title: Type 2 diabetes as a risk factor for Alzheimer's disease: the confounders, interactions, and neuropathology associated with this relationship.
abstract: We performed a systematic review and meta-analysis to explore whether type 2 diabetes mellitus (T2DM) increases the risk of Alzheimer's disease (AD). We also reviewed interactions with smoking, hypertension, and apolipoprotein E ɛ4. Using a series of databases (MEDLINE, EMBASE, PubMed, Current Contents Connect, and Google Scholar), we identified a total of 15 epidemiologic studies. Fourteen studies reported positive associations, of which 9 were statistically significant. Risk estimates ranged from 0.83 to 2.45. The pooled adjusted risk ratio was 1.57 (95% confidence interval: 1.41, 1.75), with a population-attributable risk of 8%. Smoking and hypertension, when comorbid with T2DM, had odds of 14 and 3, respectively. Of the 5 studies that investigated the interaction between T2DM and apolipoprotein E ɛ4, 4 showed positive associations, of which 3 were significant, with odds ranging from 2.4 to 4.99. The pooled adjusted risk ratio was 2.91 (95% confidence interval: 1.51, 5.61). Risk estimates were presented in the context of a key confounder-cerebral infarcts-which are more common in those with T2DM and might contribute to the manifestation of clinical AD. We provide evidence from clinico-neuropathologic studies that demonstrates the following: First, cerebral infarcts are more common than AD-type pathology in those with T2DM and dementia. Second, those with dementia at postmortem are more likely to have both AD-type and cerebrovascular pathologies. Finally, cerebral infarcts reduce the number of AD lesions required for the manifestation of clinical dementia, but they do not appear to interact synergistically with AD-type pathology. Therefore, the increased risk of clinically diagnosed AD seems to be mediated through cerebrovascular pathology.
authors: Nicholas T
authors: NT
authors: Vagelatos
authors: Guy D
authors: GD
authors: Eslick
mesh_terms: D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000473:pathology; D002544:Cerebral Infarction / Q000453:epidemiology / Q000473:pathology; D015986:Confounding Factors, Epidemiologic; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D012044:Regression Analysis; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology
chemical_list: D053327:Apolipoprotein E4
keywords: Alzheimer disease; apolipoprotein E; dementia; risk factors; type 2 diabetes mellitus