Frequency of White Matter Hyperintensities Across Neurodegenerative Syndromes Compared to Cognitively Unimpaired Individuals
Camilo Bermudez1, Angela Fought1, Ekaterina Hofrenning1, Kejal Kantarci1, Clifford Jack1, Bradley Boeve1, David Jones1, David Knopman1, Hugo Botha2, Vijay Ramanan1, Stuart McCarter1, Ronald Petersen1, Prashanthi Vemuri1, Jonathan Graff-Radford1
1Mayo Clinic, 2Mayo School of Graduate Medical Education, Rochester
Objective:
To report the relationship between white matter hyperintensity (WMH) and cognitive impairment across the spectrum of Alzheimer’s Disease (AD), Lewy Body Disease (LBD), and Frontotemporal Lobar Degeneration (FTLD) compared to controls.
Background:
WMH are well known imaging markers of brain microvascular disease associated with aging and cognition. WMH have also been associated with advanced neurodegenerative changes. However, there is limited information about WMH across the cognitive spectrum of AD, LBD, or FTLD syndromes. Consequently, it is unclear if WMH represent a risk factor to the development of cognitive impairment or represent sequela of neurodegeneration.
Design/Methods:
We included Mayo Clinic Alzheimer’s Disease Research Center (ADRC) participants who were 50 or older with MRI. Cognitive status and diagnosis were determined by committee consensus employing existing criteria. WMH volume was estimated and scaled over total intracranial volume, with severe burden defined as ≥0.98% of total intracranial volume. Associations with log-transformed WMH were tested using linear regression, adjusted for age and sex. The covariates of interest were group (controls, AD, LBD, and FTLD) tested in the whole sample and global CDR tested using impaired participants. For severe WMH burden, we evaluated mean ages for each disease.
Results:
Our cohort included 1078 participants, 166 controls, 473 AD, 247 DLB, and 192 FTLD participants. When controlling for age and sex, each disease had higher logged-WMH than controls (AD: β=0.49 SE=0.08, DLB: β=0.33 SE=0.08, and FTD: β=0.63 SE=0.09; all p<0.001). CDR was positively associated with logged-WMH (β=0.44, SE=0.04, and p<0.001). For patients with severe WMH burden, average age (with SD) was higher in AD (77.0 +/- 7.3) and DLB (75.0 +/- 5.7) compared to FTD (70.0 +/- 8.5).
Conclusions:
Differential expression of WMH across cognitive syndromes represents both a non-specific small vessel disease and neurodegeneration, which can serve as a marker of disease progression.
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