Association of white matter hyperintensity accumulation with domain-specific cognitive decline: a 15-year population-based study

Background: White matter hyperintensities (WMHs) could partly account for

cognitive deterioration in late life. We aimed to investigate the association of global

and regional WMHs with domain-specific cognitive decline in older adults.

Methods: This population-based cohort study included 510 participants (age ≥60

years, 58.4% female) who were free of dementia at baseline (2001-2004). We

assessed global and regional WMHs according to the modified Scheltens’ scale from

baseline to the 6-year follow-up, and we used a neuropsychological test battery to

assess cognitive performance in different domains from baseline to the 15-year

follow-up. Data were analyzed using linear mixed-effects models.

Results: Overall, greater loads of WMHs at baseline were associated with faster

decline in letter fluency, perceptual speed, and global cognition(P<0.05). Specifically,

higher baseline load of global WMHs was related to faster decline in executive

function (multiple-adjusted β-coefficient and 95% CI: -0.020 [-0.035, -0.006]). Higher

baseline load of periventricular WMHs was associated with faster decline in category

fluency (-0.009 [-0.016, -0.002]); this association existed only in APOE ε4 carriers

but not in non-carriers (P for interaction=0.046). Furthermore, faster accumulations

of global, deep, and periventricular WMHs were related to accelerated decline in

perceptual speed (P<0.05); faster accumulation of deep WMHs was related to

accelerated decline in executive function (-0.061 [-0.118, -0.004]) and global

cognition (-0.020[-0.038, -0.002]).

Conclusions: Greater loads of WMHs are associated with faster decline in language

fluency, perceptual speed, and global cognition in older adults. Carrying APOE ε4

allele could exacerbate the deterioration in category fluency due to higher WMH

burdens. Furthermore, the decline in perceptual speed, executive function, and

global cognition is susceptible to faster WMH accumulation.