Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Neuroscience

Supervisor

Finger, Elizabeth

Abstract

The co-occurrence of psychotic symptoms and Alzheimer’s disease (AD) is a devastating phenotype that affects around 50% of individuals with AD. We hypothesized that distinct interactions between brain structures and genetic variants in dopaminergic, cholinergic and glutamatergic neurotransmitter systems may be associated with the presence of hallucinations and delusions in AD. Using the Alzheimer’s Disease Neuroimaging Initiative, we identified participants that presented with symptoms of delusions, hallucinations, or both symptoms. PLS-CA was used to identify differences in patterns of interactions between 15 single nucleotide polymorphisms and 82 neuroanatomical regions of interest between AD patients endorsing symptoms of delusions, hallucinations, and matched AD controls. Binary logistic regression analysis was used to cross-validate identified neuroanatomical differences. Results provide preliminary evidence that genetic variants in the glutamatergic system, along with regional brain changes, may uniquely identify those with hallucinations. A trend towards significance was also found which suggests that atrophy to the frontal lobe coupled with preservation of temporal lobe structures may be associated with symptoms of delusions in patients with AD. Overall, results provide evidence of a unique signature of neuroimaging and genetic interactions which may be associated with the presence of different psychotic symptoms in AD.

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