Diabetes, Alzheimer disease, and vascular dementia
A population-based neuropathologic study
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Abstract
Objective: To investigate the relation of diabetes to dementia, Alzheimer disease (AD), and vascular dementia (VaD), through analyses of incidence, mortality, and neuropathologic outcomes in a prospective population-based study of the oldest old.
Methods: The Vantaa 85+ study included 553 residents living in the city of Vantaa, Finland, and aged ≥85 years on April 1, 1991. Survivors were reexamined in 1994, 1996, 1999, and 2001. Autopsies were performed in 291 persons who died during the follow-up (48% of total population). Diabetes was assessed according to self-report, medical record of physician-diagnosed diabetes, or use of antidiabetic medication. Macroscopic infarcts were identified from 1-cm coronal slices of cerebral hemispheres, 5-mm transverse brainstem slices, and sagittal cerebellum slices. Methenamine silver staining was used for β-amyloid, methenamine silver-Bodian staining for neurofibrillary tangles, and modified Bielschowsky method for neuritic plaques. Cox proportional hazards and multiple logistic regression models were used to analyze the association of diabetes with dementia and neuropathology, respectively.
Results: Diabetes at baseline doubled the incidence of dementia, AD, and VaD, and increased mortality. Individuals with diabetes were less likely to have β-amyloid (hazard ratio [HR] [95% confidence interval (CI)] was 0.48 [0.23–0.98]) and tangles (HR [95% CI] 0.72 [0.39–1.33]) but more likely to have cerebral infarcts (HR [95% CI] 1.88 [1.06–3.34]) after all adjustments.
Conclusion: Elderly patients with diabetes develop more extensive vascular pathology, which alone or together with AD-type pathology (particularly in APOE ε4 carriers) results in increased dementia risk.
Footnotes
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Supplemental data at www.neurology.org
e-Pub ahead of print on August 25, 2010, at www.neurology.org.
Study funding: Supported by Academy of Finland grants 120676 and 129395 and Swedish Council for Working Life and Social Research.
Disclosure: Author disclosures are provided at the end of the article.
Received January 7, 2010. Accepted in final form June 7, 2010.
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