Journal of Alzheimer's Disease - Volume 20, issue 3

Article Type: Editorial

DOI: 10.3233/JAD-2010-091580

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 687-688, 2010

Authors: Qiu, Chengxuan | Xu, Weili | Fratiglioni, Laura

Article Type: Review Article

Abstract: Alzheimer's disease (AD), the most common cause of dementia, is posing serious threat to public health and health care system in both developed and developing nations due to a rapid increase in the aging population. Identification of etiological factors for AD and active implementation of interventions targeting those modifiable factors that may prevent or postpone clinical onset of the dementing disorder will provide an opportunity to cope with this challenge. Multidisciplinary research involving epidemiology, neuropathology, and neuroimaging has provided moderately strong evidence supporting the role of vascular factors and related disorders (e.g., midlife high blood pressure and obesity, diabetes, cerebral …microvascular lesions, and smoking) as risk factors and the possible role of psychosocial factors (e.g., high educational achievements, mentally-stimulating activity, social engagement, and physical exercise) as protective factors in the development and clinical manifestation of the dementia syndrome, including AD. The implementation of long-term, multidomain interventions designed for the modification of multiple vascular risk factors and the maintenance of socially-integrated lifestyles and mentally-stimulating activities is expected to postpone the clinical onset of AD and dementia, and thus, substantially reduce the burden of the disease at both the individual and societal levels. Show more

Keywords: Alzheimer's disease, dementia, intervention, psychosocial factors, vascular factors

DOI: 10.3233/JAD-2010-091663

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 689-697, 2010

Authors: Knopman, David S. | Roberts, Rosebud

Article Type: Review Article

Abstract: Cerebrovascular disease plays an important role in cognitive disorders in the elderly. Cerebrovascular disease and Alzheimer's disease interact on several levels, with one important level being the overlap in risk factors. The major vascular risk factors such as diabetes and impaired glycemic control, hypertension, obesity, and hyper- or dyslipidemia have been associated both with Alzheimer's disease and vascular dementia. The purpose of this review is to consider the context in which vascular dementia is diagnosed, place the pathophysiological consequences of cerebrovascular disease on cognition in the context of clinical and pathological Alzheimer's disease, and then to consider the evidence for …the role of major vascular risk factors in late-life cognitive impairment, changes in brain imaging and neuropathological changes. Midlife diabetes mellitus, hypertension, and obesity are established risk factors for clinically defined Alzheimer's disease as well as vascular dementia. The basis for these relationships could either be that the risk factors lead to microvascular brain disease, promote Alzheimer pathology or both. The associations of late-life onset diabetes mellitus, hypertension, and obesity with cognitive impairment are either attenuated or reversed. The role of vascular risk factors in midlife should be the focus of public health efforts to reduce the burden of late-life cognitive impairment. Show more

Keywords: Cognitive impairment, dementia, diabetes, hyperlipidemia, hypertension, obesity, stroke, vascular dementia, vascular risk factors

DOI: 10.3233/JAD-2010-091555

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 699-709, 2010

Authors: Carlsson, Cynthia M.

Article Type: Review Article

Abstract: The prevalence of Alzheimer's disease (AD) is increasing rapidly, heightening the importance of finding effective preventive therapies for this devastating disease. Midlife vascular risk factors, including type 2 diabetes mellitus (T2DM), have been associated with increased risk of AD decades later and may serve as targets for AD prevention. Studies to date suggest that T2DM and hyperinsulinemia increase risk for AD, possibly through their effects on amyloid-β metabolism and cerebrovascular dysfunction – two early findings in preclinical AD pathology. This paper reviews the evidence supporting a relationship between T2DM, hyperinsulinemia, and diabetic dyslipidemia on the development of AD, discusses DM …treatment trials and their preliminary results on cognitive function, and proposes some strategies for optimizing future AD prevention trial design. Show more

Keywords: Alzheimer's disease, biological markers, cognition, diabetes mellitus, dyslipidemia, prevention

DOI: 10.3233/JAD-2010-100012

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 711-722, 2010

Authors: Luchsinger, José A.

Article Type: Review Article

Abstract: This manuscript provides a comprehensive review of the epidemiologic evidence linking type 2 diabetes (T2D) and its precursor conditions, elevated adiposity and hyperinsulinemia, to dementia. The mechanisms relating these conditions to dementia may be vascular and non-vascular. Elevated adiposity in middle age is related to a higher risk of dementia but the data on this association in old age is conflicting. Several studies have shown that hyperinsulinemia, a consequence of higher adiposity and insulin resistance, is also related to a higher risk of dementia, including late onset Alzheimer's disease (LOAD). Studies have consistently shown a relation of T2D with higher …dementia risk, but the associations are stronger for vascular dementia compared to LOAD. A large proportion of the world population may be at increased risk of dementia given the trends for increasing prevalence of overweight, obesity, hyperinsulinemia, and T2D. However, these associations may present a unique opportunity for prevention and treatment of dementia. There are several known modalities that are effective in the prevention and T2D and the reduction of hyperinsulinemia including lifestyle interventions, metformin, thiazolideniodones, and acarbose. Several studies in the prevention and treatment of T2D are currently measuring cognitive outcomes and will provide information on whether T2D treatment and prevention can prevent cognitive decline and dementia. Show more

Keywords: Adiposity, Alzheimer's disease, cognitive impairment, glucose, hyperinsulinemia, insulin, obesity, overweight, type 2 diabetes

DOI: 10.3233/JAD-2010-091687

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 723-736, 2010

Authors: Morley, John E. | Banks, William A.

Article Type: Review Article

Abstract: Cholesterol, omega-3 fatty acids, and triglycerides have been postulated to play roles in affecting cognition in Alzheimer's disease (AD), the elderly, and obesity. Animal, human epidemiological, and in vitro studies each suggest an important role for cholesterol in the regulation of amyloid-β (Aβ) protein and the pathogenesis of AD. In contrast, well controlled studies have failed to show an effect of cholesterol lowering with statins on cognition, indicating that the cholesterol effect is spurious or indirect, possibly mediated through other lipids. Administration of diedocosahexanoic acid (DHA), a dietary omega-3 fatty acid derived primarily from fish and plants, improves cognition and …reduces lipid peroxidation in animals, including in mouse models of AD. DHA also blocks Aβ-mediated tau phosphorylation. In humans, fish consumption or administration of DHA has been associated with cognitive improvement in many, but not all, studies. Both human and animal studies show that obesity is associated with cognitive impairments and that lowering triglycerides improves cognition. Administration of triglycerides to mice decreases learning and memory and impairs long-term potential. The effect of triglycerides may be mediated in part by inducing resistance to positive cognitive features of gastrointestinal hormones such as leptin. Overall, these studies strongly suggest that some lipids affect cognition in AD, the elderly, and obesity through a variety of mechanisms yet to be fully defined. Show more

Keywords: Alzheimer's disease, amyloid-β protein, blood-brain barrier, cholesterol, elderly, leptin, lipids, obesity, omega-3 fatty acids, triglycerides

DOI: 10.3233/JAD-2010-091576

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 737-747, 2010

Authors: de Toledo Ferraz Alves, Tânia Corrêa | Ferreira, Luiz Kobuti | Wajngarten, Mauricio | Busatto, Geraldo F.

Article Type: Review Article

Abstract: Vascular risk factors can play an important role in determining the onset of non-genetic Alzheimer's disease (AD). Most cases of AD are sporadic and late-onset, and a complex interaction between genetic predisposition and vascular risk factors has been proposed. Vascular risk factors for AD include stroke, hypertension, diabetes, homocysteine, smoking, hypercholesterolemia, heart failure and atrial fibrillation; it is possible that these can trigger cerebrovascular dysfunction and AD pathology. Explanations for these associations include the coincidence of common disorders in the elderly where vascular and cerebrovascular disease can precipitate AD, implying that the onset of dementia disease is determined by a …synergistic combination of risk factors. In this paper we review the role of cardiovascular risk factors in the pathogenesis of AD and discuss the associated brain mechanisms that can underlie the onset of AD. Cardiovascular diseases are a promising avenue of AD research because they are potentially modifiable in early adult life and provide a new perspective for the prevention of dementia. Show more

Keywords: Aging, Alzheimer's disease, dementia, vascular risk factors

DOI: 10.3233/JAD-2010-091561

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 749-763, 2010

Authors: Kamphuis, Patrick J.G.H. | Scheltens, Philip

Article Type: Review Article

Abstract: Age-related changes in nutritional status can play an important role in brain functioning. Specific nutrient deficiencies in the elderly, including omega-3 fatty acids, B-vitamins, and antioxidants among others, may exacerbate pathological processes in the brain. Consequently, the potential of nutritional intervention to prevent or delay cognitive impairment and the development of Alzheimer's disease (AD) is a topic of growing scientific interest. This review summarizes epidemiological studies linking specific nutritional deficiencies to mild cognitive impairment (MCI), as well as completed and ongoing nutritional studies in prevention of MCI and AD. Processes that underlie AD pathogenesis include: membrane/synaptic degeneration, abnormal protein processing …(amyloid-β, tau), vascular risk factors (hypertension, hypercholesterolemia), inflammation, and oxidative stress. Consideration of mechanistic evidence to date suggests that several nutritional components can effectively counteract these processes, e.g., by promoting membrane formation and synaptogenesis, enhancing memory/behavior, improving endothelial function, and cerebrovascular health. The literature reinforces the need for early intervention in AD and suggests that multi-nutritional intervention, targeting multiple aspects of the neurodegenerative process during the earliest possible phase in the development of the disease, is likely to have the greatest therapeutic potential. Show more

Keywords: Alzheimer's disease, nutrition, primary prevention, Souvenaid®, synapse formation

DOI: 10.3233/JAD-2010-091558

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 765-775, 2010

Authors: Radak, Zsolt | Hart, Nikoletta | Sarga, Linda | Koltai, Erika | Atalay, Mustafa | Ohno, Hideki | Boldogh, Istvan

Article Type: Review Article

Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting the elderly population. It is predicted that the incidence of AD will be increased in the future making this disease one of the greatest medical, social, and economic challenges for individuals, families, and the health care system worldwide. The etiology of AD is multifactorial. It features increased oxidative state and deposition of amyloid plaques and neurofibrillary tangles of protein tau in the central cortex and limbic system of the brain. Here we provide an overview of the positive impacts of exercise on this challenging disease. Regular physical activity increases the endurance …of cells and tissues to oxidative stress, vascularization, energy metabolism, and neurotrophin synthesis, all important in neurogenesis, memory improvement, and brain plasticity. Although extensive studies are required to understand the mechanism, it is clear that physical exercise is beneficial in the prevention of AD and other age-associated neurodegenerative disorders. Show more

Keywords: Amyloid-β, amyloid-β degradation, exercise, metabolism, neurotrophins, physical inactivity, sirtuins

DOI: 10.3233/JAD-2010-091531

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 777-783, 2010

Authors: Arab, Lana | Sabbagh, Marwan N.

Article Type: Review Article

Abstract: As the number of patients with Alzheimer's disease (AD) is expected to grow, finding ways to prevent and lower the risk of AD becomes a crucial matter. Risk factors for developing AD have been identified including health conditions, dietary habits, genetics and heredity, gender, education, age, and lifestyle. Interventions targeted at some of these risk factors may offer opportunities for development of an optimal preventive strategy. Lifestyle habits which include dietary habits and physical activities appear to have positive effect on modifying many risk factors. Studies have shown controversial results when it comes to the relation between the adherence to …a Mediterranean diet and /or physical activity and the incidence of AD. Many population-based studies reported the positive association between antioxidants intake (like vitamin E and C), and polyunsaturated fatty acids whether it is from the diet or supplements on the cognitive performance. Future investigations should aim to determine objectively whether lifestyle modification through diet, exercise, or vitamins/supplements truly exert risk reduction or outright prevention. In this review, lifestyle habits are reviewed as they pertain to influence on risk of developing AD as well as on cognitive decline. Epidemiological studies and animal studies are reviewed. Show more

Keywords: Alzheimer's disease, lifestyle, Mediterranean diet, physical activity, prevention, risk

DOI: 10.3233/JAD-2010-091573

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 785-794, 2010