Abstract Details

Title APOE-?4, White Matter Hyperintensities, and Cognition in Alzheimer and Lewy Body Dementia

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P8 - Poster Session 8 (8:00 AM-9:00 AM)

Poster/Presentation
Number 10-005

Objective To determine if APOE-ε4 influences the association between white matter hyperintensities (WMH) and cognitive impairment in Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB).

Background WMH observed on structural MRI indicate cerebral small vessel disease (SVD) in most cases, are risk factors for cognitive impairment and AD, and are prevalent in dementia with DLB. However, observed cognitive performance clinically does not always reflect the severity of the WMH burden.

Design/Methods

289 patients (AD=239; DLB=50) underwent volumetric MRI, neuropsychological testing, and APOE-ε4 genotyping. Total WMH volumes were quantified. Neuropsychological test scores were included in a confirmatory factor analysis (CFA) to identify cognitive domains encompassing attention/executive functions, learning/ memory, and language, and factor scores for each domain were calculated per participant. After testing interactions between WMH and APOE-ε4 in the full sample, we tested associations of WMH with factor scores using linear regression models in APOE-ε4 carriers (n=167) and non-carriers (n=122). We hypothesized that greater WMH volume would relate to worse cognition more strongly in APOE-ε4 carriers. Findings were replicated in 198 AD patients from the Alzheimer’s Disease Neuroimaging Initiative (ADNI-I), and estimates from both samples were meta-analyzed.

Results

A significant interaction was observed between WMH and APOE-ε4 for language, but not for memory or executive functions. Separate analyses in APOE-ε4 carriers and non-carriers showed that greater WMH volume was associated with worse attention/executive functions, learning/memory, and language in APOE-ε4 carriers only. In ADNI-I, greater WMH burden was associated with worse attention/executive functions and language in APOE-ε4 carriers only. No significant associations were observed in non-carriers. Meta-analyses showed that greater WMH volume was associated with worse performance on all cognitive domains in APOE-ε4 carriers only.

Conclusions

APOE-ε4 may influence the association between WMH and cognitive performance in patients with AD and DLB.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Donald Stuss	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Walter Swardfager, MSc	No disclosure on file
	No disclosure on file
Peter H. St George-Hyslop, MD, PhD (University of Toronto)	Dr. St George-Hyslop has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for TransitionBio. The institution of Dr. St George-Hyslop has received research support from NIH. Dr. St George-Hyslop has received intellectual property interests from a discovery or technology relating to health care.
Sandra E. Black, MD, F�鶹��ýӳ�� (Sunnybrook Health Science Center)	Dr. Black has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Hoffmann-La Roche. Dr. Black has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Black has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffmann-La Roche. Dr. Black has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Black has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai Limited . Dr. Black has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Black has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. The institution of Dr. Black has received research support from Hoffmann-La Roche. The institution of Dr. Black has received research support from Biogen. The institution of Dr. Black has received research support from GE Healthcare. The institution of Dr. Black has received research support from Eli Lilly. The institution of Dr. Black has received research support from Genentech. The institution of Dr. Black has received research support from NovoNordisk. The institution of Dr. Black has received research support from UCB Biopharma. The institution of Dr. Black has received research support from Alkahest Inc. The institution of Dr. Black has received research support from University of Southern California - AHEAD 3-45 Study.
Mario Masellis, MD (Sunnybrook Health Sciences Centre)	Dr. Masellis has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arkuda Therapeutics. Dr. Masellis has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ionis. Dr. Masellis has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alector. Dr. Masellis has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Wave Life Sciences. The institution of Dr. Masellis has received research support from Canadian Institutes of Health Research. The institution of Dr. Masellis has received research support from Ontario Brain Institute. The institution of Dr. Masellis has received research support from Weston Brain Institute. The institution of Dr. Masellis has received research support from Washington University. The institution of Dr. Masellis has received research support from Alector. Dr. Masellis has received publishing royalties from a publication relating to health care.

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