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

Abstract

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 PARTICIPANTSThis 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 MEASURESThe 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. RESULTSIn 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 β = 0.

Physical activity moderates the association between white matter hyperintensity burden and cognitive change

“…WMHs are white matter lesions, which present as hyperintensities on Magnetic Resonance Imaging (MRI), and reflect cerebral small vessel diseases ( Smith et al, 2008 ; Mortamais et al, 2013 ; Prins and Scheltens, 2015 ). Higher WMH burden has been shown to predict more cognitive decline in the general population at a late age ( Prins et al, 2005 ; Smith et al, 2008 ; Silbert et al, 2009 ; Godin et al, 2010 ; Inaba et al, 2011 ; Kantarci et al, 2013 ; Mortamais et al, 2013 ; Tosto et al, 2015 ; Boyle et al, 2016 ; Windham et al, 2019 ; Bangen et al, 2020 ; Rizvi et al, 2021 ). Interestingly, some subjects maintain relatively stable cognition over time despite the presence of WMH ( Kuller et al, 1998 ; Debette et al, 2010 ; Mortamais et al, 2013 ), which could be attributable to higher CR among these individuals ( Dufouil et al, 2003 ; Brickman et al, 2011 ; Murray et al, 2011 ; Vemuri et al, 2011 ).…”

Posterior white matter hyperintensities are associated with reduced medial temporal lobe subregional integrity and long-term memory in older adults

“…While we may have not expected this pattern to be restricted to occipital WMH, previous work has indeed demonstrated that posterior WMH, including parietal and occipital WMH, are more linked to earlier AD onset in older adults 49 . Additionally, posterior WMH has been associated with greater entorhinal cortical thinning, along with an increase in longitudinal CSF tau 13,14 . The neurobiological mechanism by which posterior WMH contribute more to cognitive decline is yet to be elucidated.…”

“…Despite evidence of both cerebrovascular related structural changes and MTL subregional atrophy in aging and AD, these two lines of work have been investigated mostly separately, and how these two features might be linked to memory decline has remained unclear. Additionally, while most of the work on WMH and cognition applies measures of global WMH burden, other studies point to the utility of investigating the effects of regionally specific WMH on cognition 6,13,24,25 . Likewise, the study of MTL atrophy subregionally, including hippocampal subfields and extra-hippocampal subregions, allows us to further understand these regionally specific associations 23,26…”

Research Progress on MRI for White Matter Hyperintensity of Presumed Vascular Origin and Cognitive Impairment

“…Longitudinal studies have revealed that parietal WMH is associated with left entorhinal cortical and right frontal atrophy, and total WMH volume is associated with cortical thinning in the right frontal and parietal regions. Moreover, cortical thinning is associated with poorer memory ( 29 ), and WMH progression is associated with faster cortical thinning ( 25 ). These results suggest that WMH may promote brain atrophy, leading to cognitive decline.…”

“…Previous studies have demonstrated that cortical thinning and WMH are associated with cognitive impairment ( 29 , 30 ). Longitudinal studies have revealed that parietal WMH is associated with left entorhinal cortical and right frontal atrophy, and total WMH volume is associated with cortical thinning in the right frontal and parietal regions.…”