We aimed to systematically describe the burden and distribution of white matter hyperintensities (WMH) and investigate correlations with neuropsychiatric symptoms in pathologically proven Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD).
Autopsy-confirmed cases were identified from the Sunnybrook Dementia Study, including 15 cases of AD and 58 cases of FTLD (22 FTLD-TDP cases; 10 FTLD-Tau [Pick's] cases; 11 FTLD-Tau Corticobasal Degeneration cases; and 15 FTLD-Tau Progressive Supranuclear Palsy cases). Data analyses included ANCOVA to compare the burden of WMH on antemortem brain MRI between groups and adjusted linear regression models to identify associations between WMH burden and neuropsychiatric symptoms.
Burden and regional distribution of WMH differed significantly between neuropathological groups (F5,77 = 2.67, P’ = 0.029), with the FTLD-TDP group having the highest mean volume globally (8,031.50 ± 8,889.15 mm3) and in frontal regions (4,897.45 ± 6,163.22 mm3). The AD group had the highest mean volume in occipital regions (468.25 ± 420.04 mm3). Total score on the Neuropsychiatric Inventory correlated with bilateral frontal WMH volume (β = 0.330, P = 0.006), depression correlated with bilateral occipital WMH volume (β = 0.401, P < 0.001), and apathy correlated with bilateral frontal WMH volume (β = 0.311, P = 0.009), all corrected for the false discovery rate.
These findings suggest that WMH are associated with neuropsychiatric manifestations in AD and FTLD and that WMH burden and regional distribution in neurodegenerative disorders differ according to the underlying neuropathological processes.