The occurrence of obesity, commonly estimated using body mass index (BMI), and the most common late-onset dementia, Alzheimer's disease (AD), are increasing globally. The year 2013 marked a decade of ...epidemiologic observational reports on the association between BMI and late-onset dementias. In this review, we highlight epidemiological studies that measured both mid- and late-life BMI in association with dementia. Studies investigating the association between midlife BMI and risk for dementia demonstrated generally an increased risk among overweight and obese adults. When measured in late-life, elevated BMI has been associated with lower risk. In addition, being underweight and/or having a decrease in BMI in late-life are associated with higher dementia risk compared to BMI in the normal range or stable BMI. In this review, a decade (2003-2013) of epidemiologic observational studies on associations between BMI and AD is highlighted. These observations provide a strong base for addressing biological mechanisms underlying this complex association.
Abstract Alzheimer's disease (AD) is a complex disorder with a clear genetic component. Three genes have been identified as the cause of early onset familial AD (EOAD). The most common form of the ...disease, late onset Alzheimer's disease (LOAD), is, however, a sporadic one presenting itself in later stages of life. The genetic component of this late onset form of AD has been the target of a large number of studies, because only one genetic risk factor (APOE4) has been consistently associated with the disease. However, technological advances allow new approaches in the study of complex disorders. In this review, we discuss the new results produced by genome wide association studies, in light of the current knowledge of the complexity of AD genetics.
Sex Differences in Stroke Haast, Roy AM; Gustafson, Deborah R; Kiliaan, Amanda J
Journal of Cerebral Blood Flow & Metabolism,
12/2012, Letnik:
32, Številka:
12
Book Review, Journal Article
Recenzirano
Odprti dostop
Sex differences in stroke are observed across epidemiologic studies, pathophysiology, treatments, and outcomes. These sex differences have profound implications for effective prevention and treatment ...and are the focus of this review. Epidemiologic studies reveal a clear age-by-sex interaction in stroke prevalence, incidence, and mortality. While premenopausal women experience fewer strokes than men of comparable age, stroke rates increase among postmenopausal women compared with age-matched men. This postmenopausal phenomenon, in combination with living longer, are reasons for women being older at stroke onset and suffering more severe strokes. Thus, a primary focus of stroke prevention has been based on sex steroid hormone-dependent mechanisms. Sex hormones affect different (patho)physiologic functions of the cerebral circulation. Clarifying the impact of sex hormones on cerebral vasculature using suitable animal models is essential to elucidate male–female differences in stroke pathophysiology and development of sex-specific treatments. Much remains to be learned about sex differences in stroke as anatomic and genetic factors may also contribute, revealing its multifactorial nature. In addition, the aftermath of stroke appears to be more adverse in women than in men, again based on older age at stroke onset, longer prehospital delays, and potentially, differences in treatment.
Abstract Obesity is a pandemic and a serious global health concern. Obesity is a risk factor for multiple conditions and contributes to multi-morbidities, resulting in increased health costs and ...millions of deaths each year. Obesity has been associated with changes in brain structure, cognitive deficits, dementia and Alzheimer׳s disease. Adipokines, defined as hormones, cytokines and peptides secreted by adipose tissue, may have more widespread influence and functionality in the brain than previously thought. In this review, six adipokines, and their actions in the obese and non-obese conditions will be discussed. Included are: plasminogen activator inhibitor-1 (PAI-1), interleukin-6 (IL-6), tumor necrosis factors alpha (TNF-α), angiotensinogen (AGT), adiponectin and leptin. Their functionality in the periphery, their ability to cross the blood brain barrier (BBB) and their influence on dementia processes within the brain will be discussed.
Level of adiposity is linked to manifest dementia and Alzheimer's disease in epidemiological studies. Overweight and obesity in mid- and late-life may increase risk for dementia, whereas decline in ...body weight or body mass index and underweight in years preceding and at the time of a dementia diagnosis may also relate to dementia. The role of adiposity during the period of cognitive decline is, as yet, not understood; however, some hypotheses relating adipose tissue to brain can be drawn. This review focuses on potential, varied mechanisms whereby adipose tissue may influence or interact with the brain and/or dementia risk during the dynamic period of life characterized by both body weight and cognitive decline. These mechanisms relate to: a) adipose tissue location and cell types, b) body composition, c) endocrine adipose, and d) the interplay among adipose, brain structure and function, and genes. This review will illustrate that adipose tissue is a quintessential, multifunctional tissue of the human body.
Background: Low levels of cerebrospinal fluid (CSF) β-amyloid 1–42 (Aβ42) and high total tau (T-tau) are diagnostic for manifest Alzheimer’s disease. It is not known, however, whether these ...biomarkers may be risk indicators for cognitive decline in otherwise healthy older people. Methods: The longitudinal relationship between CSF markers, Aβ42 and T-tau, measured in 1992, and change in Mini-Mental State Examination (ΔMMSE) score between 1992 and 2002 were investigated in 55 women (aged 70–84 years, mean (SD) MMSE score = 28.3 (1.5)), who were participants in the Prospective Population Study of Women in Gothenburg, Sweden. These women did not have dementia when they experienced lumbar puncture in 1992–3. Results: Over the 8-year follow-up period, ΔMMSE (range = +3 to −21 points) was correlated with Aβ42 (Spearman’s r = 0.40, p = 0.002), such that lower levels of Aβ42 were related to greater decline. This was also observed after excluding 4 women who developed dementia between 1992 and 2002 (Spearman’s r = 0.34, p = 0.019). A multivariate logistic regression model predicting a decline of ⩾5 points on the MMSE (observed in six women), or a risk of developing dementia over the 8-year follow-up period (observed in four women), including age, education, Aβ42 and T-tau as covariates, showed that Aβ42 was the sole predictor of significant cognitive decline or dementia (OR per 100 pg/ml Aβ42 = 2.24, 95% CI 1.19 to 4.22, p = 0.013). Conclusions: Low levels of CSF Aβ42 may predict cognitive decline among older women without dementia.
Introduction
High dietary intake of long chain, polyunsaturated fatty acids is associated with lower Alzheimer's disease (AD) risk.
Methods
Washington Heights‐Hamilton Heights‐Inwood Columbia Aging ...Project is a multiethnic, prospective observational study of aging and dementia among elderly (≥ 65 years). Dietary intake was measured using a food frequency questionnaire. Dietary short‐, medium‐, and long‐chain fatty acid intakes were categorized by number of carbons and double bonds. Consensus AD diagnoses were made. Associations between AD risk and dietary fatty acid and cholesterol intakes were estimated using multivariable Cox proportional hazards regression models.
Results
Of 2612 multiethnic women (67%) and men (baseline age 76.3 6.4 years), 380 developed AD over an average 4.5 years follow‐up. Lower risk of AD was associated with increasing intakes of docosahexaenoic acid (DHA; hazard ratio HR = 0.73, 95% confidence interval CI: 0.57 to 0.95, P = 0.018) and eicosapentaenoic acid (EPA; HR = 0.74, 95% CI: 0.57 to 0.95, P = 0.021), and longer AD‐free survival (P < 0.05).
Discussion
Higher intake of DHA and EPA are protective for AD.
This manuscript provides a comprehensive review of the epidemiologic evidence linking the continuum of adiposity and type 2 diabetes (T2D) with Alzheimer's disease (AD). The mechanisms relating ...adiposity and T2D to AD may include hyperinsulinemia, advanced products of glycosylation, cerebrovascular disease, and products of adipose tissue metabolism. Elevated adiposity in middle age is related to a higher risk of AD 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 AD. Hyperinsulinemia is a risk factor for T2D, and numerous studies have shown a relation of T2D with higher AD risk. The implication of these associations is that a large proportion of the world population may be at increased risk of AD 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 AD. Several studies in the prevention and treatment of T2D are currently conducting, or have planned, cognition ancillary studies. In addition, clinical trials using insulin sensitizers in the treatment or prevention of AD are under way.
The speed and severity of clinical progression after Alzheimer disease (AD) diagnosis varies and depends on multiple factors, most not well elucidated. We assessed whether body mass index (BMI) and ...1-year weight change (WC) are associated with clinical progression in amnestic mild cognitive impairment (aMCI) and early-stage AD. Longitudinal data comprising 2268 aMCI and 1506 AD participants in the National Alzheimer's Coordinating Center's Uniform Data Set were used to examine nuances of clinical progression by BMI and WC, as well as potential variations in associations by age, sex, BMI (WC model), or apolipoprotein E genotype. In aMCI, high BMI (vs. moderate BMI) was associated with slower progression; weight loss (vs. no WC) was associated with faster progression. In AD, no significant differences were observed in clinical progression by BMI or WC. The association between BMI and clinical progression varied significantly by apolipoprotein E genotype in AD, and the association between WC and clinical progression varied significantly by sex and BMI in aMCI. Baseline BMI and 1-year WC in late life may serve as early prognostic indicators in aMCI and early-stage AD. If replicated, these results may help in counseling patients on anticipated clinical progression and suggest windows of opportunity for intervention.
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