Cholinergic white matter hyperintensity volume, cognitive decline, and incident dementia in older adults
Heyang Lu, Yingzhe Wang, Yanfeng Jiang, Xingdong Chen, Mei Cui- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
White matter hyperintensities (WMHs) are frequently observed in the elderly and their severity tends to increase with age. Previous studies have revealed that WMHs are closely related to cognitive dysfunction. However, as inter‐individual variations and a clinicoradiological discrepancy exist, not all individuals with severe WMH burden experience worse cognitive performance. Furthermore, the location of WMHs appears to be a critical factor in the relationship between WMHs and cognitive function. Few studies take both volume and location of white matter hyperintensities (WMHs) into account to explore the association between WMH burden and cognitive impairment. We therefore investigated associations of cholinergic WMH volume (WMHV) with global cognitive function, cognitive decline, and incident dementia in older adults.
Method
A total of 752 older adults (mean age 60 years, 50% female) from the Taizhou Imaging Study were involved. Brain magnetic resonance imaging data at baseline and repeated measures of cognition over 5 years were collected and analyzed. WMHV in whole brain, the cholinergic pathways, and different tract classes in the Montreal Neurologic Institute standard space was obtained using the Lesion Segmentation Toolbox and tools from FMRIB Software Library. Multivariable linear regression, Cox regression, and partial correlation tests were performed.
Result
Over a median 5.67 (IQR: 2.88‐6.84) years of follow‐up, cholinergic WMHV was associated with annual decline of Mini‐Mental State Examination (MMSE) (β = ‐0.206; P = 0.006), and incident dementia (HR = 3.45; 95%CI: 2.08‐5.74). Within the cholinergic pathways, WMHs in commissural fibers were related to incident dementia. However, greater global WMHV only slightly increased the risk of incident dementia (HR = 1.03; 95%CI: 1.01‐1.06). Neither global nor cholinergic WMHV was associated with MMSE in cross‐sectional analysis.
Conclusion
Cholinergic WMHV is associated with longitudinal cognitive decline and incident dementia in older adults. Within the cholinergic pathways, commissural fiber tracts were strategic locations correlated to incident dementia. Our findings suggest cholinergic WMHV might be a potential indicator of cognitive deterioration.