Cognitive Reserve Linked to Reduced Dementia Risk Regardless of Brain Pathology

David Bennett, MD

A high degree of lifespan cognitive reserve is associated with a reduction in dementia risk, even in the presence of brain pathologies, according to data presented at the 2019 Alzheimer’s Association International Conference, July 14-18, in Los Angeles, California.¹

The study, which was simultaneously published in JAMA Neurology,² sought to examine the impact of cognitive reserve on dementia risk, as new research suggests that higher cognitive reserve may be linked to a decreased risk for dementia.

“The concept of [cognitive reserve] refers to the capacity to be resilient to age-related brain changes and the disease-related pathology in the brain without developing clinical dementia through enhanced brain network efficiency, capacity, or flexibility,” the authors, including David Bennett, MD, the Robert C. Borwell Professor of Neurological Science and director of the Rush Alzheimer's Disease Center, wrote.²

Data were collected from 2022 participants in the Rush Memory and Aging Project, which included annual follow-up from 1997 to 2018. Ultimately, 1602 dementia-free participants were included in the analysis. Information regarding cognitive reserve, including data on education, early, mid-, and late-life cognitive activities, and social activity in late life were collected at baseline. Over the course of follow-up, participants were evaluated for incident dementia; ultimately, 611 died and underwent autopsy.

The mean age of the 1602 participants was 79.6 years, of which 1216 were women. Over the course of follow-up, 386 participants developed dementia (24.1%), including 357 with Alzheimer-disease related dementia (22.3%). Multi-adjusted hazard ratios (HR) for dementia were 0.77 (95% CI, 0.59-0.99) for those who scored in the middle tertile for cognitive reserve, and 0.61 (95% CI, 0.47-0.81) for those in the highest cognitive reserve tertile compared to those in the lowest tertile (all P <.001).

Among those who underwent autopsy, there was no association found between cognitive reserve and most brain pathologies. Still, after adjustment for brain pathologies, the association of cognitive reserve with dementia remained statistically significant (HR 0.60; 95% CI, 0.42-0.86).

Participants who scored within the highest cognitive reserve tertile faced a reduced risk for dementia, even in those who presented with a high degree of Alzheimer-related brain pathology (HR 0.57; 95% CI, 0.37-0.87) and gross infarcts (HR 0.34; 95% CI, 0.18-0.62).

All told, the findings shine a light on the significance of lifespan cognitive reserve in the prevention of dementia.

“These results were consistent with other studies and the [cognitive reserve] theory that [cognitive reserve] could reduce dementia risk and compensate for or cope with dementia pathology through other pathways rather than avoiding pathology directly,” the investigators concluded.² “Our findings suggest that accumulative educational and mentally stimulating activities enhancing [cognitive reserve] throughout life might be a feasible strategy to prevent dementia, even in people with high AD or vascular pathologies. Further large population-based longitudinal studies are warranted to establish the strategies of engagement in [cognitive reserve]-related activities for the prevention of dementia.”

REFERENCES

1. Yang R, Xu H, Qi X, et al. High lifespan cognitive reserve reduces the risk of mild cognitive impairment and decelerates its progression to dementia. Presented at: 2019 Alzheimer’s Association International Conference. July 14-18, 2019; Los Angeles, CA. Abstract 31752.

2. Xu H, Yang R, Qi X, et al. Association of lifespan cognitive reserve indicator with dementia risk in the presence of brain pathologies. JAMA Neurol. Published online July 14, 2019. doi:10.1001/jamaneurol.2019.2455.