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Cognitive correlates of white matter lesion load and brain atrophy: the Northern Manhattan Study
Chuanhui Dong1, Nooshin Nabizadeh1, Michelle Caunca1
1From the Evelyn F. McKnight Brain Institute (C. Dong, N.N., M.C., T.R., R.L.S., C.B.W.); Departments of Neurology (R.L.S., C.D., N.N., T.R., C.B.W.), Human Genetics (R.L.S.), and Epidemiology and Public Health Sciences (T.R., R.L.S., C.B.W.); and Neuroscience Program (R.L.S., C.B.W.), Miller School of Medicine, University of Miami, Miami, FL; Departments of Biostatistics (Y.K.C.) and Epidemiology (M.S.V.E.), Mailman School of Public Health, Columbia University, New York, NY; Departments of Neurology (M.S.V.E.) and Psychiatry (Y.S.), the Gertrude H. Sergievsky Center (M.S.V.E., Y.S.), and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain (Y.S.), Columbia University College of Physicians and Surgeons, New York, NY; and Department of Neurology and the Center for Neuroscience (C. DeCarli), University of California at Davis, Sacramento, CA.
Objective:
We investigated white matter lesion load and global and regional brain volumes in relation to domain-specific cognitive performance in the stroke-free Northern Manhattan Study (NOMAS) population.
Methods:
We quantified white matter hyperintensity volume (WMHV), total cerebral volume (TCV), and total lateral ventricular (TLV) volume, as well as hippocampal and cortical gray matter (GM) lobar volumes in a subgroup. We used general linear models to examine MRI markers in relation to domain-specific cognitive performance, adjusting for key covariates.
Results:
MRI and cognitive data were available for 1,163 participants (mean age 70 ± 9 years; 60% women; 66% Hispanic, 17% black, 15% white). Across the entire sample, those with greater WMHV had worse processing speed. Those with larger TLV volume did worse on episodic memory, processing speed, and semantic memory tasks, and TCV did not explain domain-specific variability in cognitive performance independent of other measures. Age was an effect modifier, and stratified analysis showed that TCV and WMHV explained variability in some domains above age 70. Smaller hippocampal volume was associated with worse performance across domains, even after adjusting for APOE ε4 and vascular risk factors, whereas smaller frontal lobe volumes were only associated with worse executive function.
Conclusions:
In this racially/ethnically diverse, community-based sample, white matter lesion load was inversely associated with cognitive performance, independent of brain atrophy. Lateral ventricular, hippocampal, and lobar GM volumes explained domain-specific variability in cognitive performance.
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