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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.
- STROKE
- MOTOR NEURON DISEASE
- PARKINSON'S DISEASE
- VASCULAR DEMENTIA
- ALZHEIMER'S DISEASE
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Footnotes
JKLM and CEM are joint first authors.
X @JonathanKLMak
Contributors CEM, JKLM and SH contributed to the conception and design of the study. JKLM contributed to data acquisition and statistical analyses. JKLM and CEM drafted the manuscript. All authors critically revised the manuscript for intellectual content.
Funding This study was supported by the Swedish Research Council (2022-01608) and by Karolinska Institutet Foundation and Strategic Research Program in Epidemiology. CEM was supported by a NIHR Academic Clinical Fellowship.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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