Umeå universitets logga

Healthy aging is accompanied by progressive decline in cognitive performance and concomitant changes in brain structure and functional architecture. Age-accompanied alterations in brain function have been characterized on a network level as weaker functional connections within brain networks along with stronger interactions between networks. This phenomenon has been described as age-related differences in functional network segregation. It has been suggested that functional networks related to associative processes are particularly sensitive to age-related deterioration in segregation, possibly related to cognitive decline in aging. However, there have been only a few longitudinal studies with inconclusive results. Here, we used a large longitudinal sample of 284 participants between 25 to 80 years of age at baseline, with cognitive and neuroimaging data collected at up to three time points over a 10-year period. We investigated age-related changes in functional segregation among two large-scale systems comprising associative and sensorimotor-related resting-state networks. We found that functional segregation of associative systems declines in aging with exacerbated deterioration from the late fifties. Changes in associative segregation were positively associated with changes in global cognitive ability, suggesting that decreased segregation has negative consequences for domain-general cognitive functions. Age-related changes in system segregation were partly accounted for by changes in white matter integrity, but white matter integrity only weakly influenced the association between segregation and cognition. Together, these novel findings suggest a cascade where reduced white-matter integrity leads to less distinctive functional systems which in turn contributes to cognitive decline in aging.

Past research has shown that as individuals age, there are decreases in within-network connectivity and increases in between-network connectivity, a pattern known as functional dedifferentiation. While the mechanisms behind reduced network segregation are not fully understood, evidence suggests that age-related differences in the dopamine (DA) system may play a key role. The DA D1-receptor (D1DR) is the most abundant and age-sensitive receptor subtype in the dopaminergic system, known to modulate synaptic activity and enhance the specificity of the neuronal signals. In this study from the DyNAMiC project (N = 180, 20-79y), we set out to investigate the interplay among age, functional connectivity, and dopamine D1DR availability. Using a novel application of multivariate Partial Least squares (PLS), we found that older age, and lower D1DR availability, were simultaneously associated with a pattern of decreased within-network and increased between-network connectivity. Individuals who expressed greater distinctiveness of large-scale networks exhibited more efficient working memory. In line with the maintenance hypotheses, we found that older individuals with greater D1DR in caudate exhibited less dedifferentiation of the connectome, and greater working memory, compared to their age-matched counterparts with less D1DR. These findings suggest that dopaminergic neurotransmission plays an important role in functional dedifferentiation in aging with consequences for working memory function at older age.