Disease trajectories before dementia: evidence from a large-scale community-based prospective study

Area of Science:

• Neuroscience
• Epidemiology
• Genetics

Background:

• Systemic diseases can influence dementia onset, but the precise timing of precursor diseases is unclear.
• Understanding disease trajectories preceding dementia is crucial for effective prevention strategies.

Purpose of the Study:

• To characterize the full spectrum of temporal disease trajectories before dementia.
• To identify precursor diseases for dementia risk management and primary prevention.

Main Methods:

• Utilized UK Biobank data from 434,266 dementia-free participants and 4,638 with dementia.
• Employed phenome-wide association analysis, paired directional test, and association quantification to construct disease trajectories.
• Stratified trajectories by dementia subtypes, gender, age, and Apolipoprotein E (ApoE) status.

Main Results:

• Identified three clusters of disease trajectories preceding all-cause dementia, initiated by circulatory, metabolic, and respiratory diseases 5-15 years prior.
• Specific trajectories identified, including chronic ischemic heart disease leading to cerebral infarction or chronic renal failure before vascular dementia.
• Lipid metabolism disorders were consistently present across trajectories, irrespective of dementia subtype, gender, age, or ApoE status.

Conclusions:

• Provides a comprehensive view of longitudinal disease trajectories preceding dementia.
• Highlights midlife cardiometabolic dysfunction as a potential target for dementia screening and prevention efforts.