Comparison of Education and Episodic Memory as Modifiers of Brain Atrophy Effects on Cognitive Decline: Implications for Measuring Cognitive Reserve

Abstract

Objective: This study compared the level of education and tests from multiple cognitive domains as proxies for cognitive reserve.

Method: The participants were educationally, ethnically, and cognitively diverse older adults enrolled in a longitudinal aging study. We examined independent and interactive effects of education, baseline cognitive scores, and MRI measures of cortical gray matter change on longitudinal cognitive change.

Results: Baseline episodic memory was related to cognitive decline independent of brain and demographic variables and moderated (weakened) the impact of gray matter change. Education moderated (strengthened) the gray matter change effect. Non-memory cognitive measures did not incrementally explain cognitive decline or moderate gray matter change effects.

Conclusions: Episodic memory showed strong construct validity as a measure of cognitive reserve. Education effects on cognitive decline were dependent upon the rate of atrophy, indicating education effectively measures cognitive reserve only when atrophy rate is low. Results indicate that episodic memory has clinical utility as a predictor of future cognitive decline and better represents the neural basis of cognitive reserve than other cognitive abilities or static proxies like education.

Keywords: Aging; Brain atrophy; Cognitive decline; Cognitive reserve; Education; Gray matter change; MRI; cognitive change.

Figure 1.

Longitudinal analytic model. [The four cognitive domain scores are regressed on time in study in the Within level of the multilevel model and person-specific intercept and slope random effects from the Within model serve as primary outcomes in the Between level of the model. A global slope factor effectively summarizes covariance of the four slope random effects but individual intercepts provide optimal fit. The global slope random effect is regressed on the reserve proxy of interest (education or one of the four baseline cognitive domain scores), brain change, the interaction of the reserve proxy with brain change, and covariates. Intercept random effects are also regressed on covariates and the reserve proxy but effects on global slope are of primary interests and effects on intercepts are not reported. All effects in the Between and Within models are simultaneously estimated.]

Figure 2.

Model predicted trajectories of executive function decline by rate of gray matter change and baseline episodic memory. [Expected executive function trajectories are presented for three atrophy rates corresponding to average rates for Normal, MCI, and Dementia baseline diagnosis groups and two levels of episodic memory (+1.0 SD and −1.0 SD). Executive function slope is calculated as global cognitive slope X 1.039 (executive function slope loading in primary, multivariable analysis). The interaction of baseline episodic memory with gray matter atrophy is significant (p=0.003).]

Figure 3.

Model predicted trajectories of executive function decline by rate of gray matter change and education level. [Expected executive function trajectories are presented for three atrophy rates corresponding to average rates for Normal, MCI, and Dementia baseline diagnosis groups and two levels of education (8 and 16 years). Executive function slope is calculated as global cognitive slope X 1.039 (executive function slope loading in primary, multivariable analysis). The interaction of education with gray matter atrophy is significant (p=0.027).]

Figure 4.

Conceptual model of cognitive reserve effects of episodic memory on cognitive decline. [Rectangles represent observed variables and ovals represent latent/hypothetical variables. Observed episodic memory reflects latent variance components due to demographics, measured brain, unmeasured brain, measurement error, and cognitive reserve. Observed cognitive decline is adjusted in the regression model for demographic and measured brain effects, so the regression effect estimate of observed episodic memory on cognitive decline represents the combined effects of unmeasured brain and cognitive reserve variance components.]