Cerebral "Dirty-Appearing" White Matter in Relation to Cognitive Decline and Dementia Risk in Community-Dwelling Older Adults.

Abstract

Cerebral "dirty-appearing" or "diffusely abnormal" white matter (DAWM) represents subtle white matter abnormalities that are associated with progression of cerebral small vessel disease (cSVD), but the association with cognitive function and dementia is unclear. Our aim was to study the association between DAWM and cognitive function, long-term cognitive decline, and long-term dementia risk in community-dwelling older adults with limited baseline cSVD burden. Participants of the prospective Age-Gene/Environment Susceptibility-Reykjavik longitudinal cohort study underwent 1.5T brain MRI scans. DAWM was visually rated on baseline fluid-attenuated inversion recovery (FLAIR) MRI as a percentage of lobar white matter volume (0%, 0%-10%, 10%-25%, or >25% DAWM) per brain lobe. Baseline DAWM ratings and white matter hyperintensity (WMH) volumes were associated with memory, executive function, and processing speed cognitive domain <i>z</i>-scores at baseline and their change at follow-up (after 5.2 ± 0.2 years) and with dementia status assessed at long-term follow-up (after 10.3 ± 2.2 years). This was performed by statistical models adjusted for age, sex, vascular risk factors, and education (for the cognition analyses). From 4,163 included participants, 2,081 participants were selected based on limited baseline WMH volume on FLAIR MRI (determined by a median split) (mean age: 74.6 ± 4.9 years, 61% female). Baseline DAWM ratings were not associated with baseline cognition <i>z</i>-scores (memory: <i>B</i> = 0.01 [-0.03 to 0.04], <i>p</i> = 0.637; executive function: <i>B</i> = 0.02 [-0.05 to 0.01], <i>p</i> = 0.244; processing speed: <i>B</i> = -0.01 [-0.04 to 0.01], <i>p</i> = 0.383), nor with cognitive decline after 5 years (memory: <i>B</i> = 0.03 [-0.01 to 0.06], <i>p</i> = 0.119); executive function: <i>B</i> = 0.01 [-0.02 to 0.04], <i>p</i> = 0.508; processing speed: <i>B</i> = -0.01 [-0.03 to 0.02], <i>p</i> = 0.498), nor with increased risk of dementia after 10 years (hazard ratio [HR] 0.93 [0.84-1.03], <i>p</i> = 0.156). By contrast, baseline WMH volume was associated with baseline cognition <i>z</i>-scores (executive function: <i>B</i> = -0.09 [-0.16 to -0.02], <i>p</i> = 0.011; processing speed: <i>B</i> = -0.08 [-0.15 to -0.02], <i>p</i> = 0.007), cognitive decline in processing speed after 5 years (<i>B</i> = -0.06 [-0.12 to -0.01], <i>p</i> = 0.024), and with a higher dementia risk after 10 years (HR 1.35 [1.04-1.73], <i>p</i> = 0.025). In contrast to WMH, DAWM was not associated with baseline cognition, long-term cognitive decline, nor long-term dementia risk in community-dwelling older adults with limited cSVD burden. Although DAWM is associated with progression of cSVD, its role in the development of cognitive impairment and dementia remains unclear.