Cognitive reserve moderates the relationship between hippocampal volume and cognitive decline – but not gait decline

Abstract

AbstractBackgroundCognitive reserve (CR) accounts for individual differences in the relationship between brain health and clinical status. Common proxies of CR include education, and physical and social leisure activities. Greater CR allows individuals to cope better with poor brain health, and thereby delay the onset of cognitive impairment and dementia. Yet, whether CR protects against age‐related gait and cognitive decline is not well‐understood. Here, we examined whether CR moderates the relationship between hippocampal volume (a common marker of brain health) and age‐related decline in gait and cognition.MethodData from 101 LonGenity participants without dementia (M Age=79.33±6.09 years; 56% women) who had completed one MRI, and up to 3 years of follow‐up testing (M follow‐up=1.83±0.54 years) was examined. Gait speed was assessed during normal pace walking. Cognition was assessed with 11 neuropsychological tests, and a global cognitive composite. CR proxies (from self‐report), included cognitive (years of education), physical (number of blocks walked per day), and social (volunteering, living with someone) activities. FreeSurfer 6.0 was used to obtain hippocampal volume from structural MRIs. Linear mixed‐effects models adjusted for sex, parental longevity, cognitive impairment, and comorbidities examined the relationship between hippocampal volume and age‐related gait and cognitive decline.ResultEducation moderated the relationship between hippocampal volume and decline in figure copy performance. The number of blocks walked per day moderated the relationship between hippocampal volume and decline in global cognition, Trail Making Test (TMT)‐A, TMT‐interference, digit symbol substitution and phonemic fluency performance. Living with someone moderated the relationship between hippocampal volume and decline in global cognition, TMT‐interference, and logical memory performance. None of the CR proxies moderated the relationship between hippocampal volume and gait speed decline.ConclusionCognitive, physical, and social CR proxies moderated the relationship between hippocampal volume and age‐related cognitive decline – not age‐related gait decline. Follow‐up sensitivity analyses, however, suggested that some CR proxies (e.g. education) moderated the relationship between prefrontal volumes and age‐related gait decline – presumably because prefrontal regions are more consistently associated with gait speed. Future studies are need to confirm whether the relationship between CR and age‐related gait and cognitive decline depends on the brain health marker.