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Type 2 Diabetes Is Negatively Associated With Alzheimer's Disease Neuropathology

Departments of ¹ Psychiatry
² Biomathematical Sciences
³ Pathology, Mount Sinai School of Medicine, New York.
⁴ Psychiatry Department, Sheba Medical Center, Tel-Hashomer, Israel.
⁵ Psychiatry Service, Bronx VA Medical Center, New York.
⁶ Lilly Research Laboratories, Indianapolis, Indiana.

Address correspondence to Vahram Haroutunian, PhD, Psychiatry Research (4F-33B), Bronx VA Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468. E-mail: Vahram.Haroutunian{at}mssm.edu

Background. In cross-sectional and longitudinal studies, type 2 diabetes has been positively associated with the risk of Alzheimer's disease (AD). The present descriptive study compared diabetic and nondiabetic subjects on the severity of neuritic plaques and neurofibrillary tangles (NFTs) in the cerebral cortex and in the hippocampus.

Methods. The study included specimens from 385 consecutive autopsies of residents of a nursing home (15.8% diabetics). Mean age at death = 84 years [standard deviation (SD) = 10], 66% were female, Clinical Dementia Rating mean = 3.0 (SD = 1.6), and 32.5% had an APOE4 allele. Additional analyses limited the sample to 268 subjects (14.1% diabetics) without neuropathology other than AD.

Results. Analyses of covariance controlling for age at death, dementia severity (Clinical Dementia Rating score), and APOE4 allele indicated that diabetics had significantly fewer neuritic plaques (p =.008) and NFTs (p =.047) in the cerebral cortex than did nondiabetics. In the hippocampus, diabetics had significantly lower plaque ratings than did nondiabetics (p =.019), but the lower ratings of NFTs did not achieve statistical significance (p =.082). In the entire sample, diabetics had significantly less AD-associated neuropathology in all four analyses.

Conclusions. These results raise the possibility that the varied associations observed between diabetes and AD may be specific to as yet ill-defined subgroups of dementia and diabetic patients or may be more characteristic of younger patients than of those who survive to a mean age of 84 years. Future studies are encouraged to examine a variety of other characteristics such as age that may interact with diabetes affecting the incidence of AD.