The correlation between neuropathology levels and cognitive performance in centenarians

Area of Science:

• Neuropathology
• Neuroscience
• Gerontology

Background:

• Neurodegenerative changes are common in the oldest individuals.
• Understanding the impact of these changes on cognition is crucial.

Purpose of the Study:

• To investigate the relationship between neuropathological substrates and cognitive performance in centenarians.
• To identify specific pathologies and cognitive tests most affected.

Main Methods:

• Analysis of 85 centenarian brains from the 100-plus Study.
• Correlation of 11 neuropathological substrates with 12 ante-mortem neuropsychological tests.

Main Results:

• Varied neuropathology levels observed, including amyloid-beta, neurofibrillary tangles, TDP-43, Lewy bodies, and atherosclerosis.
• Braak-neurofibrillary tangle stage and limbic-predominant age-related TDP-43 encephalopathy (LATE) pathology showed significant associations with cognitive performance.
• The clock-drawing test was highly sensitive to multiple neuropathologies.

Conclusions:

• Specific neuropathologies, particularly Braak-NFT stage and LATE, significantly influence cognitive function in centenarians.
• Cognitive assessment, especially the clock-drawing test, can reflect underlying neuropathological burden in extreme aging.