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Diabetes is related to cerebral infarction but not to AD pathology in older persons

From Rush Alzheimer's Disease Center (Z.A., J.A.S., R.S.W., Z.W., D.A.B.), Department of Neurological Sciences (Z.A., J.A.S., R.S.W., D.A.B.), Department of Pathology (J.A.S.), Department of Behavioral Sciences (R.S.W.), Rush Institute for Healthy Aging (Y.L.), and Department of Internal Medicine (Y.L.), Rush University Medical Center, Chicago, IL; and Center for Neurobiology and Behavior (S.E.A.), University of Pennsylvania, Philadelphia.

Address correspondence and reprint requests to Dr. Zoe Arvanitakis, Rush Alzheimer's Disease Center, 600 S. Paulina, Suite 1020, Rush University Medical Center, Chicago, IL 60612.

Objective: To examine the potential relation of diabetes to common neuropathologic causes of dementia, cerebral infarction and Alzheimer disease (AD) neuropathology.

Methods: Subjects were 233 older Catholic clergy in the Religious Orders Study, who underwent detailed annual evaluations, including neuropsychological testing, and brain autopsy at time of death (mean age 86 years, 45% men). Diabetes was identified by annual direct medication inspection and history. Cognitive function proximate to death was summarized into five cognitive domains, based on 19 neuropsychological tests. Macroscopic cerebral infarctions were recorded from 1 cm coronal slabs. Neuritic plaques, diffuse plaques, and neurofibrillary tangles were counted in Bielschowsky silver-stained sections and summarized to yield composite measures of neuritic plaques, diffuse plaques, tangles, and overall AD pathology. We also used immunohistochemistry with antibodies to amyloid-ß and PHF-tau to obtain quantitative measures of amyloid burden and neurofibrillary tangle density. Multiple logistic and linear regression analyses were used to examine the relation of diabetes to cerebral infarctions and AD pathology, controlling for age, sex, and education.

Results: AD pathology was related to all five cognitive domains (p < 0.01) and infarctions were related to perceptual speed (p < 0.001). Diabetes (present in 15% subjects) was associated with an increased odds of infarction (OR = 2.47, 95% CI: 1.16, 5.24). Diabetes was not related to global AD pathology score, or to specific measures of neuritic plaques, diffuse plaques or tangles, or to amyloid burden or tangle density.

Conclusion: We found a relation between diabetes and cerebral infarction but not between diabetes and Alzheimer disease pathology in older persons.

Supported by National Institute on Aging grants K23 AG23675 (Z.A.), K08 AG00849 (J.A.S.), P30 AG10161 (D.A.B.), and R01 AG15819 (D.A.B.).

Disclosure: The authors report no conflicts of interest.

Received February 23, 2006. Accepted in final form August 22, 2006.

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