High cognitive reserve may counter dementia risk

High cognitive reserve appears to confer protection against dementia, even among people with genetic predisposition to dementia, according to a study.

Analysis of data from 210,631 dementia-free participants at least 60 years of age (mean age, 64.14 years; female, 52.60 percent) from the UK Biobank showed that high cognitive reserve reduced the risk of all-cause dementia by 34 percent compared with low cognitive reserve (hazard ratio [HR], 0.66; 95 percent confidence interval [CI], 0.61–0.70). [Br J Psychiatry 2024;224:213-220]

In Laplace regression, the incidence of all-cause dementia was delayed by 1.62 (95 percent CI, 1.35–1.88) years among participants with high cognitive reserve than among those with low cognitive reserve.

Stratified analysis based on genetic risk categories indicated a consistent association between high cognitive reserve and a decreased risk of all-cause dementia and its subtypes across all genetic risk groups. Among participants with high genetic risk for dementia, for example, high cognitive reserve was associated with a 35 percent, 39 percent, and 49 percent reduction in the likelihood of all-cause dementia, Alzheimer’s disease, and vascular dementia, respectively.

Meanwhile, there was an additive interaction between low cognitive reserve and high genetic risk on dementia, such that patients with both low cognitive reserve and high genetic risk faced a much greater likelihood of dementia (attributable proportion, 0.24; 95% CI, 0.17–0.31).

“The concept of cognitive reserve is proposed to account for individual differences in cognitive functioning in the face of brain ageing and damage… At a practical level, studies generally use certain proxies to represent cognitive reserve, with education level as the most straightforward and common proxy measure,” according to the investigators.

“Cognitive reserve is a dynamic construct that develops from a wide range of experiences over the life course, and thus multiple reserve-enhancing factors need to be considered to sufficiently capture their interplay and accumulation,” they added.

While the exact mechanisms underlying the protective effect of cognitive reserve on the risk of dementia are unclear, the investigators postulated that a high cognitive reserve helps the brain cope with changes linked to dementia rather than directly preventing it. This may be attributed to improved brain network efficiency, increased nerve cell density in certain areas, or even the growth of new neurons. [Alzheimers Dement 2020;16:1305-1311; Lancet Neurol 2012;11:1006-1012; Biol Psychiatry 2012;71:783-791; Mol Neurobiol 2015;51:187-208]

Taken together, “higher cognitive reserve may buffer the deleterious effect of predisposing genetic factors on dementia and thus highlight the importance of enhancing cognitive reserve for the prevention of dementia, especially among those at high genetic risk,” according to the investigators.

The study was limited by the use of register-based data instead of detailed neuropsychological assessments to identify dementia cases, as well as the inability to ascertain diagnoses of Alzheimer’s disease and vascular dementia through brain biopsy or postmortem examination. Additionally, the sample was restricted to older volunteers who were relatively highly educated and primarily of White European ancestry.