Risk and protective factors associated with brain grey matter patterns in a population-based cohort of cognitively...

Ageing involves heterogeneous brain grey matter (GM) patterns that may overlap with dementia-related changes. We evaluated cognitively unimpaired older adults to identify specific GM patterns, their clinical and cognitive profiles, and longitudinal trajectories.

We analysed 746 participants from the Gothenburg H70 study using random forest cross-sectional clustering based on MRI measures of cortical thickness and subcortical volume across 41 regions. Using regression-based models, we examined associations with clinical, MRI variables, biochemical, and CSF Alzheimer biomarkers (n = 286) and assessed 5-year longitudinal cognitive and brain trajectories.

Five clusters emerged, mainly differing in frontoparietal regions. Compared to Cluster 1 (reference), Cluster 2 showed diffuse GM loss, higher odds of diabetes (OR = 2.54, 95% CI [1.27-5.06]) and at-risk alcohol consumption (OR = 1.83, 95% CI [1.13-2.97]), poorer episodic memory (β =  - 0.19, p = 0.014) and visuospatial abilities (β =  - 0.21, p = 0.044), and greater longitudinal decline in MMSE (β_slope =  - 0.45, p = 0.035) and increase in white matter hyperintensity volume (β_slope = 1.84, p = 0.004). Cluster 3 showed thicker GM and lower BMI (OR = 0.57, 95% CI [0.35-0.94]). Cluster 4 had preserved GM, lower smoking habits (OR = 0.62, 95% CI [0.40-0.95]), triglyceride levels (OR = 0.55, 95% CI [0.32-0.95]) and depression (OR = 0.17, 95% CI [0.05-0.56]), higher education (OR = 2.52, 95% CI [1.08-5.87]), and better cognition in multiple domains. Cluster 5 had a mixed GM pattern and higher odds of heart disease (OR = 3.44, 95% CI [1.48-8.01]).

Cardiovascular and psychosocial factors influence GM integrity, which in turn relates to cognition. Targeting these risk factors may preserve brain health in late life.