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Association Between Neuropathology and Brain Volume in The Framingham Heart Study

Kaur, Berneet MD*; Himali, Jayandra J. PhD; Seshadri, Sudha MD; Beiser, Alexa S. PhD†,‡; Au, Rhoda PhD; McKee, Ann C. MD; Auerbach, Sanford MD; Wolf, Philip A. MD; DeCarli, Charles S. MD, FAAN*

Alzheimer Disease & Associated Disorders: July-September 2014 - Volume 28 - Issue 3 - p 219–225
doi: 10.1097/WAD.0000000000000032
Original Articles

Studies of clinical and community cohorts have shown that antemortem imaging measures of hippocampal volume have correlated with postmortem Alzheimer pathology. Fewer studies have examined the relationship between both Alzheimer and cerebrovascular pathology, and antemortem brain imaging. The aim of this study was to correlate antemortem brain magnetic resonance imaging (MRI) volumes with postmortem brain pathology (both Alzheimer-related and cerebrovascular) in a community-derived cohort from the Framingham Heart Study. Participants (n=59) from the Framingham Heart Study were included if they were enrolled in the brain autopsy program and underwent antemortem clinical evaluation, neuropsychological testing, and brain MRI. Cortical neurofibrillary tangle pathology correlated with lower total cerebral brain (β±SE=−0.04±0.01, P=0.004) and hippocampal volumes (β±SE=−0.03±0.02, P=0.044) and larger temporal horns (log-transformed, β±SE=0.05±0.01, P=0.001). Similar findings were seen between total/cortical neuritic plaques and total cerebral brain and temporal horn volume. White matter hyperintensities (also log-transformed) were best predicted by the presence of deep nuclei microinfarcts (β±SE=0.53±0.21, P=0.016), whereas hippocampal volume was significantly decreased in the presence of hippocampal sclerosis (β±SE=−1.23±0.30, P<0.001). This study showed that volumetric MRI measures correlated with postmortem Alzheimer-related and cerebrovascular neuropathology in this community-derived cohort, confirming that these MRI measures are important antemortem surrogates for these dementia-related pathologies.

*Department of Neurology, University of California, Davis, Sacramento, CA

Department of Neurology, Boston University School of Medicine, Framingham Heart Study

Department of Biostatistics, Boston University School of Public Health, Boston, MA

Supported by contract N01-HC-25195 from the National Heart, Lung, and Blood Institute’s Framingham Heart Study, National Institutes of Health; grants P30 AG10129, R01-AG08122, and R01-AG16495 from the National Institute on Aging; and grant R01-NS017950 from the National Institute of Neurological Disorders and Stroke.

The authors declare no conflicts of interest.

Reprints: Charles S. DeCarli, MD, FAAN, Department of Neurology and Center for Neuroscience University of California at Davis, 4860 Y Street, Suite 3700, Sacramento, CA 95817 (e-mail:

Received June 14, 2013

Accepted February 3, 2014

© 2014 by Lippincott Williams & Wilkins.