Meta-analysis of Alzheimer's disease risk with obesity, diabetes, and related disorders.
BACKGROUND
Late-onset Alzheimer's disease (AD) is a multifactorial and heterogeneous disorder with major risk factors including advanced age, presence of an apolipoprotein E epsilon4 (APOE4) allele, and family history of AD. Other risk factors may be obesity and diabetes and related disorders, which are highly prevalent.


METHODS
We reviewed longitudinal epidemiological studies of body mass, diabetes, metabolic syndrome, and glucose and insulin levels on risk for AD. We conducted meta-analyses of the results from these studies.


RESULTS
For obesity assessed by body mass index, the pooled effect size for AD was 1.59 (95% confidence interval [CI] 1.02-2.5; z = 2.0; p = .042), and for diabetes, the pooled effect size for AD was 1.54 (95% CI 1.33-1.79; z = 5.7; p < .001). Egger's test did not find significant evidence for publication bias in the meta-analysis for obesity (t = -1.4, p = .21) or for diabetes (t = -.86, p = .42). Since these disorders are highly comorbid, we conducted a meta-analysis combining all studies of obesity, diabetes, and abnormal glucose or insulin levels, which yielded a highly significant pooled effect size for AD of 1.63 (95% CI 1.39-1.92; z = 5.9; p < .001).


CONCLUSIONS
Obesity and diabetes significantly and independently increase risk for AD. Though the level of risk is less than that with the APOE4 allele, the high prevalence of these disorders may result in substantial increases in future incidence of AD. Physiological changes common to obesity and diabetes plausibly promote AD.
Profenno
Louis A
LA
Department of Psychiatry, State University of New York Upstate Medical University, Syracuse, New York, USA. profennl@upstate.edu
Porsteinsson
Anton P
AP
Faraone
Stephen V
SV
D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics; D015992:Body Mass Index; D048909:Diabetes Complications / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D050177:Overweight / Q000150:complications; D016016:Proportional Hazards Models; D039781:PubMed / Q000706:statistics & numerical data; D012189:Retrospective Studies; D012307:Risk Factors
D053327:Apolipoprotein E4; D007328:Insulin; D005947:Glucose