Neuropathologic Profiles and Associated Cognitive Trajectories in Community-Living Older Adults

Area of Science:

• Neuropathology
• Neuroscience
• Gerontology

Background:

• Mixed neuropathologies are frequently observed in aging brains, but their coexistence and impact on cognition are not fully understood.
• Identifying distinct neuropathologic profiles is crucial for understanding cognitive trajectories in older adults.

Purpose of the Study:

• To identify distinct neuropathologic profiles in community-dwelling older adults.
• To examine the association between these profiles and cognitive trajectories over time.

Main Methods:

• Utilized data from two large, community-based cohort studies of aging and dementia.
• Employed hierarchical clustering to identify neuropathologic profiles from autopsy data.
• Analyzed longitudinal cognitive data using functional mixed-effects models.

Main Results:

• Over 80% of 1633 participants exhibited mixed neuropathologies, with 280 unique combinations.
• Five distinct neuropathologic profiles were identified, including high ADNC, high LATE-NC/hippocampal sclerosis, high Lewy bodies, high ADNC/amyloid angiopathy, and low overall pathology.
• Profiles with high ADNC and high LATE-NC/hippocampal sclerosis showed the most significant cognitive decline.

Conclusions:

• Mixed neuropathologies are highly prevalent and complex in older adults.
• Degenerative pathologies cluster into distinct profiles, with vascular conditions being common but less defining.
• Specific profiles, particularly those involving ADNC and LATE-NC, are strongly associated with accelerated cognitive decline.