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], < .001, per each 1-unit increase) orcategorical variable (β = 3.62 [95%CI:1.77-5.47], = .002, High 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], = .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.