Linking Individual Variability of Multi-modal Connectivity, Lifestyle, Psycho-Social Factors and Cognition in Older...

Older adults exhibit greater heterogeneity than younger adults in behavior, cognition, and brain, which may be influenced by a range of factors, including lifestyle. While previous studies have assessed brain heterogeneity by evaluating the dissimilarity of individual brain connectivity, further empirical evidence is needed to understand the factors behind brain heterogeneity in older adults. Using data from the 1000BRAINS study (N = 461, aged 55-85 years), we analyzed the individual variability (IV) of the functional (IV_FC) and structural (IV_SC) connectivity across 421 brain regions. We aimed to explore the relationship between network-wise and region-wise brain connectivity IV (i.e., both IV_FC and IV_SC), lifestyle, including psycho-social factors (e.g., self-reported smoking, physical activity, alcohol consumption, and social integration), and cognitive function via partial least squares correlation, stratifying analyses by age subgroups (55-64, 65-74, and ≥ 75 years), separately. Our results showed that higher connectivity IV was linked to lower social integration and/or higher smoking, and lower cognitive performance (e.g., episodic memory and executive control). For the network-wise analysis, we observed contributions from both IV_FC and IV_SC across eight networks, especially IV_SC in the salience and ventral attention networks. Region-wise, significant contributions came primarily from the connectivity IV of specific brain regions (e.g., inferior frontal gyrus, right anterior cingulate cortex). This result pattern varied by age group. Connectivity IV was positively correlated with smoking in the age 65-74 group and negatively correlated with alcohol consumption in the age ≥ 75 years group. Overall, IV_SC contributed more than IV_FC with age. These findings suggest that unhealthy lifestyle and social isolation might be associated with differences in neural resources, which may be linked to increased individual brain heterogeneity and, in turn, to lower cognitive performance in older adults, supporting the revised Scaffolding Theory of Aging and Cognition (STAC-r).