Cognitive reserve and long-term change in cognition in aging and preclinical Alzheimer's disease.

We examined if baseline levels of cognitive reserve (CR) and of Alzheimer's disease (AD) biomarkers modify the rate of change in cognition among individuals with normal cognition at baseline (n = 303, mean baseline age = 57 years, mean follow-up = 12 years); 66 participants subsequently developed mild cognitive impairment (MCI) or dementia due to AD. CR was indexed by years of education, reading, and vocabulary measures. AD biomarkers were measured with a composite score composed of measures of amyloid, phosphorylated tau, and neurodegeneration. Higher CR scores were associated with better cognitive performance but did not modify the rate of change in cognition among those who remained cognitively normal, nor among those who progressed to MCI before symptom onset, independent of baseline biomarker levels. However, higher CR scores were associated with faster cognitive decline after symptom onset of MCI. These results suggest that the mechanism by which CR mediates the relationship between pathology and cognitive function is by delaying the onset of symptoms rather than reducing the rate of cognitive decline.