Risk and protective factors associated with brain grey matter patterns in a population-based cohort of cognitively unimpaired 70 years old.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (βslope =  - 0.45, p = 0.035) and increase in white matter hyperintensity volume (βslope = 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]). CONCLUSIONS: Cardiovascular and psychosocial factors influence GM integrity, which in turn relates to cognition. Targeting these risk factors may preserve brain health in late life.