underwent adaptive training in the -back working memory task over 12 sessions under increasing difficulty conditions. Results. Both younger and older adults exhibited sizeable behavioral plasticity through training (), which was larger in younger as compared to older adults (). Age-related differences were qualified by an interaction with COMT genotype (), and this interaction was due to decreased behavioral plasticity in older adults carrying the Val/Val genotype, while there was no effect of genotype in younger adults. Discussion. Our findings indicate that age-related changes in plasticity in working memory are critically affected by genetic variation in prefrontal dopamine metabolism. Stephan Heinzel, Thomas G. Riemer, Stefanie Schulte, Johanna Onken, Andreas Heinz, and Michael A. Rapp Copyright © 2014 Stephan Heinzel et al. All rights reserved. Hypoglycemia Is Independently Associated with Multidimensional Impairment in Elderly Diabetic Patients Thu, 13 Feb 2014 11:53:57 +0000 Aim. To identify the characteristics associated with multidimensional impairment, evaluated through the Multidimensional Prognostic Index (MPI), a validated predictive tool for mortality derived from a standardized Comprehensive Geriatric Assessment (CGA), in a cohort of elderly diabetic patients treated with oral hypoglycemic drugs. Methods and Results. The study population consisted of 1342 diabetic patients consecutively enrolled in 57 diabetes centers distributed throughout Italy, within the Metabolic Study. Inclusion criteria were diagnosis of type 2 diabetes mellitus (DM), 65 years old or over, and treatment with oral antidiabetic medications. Data concerning DM duration, medications for DM taken during the 3-month period before inclusion in the study, number of hypoglycemic events, and complications of DM were collected. Multidimensional impairment was assessed using the MPI evaluating functional, cognitive, and nutritional status; risk of pressure sores; comorbidity; number of drugs taken; and cohabitation status. The mean age of participants was 73.3 ± 5.5 years, and the mean MPI score was 0.22 ± 0.13. Multivariate analysis showed that advanced age, female gender, hypoglycemic events, and hospitalization for glycemic decompensation were independently associated with a worse MPI score. Conclusion. Stratification of elderly diabetic patients using the MPI might help to identify those patients at highest risk who need better-tailored treatment. A. Pilotto, M. Noale, S. Maggi, F. Addante, A. Tiengo, P. Cavallo Perin, G. Rengo, and G. Crepaldi Copyright © 2014 A. Pilotto et al. All rights reserved. Factors Determining Disease Duration in Alzheimer’s Disease: A Postmortem Study of 103 Cases Using the Kaplan-Meier Estimator and Cox Regression Wed, 22 Jan 2014 16:59:24 +0000 Factors associated with duration of dementia in a consecutive series of 103 Alzheimer’s disease (AD) cases were studied using the Kaplan-Meier estimator and Cox regression analysis (proportional hazard model). Mean disease duration was 7.1 years (range: 6 weeks–30 years, standard deviation = 5.18); 25% of cases died within four years, 50% within 6.9 years, and 75% within 10 years. Familial AD cases (FAD) had a longer duration than sporadic cases (SAD), especially cases linked to presenilin (PSEN) genes. No significant differences in duration were associated with age, sex, or apolipoprotein E (Apo E) genotype. Duration was reduced in cases with arterial hypertension. Cox regression analysis suggested longer duration was associated with an earlier disease onset and increased senile plaque (SP) and neurofibrillary tangle (NFT) pathology in the orbital gyrus (OrG), CA1 sector of the hippocampus, and nucleus basalis of Meynert (NBM). The data suggest shorter disease duration in SAD and in cases with hypertensive comorbidity. In addition, degree of neuropathology did not influence survival, but spread of SP/NFT pathology into the frontal lobe, hippocampus, and basal forebrain was associated with longer disease duration. R. A. Armstrong Copyright © 2014 R. A. Armstrong. All rights reserved. Arterial Elasticity, Strength, Fatigue, and Endurance in Older Women Wed, 08 Jan 2014 08:16:05 +0000 Arterial health may influence muscle function in older adults. Study purpose was to determine whether arterial elasticity is related to strength, central and peripheral fatigue, fatigue at rest, and treadmill endurance. Subjects were 91 healthy women aged >60. Treadmill endurance and maximal oxygen uptake (VO2 max) were measured. Peripheral and central fatigue for the knee extensors were evaluated using two isometric fatigue tests (one voluntary and one adding electrical stimulation). Arterial elasticity was determined using radial artery pulse wave analysis. Linear multiple regression was used in statistical analysis. Large artery elasticity was associated with central fatigue and treadmill endurance after adjusting for VO2 max and knee extension strength. Subjective fatigue at rest was related to large artery elasticity after adjusting for ethnic origin (<0.02). Strength was significantly related to small artery elasticity after adjusting for ethnic origin, leg lean tissue, age, and blood pressure. Arterial elasticity is independently related to strength and fatigue in older women, especially in the central nervous system where arterial elasticity is independently related to perceptions of fatigue at rest and central fatigue. These results suggest that arterial health may be involved with the ability of the central nervous system to activate muscle in older women. Gary R. Hunter, William H. Neumeier, C. Scott Bickel, John P. McCarthy, Gordon Fisher, Paula C. Chandler-Laney, and Stephen P. Glasser Copyright © 2014 Gary R. Hunter et al. All rights reserved. Differences in Trunk Kinematic between Frail and Nonfrail Elderly Persons during Turn Transition Based on a Smartphone Inertial Sensor Thu, 28 Nov 2013 15:40:27 +0000 Objective. Firstly, to, through instrumentation with the iPhone4 smartphone, measure and describe variability of tridimensional acceleration, angular velocity, and displacement of the trunk in the turn transition during the ten-meter Extended Timed-Get-up-and-Go test in two groups of frail and physically active elderly persons. Secondly, to analyse the differences and performance of the variance between the study groups during turn transition (frail and healthy). Design. This is a cross-sectional study of 30 subjects over 65 years, 14 frail subjects, and 16 healthy subjects. Results. Significant differences were found between the groups of elderly persons in the accelerometry () and angular displacement variables (), obtained in the kinematic readings of the trunk during the turning transitions. The results obtained in this study show a series of deficits in the frail elderly population group. Conclusions. The inertial sensor found in the iPhone4 is able to study and analyse the kinematics of the turning transitions in frail and physically active elderly persons. The accelerometry values for the frail elderly are lower than the physically active elderly, whilst variability in the readings for the frail elderly is also lower than the control group. Alejandro Galán-Mercant and Antonio I. Cuesta-Vargas Copyright © 2013 Alejandro Galán-Mercant and Antonio I. Cuesta-Vargas. All rights reserved. Clinical, Biological, and Imaging Features of Monogenic Alzheimer’s Disease Wed, 27 Nov 2013 14:25:44 +0000 The discovery of monogenic forms of Alzheimer’s Disease (AD) associated with mutations within PSEN1, PSEN2, and APP genes is giving a big contribution in the understanding of the underpinning mechanisms of this complex disorder. Compared with sporadic form, the phenotype associated with monogenic cases is somewhat broader including behavioural disturbances, epilepsy, myoclonus, and focal presentations. Structural and functional imaging show typical early changes also in presymptomatic monogenic carriers. Amyloid imaging and CSF tau/Aβ ratio may be useful in the differential diagnosis with other neurodegenerative dementias, especially, in early onset cases. However, to date any specific biomarkers of different monogenic cases have been identified. Thus, in clinical practice, the early identification is often difficult, but the copresence of different elements could help in recognition. This review will focus on the clinical and instrumental markers useful for the very early identification of AD monogenic cases, pivotal in the development, and evaluation of disease-modifying therapy. Andrea Pilotto, Alessandro Padovani, and Barbara Borroni Copyright © 2013 Andrea Pilotto et al. All rights reserved. Physiotherapists Have Accurate Expectations of Their Patients’ Future Health-Related Quality of Life after First Assessment in a Subacute Rehabilitation Setting Wed, 20 Nov 2013 14:44:02 +0000 Background. Expectations held by health professionals and their patients are likely to affect treatment choices in subacute inpatient rehabilitation settings for older adults. There is a scarcity of empirical evidence evaluating whether health professionals expectations of the quality of their patients’ future health states are accurate. Methods. A prospective longitudinal cohort investigation was implemented to examine agreement (kappa coefficients, exact agreement, limits-of-agreement, and intraclass-correlation coefficients) between physiotherapists’ () prediction of patients’ discharge health-related quality of life (reported on the EQ-5D-3L) and the actual health-related quality of life self-reported by patients () at their discharge assessment (using the EQ-5D-3L). The mini-mental state examination was used as an indicator of patients’ cognitive ability. Results. Overall, 232 (85%) patients had all assessment data completed and were included in analysis. Kappa coefficients (exact agreement) ranged between 0.37–0.57 (58%–83%) across EQ-5D-3L domains in the lower cognition group and 0.53–0.68 (81%–85%) in the better cognition group. Conclusions. Physiotherapists in this subacute rehabilitation setting predicted their patients’ discharge health-related quality of life with substantial accuracy. Physiotherapists are likely able to provide their patients with sound information regarding potential recovery and health-related quality of life on discharge. The prediction accuracy was higher among patients with better cognition than patients with poorer cognition. Steven M. McPhail, Emily Nalder, Anne-Marie Hill, and Terry P. Haines Copyright © 2013 Steven M. McPhail et al. All rights reserved. Functional Status in Behavioral Variant Frontotemporal Dementia: A Systematic Review Thu, 07 Nov 2013 09:51:30 +0000 The aim was to conduct a systematic review of studies that described the functional profile of patients with behavioral variant frontotemporal dementia (bvFTD), published between 2000 and 2013. The bibliographic search was conducted using the terms “frontotemporal dementia” and “frontotemporal lobar degeneration” in combination with “independence,” “functionality,” “basic activities of daily living,” “disability,” and scales that measure functional performance: “Disability Assessment for Dementia-DAD,” “Functional Activities Questionnaire (FAQ),” “Direct Assessment of Functional Status (DAFS).” To be included in the review, the study had to mention the characterization of the functional status of patients with bvFTD in the objectives of the study, using a previously validated instrument of functional assessment. Fourteen studies met this criterion. The reviewed studies suggested that individuals with bvFTD have greater functional impairment when compared to those with other subtypes of frontotemporal lobar degeneration or Alzheimer’s disease. The studies documented a significant association between cognitive impairment and measures of functionality in these patients. The cognitive profile of patients may predict faster functional decline. Thais Bento Lima-Silva, Valéria Santoro Bahia, Ricardo Nitrini, and Mônica Sanches Yassuda Copyright © 2013 Thais Bento Lima-Silva et al. All rights reserved. Do Fallers and Nonfallers Equally Benefit from Balance Specific Exercise Program? A Pilot Study Mon, 21 Oct 2013 14:09:49 +0000 The purpose of the study was to determine the sample size that would allow broad generalizability of the results. To investigate the differences in the responsiveness of fallers and nonfallers to a multicomponent functional balance specific program, 23 participating subjects (70.1 ± 6.6 years) were divided into nonfallers group (13) and fallers group (10). The components of the balance specific program were (1) changing of the center of gravity (CoG) in the vertical direction, (2) shifting of the CoG to the border of stability, (3) rotation of the head and body about the vertical axis, (4) standing and walking on soft surface, and (5) walking over obstacles or on a narrow path. At the end of eight months of the training program, there was no significant difference between the two groups regarding postural sway. The total center of pressure path length was used as the principal outcome measure for the sample size calculation. Based on these results the a priori sample size calculation yielded the estimate of 110 subjects required to be enrolled in order to get 20 subjects in fallers and 30 subjects in nonfallers group for the 80% power to detect the results as significant. Darja Rugelj, Marija Tomšič, and France Sevšek Copyright © 2013 Darja Rugelj et al. All rights reserved. Impact of Genetic Variants of Apolipoprotein E on Lipid Profile in Patients with Parkinson's Disease Tue, 24 Sep 2013 11:44:25 +0000 The pathogenesis of Parkinson's disease (PD) seems to involve genetic susceptibility to neurodegeneration. APOE gene has been considered a risk factor for PD. This study aimed to evaluate the association of APOE polymorphism with PD and its influence on lipid profile. We studied 232 PD patients (PD) and 169 individuals without the disease. The studied polymorphism was analyzed by PCR/RFLP. The Fisher's exact test, chi-square, ANOVA, and -test () were applied. The APOE3/3 genotype was prevalent in PD patients and Controls () followed by APOE3/4 (). Both groups showed recommended values for lipid profile, with increase in the values of total cholesterol and LDLc, as well as decreased values of triglycerides in PD patients compared with Controls ( for all of them). Increased levels of HDLc, in PD patients, were associated with the APOE3/3 versus APOE-/4 genotypes (). The APOE polymorphism does not distinguish PD patients from Controls, as opposed to the lipid profile alone or in association with APOE. Furthermore, a relationship between increase of HDLc levels and APOE3 in homozygous was found in PD patients only. Michele L. Gregório, Marcela A. S. Pinhel, Caroline L. Sado, Gabriela S. Longo, Fábio N. Oliveira, Gisele S. Amorim, Marcelo A. Nakazone, Greiciane M. Florim, Camila M. Mazeti, Denise P. Martins, Waldir A. Tognola, Antonio C. Brandão, Sidney Pinheiro Júnior, Moacir F. de Godoy, and Dorotéia R. S. Souza Copyright © 2013 Michele L. Gregório et al. All rights reserved. Familiar Music as an Enhancer of Self-Consciousness in Patients with Alzheimer’s Disease Wed, 11 Sep 2013 15:27:26 +0000 The main objective of this paper is to examine the impact of familiar music on self-consciousness (SC) in patients with Alzheimer’s disease (AD). For this purpose, two AD groups of 20 patients matched by age, educational level, gender, illness duration, and cognitive state were assessed using an SC questionnaire before and after music intervention. The SC questionnaire measured several aspects: personal identity, anosognosia, affective state, body representation, prospective memory, introspection and moral judgments. One AD group received familiar music stimulation and another AD group unfamiliar music stimulation over three months. The AD patients who received a familiar music intervention showed a stabilization or improvement in aspects of SC. By contrast, control AD group showed a deterioration of most of the SC aspects after unfamiliar music stimulation, except the SC aspects of body representation and affective state. Familiar music stimulation could be considered as an enhancer of SC in patients with Alzheimer’s disease. Eva M. Arroyo-Anlló, Juan Poveda Díaz, and Roger Gil Copyright © 2013 Eva M. Arroyo-Anlló et al. All rights reserved. Predictors for Increasing Eligibility Level among Home Help Service Users in the Japanese Long-Term Care Insurance System Mon, 09 Sep 2013 13:44:36 +0000 Objectives. This cross-sectional study described the prevalence of possible risk factors for increasing eligibility level of long-term care insurance in home help service users who were certified as support level 1-2 or care level 1-2 in Japan. Methods. Data were collected from October 2011 to November 2011. Variables included eligibility level, grip strength, calf circumference (CC), functional limitations, body mass index, memory impairment, depression, social support, and nutrition status. Results. A total of 417 subjects (109 males and 308 females, mean age 83 years) were examined. There were 109 subjects with memory impairment. When divided by cut-off values, care level 2 was found to have higher prevalence of low grip strength, low CC, and depression. Conclusions. Some potentially modifiable factors such as muscle strength could be the risk factors for increasing eligibility level. Kuniyasu Kamiya, Kenji Sasou, Makoto Fujita, and Sumio Yamada Copyright © 2013 Kuniyasu Kamiya et al. All rights reserved. The Impact of Cholesterol, DHA, and Sphingolipids on Alzheimer’s Disease Mon, 19 Aug 2013 11:16:08 +0000 Alzheimer’s disease (AD) is a devastating neurodegenerative disorder currently affecting over 35 million people worldwide. Pathological hallmarks of AD are massive amyloidosis, extracellular senile plaques, and intracellular neurofibrillary tangles accompanied by an excessive loss of synapses. Major constituents of senile plaques are 40–42 amino acid long peptides termed β-amyloid (Aβ). Aβ is produced by sequential proteolytic processing of the amyloid precursor protein (APP). APP processing and Aβ production have been one of the central scopes in AD research in the past. In the last years, lipids and lipid-related issues are more frequently discussed to contribute to the AD pathogenesis. This review summarizes lipid alterations found in AD postmortem brains, AD transgenic mouse models, and the current understanding of how lipids influence the molecular mechanisms leading to AD and Aβ generation, focusing especially on cholesterol, docosahexaenoic acid (DHA), and sphingolipids/glycosphingolipids. Marcus O. W. Grimm, Valerie C. Zimmer, Johannes Lehmann, Heike S. Grimm, and Tobias Hartmann Copyright © 2013 Marcus O. W. Grimm et al. All rights reserved. Serum Brain-Derived Neurotrophic Factor Levels in Different Neurological Diseases Mon, 19 Aug 2013 08:45:30 +0000 Consistent evidence indicates the involvement of the brain-derived neurotrophic factor (BDNF) in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson’s disease (PD). In the present study, we compared serum BDNF in 624 subjects: 266 patients affected by AD, 28 by frontotemporal dementia (FTD), 40 by Lewy body dementia (LBD), 91 by vascular dementia (VAD), 30 by PD, and 169 controls. Our results evidenced lower BDNF serum levels in AD, FTD, LBD, and VAD patients () and a higher BDNF concentration in patients affected by PD (). Analyses of effects of pharmacological treatments suggested significantly higher BDNF serum levels in patients taking mood stabilizers/antiepileptics () and L-DOPA () and significant reductions in patients taking benzodiazepines (). In conclusion, our results support the role of BDNF alterations in neurodegenerative mechanisms common to different forms of neurological disorders and underline the importance of including drug treatment in the analyses to avoid confounding effects. Mariacarla Ventriglia, Roberta Zanardini, Cristina Bonomini, Orazio Zanetti, Daniele Volpe, Patrizio Pasqualetti, Massimo Gennarelli, and Luisella Bocchio-Chiavetto Copyright © 2013 Mariacarla Ventriglia et al. All rights reserved. Preserved Transcallosal Inhibition to Transcranial Magnetic Stimulation in Nondemented Elderly Patients with Leukoaraiosis Thu, 25 Jul 2013 14:09:16 +0000 Structural corpus callosum (CC) changes in patients with leukoaraiosis (LA) are significantly associated with cognitive and motor impairment. The aim of this study is to investigate the transcallosal fibers functioning by means of transcranial magnetic stimulation (TMS) in elderly patients with LA. The resting motor threshold (rMT), the motor-evoked potentials (MEPs), and the controlateral (cSP) and ipsilateral silent periods (iSP) were determined using single-pulse TMS in 15 patients and 15 age-matched controls. The neuropsychological profile and the vascular burden at brain magnetic resonance imaging (MRI) were concomitantly explored. Patients reported abnormal scores at tests evaluating executive control functions. No significant difference was found in TMS measures of intra- and intercortical excitability. No CC lesion was evident at MRI. Transcallosal inhibitory mechanisms to TMS seem to be spared in LA patients, a finding which is in line with neuroimaging features and suggests a functional integrity of the CC despite the ischemic interruption of corticosubcortical loops implicated in cognition and behavior. The observed neurophysiological finding differs from that reported in degenerative dementia, even in the preclinical or early stage. In our group of patients, the pure extent of LA is more related to impairment of frontal lobe abilities rather than functional callosal changes. Giuseppe Lanza, Rita Bella, Salvatore Giuffrida, Mariagiovanna Cantone, Giovanni Pennisi, Concetto Spampinato, Daniela Giordano, Giulia Malaguarnera, Alberto Raggi, and Manuela Pennisi Copyright © 2013 Giuseppe Lanza et al. All rights reserved. Genetics of Alzheimer’s Disease Thu, 25 Jul 2013 14:00:53 +0000 Alzheimer’s disease is the most common form of dementia and is the only top 10 cause of death in the United States that lacks disease-altering treatments. It is a complex disorder with environmental and genetic components. There are two major types of Alzheimer’s disease, early onset and the more common late onset. The genetics of early-onset Alzheimer’s disease are largely understood with variants in three different genes leading to disease. In contrast, while several common alleles associated with late-onset Alzheimer’s disease, including APOE, have been identified using association studies, the genetics of late-onset Alzheimer’s disease are not fully understood. Here we review the known genetics of early- and late-onset Alzheimer’s disease. Perry G. Ridge, Mark T. W. Ebbert, and John S. K. Kauwe Copyright © 2013 Perry G. Ridge et al. All rights reserved. Montreal Cognitive Assessment Is Superior to Standardized Mini-Mental Status Exam in Detecting Mild Cognitive Impairment in the Middle-Aged and Elderly Patients with Type 2 Diabetes Mellitus Thu, 11 Jul 2013 13:51:40 +0000 Aim. This study compares the usefulness of Montreal Cognitive Assessment (MoCA) to Standardized Mini-Mental Status Exam (SMMSE) for diagnosing mild cognitive impairment (MCI) in Type 2 diabetes mellitus (DM) population. Methods. This prospective pilot study enrolled 30 community dwelling adults with Type 2 DM aged 50 years and above. Subjects were assessed using both the SMMSE and MoCA for MCI. In all subjects, depression and dementia were ruled out using the DSM IV criteria, and a functional assessment was done. MCI was diagnosed using the standard test, the European consortium criteria. Sensitivity and specificity analysis, positive and negative predictive values, likelihood ratios and Kappa statistic were calculated. Results. In comparison to consortium criteria, the sensitivity and specificity of MoCA were 67% and 93% in identifying individuals with MCI, and SMMSE were 13% and 93%, respectively. The positive and negative predictive values for MoCA were 84% and 56%, and for SMMSE were 66% and 51%, respectively. Kappa statistics showed moderate agreement between MoCA and consortium criteria (kappa = 0.4) and a low agreement between SMMSE and consortium criteria (kappa = 0.07). Conclusion. In this pilot study, MoCA appears to be a better screening tool than SMMSE for MCI in the diabetic population. Kannayiram Alagiakrishnan, Nancy Zhao, Laurie Mereu, Peter Senior, and Ambikaipakan Senthilselvan Copyright © 2013 Kannayiram Alagiakrishnan et al. All rights reserved. Identification of Potential or Preclinical Cognitive Impairment and the Implications of Sophisticated Screening with Biomarkers and Cognitive Testing: Does It Really Matter? Mon, 08 Jul 2013 11:27:57 +0000 The last decade has seen an enormous growth in the interest in the recognition of and intervention in those diagnosed and living with the whole range of cognitive impairment and frank dementia. In the western world, the recognition of the impact on patients, families, health care systems, and societies that dementia poses has led to great efforts to help define the indicators for current and future dementia with the intention to treat those already afflicted even with the primarily symptomatic medications that exist and to recognize those at future risk with the hope of providing counselling to forestall its future development. The idea of “early diagnosis” appears at first glance to be attractive for the purposes of future planning and research studies, but it is not clear what the benefits and risks might be if screening processes define people at risk when beneficial interventions might not yet be determined. The ethical as well as financial implications must be explored and defined before implementation of such screening becomes a normal standard of practice. Michael Gordon Copyright © 2013 Michael Gordon. All rights reserved. Cardiovascular Disease and Hip Fracture among Older Inpatients in Beijing, China Mon, 01 Jul 2013 13:06:29 +0000 Objectives. To examine the associations between cardiovascular disease (CVD) and hip fracture and to determine if these associations are attributable to hypertensive disease. Methods. Data were obtained from 2006–2010 hospitalization summary reports of 31 tertiary hospitals in Beijing, China. This study included 864,408 inpatients aged ≥55 years. Occurrence rate of hip fracture was based on the first-listed ICD-10 codes (S72.0, S72.1, and S72.2) and of CVD as comorbidities were based on the second- to the eighth-listed ICD-10 codes (I00–I99). Results. The occurrence rate of hip fracture is 53% higher among older inpatients with a diagnosis of CVD than those without (, 95% CI 1.47–1.60). Those with hip fracture were more likely to have hypertensive or cerebrovascular disease, with the risk ranging from 1.34 to 1.70. Compared with those without hip fracture, the occurrence rate of overall CVDs increased by 80%, 83%, and 16% among hip fracture patients aged 55–64, 65–79, and ≥80 years. In addition, hypertensive disease did not modify the association between cerebrovascular disease and hip fracture. Conclusion. CVD was positively associated with hip fracture, and the associations observed in this sample of Chinese inpatients were similar to those reported from cohort studies conducted in the European populations. Beibei Xu, Ling Han, Hui Liu, Jing Wang, Xiao-Yuan Bao, Han-Xu Xi, Leping Zhao, and Guo-Pei Yu Copyright © 2013 Beibei Xu et al. All rights reserved. Neuropsychiatric Symptoms of Dementia: Consent, Quality of Life, and Dignity Thu, 20 Jun 2013 13:12:49 +0000 Degenerative forms of dementia are progressive, incurable, fatal, and likely to cause suffering in conjunction with personal incapacity. Timely diagnostic disclosure and counseling can facilitate important advance care planning. The risk of harm associated with neuropsychiatric symptoms (NPS) of dementia often has to be balanced against the risk of harm associated with medication management of NPS. A palliative care framework can help preserve autonomy, quality of life, comfort, and dignity for patients with NPS. Michael J. Passmore Copyright © 2013 Michael J. Passmore. All rights reserved. Nutrition and the Risk of Alzheimer's Disease Thu, 20 Jun 2013 08:34:21 +0000 Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accounts for the major cause of dementia, and the increasing worldwide prevalence of AD is a major public health concern. Increasing epidemiological studies suggest that diet and nutrition might be important modifiable risk factors for AD. Dietary supplementation of antioxidants, B vitamins, polyphenols, and polyunsaturated fatty acids are beneficial to AD, and consumptions of fish, fruits, vegetables, coffee, and light-to-moderate alcohol reduce the risk of AD. However, many of the results from randomized controlled trials are contradictory to that of epidemiological studies. Dietary patterns summarizing an overall diet are gaining momentum in recent years. Adherence to a healthy diet, the Japanese diet, and the Mediterranean diet is associated with a lower risk of AD. This paper will focus on the evidence linking many nutrients, foods, and dietary patterns to AD. Nan Hu, Jin-Tai Yu, Lin Tan, Ying-Li Wang, Lei Sun, and Lan Tan Copyright © 2013 Nan Hu et al. All rights reserved. Comparison of Informal Care Time and Costs in Different Age-Related Dementias: A Review Wed, 05 Dec 2012 08:27:36 +0000 Objectives. Age-related dementia is a progressive degenerative brain syndrome whose prevalence increases with age. Dementias cause a substantial burden on society and on families who provide informal care. This study aims to review the relevant papers to compare informal care time and costs in different dementias. Methods. A bibliographic search was performed on an international medical literature database (MEDLINE). All studies which assessed the social economic burden of different dementias were selected. Informal care time and costs were analyzed in three care settings by disease stages. Results. 21 studies met our criteria. Mean informal care time was 55.73 h per week for Alzheimer disease and 15.8 h per week for Parkinson disease (), and the associated mean annual informal costs were $17,492 versus $3,284, respectively (). Conclusion. There is a lack of data about informal care time and costs among other dementias than AD or PD. Globally, AD is the most costly in terms of informal care costs than PD, $17,492 versus $3,284, respectively. Nadège Costa, Laura Ferlicoq, Hélène Derumeaux-Burel, Thomas Rapp, Valérie Garnault, Sophie Gillette-Guyonnet, Sandrine Andrieu, Bruno Vellas, Michel Lamure, Alain Grand, and Laurent Molinier Copyright © 2013 Nadège Costa et al. All rights reserved. Food Supplement 20070721-GX May Increase CD34+ Stem Cells and Telomerase Activity Sun, 22 Apr 2012 14:17:20 +0000 Few rejuvenation and antiaging markers are used to evaluate food supplements. We measured three markers in peripheral blood to evaluate the antiaging effects of a food supplement containing placental extract. Samples were evaluated for CD34+ cells, insulin-like growth factor 1 (IGF1), and telomerase activity, which are all markers related to aging. To control the quality of this food supplement, five active components were monitored. In total, we examined 44 individuals who took the food supplement from 1.2 months to 23 months; the average number of CD34+ cells was almost 6-fold higher in the experimental group compared with the control group. Food supplement intake did not change serum IGF1 levels significantly. Finally, the average telomerase activity was 30% higher in the subjects taking this food supplement. In summary, our results suggest that the placental extract in the food supplement might contribute to rejuvenation and antiaging. Po-Cheng Lin, Tzyy-Wen Chiou, Po-Yen Liu, Shee-Ping Chen, Hsin-I Wang, Pi-Chun Huang, Shinn-Zong Lin, and Horng-Jyh Harn Copyright © 2012 Po-Cheng Lin et al. All rights reserved. ELISA for Aging Biomarkers Induced by Telomere Dysfunction in Human Plasma Thu, 25 Nov 2010 09:52:31 +0000 Background. We identified cathelicidin related antimicrobial protein (CRAMP) secreted from telomere dysfunctional bone marrow cells of late generation telomerase knockout mice (G4mTerc−/−), increased in blood and various tissues. It can represented human aging and disease. The main aim of this study is to investigate the sensitive direct enzyme-linked immunosorbent assay (ELISA) method to analyze the human aging and disease in plasma and the detailed methods to quantify the direct ELISA of these aging biomarkers. Methods. Telomere lengths of 50 healthy persons are measured with real-time PCR in blood cells. Plasma samples from all subjects are analyzed using direct ELISA. Results. From 25 years old person to 78 years, the telomere length becomes shorter during aging. In blood plasma, the expression levels of CRAMP increases during human aging. There is the reverse correspondence between the telomere length and the plasma CRAMP level. We also find that the fresh plasma, the frozen plasma which thawed less than 3 times, and the plasma kept in the room temperature less than 3 hours are better for the ELISA analyze of CRAMP in the plasma. Conclusion. This CRAMP ELISA could become a powerful tool for investigating the relationship between human aging and telomere length shortening. Hong Jiang, Wenqing Chen, Lihui Qu, Ying Chen, Qiang He, Huiping Wang, Jianyong Wu, Zhangfei Shou, Zhenyu Ju, and Jianghua Chen Copyright © 2010 Hong Jiang et al. All rights reserved.