White matter hyperintensities in behavioral variant frontotemporal dementia and semantic variant of primary progressive aphasia

Abstract

AbstractBackgroundWhite matter hyperintensities (WMHs) are imaging abnormalities of white matter noted by hyperintense signals on fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI). When present among patients with CVRF (hypertension, diabetes, hypercholesteremia and smoking), WMHs are interpreted as cerebral vascular changes. However, WMHs in older individuals can be a feature of late onset leukodystrophies or varied neurodegenerative diseases such as Alzheimer disease (AD), Parkinson’s disease, and Frontotemporal Lobar Degeneration (FTLD). Additionally, WMHs can be present before symptom onset in neurodegenerative disorders and have been linked to the presence of some mutations, including progranulin (GRN). A clearer understanding of the underling etiology of WMHs in bvFTD and svPPA may improve management and treatment considerations.MethodsIn this cross‐sectional study, we included all participants meeting research diagnostic criteria for bvFTD (n = 152) and svPPA (n = 49) from ongoing studies at the UCSF Memory and Aging Center between the dates of September 2008 and December 2021 in comparison to a group of healthy controls enrolled at the same center with similar imaging parameters (n = 152, 1:1 matching for age and sex). All participants underwent a 3T FLAIR MRI and automated quantification of WMHs was performed. Linear regression analyses were performed to determine if WMHs were more frequent in participants with bvFTD or svPPA in comparison to controls and to explore associations with CVRF.ResultsAfter adjusting for age, sex, apolipoprotein E4 (APO‐E 4) status, and intracranial volume (ICV), both groups demonstrated a higher burden compared to controls (bvFTD (p = 0.012, R2 = 0.146) and svPPA (p = 0.008, R2 = 0.329). Modeling cardiovascular risk factors (CVRFs) as none or at least one, we did not find an association between CVRFs and WMH volume in models adjusting for ICV, ApoE4, and age among those with svPPA and bvFTD combined (p = 0.450).ConclusionIndividuals with bvFTD and svPPA appear to face a greater burden of WMHs compared to age‐ and sex‐matched healthy controls. WMHs in bvFTD and svPPA do not appear to be related CVRF.