Investigating the relationship of drugs prescribed to treat hypertension and hypercholesterolemia with disease progression in Alzheimer's disease and related dementias.

Background: Dementia is at present incurable. It is seen in a range of neurodegenerative diseases, the most common being Alzheimer's disease (AD). The debilitating neurocognitive deficits develop over time and available treatments have limited effectiveness. It is of paramount and economic concern to identify new and safe possibilities for treatment. Current treatments are aimed at managing symptoms, but do not address the underlying cause of disease. Existing medications work to minimise toxicity caused from breakdown of neurons and brain connections, and preserve neurochemical levels important in cognitive function. Hypertension and hypercholesterolemia, have been linked with increased risk of developing AD. Antihypertensive drugs may protect against AD and lead to reduced disease progression through decreasing neuropathological mechanisms. Statins treat high cholesterol. High cholesterol relates with elevated levels of β‐amyloid protein, an accumulation in brain tissue leads to formation of amyloid plaques, toxic to neurons. Cholesterol‐lowering medication lowers amyloid plaques in brain tissue. Method: Data will be obtained from the Clinical Practice Research Datalink (CPRD), an ongoing database of UK primary care data. The determined sample population, estimated at 105 471 patients, will be divided according to their prescribed medications. Data on treatments will be compared for each group against outcomes such as death and hospitalisation due to AD and related dementias. Potential confounders will be adjusted for in the regression model. Associations between the exposures and outcomes will be assessed through multivariable regression analyses; multivariable Cox regression analysis for assessing survival rate; and marginal structural models to control for treatment switching. Appropriate statistical analysis methods will also be applied to account for other biases, including: propensity score regression to minimise bias due to working with data from non‐randomised comparison of treatments; multiple imputation to account for missing data; and use of appropriate inclusion criteria to prevent collider bias. Result: We will present the results at a later time. Conclusion: This project will allow us to better understand the link between progression of neurological disorders and pharmacotherapy. [ABSTRACT FROM AUTHOR]