Global brain maintenance predicts well-preserved cognitive function: A pooled analysis of three longitudinal population-based Swedish cohorts

Korkki, S.; Narbutas, J.; Salami, A.; Ryden, L.; Kalpouzos, G.; Andersson, M.; Kern, S.; Skoog, J.; Westman, E.; Skoog, I.; Rizzuto, D.; Nyberg, L.

doi:10.1101/2025.03.04.641447

bioRxiv · 10.1101/2025.03.04.641447

Global brain maintenance predicts well-preserved cognitive function: A pooled analysis of three longitudinal population-based Swedish cohorts

Korkki, S.·Narbutas, J.·Salami, A.·Ryden, L.·Kalpouzos, G.·Andersson, M.·Kern, S.·Skoog, J.·Westman, E.·Skoog, I.·Rizzuto, D.·Nyberg, L.

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Abstract

Substantial heterogeneity in cognitive ageing is well documented. Such heterogeneity has been attributed to individual differences in brain maintenance - i.e., the relative preservation of neural resources in ageing. However, large-scale longitudinal evidence is lacking. We pooled data from three population-based Swedish cohorts (Betula, N = 196; SNAC-K, N = 472; H70, N = 688; aged 60-93 years at baseline, follow-up duration up to 7 years) to assess whether global brain maintenance is associated with better preserved cognition in ageing, and to identify lifestyle predictors of brain maintenance. In each cohort, global brain integrity was indexed by the volume of the lateral ventricles (adjusted for total intracranial volume), and general cognitive function based on a principal component analysis of four age-sensitive cognitive domains. Participants were classified into subgroups of low (i.e., aged) versus high (i.e., youth-like) brain integrity based on ventricular volume estimates available for a younger reference sample in one of the cohorts (Betula, 25-55 years, N = 60). Subgroup differences in cognition at baseline and over the follow-up were assessed with ANCOVAs and linear mixed effects models. Logistic regressions were used to examine lifestyle predictors of brain maintenance. Across cohorts, 881 individuals (64.97%) were classified into the high brain integrity subgroup at baseline and 409 individuals (49.82%) over the follow-up. Maintenance of more youth-like brain integrity was associated with better baseline cognition (p < .001) and less cognitive decline longitudinally (p < .001). Moreover, lower cardiovascular disease (CVD) risk and the absence of diabetes predicted brain maintenance at baseline (CVD risk, OR = 0.80, 95% CI [0.68, 0.93]; diabetes, OR = 0.39, 95% CI [0.26, 0.59]) and over the follow-up (CVD risk, OR = 0.79, 95% CI [0.64, 0.96]; diabetes, OR = 0.53, 95% CI [0.29, 0.94]). These findings underscore brain maintenance as a key determinant of cognitive ageing and highlight the importance of managing cardiovascular and metabolic disease risk factors for promotion of brain and cognitive health in later life.

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Korkki, S., Narbutas, J., Salami, A., Ryden, L., Kalpouzos, G., Andersson, M., Kern, S., Skoog, J., Westman, E., Skoog, I., Rizzuto, D., Nyberg, L.. 2025-03-10. Global brain maintenance predicts well-preserved cognitive function: A pooled analysis of three longitudinal population-based Swedish cohorts. https://doi.org/10.1101/2025.03.04.641447

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