Abstract Details

Title Neuropathologic Basis of White Matter Hyperintensity Accumulation

Topic Aging and Dementia

Presentation(s) S44 - (-)

Poster/Presentation
Number 001

Objective

Background Few studies have examined the neuropathologic correlates of cross-sectional WMH volumes observed on brain magnetic resonance imaging (MRI) and longitudinal WMH trajectories. Furthermore, the relationship between Alzheimer disease pathology and WMH trajectories is not well understood.

Design/Methods Sixty-six elderly participants in the Oregon Brain Aging Study were included for having an autopsy, >1 MRI scan and the last MRI scan within 24 months of death. First, multiple regression analyses, adjusted for age at MRI and duration between MRI and death, were used to examine the association between cross-sectional WMH volume obtained on the MRI most proximal to death, and several neuropathologic measures including: myelin pallor, arteriosclerosis, microvascular disease, small vessel infarcts, large vessel infarcts, atherosclerosis, neurofibrillary tangle (NFT) and neuritic plaque (NP) scores. Second, mixed-effects models were used to examine the association between longitudinal trajectory of WMH accumulation over time and neuropathologic measures. Time interaction terms for measures of myelin pallor, arteriosclerosis, microvascular disease, small vessel infarcts, large vessel infarcts, atherosclerosis, NFT and NP scores, and APOE ?4 presence were included. Analyses were adjusted for duration of follow up and age at death.

Results Mean age at death was 94.54 (SD 5.45) years. Presence of more arteriosclerosis and small vessel infarcts were associated with larger cross-sectional WMH volume. No significant associations were observed with other pathologic measures. In the mixed-effects models, presence of more arteriosclerosis, myelin pallor and higher Braak score were associated with more WMH accumulation over time.

Conclusions These findings suggest that WMH burden observed on MRI scans in very old individuals reflects the degree of small vessel ischemic disease, while the accumulation of WMH over time is likely a reflection of both vascular and neurodegenerative pathology.

Authors/Disclosures
Deniz Erten-Lyons, MD, FAAN (FDA) PRESENTER	Dr. Erten-Lyons has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Acadia Pharamceuticals.
Lisa Silbert, MD, FAAN (OHSU)	The institution of Dr. Silbert has received research support from the NIH. Dr. Silbert has received personal compensation in the range of $0-$499 for serving as a Peer Reviewer, study section with NIH.
	No disclosure on file
Hiroko H. Dodge, PhD (Massachusetts General Hospital)	No disclosure on file
	No disclosure on file
	No disclosure on file
Jonas Dorn	No disclosure on file
Joseph F. Quinn, MD, FAAN (OHSU Neurology)	Dr. Quinn has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Retrophin. Dr. Quinn has received personal compensation in the range of $500-$4,999 for serving as a DSMB with Alzheimer's Disease Cooperative Study. Dr. Quinn has received personal compensation in the range of $500-$4,999 for serving as a DSMB with Alzheimer's Therapeutic Research Institute. Dr. Quinn has a non-compensated relationship as a consultant with Cognition Therapeutics that is relevant to AAN interests or activities.
	No disclosure on file
Barry S. Oken, MD, PhD, FAAN (Oregon Health & Science Univ.)	Dr. Oken has nothing to disclose.
Randall L. Woltjer (Oregon Health & Science University)	Randall L. Woltjer has nothing to disclose.
Jeffrey A. Kaye, MD, FAAN (Oregon Hlth Sci Univ.)	Dr. Kaye has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Kaye has stock in Life Analytics. The institution of Dr. Kaye has received research support from NIH. The institution of Dr. Kaye has received research support from NSF. The institution of Dr. Kaye has received research support from AbbVie. Dr. Kaye has received intellectual property interests from a discovery or technology relating to health care.

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