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Alzheimer's Disease Promotion by Obesity: Induced Mechanisms—Molecular Links and Perspectives

DOI: 10.1155/2012/986823

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Abstract:

The incidence of AD is increasing in parallel with the increase in life expectancy. At the same time the prevalence of metabolic syndrome and obesity is reaching epidemic proportions in western populations. Stress is one of the major inducers of visceral fat and obesity development, underlying accelerated aging processes. Adipose tissue is at present considered as an active endocrine organ, producing important mediators involved in metabolism regulation as well as in inflammatory mechanisms. Insulin and leptin resistance has been related to the dysregulation of energy balance and to the induction of a chronic inflammatory status which have been recognized as important cofactors in cognitive impairment and AD initiation and progression. The aim of this paper is to disclose the correlation between the onset and progression of AD and the stress-induced changes in lifestyle, leading to overnutrition and reduced physical activity, ending with metabolic syndrome and obesity. The involved molecular mechanisms will be briefly discussed, and advisable guide lines for the prevention of AD through lifestyle modifications will be proposed. 1. Alzheimer’s Disease (AD) Alzheimer’s disease (AD) is the most common cause of dementia, accounting for 60–80% of cases, although there is growing awareness that AD is often confused with other causes of dementia. According to estimates by 2006, approximately 33.9?million people worldwide have AD [1], and Alzheimer’s Association estimates 5 to 3 million people in the US have the disease [2]. It is foreseen that the prevalence will nearly triple [1] or increase from three to four times, according to other studies, in the next 40 years due to demographic changes and a longer life expectancy [3]. Among the sixty year olds, those who show a higher prevalence are North Americans (6.4%) and Western Europeans (5.4%). For the rest there is 4.9% in Latin America. It is to outline that incidence is likely to increase in proportion to the aging population, which by 2030 would increase by 250% in industrialized countries. Previous data show that rates of dementia increase exponentially with age [4]. The incidence of dementia doubles every 5 years, from 0.66/100 persons aged 70 to 74 years to 11.30/100 persons for those aged 90 or more. A bulk of studies has provided evidence to support the role of obesity as a risk factor for AD development and the possible role of psychosocial factors (e.g., professional achievements, stimulant mental activities, social engagement, and physical activity) as protective factors. 1.1. Stress in Modern

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