Cognitive reserve, cortisol, and Alzheimer's disease biomarkers: A memory clinic study

Abstract

Introduction: Cognitive reserve might mitigate the risk of Alzheimer's dementia among memory clinic patients. No study has examined the potential modifying role of stress on this relation.

Methods: We examined cross-sectional associations of the cognitive reserve index (CRI; education, occupational complexity, physical and leisure activities, and social health) with cognitive performance and AD-related biomarkers among 113 memory clinic patients. The longitudinal association between CRI and cognition over a 3-year follow-up was assessed. We examined whether associations were influenced by perceived stress and five measures of diurnal salivary cortisol.

Results: Higher CRI scores were associated with better cognition. Adjusting for cortisol measures reduced the beneficial association of CRI on cognition. A higher CRI score was associated with better working memory in individuals with higher (favorable) cortisol AM/PM ratio, but not among individuals with low cortisol AM/PM ratio. No association was found between CRI and AD-related biomarkers.

Discussion: Physiological stress reduces the neurocognitive benefits of cognitive reserve among memory clinic patients.

Highlights: Physiological stress may reduce the neurocognitive benefits accrued from cognitively stimulating and enriching life experiences (cognitive reserve [CR]) in memory clinic patients. Cortisol awakening response modified the relation between CR and P-tau₁₈₁, a marker of Alzheimer's disease (AD). Effective stress management techniques for AD and related dementia prevention are warranted.

Keywords: amyloid beta; cerebrospinal fluid biomarkers; cognitive performance; cognitive reserve; memory clinic; perceived stress; phosphorylated tau; salivary cortisol; total tau.

FIGURE 1

Participant flow chart.