Longitudinal investigation of the role of cognitive reserve in the evolution of dementia in outpatients prescribed AChEI

The role of cognitive reserve (CR) in modulating dementia has been broadly investigated. We aimed to evaluate the long-term effects of CR on cognitive functions in outpatients newly treated with acetylcholinesterase inhibitors.Fifty older adults with dementia (age 80 ± 6.4 years) were followed up over 27 months. CR was assessed with the Cognitive Reserve Index questionnaire (CRIq), which provides a Total CR index and three proxy measures: Education, Working Activity and Leisure Time. The association between CR and cognition, evaluated by the Mini-Mental State Examination (MMSE), was tested through linear mixed models. The cognitive profile of High CR individuals (n = 16) was more fluctuating than that of patients with Low CR (n = 34) up to 15 months of treatment, showingan alternation of improvements and worsening. At linear mixed models, CRIq Total score was significantly associated with MMSE over the follow-up either when considered as continuous (β = 0.13 [95%CI:0.07-0.19], p < .001, per each 1-unit increase) orcategorical variable (β = 3.62 [95%CI:1.77-5.47], p = .002, High vs Low CR). Among the CR domains, higher CRIq Leisure-time scores were significantly associated with higher MMSE during the follow-up (β = 0.05 [95%CI:0.02-0.09], p = .009, per each 1-unit increase).The study indicates that higher CR, and especially Leisure Time-related CR, was associated with better cognitive performance in older outpatients with dementia treated with AChEI for 27 months. These findings suggest that Leisure Time-related CR could influence the evolution of dementia, and support the need of further investigations to verify the potential usefulness of interventions enhancing such domain even in advanced age