Is residual memory variance a valid method for quantifying cognitive reserve? A longitudinal application

Abstract

Cognitive reserve describes the mismatch between brain integrity and cognitive performance. Older adults with high cognitive reserve are more resilient to age-related brain pathology. Traditionally, cognitive reserve is indexed indirectly via static proxy variables (e.g., years of education). More recently, cross-sectional studies have suggested that reserve can be expressed as residual variance in episodic memory performance that remains after accounting for demographic factors and brain pathology (whole brain, hippocampal, and white matter hyperintensity volumes). The present study extends these methods to a longitudinal framework in a community-based cohort of 244 older adults who underwent two comprehensive neuropsychological and structural magnetic resonance imaging sessions over 4.6 years. On average, residual memory variance decreased over time, consistent with the idea that cognitive reserve is depleted over time. Individual differences in change in residual memory variance predicted incident dementia, independent of baseline residual memory variance. Multiple-group latent difference score models revealed tighter coupling between brain and language changes among individuals with decreasing residual memory variance. These results suggest that changes in residual memory variance may capture a dynamic aspect of cognitive reserve and could be a useful way to summarize individual cognitive responses to brain changes. Change in residual memory variance among initially non-demented older adults was a better predictor of incident dementia than residual memory variance measured at one time-point.

Keywords: Brain atrophy; Cognitive ageing; Cognitive reserve; Dementia: structural MR imaging; Memory.

Fig 1

Average changes in brain, cognitive, and residual variables as a proportion of initial values. As shown, gray matter volume, hippocampal volume, memory, language and residual memory variance decreased, and white matter hyperintensity (WMH) volume increased in the whole sample.

Fig. 2

Predicted versus actual memory performance in the three tertile groups. Tertile groups were created based on the magnitude of change in residual memory variance. Residual memory variance at each time point reflects the difference between predicted and actual memory scores at that time point. As shown, individuals in the bottom tertile exhibited greater memory decline than was predicted based on demographics and structural MRI variables. Individuals in the middle tertile exhibited comparable memory decline to what was predicted. Individuals in the top tertile exhibited improved memory despite the advancement of brain pathology.