Studying the Interplay Between Baseline Mental Health and Alzheimer's Disease Progression

Rao, Sumedha
Housini, Mohammad
Royall, Donald
Palmer, Raymond
Barber, Robert C.
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Background: In aging adults, the most common form of dementia is Alzheimer's disease (AD). AD pathogenesis involves the accumulation of beta-amyloid (Aβ) protein aggregation in plaques and tau proteins in neurofibrillary tangles that are associated with a decreased number of synapses in the brain, altered neuronal function and cell death via neurotoxicity, as well as learning and memory deficits. Clinically, the presence and severity of neuropsychiatric symptoms that AD patients present with can be reliably measured by the Neuropsychiatric Inventory Questionnaire (NPIQ). This study aims to explore the association between baseline mental health and the severity of AD progression. Methods: To measure baseline mental health, NPIQ scores were used while the change in DeltaEq was used to represent the severity of AD progression within the TARCC cohort. DeltaEq is a homolog of Delta, a reliable latent dementia proxy that represents cognitive correlates of functional status and is specific for distinguishing cases with AD from other dementia-related presentations. Most crucially, the DeltaEq homolog has been adjusted for equivalence across ethnicities. Using stratified analysis and structured equation models, the association between baseline mental health and change in was investigated. Results: The first model exploring NPIQ and the change in DeltaEq was only adjusted for baseline eq; it showed NPIQ explaining 19% of the variance in delta DeltaEq and was statistically significant at p=0.016 for Non-Hispanic Whites. With the second model, age, sex, and education were adjusted for in addition to baseline eq. NPIQ was shown to explain 25% of the variance in delta DeltaEq while being statistically significant at p=0.037 for Non-Hispanic Whites. This model was replicated in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort; NPIQ was shown to be predictive for delta DeltaEq at p=0.013. Conclusion: In Non-Hispanic Whites, worse baseline mental health has been shown to predict increased severity and progression of AD. This makes it a clinical therapeutic target with the possible benefit of impacting the course of AD in patients. The fascinating interplay between mental health and its relationship to Alzheimer's disease should be studied further with an additional focus on ethnicity.