ABSTRACT: IMPORTANCE:Telomere length has been associated with dementia and psychological stress, but its relationship with human brain size is unknown. OBJECTIVE:To determine if peripheral blood telomere length is associated with brain volume. DESIGN, SETTING, AND PARTICIPANTS:Peripheral blood leukocyte telomere length and brain volumes were measured for 1960 individuals in the Dallas Heart Study, a population-based, probability sample of Dallas County, Texas, residents, with a median (25th-75th percentile) age of 50 (42-58) years. Global and 48 regional brain volumes were assessed from the automated analysis of magnetic resonance imaging. MAIN OUTCOMES AND MEASURES:Telomere length and global and regional brain volumes. RESULTS:Leukocyte telomere length was associated with total cerebral volume (? [SE], 0.06 [0.01], P?<.001) including white and cortical gray matter volume (? [SE], 0.04 [0.01], P?=?.002; ? [SE], 0.07 [0.02], P?<.001, respectively), independent of age, sex, ethnicity, and total intracranial volume. While age was associated with the size of most subsegmental regions of the cerebral cortex, telomere length was associated with certain subsegmental regions. Compared with age, telomere length (TL) explained a sizeable proportion of the variance in volume of the hippocampus, amygdala, and inferior temporal region (hippocampus: ?TL [SE], 0.08 [0.02], R2, 0.91% vs ?age [SE], -0.16 [0.02], R2, 3.80%; amygdala: ?TL [SE], 0.08 [0.02], R2, 0.78% vs ?age [SE],-0.19 [0.02], R2,4.63%; inferior temporal: ?TL [SE], 0.07 [0.02], R2, 0.92% vs ?age [SE], -0.14 [0.02], R2, 3.98%) (P?<.001 for all). The association of telomere length and the size of the inferior and superior parietal, hippocampus, and fusiform regions was stronger in individuals older than 50 years than younger individuals (inferior parietal: ?>50 [SE], 0.13 [0.03], P?<.001 vs ??50 [SE], 0.02 [0.02], P?=?.51, P for interaction = .001; superior parietal: ?>50 [SE], 0.11 [0.03], P?<.001 vs ??50 [SE], 0.01 [0.02], P?=?.71, P for interaction = .004; hippocampus: ?>50 [SE], 0.10 [0.03], P?=?.004 vs ??50 [SE], 0.05 [0.02], P?=?.07, P for interaction = .04; fusiform: ?>50 [SE], 0.09 [0.03], P?=?.002, ??50 [SE], 0.03 [0.02], P?=?.31, P for interaction = .03). The volume of the hippocampus, amygdala, superior and inferior temporal, precuneus, lateral orbitofrontal, posterior cingulate, thalamus and ventral diencephalon were independently associated with telomere length after adjustment for all covariates (age, gender, ethnicity, total intracranial volume, body mass index, blood pressure, diabetes, smoking status, and APOE genotype). CONCLUSIONS AND RELEVANCE:To our knowledge, this is the first population-based study to date to evaluate telomere length as an independent predictor of global and regional brain size. Future studies are needed to determine how telomere length and anatomic structural changes are related to cognitive function, dementia, and psychological disease.
