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.
Highlights
Age-related cognitive decline has been linked to alterations of the dopaminergic system and its subcortical trajectories
Due to outliers/missing values in the VLMT recognition and TMT, two additional regression analyses were conducted for age and VLMT recognition, as well as age and TMT
The voxel-based morphometry (VBM) multiple regression analyses revealed a negative relationship between age and grey matter (GM) volume within the right caudate, pallidum, and putamen (Table 1; Fig. 2a-b), and a positive correlation between GM volume and VLMT recognition in the caudate (Table 1)
Summary
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. Cognitive declines in healthy aging have previously been linked to cortical and subcortical degeneration (e.g.,1), but the underlying microstructural changes are poorly understood In this regard, recent studies could show that iron accumulations within the basal ganglia (BG) closely relate to demyelination and deficits in verbal long-term memory performance[2,3]. SN/VTA iron levels do not appear to be increased[19,20], but the structural integrity of the SN/VTA, as measured with magnetization transfer ratio (MTR, a marker of myelination;21) was reduced and predictive of verbal memory performance[22]. While heme iron is functionally linked to the hemoglobin molecule, and exclusive within circulating or Scientific Reports | (2021) 11:9438
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