Association of Regional White Matter Hyperintensities With Longitudinal Alzheimer-Like Pattern of Neurodegeneration in Older Adults

This cohort study examines whether white matter hyperintensity volume is associated with cortical thinning and subsequent memory functioning and whether the association between white matter hyperintensity volume and cortical thinning differs among racial and ethnic groups. Importance Small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMH), is associated with cognitive decline and risk of clinical Alzheimer disease (AD). One way in which small vessel cerebrovascular disease could contribute to AD is through the promotion of neurodegeneration; the effect of small vessel cerebrovascular disease on neurodegeneration may differ across racial and ethnic groups. Objective To examine whether WMH volume is associated with cortical thinning over time and subsequent memory functioning and whether the association between WMH volume and cortical thinning differs among racial and ethnic groups. Design, Setting, and Participants This longitudinal community-based cohort study included older adults from northern Manhattan who were participants in the Washington Heights-Inwood Columbia Aging Project. Participants underwent two 3T magnetic resonance imaging (MRI) scans a mean of 4 years apart. Data were collected from March 2011 to January 2020. Exposures Total and regional WMH volumes. Main Outcomes and Measures The association of total and regional WMH volumes with cortical thinning over time was tested using general linear models in a vertexwise analysis. Cortical thinning was measured vertexwise by symmetrized percent change between 2 time points. The association of changes in cortical thickness with memory and whether this association differed by race and ethnicity was also analyzed. Delayed memory was a secondary outcome. Results In 303 participants (mean [SD] age, 73.16 [5.19] years, 181 [60%] women, 96 [32%] non-Hispanic White, 113 [37%] Non-Hispanic Black, 94 [31%] Hispanic), baseline WMH volumes were associated with cortical thinning in medial temporal and frontal/parietal regions. Specifically, total WMH volume was associated with cortical thinning in the right caudal middle frontal cortex (P = .001) and paracentral cortex (P = .04), whereas parietal WMH volume was associated with atrophy in the left entorhinal cortex (P = .03) and right rostral middle frontal (P < .001), paracentral (P < .001), and pars triangularis (P = .02) cortices. Thinning of the right caudal middle frontal and left entorhinal cortices was related to lower scores on a memory test administered closest to the second MRI visit (right caudal middle frontal cortex: standardized beta = 0.129; unstandardized b = 0.335; 95% CI, 0.055 to 0.616; P = .01; left entorhinal cortex: beta = 0.119; b = 0.290; 95% CI, 0.018 to 0.563; P = .03). The association of total WMH with thinning in the right caudal middle frontal and right paracentral cortex was greater in non-Hispanic Black participants compared with White participants (right caudal middle frontal cortex: beta = -0.222; b = -0.059; 95% CI, -0.114 to -0.004; P = .03; right paracentral cortex: beta = -0.346; b = -0.155; 95% CI, -0.244 to -0.066; P = .001). The association of parietal WMH with cortical thinning of the right rostral middle frontal, right pars triangularis, and right paracentral cortices was also stronger among non-Hispanic Black participants compared with White participants (right rostral middle frontal cortex: beta = -0.252; b = -0.202; 95% CI, -0.349 to -0.055; P = .007; right pars triangularis cortex: beta = -0.327; b = -0.253; 95% CI, -0.393 to -0.113; P < .001; right paracentral cortex: beta = -0.263; b = -0.337; 95% CI, -0.567 to -0.107; P = .004). Conclusions and Relevance In this study, small vessel cerebrovascular disease, operationalized as WMH, was associated with subsequent cortical atrophy in regions that overlap with typical AD neurodegeneration patterns, particularly among non-Hispanic Black older adults. Cerebrovascular disease may affect risk and progression of AD by promoting neurodegeneration and subsequent memory decline. Question What is the association of small vessel cerebrovascular disease, operationalized as white matter hyperintensities (WMH), with cortical thinning in a racially and ethnically diverse population of older adults? Findings In this cohort study of 303 older adults, increased parietal WMH volume was associated with left entorhinal cortex thinning over 4 years, while both total and parietal WMH were associated with frontal and parietal cortical thinning; cortical thinning, in turn, was associated with worse memory. The association between WMH and cortical thinning was strongest among Black participants. Meaning In this study, WMH were associated with cortical thinning in older adults, particularly non-Hispanic Black participants, in a pattern similar to the neurodegeneration in early stages of Alzheimer disease.

Automated summary

This study found that white matter hyperintensity volume is associated with cortical thinning and subsequent memory functioning, with variations in the association among different racial and ethnic groups. Particularly, the impact of small vessel cerebrovascular disease on cortical thinning is stronger among non-Hispanic Black participants, which may influence the risk and progression of Alzheimer's disease.