title: Variation in longevity gene KLOTHO is associated with greater cortical volumes.
abstract: OBJECTIVE
  Identifying genetic variation associated with brain structures in aging may elucidate new biologic mechanisms underlying resilience to cognitive decline. We investigated whether carrying one copy of the protective haplotype "KL-VS" in longevity gene KLOTHO (KL) is associated with greater gray matter volume in healthy human aging compared to carrying no copies.
  
  
  METHODS
  We performed unbiased whole-brain analysis in cognitively normal older adults from two independent cohorts to assess the relationship between KL-VS and gray matter volume using voxel-based morphometry.
  
  
  RESULTS
  We found that KL-VS heterozygosity was associated with greater volume in right dorsolateral prefrontal cortex (rDLPFC). Because rDLPFC is important for executive function, we analyzed working memory and processing speed in individuals. KL-VS heterozygosity was associated with enhanced executive function. Larger rDLPFC volume correlated with better executive function across the lifespan examined. Statistical analysis suggested that volume partially mediates the effect of genotype on cognition.
  
  
  CONCLUSIONS
  These results suggest that variation in KL is associated with bigger brain volume and better function.
authors: Department of Neurology, University of California San Francisco San Francisco, California, 94158.
authors: Jennifer S
authors: JS
authors: Yokoyama
authors: Department of Neurology, University of California San Francisco San Francisco, California, 94158.
authors: Virginia E
authors: VE
authors: Sturm
authors: Department of Neurology, University of California San Francisco San Francisco, California, 94158.
authors: Luke W
authors: LW
authors: Bonham
authors: Department of Neurology and Semel Institute for Neuroscience and Human Behavior, The David Geffen School of Medicine at University of California Los Angeles Los Angeles, California, 90095.
authors: Eric
authors: E
authors: Klein
authors: Department of Biomedical Engineering, Illinois Institute of Technology Chicago, Illinois, 60616 ; Rush Alzheimer's Disease Center, Rush University Medical Center Chicago, Illinois, 60612.
authors: Konstantinos
authors: K
authors: Arfanakis
authors: Rush Alzheimer's Disease Center, Rush University Medical Center Chicago, Illinois, 60612.
authors: Lei
authors: L
authors: Yu
authors: Department of Neurology and Semel Institute for Neuroscience and Human Behavior, The David Geffen School of Medicine at University of California Los Angeles Los Angeles, California, 90095.
authors: Giovanni
authors: G
authors: Coppola
authors: Department of Neurology, University of California San Francisco San Francisco, California, 94158.
authors: Joel H
authors: JH
authors: Kramer
authors: Rush Alzheimer's Disease Center, Rush University Medical Center Chicago, Illinois, 60612.
authors: David A
authors: DA
authors: Bennett
authors: Department of Neurology, University of California San Francisco San Francisco, California, 94158.
authors: Bruce L
authors: BL
authors: Miller
authors: Department of Neurology, University of California San Francisco San Francisco, California, 94158.
authors: Dena B
authors: DB
authors: Dubal