Compression of cognitive decline and cognitive resilience in extreme longevity

Compressing the duration of cognitive impairment is critical to preserve quality of life until the end. To what extent cognitive decline is compressed and cognitive resilience increases with extreme longevity is not well understood.

We used data from 13,999 deceased participants from the National Alzheimer's Coordinating Center cohort, including 8,146 with neuropathological data. Cognitive function was assessed annually (median follow-up: 4.9 years). We evaluated cognitive trajectories before death and cognitive resilience (defined as high neuropathological burden without dementia) across lifespan groups (ages 50-100+ years).

Participants with longer lifespans, particularly centenarians, exhibited slower cognitive decline and shorter periods of cognitive impairment before death, although distinct cognitive trajectories existed among centenarians. Cognitive resilience also increased with longer lifespans, but associated factors varied. Apolipoprotein E ε2 was associated with higher cognitive resilience only in centenarians.

Our findings support a general compression of cognitive decline and increased cognitive resilience in extreme longevity.

Individuals with longer lifespans, especially centenarians, generally exhibited better cognitive function and slower cognitive decline toward the end of life, suggesting a compression of cognitive decline in extreme longevity. Although there was a compression of cognitive decline at the group level among centenarians, heterogeneous cognitive trajectories before death were observed across individuals. The relationship between neuropathological burden and dementia risk attenuated with longer lifespans, indicating greater cognitive resilience in individuals with extreme longevity. The associations of both genetic and modifiable factors with cognitive resilience varied by lifespan.