Behavior Genetics

, Volume 40, Issue 2, pp 146–156 | Cite as

White Matter Integrity in the Splenium of the Corpus Callosum is Related to Successful Cognitive Aging and Partly Mediates the Protective Effect of an Ancestral Polymorphism in ADRB2

  • Lars Penke
  • Susana Muñoz Maniega
  • Lorna M. Houlihan
  • Catherine Murray
  • Alan J. Gow
  • Jonathan D. Clayden
  • Mark E. Bastin
  • Joanna M. Wardlaw
  • Ian J. Deary
Original Research


It has recently been reported that the evolutionarily ancestral alleles of two functional polymorphisms in the β2-adrenergic receptor gene (ADRB2) were related to higher cognitive ability in the 70 year old participants of the Lothian Birth Cohort 1936 (LBC1936). One emerging important factor in cognitive aging is the integrity of white matter tracts in the brain. Here, we used diffusion tensor MRI-based tractography to assess the integrity of eight white matter tracts in a subsample of the LBC1936. Higher integrity of the splenium of the corpus callosum predicted better cognitive ability in old age, even after controlling for IQ at age 11. Also, the ancestral allele of one ADRB2 SNP was associated with both splenium integrity and better cognitive aging. While the effects of the SNP and splenium integrity on cognitive aging were largely independent, there was some evidence for a partial mediation effect of ADRB2 status via splenium integrity.


Cognitive aging Diffusion tensor MRI White matter tractography Splenium corpus callosum ADRB2 Comparative genomics 



LP, SMM and CM are funded by the UK Medical Research Council. LP, AJG, and the LBC1936 data collection were supported by the Disconnected Mind project ( funded by Help the Aged and Research into Ageing. JMW is part-funded by the Scottish Funding Council as part of the SINAPSE Collaboration. We thank the study secretary Paula Davies, Janie Corley and Ross Henderson for data collection and data entry; the nurses, radiographers and other staff at the Wellcome Trust Clinical Research Facility and the SFC Brain Imaging Research Centre ( where the data were collected; and the staff at Lothian Health Board and at the SCRE Centre, University of Glasgow. The work was undertaken within The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative. Funding from the BBSRC, EPSRC, ESRC and MRC is gratefully acknowledged.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Lars Penke
    • 1
  • Susana Muñoz Maniega
    • 2
    • 3
  • Lorna M. Houlihan
    • 1
  • Catherine Murray
    • 4
  • Alan J. Gow
    • 1
  • Jonathan D. Clayden
    • 5
  • Mark E. Bastin
    • 2
    • 6
  • Joanna M. Wardlaw
    • 2
    • 3
  • Ian J. Deary
    • 1
  1. 1.Centre for Cognitive Ageing and Cognitive Epidemiology, Department of PsychologyThe University of EdinburghEdinburghUK
  2. 2.Centre for Cognitive Ageing and Cognitive EpidemiologyThe University of EdinburghEdinburghUK
  3. 3.Department of Clinical NeurosciencesThe University of EdinburghEdinburghUK
  4. 4.Department of PsychologyThe University of EdinburghEdinburghUK
  5. 5.Institute of Child HealthUniversity College LondonLondonUK
  6. 6.Department of Medical and Radiological Sciences (Medical Physics)The University of EdinburghEdinburghUK

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