Specific and general relationships between cortical thickness and cognition in older adults: a longitudinal study.

Prior studies suggest that relationships between regional cortical thickness and domain-specific cognitive performance can be mediated by the relationship between global cortical thickness and domain-general cognition. Whether such findings extend to longitudinal cognitive change remains unclear. Here, we examined the relationships in healthy older adults between cognitive performance, longitudinal cognitive change over 3 years, and cortical thickness at baseline of the left and right inferior frontal gyrus (IFG) and left and right hemispheres. Both right IFG and right hemisphere thickness predicted baseline general cognition and domain-specific cognitive performance. Right IFG thickness was also predictive of longitudinal memory change. However, right IFG thickness was uncorrelated with cognitive performance and memory change after controlling for the mean thickness of other ipsilateral cortical regions. In addition, most identified associations between cortical thickness and specific cognitive domains were nonsignificant after controlling for the variance shared with other cognitive domains. Thus, relationships between right IFG thickness, cognitive performance, and memory change appear to be largely accounted for by more generic relationships between cortical thickness and cognition. This article is part of the Virtual Special Issue titled "COGNITIVE NEUROSCIENCE OF HEALTHY AND PATHOLOGICAL AGING". The full issue can be found on ScienceDirect athttps://www.sciencedirect.com/journal/neurobiology-of-aging/special-issue/105379XPWJP.

Recollection-related hippocampal fMRI effects predict longitudinal memory change in healthy older adults.

Prior fMRI studies have reported relationships between memory-related activity in the hippocampus and in-scanner memory performance, but whether such activity is predictive of longitudinal memory change remains unclear. Here, we administered a neuropsychological test battery to a sample of cognitively healthy older adults on three occasions, the second and third sessions occurring one month and three years after the first session. Structural and functional MRI data were acquired between the first two sessions. The fMRI data were derived from an associative recognition procedure and allowed estimation of hippocampal effects associated with both successful associative encoding and successful associative recognition (recollection). Baseline memory performance and memory change were evaluated using memory component scores derived from a principal components analysis of the neuropsychological test scores. Across participants, right hippocampal encoding effects correlated significantly with baseline memory performance after controlling for chronological age. Additionally, both left and right hippocampal associative recognition effects correlated negatively with longitudinal memory decline after controlling for age, and the relationship with the left hippocampal effect remained after also controlling for left hippocampal volume. Thus, in cognitively healthy older adults, the magnitude of hippocampal recollection effects appears to be a robust predictor of future memory change.

Age moderates the relationship between cortical thickness and cognitive performance.

Findings from cross-sectional and longitudinal magnetic resonance imaging (MRI) studies indicate that cortical thickness declines across the adult lifespan, with regional differences in rate of decline. Global and regional thickness have also been found to co-vary with cognitive performance. Here we examined the relationships between age, mean cortical thickness, and associative recognition performance across three age groups (younger, middle-aged and older adults; total n = 133). Measures of cortical thickness were obtained using a semi-automated method. Older age was associated with decreased memory performance and a reduction in mean cortical thickness. After controlling for the potentially confounding effects of head motion, mean cortical thickness was negatively associated with associative memory performance in the younger participants, but was positively correlated with performance in older participants. A similar but weaker pattern was evident in the relationships between cortical thickness and scores on four cognitive constructs derived from a neuropsychological test battery. This pattern is consistent with prior findings indicating that the direction of the association between cortical thickness and cognitive performance reverses between early and later adulthood. In addition, head motion was independently and negatively correlated with associative recognition performance in younger and middle-aged, but not older, participants, suggesting that variance in head motion is determined by multiple factors that vary in their relative influences with age.

Independent contributions of fMRI familiarity and novelty effects to recognition memory and their stability across the adult lifespan.

The impact of age on the neural correlates of familiarity-driven recognition memory has received relatively little attention. Here, the relationships between age, the neural correlates of familiarity, and memory performance were investigated using an associative recognition test in young, middle-aged and older participants. Test items comprised studied, rearranged (items studied on different trials) and new word pairs. fMRI 'familiarity effects' were operationalized as greater activity for studied test pairs incorrectly identified as 'rearranged' than for correctly rejected new pairs. The reverse contrast was employed to identify 'novelty' effects. Estimates of familiarity strength were slightly but significantly lower for the older relative to the younger group. With the exception of one region in dorsal medial prefrontal cortex, fMRI familiarity effects (which were identified in medial and lateral parietal cortex, dorsal medial and left lateral prefrontal cortex, and bilateral caudate among other regions) did not differ significantly with age. Age-invariant 'novelty effects' were identified in the anterior hippocampus and the perirhinal cortex. When entered into the same regression model, familiarity and novelty effects independently predicted familiarity strength across participants, suggesting that the two classes of memory effect reflect functionally distinct mnemonic processes. It is concluded that the neural correlates of familiarity-based memory judgments, and their relationship with familiarity strength, are largely stable across much of the healthy adult lifespan.

The relationships between age, associative memory performance, and the neural correlates of successful associative memory encoding.

Using functional magnetic resonance imaging, subsequent memory effects (greater activity for later remembered than later forgotten study items) predictive of associative encoding were compared across samples of young, middle-aged, and older adults (total N = 136). During scanning, participants studied visually presented word pairs. In a later test phase, they discriminated between studied pairs, "rearranged" pairs (items studied on different trials), and new pairs. Subsequent memory effects were identified by contrasting activity elicited by study pairs that went on to be correctly judged intact or incorrectly judged rearranged. Effects in the hippocampus were age-invariant and positively correlated across participants with associative memory performance. Subsequent memory effects in the right inferior frontal gyrus (IFG) were greater in the older than the young group. In older participants only, both left and, in contrast to prior reports, right IFG subsequent memory effects correlated positively with memory performance. We suggest that the IFG is especially vulnerable to age-related decline in functional integrity and that the relationship between encoding-related activity in right IFG and memory performance depends on the experimental context.

The neural correlates of recollection and retrieval monitoring: Relationships with age and recollection performance.

The relationships between age, retrieval-related neural activity, and episodic memory performance were investigated in samples of young (18-29yrs), middle-aged (43-55yrs) and older (63-76yrs) healthy adults. Participants underwent fMRI scanning during an associative recognition test that followed a study task performed on visually presented word pairs. Test items comprised pairs of intact (studied pairs), rearranged (items studied on different trials) and new words. fMRI recollection effects were operationalized as greater activity for studied pairs correctly endorsed as intact than for pairs incorrectly endorsed as rearranged. The reverse contrast was employed to identify retrieval monitoring effects. Robust recollection effects were identified in the core recollection network, comprising the hippocampus, along with parahippocampal and posterior cingulate cortex, left angular gyrus and medial prefrontal cortex. Retrieval monitoring effects were identified in the anterior cingulate and right dorsolateral prefrontal cortex. Neither recollection effects within the core network, nor the monitoring effects differed significantly across the age groups after controlling for individual differences in associative recognition performance. Whole brain analyses did however identify three clusters outside of these regions where recollection effects were greater in the young than in the other age groups. Across-participant regression analyses indicated that the magnitude of hippocampal and medial prefrontal cortex recollection effects, and both of the prefrontal monitoring effects, correlated significantly with memory performance. None of these correlations were moderated by age. The findings suggest that the relationships between memory performance and functional activity in regions consistently implicated in successful recollection and retrieval monitoring are stable across much of the healthy adult lifespan.

The Effects of Age on the Neural Correlates of Recollection Success, Recollection-Related Cortical Reinstatement, and Post-Retrieval Monitoring.

Functional magnetic resonance imaging (fMRI) was used to investigate whether age-related differences in episodic memory performance are accompanied by a reduction in the specificity of recollected information. We addressed this question by comparing recollection-related cortical reinstatement in young and older adults. At study, subjects viewed objects and concrete words, making 1 of 2 different semantic judgments depending on the study material. Test items were words that corresponded to studied words or the names of studied objects. Subjects indicated whether each test item was recollected, familiar, or novel. Reinstatement of information differentiating the encoding tasks was quantified both with a univariate analysis of the fMRI signal and with a multivoxel pattern analysis, using a classifier that had been trained to discriminate between the 2 classes of study episode. The results of these analyses converged to suggest that reinstatement did not differ according to age. Thus, there was no evidence that specificity of recollected information was reduced in older individuals. Additionally, there were no age effects in the magnitude of recollection-related modulations in regional activity or in the neural correlates of post-retrieval monitoring. Taken together, the findings suggest that the neural mechanisms engaged during successful episodic retrieval can remain stable with advancing age.

Sensitivity of negative subsequent memory and task-negative effects to age and associative memory performance.

The present fMRI experiment employed associative recognition to investigate the relationships between age and encoding-related negative subsequent memory effects and task-negative effects. Young, middle-aged and older adults (total n=136) were scanned while they made relational judgments on visually presented word pairs. In a later memory test, the participants made associative recognition judgments on studied, rearranged (items studied on different trials) and new pairs. Several regions, mostly localized to the default mode network, demonstrated negative subsequent memory effects in an across age-group analysis. All but one of these regions also demonstrated task-negative effects, although there was no correlation between the size of the respective effects. Whereas negative subsequent memory effects demonstrated a graded attenuation with age, task-negative effects declined markedly between the young and the middle-aged group, but showed no further reduction in the older group. Negative subsequent memory effects did not correlate with memory performance within any age group. By contrast, in the older group only, task-negative effects predicted later memory performance. The findings demonstrate that negative subsequent memory and task-negative effects depend on dissociable neural mechanisms and likely reflect distinct cognitive processes. The relationship between task-negative effects and memory performance in the older group might reflect the sensitivity of these effects to variations in amount of age-related neuropathology. This article is part of a Special Issue entitled SI: Memory.