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Abstract Details

Interactions Between Brain Structures and Genetic Variants in Neurotransmitter Systems as Potential Biomarkers for Hallucinations and Delusions in Alzheimer’s Disease
Aging, Dementia, and Behavioral Neurology
P1 - Poster Session 1 (5:30 PM-6:30 PM)
9-012

To investigate the interaction between regional brain structure and single nucleotide polymorphisms (SNPs) in neurotransmitter systems and the presence of hallucinations and delusions in Alzheimer’s disease (AD).

 

Approximately 50% of individuals with AD develop hallucinations and/or delusions. While these symptoms likely arise from dissociable cognitive processes, they are typically modeled together as “psychotic” symptoms and associations with brain structure or genotype are explored separately. We hypothesized that distinct interactions between regional brain structure and genetic polymorphisms in cholinergic, dopaminergic or glutamatergic neurotransmitter systems give rise to the presence of hallucinations and delusions in patients with AD.

Partial least squares correspondence analysis was used to analyze the relationship between structural neuroimaging measures and 15 SNPs in a cross-sectional cohort of participants from the Alzheimer’s Disease Neuroimaging Initiative. Significance of each component was tested using 1000 permutations (p < 0.05). Significance of the variables contributing to each component was assessed using 1000 bootstrapped samples (bootstrap ratio > 2.0).
Preliminary analysis identified one significant component (p = .01) which showed an underlying association between brain structure and genetic data. Boot strap analysis showed that greater cortical thickness of the right superior parietal region and smaller volumes of bilateral nucleus accumbens were associated with rs1806201 in the GRIN2B gene and with both rs1076560  and rs1800497 within the DRD2 gene. In post hoc comparisons, this pattern of brain structure separated participants with hallucinations from those without, while the combination of SNPs separated participants with hallucinations and/or delusions from those without either symptom. Additional SNPs in the DRD2, GRIN2B, and GRIN3A genes were found to be related to the absence of psychotic symptoms in this cohort.
 

The interaction between brain structure and genetic polymorphisms in dopaminergic and glutamatergic systems may mediate the development of hallucinations and delusions in AD.
Authors/Disclosures
Juweiriya Ahmed, BSc (University of Toronto)
PRESENTER 		No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
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No disclosure on file
Stephen H. Pasternak, MD, PhD (Cognitive Neurology and Alzheimer's Disease Research Centre) Dr. Pasternak has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Lilly. Dr. Pasternak has stock in Zywie Bio LLC. The institution of Dr. Pasternak has received research support from Zywie Bio LLC. Dr. Pasternak has received intellectual property interests from a discovery or technology relating to health care.
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.
Elizabeth Finger, MD, FAAN Dr. Finger has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vigil Neuro. Dr. Finger has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Denali Therapeutics. The institution of Dr. Finger has received research support from CIHR. The institution of Dr. Finger has received research support from Physician Servcices Incorporated. The institution of Dr. Finger has received research support from Weston Foundation. Dr. Finger has received personal compensation in the range of $500-$4,999 for serving as a Annual Meeting Course Director with 好色先生.