# Intervention‐related changes in variability of dynamic functional connectivity and the relationship to cognition in older adults at risk for Alzheimer's disease

## TL;DR

A physical activity intervention reduced brain connectivity variability in older adults at risk for Alzheimer's, which was linked to better cognitive performance.

## Contribution

This study shows that physical activity can reduce age-related variability in brain connectivity linked to Alzheimer's risk and cognitive improvement.

## Key findings

- The intervention group showed decreased modularity and maintained system segregation in the DefaultC network compared to the control group.
- Reduced variability in DefaultC network modularity correlated with improved performance on a cognitive task.
- The DefaultC network includes brain regions vulnerable to Alzheimer's pathology.

## Abstract

Aging is associated with a decline in specific cognitive abilities and increased variability of dynamic functional connectivity (v‐dFC; Jauny et al., 2022), across the whole brain (Yang et al., 2023) and in the default network (Douw et al., 2016; Madhyastha & Grabowski, 2014). We investigated the extent to which age‐related changes in v‐dFC would be mitigated by an intervention to enhance physical activity in older adults at risk for Alzheimer's disease (AD) and whether the changes in v‐dFC were related to cognitive improvements.

50 participants from the PREVENT‐AD longitudinal cohort (Tremblay‐Mercier et al., 2021) with a family history of AD were assigned to the intervention (N = 21; Mage=69.8 years) or the active control group (N = 29; Mage=70.3 years) for a four‐week randomized controlled trial. Multi‐echo gradient‐echo EPI sequence was used to acquire resting‐state functional MRI data at baseline and post‐intervention. Using Schaefer's 200 parcellation across Yeo's 17 networks, the dFC matrices were constructed with the Multiplication of Temporal Derivatives method (Shine et al., 2015; 10 TR overlapping windows). Modularity, system segregation (Chan et al., 2014), within‐network and between‐network FC of the DefaultA/B/C and ControlA/B/C networks were calculated for each dFC matrix. V‐dFC was defined as the standard deviation of these measures. Group by time interactions effects on v‐dFC were estimated after controlling for age, education, sex, motion and APOE4 carriership status. Change scores in v‐dFC measures were correlated with changes in cognitive performance on digit span and digit symbol matching tasks.

The intervention group showed decreased modularity and maintained system segregation within‐DefaultC, between DefaultC—ControlC v‐dFC, compared to the control group who showed increased v‐dFC (Figure 1) after the intervention period relative to baseline. The baseline to post‐intervention decrease in v‐dFC of modularity was related to concurrent improvement in digit symbol matching task performance (Figure 2).

An intervention to enhance physical activity mitigated age‐related increases in v‐dFC network segregation and connectivity of the DefaultC subnetwork. DefaultC corresponds to the medial temporal lobe subsystem (Andrews‐Hanna et al., 2010), including the parahippocampal, retrosplenial and inferior parietal regions, which are highly vulnerable to AD pathology (Buckner et al., 2005).