Associations of Lifetime Cognitive Enrichment With Incident Alzheimer Disease Dementia, Cognitive Aging, and Cognitive Resilience.

Higher lifetime cognitive enrichment was associated with significantly lower hazards of developing Alzheimer disease dementia.

• One unit higher in lifetime enrichment was associated with 38% lower hazards of developing AD dementia (hazard ratio 0.62, 95% CI 0.52-0.73, p < 0.001).
• Study involved 1,939 participants (75% female, mean baseline age = 79.6) free of dementia at baseline.
• 551 participants developed AD dementia over an average of 7.6 years of follow-up.
• Proportional hazards models were used to test the association with incident AD dementia.

High lifetime cognitive enrichment was associated with delayed onset of Alzheimer disease dementia by approximately 5 years.

• High lifetime enrichment (90th percentile) compared with low (10th percentile) was associated with a mean of 5 years delayed onset of AD dementia.
• Mean age of AD dementia onset was tested using an accelerated failure time model.
• This represents a clinically meaningful difference in disease onset between individuals at the extremes of the lifetime enrichment distribution.

Lifetime cognitive enrichment was positively associated with cognitive function at baseline and a slower rate of cognitive decline.

• Lifetime enrichment was positively associated with cognitive function at baseline (estimate = 0.31, SE = 0.02, p < 0.001).
• Lifetime enrichment was associated with a slower rate of cognitive decline (estimate = 0.02, SE = 0.01, p = 0.002).
• Associations were tested using linear mixed-effects models.
• These associations were observed in the full sample of 1,939 participants over a mean 7.6 years of follow-up.

In an autopsied subset, lifetime cognitive enrichment did not show meaningful associations with neuropathologic indices of ADRD pathology.

• The deceased subset included 948 participants.
• Nine ADRD pathologic indices were examined.
• The lack of association with neuropathology suggests that the cognitive benefits of lifetime enrichment do not operate primarily through reduction of pathologic burden.

In the autopsied subset, lifetime cognitive enrichment remained associated with higher cognitive function and slower cognitive decline after adjusting for common ADRD pathologies, indicating cognitive resilience.

• Lifetime cognitive enrichment was associated with higher cognitive function proximate to death after adjusting for pathology (estimate = 0.32, SE = 0.06, p < 0.001).
• Lifetime enrichment was associated with a slower rate of cognitive decline after adjusting for pathology (estimate = 0.014, SE = 0.01, p = 0.02).
• Cognitive resilience was operationalized as cognitive decline after adjusting for common ADRD pathologies.
• These findings were based on the deceased subset of n = 948 participants from the Rush Memory and Aging Project.

The study used a composite measure of lifetime cognitive enrichment derived from survey data in a longitudinal clinicopathologic cohort.

• Participants were older individuals from Northeastern Illinois who participated in the Rush Memory and Aging Project.
• Participants were free of dementia at baseline and completed surveys reflecting lifetime enrichment.
• Annual clinical evaluations were conducted over follow-up.
• A subset of deceased participants underwent neuropathologic examination, enabling clinicopathologic analyses.