Abstract Details

Title Cholinergic-Related White Matter Lesion Load is Associated with Alzheimer’s Disease-Signature Cortical Thickness: The Northern Manhattan Study

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 9-014

Objective

Examine associations between white matter hyperintensity volume (WMHV) in cholinergic-related white matter tracts (ChT-WMHV), Alzheimer's Disease (AD)-signature cortical thickness, and hippocampal volume.

Background Cerebral small vessel disease (CSVD) is a potential target for preventing vascular cognitive impairment, and its phenotype can overlap with clinical AD. AD pathology damages the cholinergic system, but effects of CSVD on these pathways are less well understood.

Design/Methods Clinically stroke-free participants from the Northern Manhattan Study with both regional WMHV and gray matter measurements were included (N=894). Tract-specific WMHVs were quantified through FSL using the Johns Hopkins University white matter tract atlas. We used Freesurfer 5.1 to estimate hippocampal volume and cortical thickness (both expressed as z-scores). ChT-WMHV was computed as the sum of WMHVs in relevant tracts based on previous literature. AD-signature cortical thickness was computed as the mean cortical thickness across 12 relevant cortical regions based on previous literature. To examine associations, we used multivariable linear regression models adjusted for sociodemographics and vascular risk factors. Linear mixed-effects models were used to assess whether the effect of ChT-WMHV on cortical thickness differed across regions within the AD-signature.

Results

Participants had a mean (SD) age=70 (9) years, education=10 (5) years; 63% were women and 67% Hispanics/Latinos. Participants with ChT-WMHV in the highest quartile had smaller AD-signature cortical thickness compared to those in the lowest quartile (β [95% CI] = -0.3 [-0.5, -0.1]). Associations differed by region (P for interaction<.05), and the strongest association was found in the temporal pole (β [95% CI] = -0.1 [-0.2, -0.09], highest vs. lowest quartile of ChT-WMHV). ChT-WMHV was not significantly associated with hippocampal volume.

Conclusions

Small vessel damage in cholinergic white matter tracts may be associated with AD-related gray matter atrophy. Future studies should examine how cholinergic WMHV impacts gray matter changes and longitudinal cognitive trajectories.

Authors/Disclosures
Michelle R. Caunca, MD, PhD (UCSF) PRESENTER	Ms. Caunca has nothing to disclose.
Ken Cheung	Ken Cheung has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Tsumura.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Mitchell S. Elkind, MD, MS, FAAN	Dr. Elkind has received personal compensation for serving as an employee of American Heart Association. Dr. Elkind has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Atria Academy.
Ralph L. Sacco, MD, MS, FAHA	Dr. Sacco has received personal compensation in the range of $100,000-$499,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Heart Association. The institution of Dr. Sacco has received research support from NIH, NINDS, NCATS, NIMHD. The institution of Dr. Sacco has received research support from FL Department of Health. Dr. Sacco has received research support from University of Washington, Seattle. Dr. Sacco has received publishing royalties from a publication relating to health care.
Tatjana Rundek, MD, PhD	The institution of Dr. Rundek has received research support from NIH.
Clinton B. Wright, MD, FAAN (NINDS)	An immediate family member of Dr. Wright has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Wright has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Abali Milne Kalil. Dr. Wright has received publishing royalties from a publication relating to health care. An immediate family member of Dr. Wright has received personal compensation in the range of $500-$4,999 for serving as a surveyor with ASTRO.

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