When functional blurring becomes deleterious: Reduced system segregation is associated with less white matter integrity and cognitive decline in aging
Robin Pedersen,
Linda Geerligs,
Micael Andersson,
Tetiana Gorbach,
Bárbara Avelar-Pereira,
Anders Wåhlin,
Anna Rieckmann,
Lars Nyberg,
Alireza Salami
Affiliations
Robin Pedersen
Department of Integrative Medical Biology, Umeå University, Umeå, Sweden; Umeå Center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden; Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, Umeå, Sweden; Corresponding author at: Department of Integrative Medical Biology, Johan Bures väg 12, Biologihuset, Umeå University, SE-901 87 Umeå, Sweden.
Linda Geerligs
Donders Institute for Brain, Cognition and Behaviour, Radbound University, Nijmegen, the Netherlands
Micael Andersson
Department of Integrative Medical Biology, Umeå University, Umeå, Sweden; Umeå Center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden; Department of Radiation Sciences, Umeå University, Umeå, Sweden
Tetiana Gorbach
Department of Integrative Medical Biology, Umeå University, Umeå, Sweden; Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, Umeå, Sweden; Department of Statistics, Umeå School of Business, Economics and Statistics, Umeå University, Umeå, Sweden
Bárbara Avelar-Pereira
Department of Psychiatry and Behavioral Sciences, School of Medicine, Stanford University, Stanford, California, USA; Aging Research Center (ARC), Karolinska Institutet and Stockholm University, Stockholm, Sweden
Anders Wåhlin
Umeå Center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden; Department of Radiation Sciences, Umeå University, Umeå, Sweden
Anna Rieckmann
Department of Integrative Medical Biology, Umeå University, Umeå, Sweden; Umeå Center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden; Department of Radiation Sciences, Umeå University, Umeå, Sweden
Lars Nyberg
Department of Integrative Medical Biology, Umeå University, Umeå, Sweden; Umeå Center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden; Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, Umeå, Sweden; Department of Radiation Sciences, Umeå University, Umeå, Sweden
Alireza Salami
Department of Integrative Medical Biology, Umeå University, Umeå, Sweden; Umeå Center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden; Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, Umeå, Sweden; Aging Research Center (ARC), Karolinska Institutet and Stockholm University, Stockholm, Sweden
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.
