Research square · 2025
Risk and protective factors associated with brain grey matter patterns in a population-based cohort of cognitively unimpaired 70-year-olds.
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Lorenzon Giulia, Marseglia Anna, Poulakis Konstantinos, Imbimbo Camillo, Rydén Lina, Galaris Evangelos, Lindberg Olof, Shams Sara, Mohanty Rosaleena, Ferreira Daniel, Kivipelto Miia, Eriksdotter Maria, Kern Silke, Skoog Ingmar, Westman Eric
Аннотация
BACKGROUND: Aging involves heterogeneous brain grey matter (GM) loss 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 analyzed 746 participants from the Gothenburg H70 Study using random forest clustering based on MRI measures of cortical thickness and subcortical volume across 41 regions. We examined associations with clinical and MRI variables, APOE status, and CSF Alzheimer biomarkers (n = 286), and assessed 5-year cognitive and brain trajectories using regression models.
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 risk alcohol consumption (OR = 1.83, 95%CI [1.13-2.97]), poorer episodic memory (β=-0.190, p = 0.014) and visuospatial abilities (β =-0.209, p = 0.044), and greater longitudinal decline in MMSE (βslope = - 0.448, p = 0.035) and increase in white matter hyperintensity volume (βslope = 1.843, p = 0.004). Clusters 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]), triglycerides 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 mixed GM pattern and higher odds of heart disease (OR = 3.44, 95%CI [1.48-8.01]).
CONCLUSIONS: Cardiovascular and psychosocial factors are key determinants of GM integrity and cognition. Targeting these risks factors may preserve brain health in late life.
METHODS: We analyzed 746 participants from the Gothenburg H70 Study using random forest clustering based on MRI measures of cortical thickness and subcortical volume across 41 regions. We examined associations with clinical and MRI variables, APOE status, and CSF Alzheimer biomarkers (n = 286), and assessed 5-year cognitive and brain trajectories using regression models.
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 risk alcohol consumption (OR = 1.83, 95%CI [1.13-2.97]), poorer episodic memory (β=-0.190, p = 0.014) and visuospatial abilities (β =-0.209, p = 0.044), and greater longitudinal decline in MMSE (βslope = - 0.448, p = 0.035) and increase in white matter hyperintensity volume (βslope = 1.843, p = 0.004). Clusters 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]), triglycerides 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 mixed GM pattern and higher odds of heart disease (OR = 3.44, 95%CI [1.48-8.01]).
CONCLUSIONS: Cardiovascular and psychosocial factors are key determinants of GM integrity and cognition. Targeting these risks factors may preserve brain health in late life.