White matter hypertensity burden varies in empirically derived incident MCI subtypes

Abstract

AbstractBackgroundWhite matter changes and Alzheimer’s disease pathology frequently co‐exist in the population. Recently we empirically derived subtypes of incident mild cognitive impairment (MCI) and found that there was significant heterogeneity not only in cognitive impairment profiles but also gray matter atrophy suggesting that multiple etiologies may contribute to cognitive impairment in these subtypes. The aim of this study was to examine differences in white matter hyperintensity (WMH) volume in these same MCI subtypes and investigate amyloid deposition in a smaller subset.MethodWe analyzed data from 188 participants with incident MCI enrolled in the population‐based Mayo Clinic Study of Aging (MCSA) identified as having one of four MCI subtypes: subtle cognitive impairment (SCI), amnestic, dysnomic, and dysexecutive. All participants completed 3T imaging at the time of the MCI diagnosis. Using WMH volume scaled by TIV and PIB SUVR, we compared each MCI subtype to 344 cognitively impaired (CU) participants (mean age 78; 46% women) and each other.ResultThe amnestic (n = 83; mean age 80; 43% women), dysnomic (n = 30; mean age 84; 47% women) and dysexecutive subtypes (n = 49; mean age 83; 35% women) had significantly higher WMH volumes compared to CU (p < .02) while the SCI subtype (n = 26; mean age 80; 23% women) did not differ from CU (p = .76). Amongst the MCI subtypes, the amnestic (p = .04) and dysexecutive subtypes (p = .01) had significantly higher WMH volumes than the SCI subtype [Figure 1]. In a smaller subset of individuals who also completed PiB‐PET (17/26 SCI; 39/83 amnestic; 10/30 dysnomic, 28/49 dysexecutive), we found evidence for higher amyloid load in all MCI subgroups except the SCI group (p<0.05) in comparison to CU.ConclusionWe found significantly elevated levels of WMH and amyloid burden in amnestic, dysnomic, and dysexecutive subtypes of incident MCI supporting the notion that both vascular changes and amyloid contribute to the development of clinical symptoms. Surprisingly, WMH and amyloid positivity were not high in SCI suggesting that the pathophysiology in this group needs further investigation.