The relationship of parental longevity with the aging brain—results from UK Biobank

Abstract

A few studies report that parental longevity is associated with preserved cognition and physical function and lower risk of Alzheimer’s disease. However, data on structural neuroimaging correlates of parental longevity and its spatial distribution are limited. This study aims to examine relationships of parental longevity with regional brain structure and to explore sex differences. We identified 12,970 UK Biobank participants (mean age = 64.4, 51.5%women) with data on parental longevity, regional gray matter volumes, and white matter microstructure. Participants were categorized based on whether at least one parent lived to age 85 or older or neither parent survived to age 85. Associations of parental longevity, maternal, and paternal longevity with each neuroimaging marker of interest were examined using linear regression, adjusted for demographics, APOE e4 status, lifestyle, and cardiometabolic conditions. Compared to participants whose both parents died before 85 (43%), those with at least one parent surviving to 85 (57%) had greater volumes in hippocampus, parahippocampal gyrus, middle temporal lobe, and primary sensorimotor cortex and had lower mean diffusivity in posterior thalamic radiation and uncinate fasciculus. Associations were prominent with maternal longevity. Adjustment for cardiometabolic conditions did not affect observed associations except mean diffusivity in posterior thalamic radiation. There were no structural differences in other areas. Parental longevity is associated with preserved brain structure localized in primary sensorimotor cortex and temporal areas including hippocampus. These relationships are prominent with maternal longevity. Longitudinal studies are needed to determine whether changes in these brain structures account for the association between parental longevity and dementia.

This is a preview of subscription content, access via your institution.

Code availability

Upon request.

Data availability

Upon request.

References

  1. Adams ER, Nolan VG, Andersen SL, Perls TT, Terry DF. Centenarian offspring: start healthier and stay healthier. J Am Geriatr Soc. 2008;56(11):2089–92.

    PubMed  PubMed Central  Article  Google Scholar 

  2. Alber J, et al. White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID): knowledge gaps and opportunities. Alzheimers Dement (N Y). 2019;5:107–17.

    Article  Google Scholar 

  3. Alexander AL, Lee JE, Lazar M, Field AS. Diffusion tensor imaging of the brain. Neurotherapeutics. 2007;4(3):316–29.

    PubMed  PubMed Central  Article  Google Scholar 

  4. Alfaro-Almagro F, Jenkinson M, Bangerter NK, Andersson JLR, Griffanti L, Douaud G, et al. Image processing and quality control for the first 10,000 brain imaging datasets from UK Biobank. Neuroimage. 2018;166:400–24.

    PubMed  PubMed Central  Article  Google Scholar 

  5. Altmann-Schneider I, de Craen AJM, Slagboom PE, Westendorp RGJ, van Buchem MA, Maier AB, et al. Brain tissue volumes in familial longevity: the Leiden longevity study. Aging Cell. 2012;11(6):933–9.

    CAS  PubMed  Article  Google Scholar 

  6. Alves GS, Sudo FK, Alves CEO, Ericeira-Valente L, Moreira DM, Engelhardt E, et al. Diffusion tensor imaging studies in vascular disease: a review of the literature. Dement Neuropsychol. 2012;6(3):158–63.

    PubMed  PubMed Central  Article  Google Scholar 

  7. Andersen SL, et al. Reduced prevalence and incidence of cognitive impairment among centenarian offspring. J Gerontol A Biol Sci Med Sci. 2018.

  8. Atkins JL, Pilling LC, Ble A, Dutta A, Harries LW, Murray A, et al. Longer-lived parents and cardiovascular outcomes: 8-year follow-up in 186,000 U.K. Biobank participants. J Am Coll Cardiol. 2016;68(8):874–5.

    PubMed  Article  Google Scholar 

  9. Ayers E, Barzilai N, Crandall JP, Milman S, Verghese J. Association of exceptional parental longevity and physical function in aging. Age (Dordr). 2014;36(4):9677.

    Article  Google Scholar 

  10. Ayers E, Barzilai N, Crandall JP, Milman S, Verghese J. Association of family history of exceptional longevity with decline in physical function in aging. J Gerontol A Biol Sci Med Sci. 2017;72(12):1649–55.

    PubMed  PubMed Central  Article  Google Scholar 

  11. Barzilai N, Gabriely I, Gabriely M, Iankowitz N, Sorkin JD. Offspring of centenarians have a favorable lipid profile. J Am Geriatr Soc. 2001;49(1):76–9.

    CAS  PubMed  Article  Google Scholar 

  12. Basser PJ, Mattiello J, LeBihan D. MR diffusion tensor spectroscopy and imaging. Biophys J. 1994;66(1):259–67.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  13. Bigarella RL, Schumacher-Schuh AF, da Silva E, Chaves MLF. Sex differential effect of parental longevity on the risk of dementia. J Am Geriatr Soc. 2014;62(2):393–5.

    PubMed  Article  Google Scholar 

  14. Bucci L, Ostan R, Cevenini E, Pini E, Scurti M, Vitale G, et al. Centenarians’ offspring as a model of healthy aging: a reappraisal of the data on Italian subjects and a comprehensive overview. Aging (Albany NY). 2016;8(3):510–9.

    Article  Google Scholar 

  15. Craig CL, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003;35(8):1381–95.

    Article  Google Scholar 

  16. Dutta A, Henley W, Robine JM, Llewellyn D, Langa KM, Wallace RB, et al. Aging children of long-lived parents experience slower cognitive decline. Alzheimers Dement. 2014;10(5 Suppl):S315–22.

    PubMed  Article  Google Scholar 

  17. Fry A, Littlejohns TJ, Sudlow C, Doherty N, Adamska L, Sprosen T, et al. Comparison of sociodemographic and health-related characteristics of UK Biobank participants with those of the general population. Am J Epidemiol. 2017;186(9):1026–34.

    PubMed  PubMed Central  Article  Google Scholar 

  18. George K, Das JM. Neuroanatomy, thalamocortical radiations. Treasure Island: StatPearls; 2020.

    Google Scholar 

  19. Gubbi S, Schwartz E, Crandall J, Verghese J, Holtzer R, Atzmon G, et al. Effect of exceptional parental longevity and lifestyle factors on prevalence of cardiovascular disease in offspring. Am J Cardiol. 2017;120(12):2170–5.

    PubMed  PubMed Central  Article  Google Scholar 

  20. He YH, et al. Familial longevity study reveals a significant association of mitochondrial DNA copy number between centenarians and their offspring. Neurobiol Aging. 2016;47:218 e11–8.

    Article  Google Scholar 

  21. Hoogenboom WS, Marder TJ, Flores VL, Huisman S, Eaton HP, Schneiderman JS, et al. Cerebral white matter integrity and resting-state functional connectivity in middle-aged patients with type 2 diabetes. Diabetes. 2014;63(2):728–38.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  22. Hsu JL, Chen YL, Leu JG, Jaw FS, Lee CH, Tsai YF, et al. Microstructural white matter abnormalities in type 2 diabetes mellitus: a diffusion tensor imaging study. Neuroimage. 2012;59(2):1098–105.

    PubMed  Article  Google Scholar 

  23. Ikeda A, et al. Parental longevity and mortality amongst Japanese men and women: the JACC study. J Intern Med. 2006;259(3):285–95.

    CAS  PubMed  Article  Google Scholar 

  24. Lipton RB, Hirsch J, Katz MJ, Wang C, Sanders AE, Verghese J, et al. Exceptional parental longevity associated with lower risk of Alzheimer’s disease and memory decline. J Am Geriatr Soc. 2010;58(6):1043–9.

    PubMed  PubMed Central  Article  Google Scholar 

  25. Murabito JM, Beiser AS, DeCarli C, Seshadri S, Wolf PA, Au R. Parental longevity is associated with cognition and brain ageing in middle-aged offspring. Age Ageing. 2014;43(3):358–63.

    PubMed  Article  Google Scholar 

  26. Papageorgiou I, Astrakas LG, Xydis V, Alexiou GA, Bargiotas P, Tzarouchi L, et al. Abnormalities of brain neural circuits related to obesity: a diffusion tensor imaging study. Magn Reson Imaging. 2017;37:116–21.

    PubMed  Article  Google Scholar 

  27. Pierpaoli C, Basser PJ. Toward a quantitative assessment of diffusion anisotropy. Magn Reson Med. 1996;36(6):893–906.

    CAS  PubMed  Article  Google Scholar 

  28. Pilling LC, Kuo CL, Sicinski K, Tamosauskaite J, Kuchel GA, Harries LW, et al. Human longevity: 25 genetic loci associated in 389,166 UK biobank participants. Aging (Albany NY). 2017;9(12):2504–20.

    CAS  Article  Google Scholar 

  29. Reijmer YD, Brundel M, de Bresser J, Kappelle LJ, Leemans A, Biessels GJ, et al. Microstructural white matter abnormalities and cognitive functioning in type 2 diabetes: a diffusion tensor imaging study. Diabetes Care. 2013;36(1):137–44.

    PubMed  Article  Google Scholar 

  30. Shadyab AH, Manson JAE, Li W, Gass M, Brunner RL, Naughton MJ, et al. Parental longevity predicts healthy ageing among women. Age Ageing. 2018;47(6):853–60.

    PubMed  PubMed Central  Article  Google Scholar 

  31. Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J, et al. UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 2015;12(3):e1001779.

    PubMed  PubMed Central  Article  Google Scholar 

  32. Terry DF, Evans JC, Pencina MJ, Murabito JM, Vasan RS, Wolf PA, et al. Characteristics of Framingham offspring participants with long-lived parents. Arch Intern Med. 2007;167(5):438–44.

    PubMed  Article  Google Scholar 

  33. Timmers PR, Mounier N, Lall K, Fischer K, Ning Z, Feng X, et al. Genomics of 1 million parent lifespans implicates novel pathways and common diseases and distinguishes survival chances. Elife. 2019;8.

  34. Williams OA, An Y, Beason-Held L, Huo Y, Ferrucci L, Landman BA, et al. Vascular burden and APOE epsilon4 are associated with white matter microstructural decline in cognitively normal older adults. Neuroimage. 2019;188:572–83.

    CAS  PubMed  Article  Google Scholar 

  35. Yarnell J, Yu S, Patterson C, Cambien F, Arveiler D, Amouyel P, et al. Family history, longevity, and risk of coronary heart disease: the PRIME study. Int J Epidemiol. 2003;32(1):71–7.

    PubMed  Article  Google Scholar 

Download references

Acknowledgment

The present study was conducted under the UK Biobank application number 14631.

Funding

This research was supported by the Intramural Research Program of the National Institute on Aging. 

Author information

Affiliations

Authors

Corresponding author

Correspondence to Qu Tian.

Ethics declarations

The UK Biobank study protocol was approved by the National Research Ethics Service Committee (reference 11/NW/0382).

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations

About this article

Verify currency and authenticity via CrossMark

Cite this article

Tian, Q., Pilling, L.C., Atkins, J.L. et al. The relationship of parental longevity with the aging brain—results from UK Biobank. GeroScience 42, 1377–1385 (2020). https://doi.org/10.1007/s11357-020-00227-8

Download citation

Keywords

  • Parental longevity
  • Neuroimaging
  • MRI
  • DTI
  • Brain structure
  • Aging