Functional activation features of memory in successful agers across the adult lifespan

Abstract

Much neuroimaging research has explored the neural mechanisms underlying successful cognitive aging. Two different patterns of functional activation, maintenance of youth-like activity and compensatory novel recruitment, have been proposed to represent different brain functional features underlying individual differences in cognitive aging. In this study, we investigated the functional features in individuals across the adult lifespan who appeared to resist age-related cognitive decline, in comparison to those with typical age-related declines, over the course of four years. We first implemented latent mixture modeling, a data-driven approach, to classify participants as successful and average agers in middle-aged, young-old, and very old groups, based on their baseline and longitudinal cognitive performance. Then, using fMRI with a subsequent memory paradigm at the follow-up visit, brain activation specifically related to successful encoding (i.e., subsequent memory effect: subsequently remembered with high confidence > subsequently forgotten) was compared between people who established successful cognitive aging versus average aging in the three age groups. Several differences in the subsequent memory effect were revealed. First, across core task-related regions commonly used during successful encoding, successful agers exhibited high subsequent memory effect, at a level comparable to the young control group, until very old age; in contrast, average agers showed reduced subsequent memory effect, compared to successful agers, beginning in young-old age when memory performance also reduced in average agers, compared to successful agers. Second, additional recruitment in prefrontal clusters, distant from the core task-related regions, were identified in the left superior frontal and right orbitofrontal cortices in successful agers of young-old age, possibly reflecting functional compensation in successful aging. In summary, successful agers demonstrate a pattern of youth-like activation spanning from middle age to young-old age, as well as novel frontal recruitment in young-old age. Overall, our study demonstrated evidence of two neural patterns related to successful cognitive aging, offering an integrated view of functional features underlying successful aging, and suggests the importance of studying individuals across the lifespan to understand brain changes occurring in mid and early-late life.

Keywords: Brain maintenance; Compensation; Dedifferentiation; Subsequent memory; Successful aging; fMRI.

Fig. 1.

(a) Presentation of the scene pictures in the scanner during the encoding phase. (b). Example of encoded and matching lure pictures.

Fig. 2.

Latent change score model simultaneously estimates cross-sectional performance and longitudinal change in four cognitive domains. Cross-time residual autocorrelations were allowed for measures from a repeated task but not depicted for simplicity. For measures from the same task, correlations were also specified but not depicted in the diagram. See Cognitive Measures in Methods for abbreviations.

Fig. 3.

Spaghetti plot of longitudinal cognitive change over four years. Each line represents one individual in the study, going from the baseline score to the follow-up performance score. Lines are color-coded based on the longitudinal change: red means decline, yellow means stability, and green means performance increase, likely due to practice effect. The solid lines represent participants who continued to participate, and dashed lines represent participants who dropped out of the study (their scores were estimated using full information maximum likelihood estimation; they were included to aid visual interpretation, but not included in any further analysis). Black lines overlaying individual lines represent the mean level and change of the corresponding age decade.

Fig. 4.

Longitudinal cognitive change of two classes (average agers in red, successful agers in green) in four cognitive domains over four years. In all three age groups (middle-aged, young-old, very old), two classes of individuals with distinct patterns of cognitive aging profiles were identified using latent mixture modeling, with one class in red and the other class in green. Young adults (in blue) were included for reference visualization.

Fig. 5.

Subsequent memory performance, indexed by d’ (ZPr(HiC-hit) – ZPr(HiC-FA)), separated by successful and average agers in three age groups. ** p <.01

Fig. 6.

Significant clusters demonstrating subsequent memory effect (high-confidence remembered > forgotten). Height-threshold at p < .001. Voxel-wise family-wise error (FWE) corrected at p < .05.

Fig. 7.

Estimated marginal means of subsequent memory effect, adjusted for sex and education, in successful and average agers in middle-aged, young-old and very old adults in four subsequent-memory-defined ROIs. Successful agers tended to have higher subsequent memory effect than average agers, particularly in the young-old group for the fusiform/parahippocampal regions.

Fig. 8.

Mean subsequent memory effect in middle-aged, young-old, and very old adults, compared to the young reference group, separately for successful and average agers. * p<.05. ** p<.01. All significant effects survived multiple comparison correction (q’s > .05).

Fig. 9.

(a) Clusters showing significantly higher subsequent memory effect in successful agers than average agers in young-old age. FWE corrected at p < .05. (b) Activation map of subsequent memory effect in young (reference) adults. No correction applied for visualization purpose. (c) Activation map of subsequent memory effect in successful young-old agers. No correction applied for visualization purpose.

Fig. 10.

Higher subsequent memory effect activity associated with better longitudinal cognitive maintenance and higher baseline and follow-up scores. EMDIF: Episodic Memory Change Score. REASDIF: Inductive Reasoning Change Score. PSDIF: Processing Speed Change Score. WMDIF: Working Memory Change Score.