Alzheimer Disease: Gustafson DR

Luchsinger JA, Gustafson DR. · Gertrude H. Sergievsky Center, New York, NY 10032, USA. · J Alzheimers Dis. · Pubmed #19387106 links to  free full text

Abstract: 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.

Luchsinger JA, Gustafson DR. · Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, New York, USA. · Curr Opin Clin Nutr Metab Care. · Pubmed #19057182 No free full text.

Abstract: PURPOSE OF REVIEW: Alzheimer's disease is the most common form of dementia. There are no known preventive or curative measures. There is increasing evidence for the role of total adiposity, usually measured clinically as BMI, and central adiposity, in Alzheimer's disease. This topic is of enormous public health importance given the global epidemic of high adiposity and its consequences. RECENT FINDINGS: Salient publications in 2007 and 2008 showed that (a) central adiposity in middle age predicts dementia in old age; (b) the relation between high adiposity and dementia is attenuated with older age; (c) waist circumference in old age, a measure of central adiposity, may be a better predictor of dementia than BMI; (d) lower BMI predicts dementia in elderly people; and (e) weight loss may precede dementia diagnosis by decades, which may explain seemingly paradoxical findings. SUMMARY: The possibility that high adiposity increases Alzheimer's disease risk is alarming given global trends of overweight and obesity in the general population. However, prevention and manipulation of adiposity may also provide a means to prevent Alzheimer's disease. Treatment of weight loss in Alzheimer's disease may also be important but is beyond the score of this review.

Zetterberg M, Landgren S, Andersson ME, Palmér MS, Gustafson DR, Skoog I, Minthon L, Thelle DS, Wallin A, Bogdanovic N, Andreasen N, Blennow K, Zetterberg H. · Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Section of Ophthalmology, The Sahlgrenska Academy at Göteborg University, Mölndal, Sweden. · Am J Med Genet B Neuropsychiatr Genet. · Pubmed #18163432 No free full text.

Abstract: Alzheimer's disease (AD) and age-related macular degeneration (AMD) share several epidemiological and biochemical features. The present study aimed to assess the possible influence of the AMD-associated complement factor H (CFH) Y402H (1277T > C) polymorphism on the risk of AD. Caucasian subjects (n = 800) meeting the criteria for probable (n = 717) or definite (n = 83) AD and Caucasian non-demented controls (n = 1265) were included in this multi-center case-control study, in which genotype and allele frequencies of the CFH 1277T > C polymorphism were determined and related to diagnosis, APOE genotype, Mini-Mental State Examination score (MMSE) and the cerebrospinal fluid (CSF) biomarkers total-tau (T-tau), phospho-tau(181) (P-tau(181)), and beta-amyloid(1-42) (Abeta(1-42)). The AMD-associated CFH genotypes (1277CC and 1277TC) were overrepresented in subjects with AD as compared to control individuals (P = 0.029). Positive C carrier status was associated with an odds ratio (OR) for AD of 1.24 (95% confidence interval [CI] 1.02-1.50). When APOE epsilon4 carrier status was included in the regression model, this association was even stronger (OR 1.34, 95% CI: 1.08-1.65, P = 0.007). Subgroup analysis showed that the association between CFH C allele positivity and AD was only evident for individuals carrying the APOE epsilon4 allele. Positive C carrier status was also associated with lower levels of CSF Abeta(1-42) selectively in the control group in an APOE epsilon4-independent manner (P = 0.003). In conclusion, the CFH 1277T > C polymorphism seems to influence the risk of AD and there appears to be an interaction between CFH 1277C and APOE epsilon4 alleles. The CFH 1277C allele may predispose patients for co-morbidity in AD and AMD.

Cereda E, Sacchi MC, Malavazos AE, Whitmer RA, Gustafson DR, Barrett-Connor E, Haan MN, Gunderson EP, Yaffe K. · No affiliation provided · Neurology. · Pubmed #19289749 No free full text.

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