White matter hyperintensities in autopsy-confirmed frontotemporal lobar degeneration and Alzheimer’s disease
Open Access
- 13 July 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Alzheimer's Research & Therapy
- Vol. 13 (1), 1-16
- https://doi.org/10.1186/s13195-021-00869-6
Abstract
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). Healthy matched controls (n = 35) were included for comparison purposes. Data analyses included ANCOVA to compare the burden of WMH on antemortem brain MRI between groups, adjusted linear regression models to identify associations between WMH burden and neuropsychiatric symptoms, and image-guided pathology review of selected areas of WMH from each pathologic group. 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 (8032 ± 8889 mm3) and in frontal regions (4897 ± 6163 mm3). The AD group had the highest mean volume in occipital regions (468 ± 420 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. Image-guided neuropathological assessment of selected cases with the highest burden of WMH in each pathologic group revealed presence of severe gliosis, myelin pallor, and axonal loss, but with no distinguishing features indicative of the underlying proteinopathy. 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.Keywords
Funding Information
- Weston Brain Institute
- Canadian Institutes of Health Research (MOP327387, MOP13129)
This publication has 41 references indexed in Scilit:
- National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approachActa Neuropathologica, 2011
- A harmonized classification system for FTLD-TDP pathologyActa Neuropathologica, 2011
- Correlations between MRI white matter lesion location and executive function and episodic memoryNeurology, 2011
- TDP-43 subtypes are associated with distinct atrophy patterns in frontotemporal dementiaNeurology, 2010
- Nomenclature for neuropathologic subtypes of frontotemporal lobar degeneration: consensus recommendationsActa Neuropathologica, 2008
- Staging of Neurofibrillary Pathology in Alzheimer's Disease: A Study of the BrainNet Europe ConsortiumBrain Pathology, 2008
- Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar DegenerationActa Neuropathologica, 2007
- Novel splicing mutation in the progranulin gene causing familial corticobasal syndromeBrain, 2006
- National Institute of Neurological Disorders and Stroke–Canadian Stroke Network Vascular Cognitive Impairment Harmonization StandardsStroke, 2006
- White Matter Hyperintensities on MRI in the Neurologically Nondiseased ElderlyStroke, 1995