http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2013 , Hindawi Publishing Corporation . All rights reserved. Thu, 18 Apr 2013 19:25:50 +0000 http://www.hindawi.com/journals/ijad/2013/849128/ Jeremy H. Toyn, Adele Rowley, Yasuji Matsuoka, Taisuke Tomita, and Bruno P. Imbimbo Copyright © 2013 Jeremy H. Toyn et al. All rights reserved. Thu, 18 Apr 2013 18:57:50 +0000 http://www.hindawi.com/journals/ijad/2013/516852/ Hiroyuki Umegaki, Hajime Takechi, and Hiroko H. Dodge Copyright © 2013 Hiroyuki Umegaki et al. All rights reserved. Thu, 14 Mar 2013 18:23:01 +0000 http://www.hindawi.com/journals/ijad/2013/823528/ Substantial evidence implicates -amyloid (A) peptides in the etiology of Alzheimer’s disease (AD). A is produced by the proteolytic cleavage of the amyloid precursor protein by - and -secretase suggesting that -secretase inhibition may provide therapeutic benefit for AD. Although many -secretase inhibitors have been shown to be potent at lowering A, some have also been shown to have side effects following repeated administration. All of these side effects can be attributed to altered Notch signaling, another -secretase substrate. Here we describe the in vivo characterization of the novel -secretase inhibitor SCH 697466 in rodents. Although SCH 697466 was effective at lowering A, Notch-related side effects in the intestine and thymus were observed following subchronic administration at doses that provided sustained and complete lowering of A. However, additional studies revealed that both partial but sustained lowering of Aand complete but less sustained lowering of A were successful approaches for managing Notch-related side effects. Further, changes in several Notch-related biomarkers paralleled the side effect observations. Taken together, these studies demonstrated that, by carefully varying the extent and duration of A lowering by -secretase inhibitors, it is possible to obtain robust and sustained lowering of A without evidence of Notch-related side effects. Lynn A. Hyde, Qi Zhang, Robert A. Del Vecchio, Prescott T. Leach, Mary E. Cohen-Williams, Lei Chen, Gwendolyn T. Wong, Nansie A. McHugh, Joseph Chen, Guy A. Higgins, Theodros Asberom, Wei Li, Dmitri Pissarnitski, Diane Levitan, Amin A. Nomeir, John W. Clader, Lili Zhang, and Eric M. Parker Copyright © 2013 Lynn A. Hyde et al. All rights reserved. Thu, 28 Feb 2013 14:07:19 +0000 http://www.hindawi.com/journals/ijad/2013/164919/ Background. A new public long-term care (LTC) insurance was launched in 2000 in Japan. However, there have been few studies involving factors that increase LTC costs of demented subjects; no follow-up studies involving the Government-Certified Index (GCI) and requisite costs related to the causes of dementia. Method. An epidemiological survey was conducted in a rural area in Japan in 1999, and 271 subjects were diagnosed as dementia patients. Age, sex, mini-mental state examination, clinical dementia rating, activity of daily living, causes of dementia, and coexisting physical disease were confirmed. After the LTC insurance has been launched, we tracked the GCI stages and payment amounts every month for 8 years. Result. 209 subjects were certified to be eligible for LTC insurance; however, 13 did not receive any payment. Only 49 out of 209 were alive after the follow-up period. The most common cause of dementia was Alzheimer’s disease (AD), followed by vascular dementia (VaD). There was no significant difference between the mortality rates of the two groups. VaD subjects required higher costs than AD subjects in the total certified period and in GCI stage 5. Conclusion. Our results indicate that causes of dementia can have an impact on the requisite costs for the LTC insurance. Shunichiro Shinagawa, Shiori Nakamura, Makoto Iwamoto, Norifumi Tsuno, Masahiro Shigeta, and Kazuhiko Nakayama Copyright © 2013 Shunichiro Shinagawa et al. All rights reserved. Wed, 09 Jan 2013 10:11:15 +0000 http://www.hindawi.com/journals/ijad/2013/473181/ Thomas Leyhe, Taher Darreh-Shori, Christoph Laske, Michelle M. Mielke, and Walter Maetzler Copyright © 2013 Thomas Leyhe et al. All rights reserved. Mon, 31 Dec 2012 15:56:15 +0000 http://www.hindawi.com/journals/ijad/2012/591392/ γ-Secretase cleaves the carboxyl-terminal fragment (βCTF) of APP not only in the middle of the transmembrane domain (γ-cleavage), but also at sites close to the membrane/cytoplasm boundary (ε-cleavage), to produce the amyloid β protein (Aβ) and the APP intracellular domain (AICD), respectively. The AICD49–99 and AICD50–99 species were identified as counterparts of the long Aβ species Aβ48 and Aβ49, respectively. We found that Aβ40 and AICD50–99 were the predominant species in cells expressing wild-type APP and presenilin, whereas the production of Aβ42 and AICD49–99 was enhanced in cells expressing familial Alzheimer’s disease mutants of APP and presenilin. These long Aβ species were identified in cell lysates and mouse brain extracts, which suggests that ε-cleavage is the first cleavage of βCTF to produce Aβ by γ-secretase. Here, we review the progress of research on the mechanism underlying the proteolysis of the APP transmembrane domain based on tri- and tetrapeptide release. Mako Takami and Satoru Funamoto Copyright © 2012 Mako Takami and Satoru Funamoto. All rights reserved. Wed, 26 Dec 2012 11:42:34 +0000 http://www.hindawi.com/journals/ijad/2012/548157/ The growing understanding of the use of biomarkers in Alzheimer's disease (AD) may enable physicians to make more accurate and timely diagnoses. Florbetaben, a beta-amyloid tracer used with positron emission tomography (PET), is one of these diagnostic biomarkers. This analysis was undertaken to explore the potential value of florbetaben PET in the diagnosis of AD among patients with suspected dementia and to identify key data that are needed to further substantiate its value. A discrete event simulation was developed to conduct exploratory analyses from both US payer and societal perspectives. The model simulates the lifetime course of disease progression for individuals, evaluating the impact of their patient management from initial diagnostic work-up to final diagnosis. Model inputs were obtained from specific analyses of a large longitudinal dataset from the New England Veterans Healthcare System and supplemented with data from public data sources and assumptions. The analyses indicate that florbetaben PET has the potential to improve patient outcomes and reduce costs under certain scenarios. Key data on the use of florbetaben PET, such as its influence on time to confirmation of final diagnosis, treatment uptake, and treatment persistency, are unavailable and would be required to confirm its value. Shien Guo, Denis Getsios, Luis Hernandez, Kelly Cho, Elizabeth Lawler, Arman Altincatal, Stephan Lanes, and Michael Blankenburg Copyright © 2012 Shien Guo et al. All rights reserved. Wed, 19 Dec 2012 10:11:03 +0000 http://www.hindawi.com/journals/ijad/2012/210756/ The Amyloid Hypothesis states that the cascade of events associated with Alzheimer's disease (AD)—formation of amyloid plaques, neurofibrillary tangles, synaptic loss, neurodegeneration, and cognitive decline—are triggered by Aβ peptide dysregulation (Kakuda et al., 2006, Sato et al., 2003, Qi-Takahara et al., 2005). Since γ-secretase is critical for Aβ production, many in the biopharmaceutical community focused on γ-secretase as a target for therapeutic approaches for Alzheimer's disease. However, pharmacological approaches to control γ-secretase activity are challenging because the enzyme has multiple, physiologically critical protein substrates. To lower amyloidogenic Aβ peptides without affecting other γ-secretase substrates, the epsilon (ε) cleavage that is essential for the activity of many substrates must be preserved. Small molecule modulators of γ-secretase activity have been discovered that spare the ε cleavage of APP and other substrates while decreasing the production of Aβ42. Multiple chemical classes of γ-secretase modulators have been identified which differ in the pattern of Aβ peptides produced. Ideally, modulators will allow the ε cleavage of all substrates while shifting APP cleavage from Aβ42 and other highly amyloidogenic Aβ peptides to shorter and less neurotoxic forms of the peptides without altering the total Aβ pool. Here, we compare chemically distinct modulators for effects on APP processing and in vivo activity. Barbara Tate, Timothy D. McKee, Robyn M. B. Loureiro, Jo Ann Dumin, Weiming Xia, Kevin Pojasek, Wesley F. Austin, Nathan O. Fuller, Jed L. Hubbs, Ruichao Shen, Jeff Jonker, Jeff Ives, and Brian S. Bronk Copyright © 2012 Barbara Tate et al. All rights reserved. Mon, 17 Dec 2012 16:16:47 +0000 http://www.hindawi.com/journals/ijad/2012/289412/ The γ-secretase complex is a promising target in Alzheimer’s disease because of its role in the amyloidogenic processing of β-amyloid precursor protein. This enzyme also catalyzes the cleavage of Notch receptor, resulting in the nuclear translocation of intracellular Notch where it modulates gene transcription. Notch signaling is essential in cell fate decisions during embryogenesis, neuronal differentiation, hematopoiesis, and development of T and B cells, including splenic marginal zone (MZ) B cells. This B cell compartment participates in the early phases of the immune response to blood-borne bacteria and viruses. Chronic treatment with the oral γ-secretase inhibitor RO4929097 resulted in dose-dependent decreased cellularity (atrophy) of the MZ of rats and mice. Significant decreases in relative MZ B-cell numbers of RO4929097-treated animals were confirmed by flow cytometry. Numbers of MZ B cells reverted to normal after a sufficient RO4929097-free recovery period. Functional characterization of the immune response in relation to RO4929097-related MZ B cell decrease was assessed in mice vaccinated with inactivated vesicular stomatitis virus (VSV). Compared with the immunosuppressant cyclosporin A, RO4929097 caused only mild and reversible delayed early neutralizing IgM and IgG responses to VSV. Thus, the functional consequence of MZ B cell decrease on host defense is comparatively mild. Maria Cristina de Vera Mudry, Franziska Regenass-Lechner, Laurence Ozmen, Bernd Altmann, Matthias Festag, Thomas Singer, Lutz Müller, Helmut Jacobsen, and Alexander Flohr Copyright © 2012 Maria Cristina de Vera Mudry et al. All rights reserved. Mon, 17 Dec 2012 12:18:54 +0000 http://www.hindawi.com/journals/ijad/2012/295207/ -Secretase modulation has been proposed as a potential disease modifying anti-Alzheimer’s approach. -Secretase modulators (GSMs) cause a product shift from the longer amyloid-beta (Aβ) peptide isoforms to shorter, more soluble, and less amyloidogenic isoforms, without inhibiting APP or Notch proteolytic processing. As such, modulating -secretase may avoid some of the adverse effects observed with -secretase inhibitors. Since the termination of the GSM tarenfurbil in 2008 due to negative phase III trial results, a considerable progress has been made towards more potent and better brain penetrable compounds. However, an analysis of their lipophilic efficiency indices indicates that their increased potency can be largely attributed to their increased lipophilicity. The need for early and chronic dosing with GSMs will require high-safety margins. This will be a challenge to achieve with the current, highly lipophilic GSMs. We will demonstrate that by focusing on the drug-like properties of GSMs, a combination of high in vitro potency and reduced lipophilicity can be achieved and does result in better tolerated compounds. The next hurdle will be to translate this knowledge into GSMs which are highly efficacious and safe in vivo. Harrie J. M. Gijsen and Marc Mercken Copyright © 2012 Harrie J. M. Gijsen and Marc Mercken. All rights reserved. Sun, 09 Dec 2012 08:29:27 +0000 http://www.hindawi.com/journals/ijad/2012/171327/ Neelum T. Aggarwal, Manjari Tripathi, Hiroko H. Dodge, Suvarna Alladi, and Kaarin J. Anstey Copyright © 2012 Neelum T. Aggarwal et al. All rights reserved. Mon, 03 Dec 2012 11:08:45 +0000 http://www.hindawi.com/journals/ijad/2012/509529/ Sirtuins are highly conserved NAD+-dependent enzymes that were shown to have beneficial effects against age-related diseases. Aging is the major risk factor for all neurodegenerative disorders including Alzheimer’s Disease (AD). Sirtuins have been widely studied in the context of AD using different mouse models. In most of these studies, overexpression of SIRT1 has been shown to have protective effects against AD. Therefore, designing therapeutics based on increasing SIRT1 activity might be important for investigating the ways of treatment for this disease. This paper summarizes the recent research on the effect of SIRT1 in AD animal models and also the potential of SIRT1 being a therapeutical target for AD. Gizem Donmez Copyright © 2012 Gizem Donmez. All rights reserved. Wed, 28 Nov 2012 11:38:44 +0000 http://www.hindawi.com/journals/ijad/2012/598371/ Lee-Way Jin Copyright © 2012 Lee-Way Jin. All rights reserved. Wed, 24 Oct 2012 18:42:58 +0000 http://www.hindawi.com/journals/ijad/2012/638267/ The problems and needs of older people are often associated with mental illness, characterized by a set of clinical manifestations, which constitute important domains for investigation and clinical practice. This paper presents the results of a pilot study whose main purpose was to identify met and unmet needs and to analyze the relationship between those needs, psychopathology and functionality in older people with mental health problems. A sample of 75 patients aged 65 or over, of both sexes, diagnosed with mental illness using ICD-9. The main diagnoses were depression (36%) and dementia (29.3%). Most patients had cognitive impairment (MMSE, 52%; CDT, 66.7%), depression (GDS, 61.3%), anxiety (ZAS, 81.3%), and moderate dependence (BI, 49.3% and LI, 77.3%). The main unmet needs found were daytime activities (40%), social benefits (13.3%), company (10.7%), psychological distress (9.3%), and continence (8%). The majority of these unmet needs occur with dementia patients. The majority of the carers of these patients had global needs (met and unmet) in terms of psychological distress. Findings also reveal that a low level of functionality is associated with dementia diagnoses. The association analyses suggest that dementia is an important determinant of the functional status and needs. Joaquim Passos, Carlos Sequeira, and Lia Fernandes Copyright © 2012 Joaquim Passos et al. All rights reserved. Mon, 22 Oct 2012 14:20:30 +0000 http://www.hindawi.com/journals/ijad/2012/391438/ Protein clearance is critical for the maintenance of the integrity of neuronal cells, and there is accumulating evidence that in most—if not all—neurodegenerative disorders, impaired protein clearance fundamentally contributes to functional and structural alterations eventually leading to clinical symptoms. Dysfunction of protein clearance leads to intra- and extraneuronal accumulation of misfolded proteins and aggregates. The pathological hallmark of Lewy body disorders (LBDs) is the abnormal accumulation of misfolded proteins such as alpha-synuclein (Asyn) and amyloid-beta (Abeta) in a specific subset of neurons, which in turn has been related to deficits in protein clearance. In this paper we will highlight common intraneuronal (including autophagy and unfolded protein stress response) and extraneuronal (including interaction of neurons with astrocytes and microglia, phagocytic clearance, autoimmunity, cerebrospinal fluid transport, and transport across the blood-brain barrier) protein clearance mechanisms, which may be altered across the spectrum of LBDs. A better understanding of the pathways underlying protein clearance—in particular of Asyn and Abeta—in LBDs may result in the identification of novel biomarkers for disease onset and progression and of new therapeutic targets. Michela Deleidi and Walter Maetzler Copyright © 2012 Michela Deleidi and Walter Maetzler. All rights reserved. Thu, 18 Oct 2012 09:50:01 +0000 http://www.hindawi.com/journals/ijad/2012/910757/ Parkinson’s disease is characterized by a substantial cognitive heterogeneity, which is apparent in different profiles and levels of severity. To date, a distinct clinical profile for patients with a potential risk of developing dementia still has to be identified. We introduce a data-driven approach to detect different cognitive profiles and stages. Comprehensive neuropsychological data sets from a cohort of 121 Parkinson’s disease patients with and without dementia were explored by a factor analysis to characterize different cognitive domains. Based on the factor scores that represent individual performance in each domain, hierarchical cluster analyses determined whether subgroups of Parkinson’s disease patients show varying cognitive profiles. A six-factor solution accounting for 65.2% of total variance fitted best to our data and revealed high internal consistencies (Cronbach’s alpha coefficients ). The cluster analyses suggested two independent patient clusters with different cognitive profiles. They differed only in severity of cognitive impairment and self-reported limitation of activities of daily living function but not in motor performance, disease duration, or dopaminergic medication. Based on a data-driven approach, divers cognitive profiles were identified, which separated early and more advanced stages of cognitive impairment in Parkinson’s disease without dementia. Importantly, these profiles were independent of motor progression. Inga Liepelt-Scarfone, Susanne Gräber, Monika Fruhmann Berger, Anne Feseker, Gülsüm Baysal, Ilona Csoti, Jana Godau, Alexandra Gaenslen, Heiko Huber, Karin Srulijes, Kathrin Brockmann, and Daniela Berg Copyright © 2012 Inga Liepelt-Scarfone et al. All rights reserved. Mon, 15 Oct 2012 14:34:37 +0000 http://www.hindawi.com/journals/ijad/2012/124215/ Background/Aims. Diabetes might increase the risk of Alzheimer’s disease (AD). For detecting dementia, it is typical to obtain informants’ perceptions of cognitive deficits, but such interviews are usually difficult in routine care. We aimed to develop a model for predicting mild to moderate AD using a self-reported questionnaire and by evaluating vascular risk factors for dementia in elderly subjects with diabetes. Methods. We recruited 286 diabetic and 155 nondiabetic elderly subjects. There were 25 patients with AD and 261 cognitively normal individuals versus 30 with AD and 125 normal subjects, respectively. Each participant answered subjective questions on memory deficits and daily functioning. Information on vascular risk factors was obtained from clinical charts, and multivariate logistic regression was used to develop a model for predicting AD. Results. The predicted probabilities used in screening for AD in diabetic subjects constituted age, education, lower diastolic blood pressure, subjective complaints of memory dysfunction noticeable by others, and impaired medication, shopping, and travel outside a familiar locality. Receiver operating characteristic analysis revealed a satisfactory discrimination for AD specific for diabetic elderly subjects, with 95.2% sensitivity and 90.6% specificity. Conclusion. This is the first useful index that can prescreen for AD in elderly subjects with diabetes. Toshioki Matsuzawa, Toshihiro Takata, Koichi Yokono, Hiroo Ueda, Kensuke Moriwaki, Isao Kamae, Katsuya Urakami, and Takashi Sakurai Copyright © 2012 Toshioki Matsuzawa et al. All rights reserved. Sun, 14 Oct 2012 09:38:40 +0000 http://www.hindawi.com/journals/ijad/2012/406852/ Background. We describe the trends in prevalence and mortality of dementia among older people in Hong Kong over time. Projections of the number of older people with dementia through 2039 and estimation of the disease burden are also included. Methods. Prevalence data were extracted from previous studies in Hong Kong. Mortality data were obtained from the Department of Health of Hong Kong. Projections of the number of people with dementia were calculated by applying the prevalence rates of dementia obtained from previous studies to Hong Kong population projections. The burden of dementia was measured by Disability-Adjusted Life Years (DALYs). Results. The number of people aged 60 and above with dementia is projected to increase by 222%, from 103,433 in 2009 to 332,688 in 2039, with a large proportion of those living in institutions. The number of deaths due to dementia among people aged 60 and above has more than doubled between 2001 and 2009. Mortality rates for dementia have also risen. In 2006, about 286,313 DALYS were lost due to dementia. Conclusions. The information presented may be used to formulate a long-term care strategy for dementia of the ageing population in Hong Kong. Ruby Yu, Pui Hing Chau, Sarah M. McGhee, Wai Ling Cheung, Kam Che Chan, Sai Hei Cheung, and Jean Woo Copyright © 2012 Ruby Yu et al. All rights reserved. Wed, 10 Oct 2012 15:42:38 +0000 http://www.hindawi.com/journals/ijad/2012/324016/ Background. Alzheimer's disease (AD) is the most common cause of dementia in the elderly. AD is characterized by the accumulation of amyloid plaques and neurofibrillary tangles and by massive neuronal loss in the brain. There is epidemiologic and pathologic evidence that AD is associated with vascular risk factors and vascular diseases, contributing to cerebral hypoperfusion with consecutive stimulation of angiogenesis and upregulation of proangiogenic factors such as Angiopoietin-1 (Ang-1). Methods. In the present study, we measured Ang-1 serum levels in 42 patients with AD, 20 patients with mild cognitive impairment (MCI), and in 40 healthy elderly controls by ELISA. Results. We found significantly increased Ang-1 serum levels in patients with AD compared to control subjects . There was no significant difference between MCI patients and healthy controls or between AD and MCI patients . The degree of cognitive impairment as measured by the mini-mental status examination (MMSE) score was significantly correlated with the Ang-1 serum levels in all patients and healthy controls. Conclusions. We found significantly increased Ang-1 serum levels in AD patients. We could also show an association between Ang-1 serum levels and the cognitive status in all patients and healthy controls. Thus, serum Ang-1 could be a potential candidate for a biomarker panel for AD diagnosis. Brigitte Schreitmüller, Thomas Leyhe, Elke Stransky, Niklas Köhler, and Christoph Laske Copyright © 2012 Brigitte Schreitmüller et al. All rights reserved. Wed, 03 Oct 2012 12:58:27 +0000 http://www.hindawi.com/journals/ijad/2012/956354/ There is a paucity of data regarding trends in dementia and its subtype prevalence in Japan. Our aims in the current paper are to: (1) summarize epidemiological studies of dementia in Japan including relevant details of study protocol and diagnostic criteria, (2) compare the age-specific prevalence of all-cause dementia among studies, and (3) assess the trends in Alzheimer's disease (AD) versus vascular dementia (VaD) over time. We reviewed diagnostic criteria, all-cause dementia prevalence, and the AD/VaD ratio from 8 large population studies of dementia in Japan. Compared with the Okinawa 1992 study, studies conducted in 1994, 1998, 2005, and 2008 had a higher prevalence of all-cause dementia using Poisson regression models, after controlling for age and sex. In contrast to the US and some European countries, all-cause dementia prevalence is increasing in Japan. The prevalence of AD as opposed to VaD seems to be increasing over time, but large variability in diagnostic criteria, possible regional variability, and differences in prevalence of subtypes of dementia between men and women make it difficult to draw a conclusion about this trend at the national level. Further studies, for example, comparing the population attributable risk of vascular diseases to the prevalence and incidence of dementia could help to clarify the regional variations in etiological subtypes. Hiroko H. Dodge, Teresa J. Buracchio, Gwenith G. Fisher, Yutaka Kiyohara, Kenichi Meguro, Yumihiro Tanizaki, and Jeffrey A. Kaye Copyright © 2012 Hiroko H. Dodge et al. All rights reserved. Sun, 30 Sep 2012 09:44:08 +0000 http://www.hindawi.com/journals/ijad/2012/162960/ The proportion of male caregivers is rapidly increasing. However, there are few large scale studies exploring gender differences in the burden or coping with caregiving. We investigated this among caregivers of patients with dementia. The study cohort consisted of 335 dyads of wife-husband couples from two studies including dementia patients and their spousal caregivers. Baseline mini-mental state examination (MMSE), clinical dementia rating scale (CDR), neuropsychiatric inventory (NPI), cornell depression scale and charlson comorbidity index (CCI) were used to describe patients with dementia, Zarit burden scale and geriatric depression scale were used to measure experienced burden and depression of caregivers. Mean age of caregivers was 78 years. There were no differences in depression, satisfaction with life, or loneliness according to caregivers' gender. Male caregivers had more comorbidities than females (CCI 1.9 versus 1.1, ), and the wives of male caregivers had a more severe stage of dementia than husbands of female caregivers (CDR, ; MMSE14.0 versus 17.7, ). However, the mean Zarit burden scale was significantly lower among male than female caregivers (31.5 versus 37.5; ). Lower education of male caregivers tended to be associated with less experienced burden. In conclusion, male caregivers of dementia experienced lower burden than female caregivers despite care recipients' more severe disease. Minna Maria Pöysti, Marja-Liisa Laakkonen, Timo Strandberg, Niina Savikko, Reijo Sakari Tilvis, Ulla Eloniemi-Sulkava, and Kaisu Hannele Pitkälä Copyright © 2012 Minna Maria Pöysti et al. All rights reserved. Sat, 29 Sep 2012 15:31:39 +0000 http://www.hindawi.com/journals/ijad/2012/673584/ Background. Incipient Alzheimer's disease is often disguised as depressive disorder. Over the course of AD, depressive symptoms are even more frequent. Hence, treatment with antidepressants is common in AD. It was the goal of the present study to assess whether two common antidepressants with different mechanisms of action affect spatial learning in a transgenic animal model of Alzheimer's disease. Methods. We assessed spatial memory of male wild-type and B6C3-Tg(APPswe,PSEN1dE9)85Dbo (APP23) transgenic animals in a complex dry-land maze. Animals were treated with citalopram (10 mg/kg) and bupropion (20 mg/kg). Results. Moving and resting time until finding the goal zone decreased in 4.5-month-old sham-treated wild-type animals and, to a lesser extent, in APP23 animals. Compared with sham-treated APP23 animals, treatment with bupropion reduced resting time and increased speed. On treatment with citalopram, moving and resting time were unchanged but speed decreased. Length of the path to the goal zone did not change on either bupropion or citalopram. Conclusion. Bupropion increases psychomotor activity in APP23 transgenic animals, while citalopram slightly reduces psychomotor activity. Spatial learning per se is unaffected by treatment with either bupropion or citalopram. Katharina L. Neumeister and Matthias W. Riepe Copyright © 2012 Katharina L. Neumeister and Matthias W. Riepe. All rights reserved. Wed, 26 Sep 2012 15:47:06 +0000 http://www.hindawi.com/journals/ijad/2012/531646/ We report that music therapy is effective in the treatment of Alzheimer’s disease. We found that the secretion of 17-estradiol and testosterone, hormones that are supposed to have preventive effects on Alzheimer’s disease, is significantly increased by music therapy. During the sessions, patients with Alzheimer’s disease were allowed to listen to music and songs with verbal contact from the therapist. It was found that problematic behaviors such as poriomania (fugue) had decreased. Music therapy has the potential as an alternative treatment for adverse hormone replacement therapy. H. Fukui, A. Arai, and K. Toyoshima Copyright © 2012 H. Fukui et al. All rights reserved. Wed, 26 Sep 2012 09:08:55 +0000 http://www.hindawi.com/journals/ijad/2012/437025/ Dementia with Lewy bodies (DLB) is a common subtype of dementia in the elderly. DLB is neuropathologically characterized by the presence of Lewy bodies and Lewy neurites, both of which are composed of α-synuclein. Although α-synuclein was initially considered to be an exclusively intracellular protein, it has been found to be secreted into biological fluids. α-Synuclein in biological fluids such as cerebrospinal fluid (CSF) and blood has been discussed as a potential biomarker of DLB and α-synuclein-related disorders, because α-synuclein is characteristically accumulated in the brain of patients with these disorders. The α-synuclein level in CSF has been examined by several investigators, and the majority of studies have shown a reduction in CSF α-synuclein level in DLB and α-synuclein-related disorders. Discrepant findings of studies of plasma α-synuclein level in patients with DLB have been reported. Because the level of α-synuclein stored in red blood cells is considerably high, blood contamination and haemolysis during sample collection and processing should be considered as a confounding factor for quantification of α-synuclein. Here, the recent progress in the studies of α-synuclein as a biomarker of DLB and their potential clinical applications are reviewed. Kensaku Kasuga, Masatoyo Nishizawa, and Takeshi Ikeuchi Copyright © 2012 Kensaku Kasuga et al. All rights reserved. Mon, 17 Sep 2012 13:59:49 +0000 http://www.hindawi.com/journals/ijad/2012/979804/ Clinicians and researchers alike are in need of quantitative and robust measurement tools to assess medial temporal lobe atrophy (MTA) due to Alzheimer’s disease (AD). We recently proposed a morphological metric, extracted from T1-weighted magnetic resonance images (MRI), to track and estimate MTA in cohorts of controls, AD, and mild cognitive impairment subjects, at high-risk of progression to dementia. In this paper, we investigated its reliability through analysis of within-session scan/repeat images and scan/rescans from large multicenter studies. In total, we used MRI data from 1051 subjects recruited at over 60 centers. We processed the data identically and calculated our metric for each individual, based on the concept of distance in a high-dimensional space of intensity and shape characteristics. Over 759 subjects, the scan/repeat change in the mean was 1.97% (SD: 21.2%). Over three subjects, the scan/rescan change in the mean was 0.89% (SD: 22.1%). At this level, the minimum trial size required to detect this difference is 68 individuals for both samples. Our scan/repeat and scan/rescan results demonstrate that our MTA assessment metric shows high reliability, a necessary component of validity. Simon Duchesne, Fernando Valdivia, Abderazzak Mouiha, and Nicolas Robitaille Copyright © 2012 Simon Duchesne et al. All rights reserved. Sun, 16 Sep 2012 10:42:25 +0000 http://www.hindawi.com/journals/ijad/2012/376138/ A novel vaccine addressing the major hallmarks of Alzheimer’s disease (AD), senile plaque-like deposits of amyloid beta-protein (Aβ), neurofibrillary tangle-like structures, and glial proinflammatory cytokines, has been developed. The present vaccine takes a new approach to circumvent failures of previous ones tested in mice and humans, including the Elan-Wyeth vaccine (AN1792), which caused massive T-cell activation, resulting in a meningoencephalitis-like reaction. The EB101 vaccine consists of A𝛽1-42 delivered in a novel immunogen-adjuvant composed of liposomes-containing sphingosine-1-phosphate (S1P). EB101 was administered to APPswe/PS1dE9 transgenic mice before and after AD-like pathological symptoms were detectable. Treatment with EB101 results in a marked reduction of Aβ plaque burden, decrease of neurofibrillary tangle-like structure density, and attenuation of astrocytosis. In this transgenic mouse model, EB101 reduces the basal immunological interaction between the T cells and immune activation markers in the affected hippocampal/cortical areas, consistent with decreased amyloidosis-induced inflammation. Therefore, immunization with EB101 prevents and reverses AD-like neuropathology in a significant manner by halting disease progression without developing behavioral spatial deficits in transgenic mice. Iván Carrera, Ignacio Etcheverría, Lucía Fernández-Novoa, Valter Lombardi, Ramón Cacabelos, and Carmen Vigo Copyright © 2012 Iván Carrera et al. All rights reserved. Thu, 13 Sep 2012 15:25:57 +0000 http://www.hindawi.com/journals/ijad/2012/703871/ Background. Considerable research documents an association between pro- and anti-inflammatory markers and Alzheimer's disease (AD), yet the differential relation between these markers and neuropsychological functioning in AD and nondemented controls has received less attention. The current study sought to evaluate the relationship between peripheral markers of inflammation (both pro- and anti-inflammatory) and neuropsychological functioning through the Texas Alzheimer's Research and Care Consortium (TARCC) cohort. Methods. There were 320 participants (Probable AD n=124, Controls n=196) in the TARCC Longitudinal Research Cohort available for analysis. Regression analyses were utilized to examine the relation between proinflammatory and anti-inflammatory markers and neuropsychological functioning. Follow-up analyses were conducted separately by case versus control status. Results. Proinflammatory and anti-inflammatory markers were found to be associated with neuropsychological testing. Third tertile proinflammatory markers were negatively associated with measures of attention and language, and anti-inflammatory markers were positively associated with measures of immediate verbal memory and delayed verbal and visual memory. Conclusions. These findings support the link between peripheral inflammatory markers and neuropsychological functioning and suggest the utility of examining profiles of inflammatory markers in the future. Valerie H. Balldin, James R. Hall, Robert C. Barber, Linda Hynan, Ramon Diaz-Arrastia, and Sid E. O'Bryant Copyright © 2012 Valerie H. Balldin et al. All rights reserved. Tue, 11 Sep 2012 10:01:55 +0000 http://www.hindawi.com/journals/ijad/2012/903645/ The objective of this paper is to understand how the public’s beliefs in five countries may change as more families have direct experience with Alzheimer’s disease. The data are derived from a questionnaire survey conducted by telephone (landline and cell) with 2678 randomly selected adults in France, Germany, Poland, Spain, and the United States. The paper analyzes the beliefs and anticipated behavior of those in each country who report having had a family member with Alzheimer’s disease versus those who do not. In one or more countries, differences were found between the two groups in their concern about getting Alzheimer’s disease, knowledge that the disease is fatal, awareness of certain symptoms, and support for increased public spending. The results suggest that as more people have experience with a family member who has Alzheimer’s disease, the public will generally become more concerned about Alzheimer’s disease and more likely to recognize that Alzheimer’s disease is a fatal disease. The findings suggest that other beliefs may only be affected if there are future major educational campaigns about the disease. The publics in individual countries, with differing cultures and health systems, are likely to respond in different ways as more families have experience with Alzheimer’s disease. Robert J. Blendon, John M. Benson, Elizabeth M. Wikler, Kathleen J. Weldon, Jean Georges, Matthew Baumgart, and Beth A. Kallmyer Copyright © 2012 Robert J. Blendon et al. All rights reserved. Sun, 09 Sep 2012 08:53:14 +0000 http://www.hindawi.com/journals/ijad/2012/674589/ The aim of this study is to analyze dual-task effects on free and adaptive gait in Alzheimer's disease (AD) patients. Nineteen elders with AD participated in the study. A veteran neuropsychiatrist established the degree of AD in the sample. To determine dual-task effects on free and adaptive gait, patients performed five trials for each experimental condition: free and adaptive gait with and without a dual-task (regressive countdown). Spatial and temporal parameters were collected through an optoelectronic tridimensional system. The central stride was analyzed in free gait, and the steps immediately before (approaching phase) and during the obstacle crossing were analyzed in adaptive gait. Results indicated that AD patients walked more slowly during adaptive gait and free gait, using conservative strategies when confronted either with an obstacle or a secondary task. Furthermore, patients sought for stability to perform the tasks, particularly for adaptive gait with dual task, who used anticipatory and online adjustments to perform the task. Therefore, the increase of task complexity enhances cognitive load and risk of falls for AD patients. Diego Orcioli-Silva, Lucas Simieli, Fabio Augusto Barbieri, Florindo Stella, and Lilian Teresa Bucken Gobbi Copyright © 2012 Diego Orcioli-Silva et al. All rights reserved. Tue, 04 Sep 2012 15:45:27 +0000 http://www.hindawi.com/journals/ijad/2012/731063/ Caspase-mediated truncation of tau is associated with aggregation. We examined the impact of manipulation of caspase activity on intracellular aggregation of a mutant form of tau (3PO) that forms spontaneous aggregates. Treatment with the caspase inhibitor Z-VAD-fmk reduced both N and C-terminal tau truncation but did not significantly reduce aggregation. Treatment with staurosporine, which activated caspases, increased C-terminal but not N-terminal truncation and enhanced aggregation. These findings suggest that caspase activation is one potential route, rather than an obligatory initiation step, in aggregation, and that N- and C-terminal truncation contribute differentially to aggregation. Sangmook Lee and Thomas B. Shea Copyright © 2012 Sangmook Lee and Thomas B. Shea. All rights reserved.