Brain morphology, cognition, and β-amyloid in older adults with superior memory performance

Abstract

The mechanisms underlying superior cognitive performance in some older adults are poorly understood. We used a multimodal approach to characterize imaging and cognitive features of 26 successful agers (SA; defined by superior episodic memory ability) and 103 typical older adults. Cortical thickness was greater in multiple regions in SA including right anterior cingulate and prefrontal cortex and was related to baseline memory performance. Similarly, hippocampal volume was greater in SA and associated with baseline memory. SA also had lower white matter hypointensity volumes and faster processing speed. While PiB burden did not differ, there was a significant group interaction in the relationship between age and PiB such that older SA individuals were less likely to have high brain β-amyloid. Over time, memory performance in typical older adults declined more rapidly than in SA, although there was limited evidence for different rates of brain atrophy. These findings indicate that superior memory in aging is related to greater cortical and white matter integrity as well as slower decline in memory performance.

Keywords: Cognitive reserve; Cognitive resilience; MRI; PET; Superaging; Superior memory.

Figure 1. SA have better baseline cognition across domains

Domain-specific average z-scores revealed significantly higher performance in SA compared to TOA. The episodic memory domain score did not include any subscores of the CVLT because they would be highly correlated with CVLT LDFR which was used to define SA. Domain scores in the older adults (SA and TOA) and YA were z-normalized according to age-appropriate mean and standard deviations. Differences between older adults and YA are interpreted as differences in normal-for-age performance. SA=successful agers, TOA=typical older adults, YA= young adults, n.s.=not significant; *p<0.05; **p<0.001.

Figure 2. SA do not experience typical episodic memory decline

Linear mixed effects (LME) models were used to extract predicted longitudinal trajectories for each cognitive domain in both experimental groups. Trajectories for episodic memory (left) domain scores showed a group by time interaction effect such that TOA declined while SA did not. For working memory (center) and processing speed (right) both groups declined at similar rates. SA=successful agers, TOA=typical older adults, *p<0.05.

Figure 3. Specific cortical regions are thicker in SA

A) Whole brain cortical thickness analyses revealed regions of cortex that were significantly thicker in SA compared to TOA (p>0.05, uncorrected). There were no regions where cortex was thicker in TOA. B) Mean thickness values were extracted for difference regions in the LH and RH and plotted to illustrate the differences between groups. Bilateral mean thickness across the whole cortex was also extracted for each participant. There were no differences in whole cortex thickness between SA and TOA. SA=successful agers, TOA=typical older adults, YA=young adults, LH=left hemisphere, RH=right hemisphere, MCC=middle cingulate cortex, ACC=anterior cingulate cortex, mPFC=medial prefrontal cortex, ***p<0.0001; ****p<0.00001; n.s.=not significant

Figure 4. SA have greater hippocampal volume, which is related to their superior memory performance

A) Hippocampal volume was greater in SA than TOA. Both older adult groups had significantly lower hippocampal volume than YA. B) ICV-adjusted, bilateral hippocampal volume was related to baseline episodic memory performance across all older adult participants. † denotes volumes that have been adjusted by intracranial volume (ICV). SA=successful agers, TOA=typical older adults, YA=young adults, **p<0.001; ***p<0.0001; ****p<0.00001

Figure 5. Aβ accumulation is similar in SA and TOA but advanced age, superior memory and PiB positivity appear to be incompatible

A) There was no difference in global PiB DVR between SA and TOA. B) SA showed a significant negative relationship between global PiB DVR and age while TOA did not. There was a significant group interaction. C) Global PiB DVR was not predictive of episodic memory performance cross-sectionally in either SA or TOA. D) Global PiB DVR significantly predicted decline in episodic memory performance in TOA, but not SA. SA=successful agers, TOA=typical older adults, PiB DVR= Pittsburg Compound B distribution volume ratio, n.s.=not significant