Strategic locations of white matter hyperintensities associated with cognitive impairment across the cognitive spectrum among rural older adults: a population-based study

The location of white matter hyperintensities (WMH) is crucial for cognitive impairment. We sought to identify tract-based strategic locations of WMH that are associated with cognitive impairment across the cognitive spectrum from low cognitive function and subjective cognitive decline (SCD) through mild cognitive impairment (MCI) to dementia among rural-dwelling older adults. This population-based study included 1253 participants (age ≥ 60 years; 59.06% women) in MIND-China who underwent structural brain MRI in 2018–2020. We used a neuropsychological test battery to assess cognitive function and defined SCD, MCI, and dementia following international criteria. We used the Lesion Prediction Algorithm to segment WMH volumes and the Johns Hopkins University International Consortium for Brain Mapping probabilistic fiber tract atlas to further segment WMH volumes within 11 white matter tracts. Data were analyzed using logistic and linear regression models. Greater WMH volumes in anterior thalamic radiation (ATR), corticospinal tract (CST), forceps major (FMa), forceps minor (FMi), inferior fronto-occipital fasciculus (IFOF), and superior longitudinal fasciculus (SLF) were significantly associated with dementia (false discovery rate [FDR]-corrected P < 0.05). The receiver operating characteristic curves showed outperformance of WMH volumes in ATR, CST, and FMi than total WMH volume in differentiating dementia from normal cognition. The tract-specific WMH were not significantly associated with SCD and MCI after FDR correction for multiple comparisons. In dementia-free participants, higher WMH volumes in ATR and FMa were significantly associated with a lower memory z-score; and higher WMH volumes in CST, FMa, IFOF, and SLF with a lower z-score of verbal fluency (all P < 0.05). ATR, CST, and FMi represent strategic locations where greater WMH volumes were independently associated with poorer cognitive function across the cognitive spectrum in older adults, emphasizing the importance of tract-specific WMH in cognitive phenotypes.