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

Abstract

White matter hyperintensities are a marker of small vessel cerebrovascular disease that are strongly related to cognition in older adults. Similarly, medial temporal lobe atrophy is well-documented in aging and Alzheimer's disease and is associated with memory decline. Here, we assessed the relationship between lobar white matter hyperintensities, medial temporal lobe subregional volumes, and hippocampal memory in older adults. We collected MRI scans in a sample of 139 older adults without dementia (88 females, mean age (SD) = 76.95 (10.61)). Participants were administered the Rey Auditory Verbal Learning Test (RAVLT). Regression analyses tested for associations among medial temporal lobe subregional volumes, regional white matter hyperintensities and memory, while adjusting for age, sex, and education and correcting for multiple comparisons. Increased occipital white matter hyperintensities were related to worse RAVLT delayed recall performance, and to reduced CA1, dentate gyrus, perirhinal cortex (Brodmann area 36), and parahippocampal cortex volumes. These medial temporal lobe subregional volumes were related to delayed recall performance. The association of occipital white matter hyperintensities with delayed recall performance was fully mediated statistically only by perirhinal cortex volume. These results suggest that white matter hyperintensities may be associated with memory decline through their impact on medial temporal lobe atrophy. These findings provide new insights into the role of vascular pathologies in memory loss in older adults and suggest that future studies should further examine the neural mechanisms of these relationships in longitudinal samples.

Longitudinal evidence for a mutually reinforcing relationship between white matter hyperintensities and cortical thickness in cognitively unimpaired older adults

“…Even after adjusting for shared risk factors, we found evidence for a negative correlation between the initial thickness of the cerebral cortex and the initial volume of WMH, in line with previous work [3,6,10,[23][24][25]. While other factors may contribute to this relationship, which we did not include in our analysis (e.g., genetics and lifestyle), this observation, found in a relatively healthy sample, suggests shared underlying pathological mechanisms.…”

“…Both processes appear to be influenced by genetic and lifestyle factors [2,[10][11][12][13][14][15] as well as by the onset and progression of neurodegenerative and cerebrovascular diseases [1,2,9,[16][17][18][19][20]. Although overlapping risk factors may offer an initial explanation for their concomitance [3,6,11,21,22], their persistent association after controlling for demographics and traditional cardiovascular risk factors [3,6,10,[23][24][25] has sparked more than three decades of research into coupled temporal dynamics [3,26].…”