Risk factors of brain atrophy in cognitively normal elderly

Abstract Background Lifestyle‐related risk factors (e.g., smoking) and common health problems (e.g., hypertension) have been found to be associated with brain atrophy. However, it is still not clear about their independent contribution to brain atrophy, especially among the elderly with normal cognition. Here, we aim to identify the independent risk factors of brain atrophy in cognitively normal elderly. Method We included 419 elderly subjects with normal cognition (Table 1) from the ADNI database (ADNI1/ADNI2/ADNI‐GO) who had available data of lifestyle‐related risk factors (alcohol abuse, smoking) and common health problems (obesity, hypertension, high cholesterol, high triglycerides, sleep disturbance) and underwent 3D T1‐weighted MRI scans at baseline. The T1‐weighted images were processed with AccuBrain IV2.0 to quantify the brain volumetric measures as listed in Table 2. Univariate analyses were performed with ANCOVA to investigate the influence of the risk factors for each brain volumetric measure, while age, gender, education and APOE4 carrier were covaried out. The independent contribution of the risk factors were further identified by entering them together in a multivariate linear regression model as predictors of brain atrophy using backward elimination. Result In the univariate analyses, obesity showed the most widely influence of brain atrophy throughout the brain, followed by hypertension which contributed to atrophy in cerebellum and part of cortical gray matter (GM), alcohol abuse that contributed to atrophy in part of basal ganglia structures, high triglycerides for atrophy of pons and cerebellum, and smoking for medial temporal lobe atrophy (Table 3). When other risk factors were also considered (Table 4), the contribution of obesity to the atrophy of most brain regions remained significant. Hypertension, alcohol abuse and smoking also showed independent contributions (p<0.05) to the atrophy of several brain regions, while sleep disturbance (for brain parenchyma) and high triglycerides (for cerebellum) only presented mild independent contribution (0.05<p<0.10) to brain atrophy. Conclusion Obesity presented most independent contribution to brain atrophy in cognitively normal elderly, followed by hypertension, alcohol abuse and smoking. These results may facilitate the interpretation of brain atrophy in normal subjects and intervention of reversible brain atrophy caused by specific risk factors.