Nonagenarians and centenarians represent a quickly growing age group worldwide. In parallel, the prevalence of dementia increases substantially, but how to define dementia in this oldest-old age segment remains unclear. Although the idea that the risk of Alzheimer&#39;s disease (AD) decreases after age 90 has now been questioned, the oldest-old still represent a population relatively resistant to degenerative brain processes. 
Brain aging is characterised by the formation of neurofibrillary tangles (NFTs) and senile plaques (SPs) as well as neuronal and synaptic loss in both cognitively intact individuals and patients with AD. In nondemented cases NFTs are usually restricted to the hippocampal formation, whereas the progressive involvement of the association areas in the temporal neocortex parallels the development of overt clinical signs of dementia. In contrast, there is little correlation between the quantitative distribution of SP and AD severity. 
The pattern of lesion distribution and neuronal loss changes in extreme aging relative to the younger-old. In contrast to younger cases where dementia is mainly related to severe NFT formation within adjacent components of the medial and inferior aspects of the temporal cortex, oldest-old individuals display a preferential involvement of the anterior part of the CA1 field of the hippocampus whereas the inferior temporal and frontal association areas are relatively spared. This pattern suggests that both the extent of NFT development in the hippocampus as well as a displacement of subregional NFT distribution within the Cornu ammonis (CA) fields may be key determinants of dementia in the very old. Cortical association areas are relatively preserved. The progression of NFT formation across increasing cognitive impairment was significantly slower in nonagenarians and centenarians compared to younger cases in the CA1 field and entorhinal cortex. The total amount of amyloid and the neuronal loss in these regions were also significantly lower than those reported in younger AD cases. Overall, there is evidence that pathological substrates of cognitive deterioration in the oldest-old are different from those observed in the younger-old. Microvascular parameters such as mean capillary diameters may be key factors to consider for the prediction of cognitive decline in the oldest-old. Neuropathological particularities of the oldest-old may be related to &#8220;longevity-enabling&#8221; genes although little or nothing is known in this promising field of future research.

A. von Gunten

K. Ebbing

A. Imhof

P. Giannakopoulos

E. K&#246;vari

Brain Aging in the Oldest-Old

Lung cancer is the leading cause of cancer-related mortality in both men and women and approximately 219,440 new cases of nonsmall cell lung cancer (NSCLC) were estimated to occur in the USA in 2009, which caused 159,390 NSCLC-related deaths. More than 50&#37; of cases of advanced NSCLC are diagnosed in patients older than age 65, and recent Surveillance Epidemiology and End Results (SEERs) data suggest that the median age at diagnosis is 70 years. Until recently, the disease has been undertreated in this patient population, with a perception among many clinicians that elderly patients do not tolerate chemotherapy or radiotherapy. So, single agent chemotherapy is the recommended approach by the ASCO and International Expert Panels in unselected patients. The introduction of novel targeted therapies, such as Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) which improved survival versus placebo in patients who had previously failed on chemotherapy, gives clinicians new, effective, and better tolerated options to consider when treating NSCLC in elderly patients. This paper describes the advances of EGFR TKIs for elderly patients with advanced NSCLC.

F. Meriggi

A. Zaniboni

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Elderly Patients with Advanced Non-Small Cell Lung Cancer

Background. Cardiovascular disease is the principal cause of mortality in older individuals, and more than 80&#37; of deaths due to coronary heart disease or stroke occur in patients over 65 years of age. Hyperlipidemia is one of the main modifiable risk factors for cardiovascular disease. Current guidelines recommend the use of statins to reduce low-density lipoprotein cholesterol to appropriate targets based on an individual&#39;s cardiovascular risk, and clearly state that older age should not be a barrier to treatment. Despite extensive evidence demonstrating clear benefit with statin therapy in older individuals, this population remains chronically undertreated. 
Scope. This paper provides an overview of the current evidence available regarding the efficacy and safety of statin therapy to reduce cardiovascular risk in older patients. We use hypothetical case studies to address some of the questions frequently posed by physicians responsible for the cardiovascular health of older patients. Conclusions. Various factors may account for the failure to provide appropriate treatment, including a lack of awareness of clinical benefits and perceived safety issues. However, if current guidelines are followed and older patients treated to appropriate LDL-C goals, the likelihood of cardiovascular events will be reduced in this high-risk population. Employing an evidence-based approach to the management of cardiovascular risk in older patients is likely to yield benefits in terms of overall cardiovascular burden.

N. K. Wenger

S. J. Lewis

Use of Statin Therapy to Reduce Cardiovascular Risk in Older Patients

The purpose of this study was to investigate whether age-related differences in stepping response influence postural control when stepping onto a known soft surface under dual task conditions. Nine young and eleven older female adults participated. First, they stepped on a flat surface while grasping an empty cup (single task), and then they repeated the task while grasping a cup filled with water (dual task). For the second experiment, they stepped on a soft surface placed in front of them while performing the above tasks. The main result was that &#37;DIP (initiation phase as a percentage of the total stepping task time) was significantly higher for older than for young adults during the dual task on the soft surface. In conclusion, caution due to previous experience may increase attentional demand during dual tasks and lengthen the time required for central nervous processing in order to avoid losing postural stability in older adults, resulting in reductions in step velocity and step length compared to those in young adults.

Nobuko Harada

Shuichi Okada

Shinya Negoro

Age-Related Differences in Stepping Response When Stepping onto a Known Soft Surface under Dual Task Conditions

Executive function (EF) is believed to control or influence the integration and application of cognitive functions such as attention and memory and is an important area of research in cognitive aging. Recent studies and reviews have concluded that there is no single test for EF. Results from first-order latent variable modeling have suggested that little, if any, variability in cognitive performance can be directly (and uniquely) attributed to EF; so instead, we modeled EF, as it is conceptualized, as a higher-order function, using elements of the CERAD neuropsychological battery. Responses to subtests from two large, independent cohorts of nondemented elderly persons were modeled with three theoretically plausible structural models using confirmatory factor analysis. Robust fit statistics, generated for the two cohorts separately, were consistent and support the conceptualization of EF as a higher-order cognitive faculty. Although not specifically designed to assess EF, subtests of the CERAD battery provide theoretically and empirically robust evidence about the nature of EF in elderly adults.

Rochelle E. Tractenberg

Gerda Fillenbaum

Paul S. Aisen

David E. Liebke

Futoshi Yumoto

Maragatha N. Kuchibhatla

What the CERAD Battery Can Tell Us about Executive Function as a Higher-Order Cognitive Faculty

Although cardiovascular diseases are less prevalent in premenopausal women than in men, their occurrence in women increases at the onset of menopause, and the loss of female sex hormones contributes to the striking increase in cardiovascular morbidity and mortality in postmenopausal women. We present here a description of age-related disruption of lipid homeostasis, which particularly affects 3-hydroxy 3-methylglutaryl Coenzyme A reductase, the key rate-limiting enzyme in the cholesterol biosynthetic pathway. We further discuss the age- and gender-related dysregulation of this enzyme, providing new evidence for the different mechanisms driving dyslipidemia in elderly men and women. In addition, we introduce pharmacological methods of regulating HMGR and maintaining cholesterol homeostasis.

Laura Trapani

Valentina Pallottini

Age-Related Hypercholesterolemia and HMG-CoA Reductase Dysregulation: Sex Does Matter (A Gender Perspective)

Cholesterol is an essential molecule for brain homeostasis; yet, hypercholesterolemia and its numerous complications are believed to play a role in promoting multiple aspects of brain pathogenesis. An ever increasing number of individuals in modern Western Society are regularly consuming diets high in fat which promote the development of hypercholesterolemia. Additionally, modern societies are becoming increasingly aged, causing a collision between increased hypercholesterolemia and increased aging, which will likely lead to the development of increased pathological conditions due to hypercholesterolemia, thereby promoting deleterious neurochemical and behavioral changes in the brain. Lastly, while beneficial in controlling cholesterol levels, the long-term use of statins itself may potentially promote adverse effects on brain homeostasis, although specifics on this remain largely unknown. This review will focus on linking the current understanding of diet-induced hypercholesterolemia (as well as statin use) to the development of oxidative stress, neurochemical alterations, and cognitive disturbances in the aging brain.

Romina M. Uranga

Jeffrey N. Keller

Diet and Age Interactions with Regards to Cholesterol Regulation and Brain Pathogenesis

The proteasome is considered the most important proteolytic system for removal of damaged proteins with aging. Using fluorogenic peptide substrates, the chymotrypsin-like, the trypsin-like, and the peptidylglutamyl peptidase activities of the proteasome were measured in the soluble fractions of liver, brain, and lens rat homogenates. Specific activity was significantly decreased in liver and brain homogenates with maturation of the animal, that is, from newborn (7 days old) to fertile rats (2&#x2013;4 months old). Rat lens homogenate exhibited an increase in activity with maturation and also with aging. Chymotrypsin-like activity was stimulated by calcium and this proteolytic activity was significantly decreased with maturation of the rat brain. The Michaelis-Menten constant (<svg style="vertical-align:-3.3907pt;width:23.325001px;" id="M1" height="15.4" version="1.1" viewBox="0 0 23.325001 15.4" width="23.325001" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><path id="x1D43E" d="M764 650l-7 -26q-61 -10 -91.5 -22.5t-76.5 -48.5l-235 -184q104 -152 208 -276q31 -37 54.5 -48.5t68.5 -16.5l-7 -28h-156q-138 170 -213 284q-19 29 -33.5 35t-33.5 -7l-29 -173q-15 -75 -5.5 -90.5t74.5 -20.5l-5 -28h-260l7 28q58 5 74 21.5t30 89.5l70 378&#xA;q12 68 2 83t-72 22l6 28h257l-7 -28q-62 -7 -76 -21.5t-27 -83.5l-32 -172q29 11 78 46q112 84 217 179q18 16 23.5 25.5t-1 14.5t-26.5 8l-30 4l5 28h249z" /></g>

			<g transform="matrix(.012,-0,0,-.012,13.25,15.187)"><path id="x1D45A" d="M766 88q-40 -45 -83.5 -72.5t-63.5 -27.5q-39 0 -16 103l49 224q15 68 -10 68q-36 0 -112.5 -78.5t-105.5 -133.5q-27 -101 -38 -165q-35 -4 -77 -18l-6 6q42 153 70 288q12 55 10 78t-19 23q-38 0 -114 -80.5t-101 -131.5q-24 -68 -41 -165q-36 -3 -76 -18l-8 6&#xA;q56 202 87 347q7 33 -3 33q-8 0 -31.5 -17.5t-41.5 -35.5l-12 28q42 45 84 72t63 27q44 0 10 -124l-20 -75h2q92 121 193 178q36 21 64 21q62 0 28 -159l-8 -37h2q50 67 103.5 112t94.5 65q39 19 62 19q60 0 23 -156l-45 -189q-9 -39 2 -39q17 0 71 49z" /></g>

		
	
</svg>) increased with age in rat liver and lens, indicating a loss of affinity for its substrates by the proteasome in the animal with maturation and aging. The present data suggest that the loss of function of the proteasome with maturation may be due to structural changes of the proteasome or a decreased content of regulatory components.

A. Petersen

A. Honarvar

M. Zetterberg

Changes in Activity and Kinetic Properties of the Proteasome in Different Rat Organs during Development and Maturation

Acquired hemophilia A (AHA) is a very rare disease, caused by the development of autoantibodies, directed against circulating factor VIII of coagulation. Age distribution is bimodal, with a first peak occurring among young women in the postpartum period, and a second major peak of incidence among elderly patients in whom it is frequently associated with malignancy and drugs. This disease often represents a life-threatening bleeding condition, especially in the elderly, thus requiring a prompt therapeutic intervention, including control of acute bleeding and eradication of the inhibitor by immunosuppressive therapy. The diagnosis of AHA should be considered in any elderly patient who presents with bleeding and prolonged activated Partial Thromboplastin Time. Moreover, the coexistence of a series of underlying diseases associated with AHA should be always searched for. An early recognition and an adequate treatment of this coagulation disorder and of the possible associated diseases play a significant role for a favourable outcome, but concomitant morbidities in the elderly may limit aggressive therapy and may complicate the clinical scenario.
We report 3 consecutive elderly patients successfully treated with recombinant activated factor VII and standard immunosuppressive regimens, with remission of the disease.

Antonella Tufano

Antonio Coppola

Anna Guida

Ernesto Cimino

Angela Maria De Gregorio

Anna Maria Cerbone

Giovanni Di Minno

Acquired Haemophilia A in the Elderly: Case Reports

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Current Gerontology and Geriatrics Research publishes research based on molecular, cellular, organismal aspects of gerontological research and in diagnosis, treatment, evaluation and educational aspects of geriatrics research.

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Current Gerontology and Geriatrics Research publishes research based on molecular, cellular, organismal aspects of gerontological research and in diagnosis, treatment, evaluation and educational aspects of geriatrics research.

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Current Gerontology and Geriatrics Research

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Current Gerontology and Geriatrics Research