Current Alzheimer Research - Volume 4, Issue 2, 2007

There is a worldwide increase in obesity and this increase is of epidemic proportions in the United States [1]. In the last few years, a number of epidemiological studies have pointed to a link between obesity at midlife and the risk of late-life dementia and Alzheimer's disease (AD) [2]. Obesity is a key component of metabolic syndrome which is defined as a clustering of central adiposity, insulin resistance, atherogenic dyslipide Read More

The increasing prevalence of obesity world-wide has an expected consequent increase in diabetes and cardiovascular disease. Less attention has been paid to the effect of obesity on dementia. This overview discusses methodological issues related to the epidemiologic study of obesity and dementia, reviews results of long-term prospective studies, and briefly considers possible mechanisms for an obesity-dementia associati Read More

Prior work has suggested that obesity and overweight as measured by body mass index (BMI) increases risk of dementia. It is unknown if there is a difference in the risk of developing Alzheimer disease (AD) versus vascular dementia (VaD) associated with high body weight. The goal of this study was to examine the association between midlife BMI and risk of both AD and VaD an average of 36 years later in a large (N= 10,136) an Read More

Background: Obesity has been related to the incidence of dementia but its impact on cognitive performance in persons without dementia is less clear. We hypothesized that mid-life obesity may modulate the impact of conventional cardiovascular risk factors (CVRF) on cognitive impairment. We tested this hypothesis in the community-based Framingham Offspring Study sample. Methods: At Examination cycle 4 (1988-90) of t Read More

Adipose tissue is the largest endocrine gland in the body, yet only recently has its role in neurodegenerative disease been considered. Prospective population level evidence has emerged to show that both obesity and overweight, is associated with an increased risk of all cause dementia, Alzheimer's disease (AD), and underlying neurodegenerative changes. Weight loss in late life however is associated with dementia, and t Read More

Over 33% of women and 20% of men aged 65 and older will develop dementia during their lifetime, and many more will develop a milder form of cognitive impairment. Given the anticipated exponential increase in both the incidence and prevalence of cognitive impairment in the next century, it is critical to identify preventative strategies to thwart this critical public health issue. The metabolic syndrome is comprised of five card Read More

The objective of this manuscript is to provide a comprehensive review of the relation between adiposity and Alzheimer's disease (AD), its potential mechanisms, and issues in its study. Adiposity represents the body fat tissue content. When the degree of adiposity increases it can be defined as being overweight or obese by measures such as the body mass index. Being overweight or obese is a cause of hyperinsulinemia and dia Read More

Brain imaging has played a major role in exploring abnormalities of brain structure and function in aging and dementia. Recently, with reports linking obesity to cognitive decline and dementia, magnetic resonance imaging has been used to investigate how brain structure may be altered with obesity. These studies have convincingly demonstrated both generalized and regional brain atrophy and changes in white matter in Read More

Epidemiologic studies have provided important clues about the etiology, prognosis and options for prevention and treatment of AD, and sub-clinical changes in cognition and brain structure. A brief review is given of what we have learned from epidemiologic studies of risk factors and natural history. This is followed by a discussion of how these findings could inform the design of basic research strategies that may further the tr Read More

Emerging evidence suggests that components of the metabolic syndrome either in isolation or in aggregate may impact the onset or severity of neurodegenerative processes, including those physiologic changes that lead to Alzheimer's Disease (AD). Several animal models that were originally designed to interrogate the metabolic syndrome are readily available. These models can now be used to support studies that Read More

Insulin modulates cognition and other aspects of normal brain function. Insulin resistance is characterized by chronic peripheral insulin elevations, and it is accompanied by reduced brain insulin levels and insulin activity. Obesity, type 2 diabetes mellitus and hypertension are strongly associated with insulin resistance. In addition, insulin resistance increases the risk of age-related memory impairment and Alzheimer's disease. Poss Read More

Identification of genes and pathways that alter lifespan has allowed for new insights into factors that control the aging process as well as disease. While strong molecular links exist between aging and metabolism, we hypothesize that targeting the mechanisms involved in aging will also give rise to therapeutics that treat other devastating age-related diseases, such as neurodegeneration, cancer, inflammation and cardiovasc Read More

Alzheimer's disease (AD) is a devastating neurodegenerative disease for which there are no highly effective therapies. A novel therapeutic approach to the treatment of AD is the use of agonists of the nuclear receptor, peroxisome proliferators-activated receptor gamma (PPARγ). PPARγ is a ligand activated transcription factor whose best described roles are to regulate lipid metabolism and inflammation. Agonists of PPAR Read More

Mounting evidence suggests that copper may influence the progression of Alzheimer's disease by reducing clearance of the amyloid beta protein (Aß) from the brain. We propose that Aβ is cleared from the brain by tagging along with cholesterol/ApoE in traversing the BBB, with subsequent incorporation into HDL for delivery of the toxin to the liver. It is suggested that either ABC-A1 or LRP, or both are involved in Aβ transport Read More

Studies, ranging from epidemiological to in vitro and in vivo experimental settings have provided convincing evidence that different aspects of brain lipid metabolism may influence Alzheimer disease pathogenesis through effects on β-amyloid deposition and clearance. It has been demonstrated that transcription factors called nuclear liver X receptors (LXR) and their responsive genes provide natural regulatory mechanisms and i Read More

Liver X receptors (LXRα and LXRβ ) are oxysterol receptors that function as master transcription factors mediating cholesterol homeostasis in the periphery. LXRs regulate the levels of the ABCA1 and ABCG1 cholesterol transporters as well as apolipoproteins (apoE and apoC) in various cells thereby affecting cholesterol transport and metabolism. In the brain, LXRs regulate ABCA1 in both neurons and glia resulting in choleste Read More

Alzheimer disease (AD) includes inflammatory processes in the senile plaques and surrounding glia, with increased expression of acute phase proteins such as C-reactive protein (CRP) and IL-6. Increased IL-6 expression during normal brain aging suggests a link of age-related inflammation to the onset of AD during aging. Blood levels of CRP and IL-6 are also associated with higher risk of Alzheimer disease and cognitive decl Read More

Cerebrovascular dysfunction contributes to the cognitive decline and dementia in Alzheimer's disease (AD), and may precede cerebral amyloid angiopathy and brain accumulation of the Alzheimer's neurotoxin, amyloid β-peptide (Aβ). The blood-brain barrier (BBB) is critical for brain Aβ homeostasis and regulates Aβ transport via two main receptors, the low density lipoprotein receptor related protein 1 (LRP1) and the re Read More

In mammals, glucocorticoid actions appear to have evolved to maintain and enhance energy stores to be used for life-saving gluconeogenesis. They act on the brain to stimulate search behaviors, palatable feeding and emotionally relevant memories, and they act on the body to mobilize stored peripheral energy and direct it to central depots that serve the substrate needs of the liver. Our work in rats shows that searchin Read More

The original glucocorticoid (GC) hypothesis of brain aging and Alzheimer's disease proposed that chronic exposure to GCs promotes hippocampal aging and AD. This proposition arose from a study correlating increasing plasma corticosterone with hippocampal astrocyte reactivity in aging rats. Numerous subsequent studies have found evidence consistent with this hypothesis, in animal models and in humans. However, several r Read More