Wednesday, November 8, 2023

Clinical biomarker-based biological ageing and future risk of neurological disorders in the UK Biobank

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  1. Jonathan K L Mak1,
  2. Christopher E McMurran1,2,
  3. Sara Hägg1
  1. Correspondence to Jonathan K L Mak, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 171 77, Sweden; jonathan.mak@ki.se

Abstract

Background: Many common neurological disorders are associated with advancing chronological age, but their association with biological age (BA) remains poorly understood.

Methods: We studied 325 870 participants in the UK Biobank without a diagnosed neurological condition at baseline and generated three previously-described measures of BA based on 18 routinely measured clinical biomarkers (PhenoAge, Klemera-Doubal method age (KDMAge), homeostatic dysregulation age). Using survival models, we assessed the effect of advanced BA on incident neurological diagnoses, including all-cause and cause-specific dementia, ischaemic stroke, Parkinson’s disease and motor neuron disease.

Results: During a mean follow-up of 9.0 years, there were 1397 incident cases of dementia and 2515 of ischaemic stroke, with smaller case numbers of other diagnoses. The strongest associations with a 1 SD in BA residual were seen for all-cause dementia (KDMAge HR=1.19, 95% CI=1.11 to 1.26), vascular dementia (1.41, 1.25 to 1.60) and ischaemic stroke (1.39, 1.34 to 1.46). Weaker associations were seen for Alzheimer’s disease and motor neuron disease, while, in contrast, HRs for Parkinson’s disease tended to be <1. Results were largely consistent after adjustment for disease-specific covariates including common cardiometabolic risk factors.

Conclusions: Advanced BA calculated from routine clinical biomarker results increases the risk of subsequent neurological diagnoses including all-cause dementia and ischaemic stroke.

https://creativecommons.org/licenses/by/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

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