Background: Few studies take both the volume and location of white matter hyperintensities (WMHs) into account to explore the association between WMH burden within the cholinergic pathways and cognitive impairment. We aimed to investigate associations of cholinergic WMH volume (WMHV) with global cognitive function, cognitive decline, and incident dementia in older adults, which may help us identify a potential imaging biomarker.
Methods: We assessed non-demented participants (n = 751, mean age 60 years) from the Taizhou Imaging Study with brain MRI at baseline and repeated measures of cognition over 5 years of follow-up. WMHV in the whole brain, the cholinergic pathways, and different tracts in the Montreal Neurologic Institute (MNI) standard space were analyzed. Linear regression, Cox regression, and partial correlation tests were performed to investigate associations between global and regional WMHV and cognitive outcomes.
Results: During follow-up, cholinergic WMHV was associated with an annual decline of Mini-Mental State Examination (MMSE) (β coefficient, -0.239; P = 0.004), and incident dementia (HR = 3.54; 95%CI: 2.05-6.10). Within the cholinergic pathways, WMHs in corpus callosum and corona radiata were significantly related to incident dementia. Global WMHV was also associated with global cognitive decline (β coefficient, -0.049; P = 0.002). However, greater global WMHV only slightly increased the risk of incident dementia (HR = 1.23; 95%CI: 1.11-1.35). Neither global nor cholinergic WMHV was associated with MMSE in cross-sectional analysis.
Conclusions: Cholinergic WMHV is associated with longitudinal cognitive decline and incident dementia in older adults, which might result from disruption of corpus callosum and corona radiata. These findings highlight the value of cholinergic WMHV as a potential indicator of cognitive deterioration.
Keywords: Cholinergic degeneration; Cognitive dysfunction; Neuroimaging; White matter hyperintensity.
© 2025. The Author(s).