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

Abstract

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.

Keywords: Biomarkers; Cognitive change; Cognitive reserve; Longitudinal; Preclinical Alzheimer's disease.

Figure 1. Timeline showing the design of the BIOCARD study

Types of data collected each year for the BIOCARD study between 1995 and 2016.

Figure 2. Estimates of longitudinal cognitive change by follow-up diagnosis and baseline cognitive reserve composite score

Estimates from linear mixed effects model predicting longitudinal cognitive composite scores over time among four groups: (1) low CR/normal (black line) are individuals with CR scores below the median who remained cognitively normal over time; (2) high CR/normal (blue line) are individuals with CR scores at or above the median who remained cognitively normal; (3) low CR/progressed (red line) are individuals with CR scores below the median who progressed to MCI at follow-up; and (4) high CR/progressed (green line) are individuals with CR scores at or above the median who progressed to MCI at follow-up. Estimates are adjusted for baseline age, gender, and the age × time interaction. The number of participants contributing data at each time point is shown in the table below the figure.

Figure 3. Estimates of longitudinal cognitive change by level of baseline biomarker and cognitive reserve composite scores

Estimates from linear mixed effects model predicting longitudinal cognitive composite scores over time among four groups: (1) low CR/low biomarker (black line) are individuals with CR scores below the median and biomarker composite scores below the median; (2) high CR/low biomarker (blue line) are individuals with CR scores at or above the median and biomarker scores below the median; (3) low CR/high biomarker (red line) are individuals with CR scores below the median and biomarker scores at or above the median; and (4) high CR/high biomarker (green line) are individuals with CR scores at or above the median and biomarker scores at or above the median. Estimates are adjusted for baseline age, gender, and the age × time interaction.