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Age-related iron accumulation and demyelination in the basal ganglia are closely related to verbal memory and executive functioning.

ABSTRACT: Age-related cognitive decline has been linked to alterations of the dopaminergic system and its subcortical trajectories. Recent work suggests a critical role of iron accumulation within the basal ganglia (BG) in verbal memory performance, and increased iron levels have been related to demyelination. However, the specificity of age-related iron increases with respect to cognitive functions remains unclear. Therefore, we investigated the interplay of age, cognitive performance, and structural integrity of the BG. In total, 79 healthy older participants underwent a broad cognitive assessment (fluid and crystallized intelligence, verbal and numeric memory, processing speed, executive functions) and structural MRI. As expected, performance in most cognitive tests had a negative relationship with age. Moreover, BG grey matter volume and magnetization transfer (MT, indicative of myelin) decreased, and R2* (indicative of iron) increased with age. Importantly, R2* and demyelination negatively correlated with verbal memory and executive functions. Within the SN/VTA, age correlated negatively with MT, but there was no clear evidence in favor of a relationship between behavior and R2* or MT. Our results suggest that age-related increases in iron and demyelination within the BG, which are part of a fronto-striatal network, not only impact on verbal memory but also executive functions.

SUBMITTER: Biel D

PROVIDER: S-EPMC8093241 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Declines in cognitive functioning are commonly experienced with aging, yet there is wide variation in the nature and extent of these changes. Previous research has shown associations between the frequency of engaging in stimulating cognitive activities and performance on cognitive tests. However, it is not known whether it is important to increase the amount of cognitive activity as one gets older in order to curtail cognitive declines. We examined cognitive activities and cognition in a national sample of 2,130 community-dwelling middle-aged and older adults from the Midlife in the United States longitudinal study. Participants completed cognitive assessments of episodic memory (EM) and executive functioning (EF) on two occasions, ~9 years apart. At the first assessment, participants ranged in age between 33 and 83 years (M = 55.76, SD = 11.09), with 56.1% women. Multilevel models were tested to examine educational level and change in cognitive activity as predictors of change in EM and EF, controlling for initial level of cognitive activity and key correlates of cognitive decline. Results indicated that increases in cognitive activity were important over and above earlier levels of cognitive activity for reducing declines in EF. Further analysis also showed differential results by educational level. Increased cognitive activity was not associated with changes in EF among individuals with a college degree. In contrast, individuals without a college degree who increased their cognitive activity showed significantly less decline in EF compared to those without a college degree who decreased or maintained their cognitive activity across the 9 years. Thus, the results suggest that increased engagement in cognitive activity makes more of a difference for EF declines among those without a college degree. The results have particular relevance given that aging-related changes in domains such as work status, health, or social relationships can lead to reductions in stimulating cognitive activities. The findings emphasize the importance of increasing cognitive activities especially among those with lower educational attainment.

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Age-related iron accumulation and demyelination in the basal ganglia are closely related to verbal memory and executive functioning.

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