title: Effect of leukocyte telomere length on total and regional brain volumes in a large population-based cohort.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Telomere length and global and regional brain volumes.
  
  
  RESULTS
  Leukocyte telomere length was associated with total cerebral volume (β [SE], 0.06 [0.01], P <.001) including white and cortical gray matter volume (β [SE], 0.04 [0.01], P = .002; β [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: βTL [SE], 0.08 [0.02], R2, 0.91% vs βage [SE], -0.16 [0.02], R2, 3.80%; amygdala: βTL [SE], 0.08 [0.02], R2, 0.78% vs βage [SE],-0.19 [0.02], R2,4.63%; inferior temporal: βTL [SE], 0.07 [0.02], R2, 0.92% vs βage [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: β>50 [SE], 0.13 [0.03], P <.001 vs β≤50 [SE], 0.02 [0.02], P = .51, P for interaction = .001; superior parietal: β>50 [SE], 0.11 [0.03], P <.001 vs β≤50 [SE], 0.01 [0.02], P = .71, P for interaction = .004; hippocampus: β>50 [SE], 0.10 [0.03], P = .004 vs β≤50 [SE], 0.05 [0.02], P = .07, P for interaction = .04; fusiform: β>50 [SE], 0.09 [0.03], P = .002, β≤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
  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.
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, Dallas.
authors.forename: Kevin S
authors.initials: KS
authors.lastname: King
authors.affiliation: Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas3Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.
authors.forename: Julia
authors.initials: J
authors.lastname: Kozlitina
authors.affiliation: Department of Neurology, University of Texas Southwestern Medical Center, Dallas5Editor, JAMA Neurology.
authors.forename: Roger N
authors.initials: RN
authors.lastname: Rosenberg
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, Dallas.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Peshock
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, Dallas.
authors.forename: Roderick W
authors.initials: RW
authors.lastname: McColl
authors.affiliation: Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas3Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.
authors.forename: Christine K
authors.initials: CK
authors.lastname: Garcia
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000473:pathology; D000679:Amygdala / Q000473:pathology; D001921:Brain / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D015331:Cohort Studies; D004027:Diencephalon / Q000473:pathology; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D066128:Gray Matter / Q000473:pathology; D006179:Gyrus Cinguli / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007962:Leukocytes / Q000648:ultrastructure*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D010296:Parietal Lobe / Q000473:pathology; D016615:Telomere / Q000235:genetics*; D013702:Temporal Lobe / Q000473:pathology; D013788:Thalamus / Q000473:pathology; D066127:White Matter / Q000473:pathology; D055815:Young Adult
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