Snapshot of disease continuum centered on Alzheimer's disease: Exploring modifiable risk factors

Abstract

Alzheimer's disease (AD) is a leading neurodegenerative disorder, characterized by progressive cognitive decline and memory impairment, with a complex etiology involving genetic, environmental, and lifestyle factors. Traditionally, AD has been studied in isolation, but emerging evidence highlights its interconnectedness with various comorbidities across multiple organ systems. This study introduces a Disease-Wide Association Study (DWAS) approach to explore the disease continuum centered around AD. Using the FinnGen cohort, which includes over 392,000 participants, this study systematically analyzed the comorbidities associated with AD, spanning cardiovascular, metabolic, musculoskeletal, digestive, and oncological conditions. These findings reveal that AD is part of a much broader, systemic disease continuum, with shared pathophysiological mechanisms, including chronic inflammation, metabolic dysregulation, and vascular health, which may influence AD onset and progression. Temporal analysis of pre- and post-AD comorbidities identifies modifiable risk factors such as hypertension, atherosclerosis, and type 2 diabetes that may not only precede AD but also exacerbate its progression. The study emphasizes the importance of an integrated care approach for AD patients, addressing both neurological and systemic health to improve outcomes. Furthermore, by identifying modifiable risk factors, this research opens new avenues for early interventions aimed at delaying or preventing AD. These findings challenge the traditional view of AD as an isolated disease and provide insights into the shared etiology of AD and its comorbidities, offering potential targets for personalized therapeutic strategies and public health policies.