We examined the relationship of diabetes and hemoglobin A1C (A1C) to 2 common causes of dementia. The study included 1228 subjects who underwent annual clinical evaluations and a brain autopsy at death, as part of a Rush longitudinal cohort study of aging. A total of 433 subjects had A1C data available. Neuropathologic evaluations documented the size and location of infarcts. Modified silver stain-based Alzheimer disease (AD) measures included global and regional scores. We used regression analyses to examine associations of diabetes and A1C with overall and regional neuropathology. Diabetes [odds ratio (OR)=0.94; 95% confidence interval (CI), 0.73-1.20) and A1C (OR=0.83; 95% CI, 0.62-1.10) were not associated with global AD pathology across the brain, nor with overall or individual measures of neuropathology in mesial temporal or neocortical regions separately (all P>0.05). Diabetes was associated with a higher odds of any infarct (OR=1.43; 95% CI, 1.07-1.90), and particularly with gross (OR=1.53; 95% CI, 1.14-2.06) but not microinfarcts (P=0.06), and subcortical (OR=1.79; 95% CI, 1.34-2.39) but not cortical infarcts (P=0.83). In summary, we found no relationship of diabetes or A1C with global or regional AD pathology, including in the mesial temporal lobe. Diabetes is associated with gross subcortical infarcts. Our results suggest that the diabetes-dementia link is based on subcortical vascular pathology and not on regional AD pathology.
*Rush Alzheimer’s Disease Center
Departments of †Neurological Sciences
§Behavioral Sciences, Rush University Medical Center, Chicago, IL
∥Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Johns Hopkins University, Baltimore, MD
¶Department of Neurology, Harvard Medical School, Interdisciplinary Brain Center, Massachusetts General Hospital, Boston, MA
J.J.P. and Z.A. conducted the literature search, drafted the first version of the manuscript, and revised the manuscript. Z.A. conceptualized the study, collected data, designed the study, analyzed and interpreted data, and had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. J.A.S. conceptualized the study, collected data, and revised the manuscript. A.W.C. analyzed and interpreted data, and revised the manuscript. S.E.L., L.L.B., R.S.A., S.E.A., and D.A.B. collected data and made critical revisions to the manuscript. D.A.B., L.L.B., J.A.S., and Z.A. obtained study funding.
Supported by the National Institutes of Health grants P30 AG10161, RF1 AG15819, R01 AG17917, RF1 AG022018, R01 AG40039, and R01 NS084965.
The authors declare no conflicts of interest.
Reprints: Zoe Arvanitakis, MD, MS, Rush Alzheimer’s Disease Center, Professor, Department of Neurological Sciences, Rush University Medical Center, 600S. Paulina Ave., Suite 1020, Chicago, IL 60612.
Received August 15, 2016
Accepted August 28, 2016