In a recently published study, Dr Journal of Neurology, Neurosurgery and PsychiatryResearchers examined the relationship between three clinical biomarker-based measures of biological age (BA) and the risk of age-related neurological diseases in United Kingdom Biobank (UKBB) participants.
They compared the effect of advanced biological age on time-to-event models for cause-specific and all-cause dementia, ischemic stroke, motor neuron disease (MND), and Parkinson’s disease (PD).
Study: Clinical biomarker-based biological aging and future risk of neurological disease in the UK Biobank. Image Credit: Chinnapong/Shutterstock.com
Aging increases the risk of various neurological diseases. Many common neurological diseases have been associated with chronological aging (CA; however, their relationship to biological age (BA) is unknown. Measures of biological age, such as the epigenetic clock, telomere length, and composite biomarkers, have been developed to describe age-related events. More sophisticated than CA.
Clinically relevant BA measurement methods exploit changes in levels of routinely used clinical biomarkers, with studies reporting that in cases where BA exceeds CA, increased risk of anxiety, depression, cancer, and death.
However, limited research has examined links between measures of biological age and the likelihood of neurological disease, warranting further research.
About the study
Researchers assessed the link between biological age and incidence of neurological disease among UKBB participants in a prospective cohort study.
The team studied 325,870 UKBB participants aged 37 to 73, recruited from 2006 to 2010. Participants did not suffer from neurological conditions at the start of the study.
Three previously described biological age measures based on 18 routinely assessed biomarkers [Klemera-Doubal method age (KDMAge), PhenoAge, and homeostatic dysregulation age (HDAge)] was used for analysis.
Individuals with incomplete data on biological age measurements and covariates and those with a history of dementia, ischemic stroke, MND or PD were excluded. United States National Health and Nutrition Examination Survey (US NHANES) data were combined with biomarker information to train and validate the BA measures.
At the start of the study, participants filled out questionnaires, completed functional and physical measurements, and provided biological samples.
The team assessed the effect of advanced biological age on new-onset neurological diagnoses, including cause-specific and all-cause dementia, ischemic stroke, MND and PD, using survival models.
Neurological disorders were diagnosed using International Classification of Diseases, Tenth Revision (ICD-10) codes obtained from inpatient hospitals, and mortality register records. Participants were followed until diagnosis, death, or study discontinuation, whichever occurred first.
PhenoAge and KDMAge were regressed on chronological age so that residual values could be considered as deviations between biological and chronological age. HDAz values were derived from individual physiological deviations from a disease-free reference sample and were log-transformed before evaluation due to skewed distributions.
Cox proportional-hazards regression modeling was performed to determine hazard ratios (HRs). Adjusted for year of birth, sex, body mass index (BMI), ethnicity, alcohol intake, smoking status and deprivation.
The average age of study participants was 56 years, and 54% were female. During the nine-year follow-up period (mean), 1,397 cases, 2,515 cases, 679 cases, and 203 cases of dementia, ischemic stroke, Parkinson’s disease, and motor neuron disease were reported, respectively. KDMAge (HR, 1.3), PhenoAge (HR, 1.3), and HDAge (HR, 1.2) were significantly associated with any-cause dementia risk.
All biological age measures were strongly associated with vascular dementia, while weaker links were observed for the development of Alzheimer’s disease (AD).
Similarly, the team found a significantly higher risk of ischemic stroke in measures of biological age: KDMAge (HR, 1.4), PhenoAge (HR, 1.4), and HDAge (HR, 1.3). Weakly positive associations were observed between advanced biological age and MND risk, and only HDAge showed a significant association with motor neuron disease (HR 1.2).
Similarly, non-significant associations were found between biological age and PD risk; However, in contrast to the other results, the HR values obtained for PD were below 1.0 (HR values were 0.96, 0.95, and 0.88 for KDMAge, PhenoAge, and HDAge, respectively).
Stratification by gender and age yielded similar results, although biological age was more strongly associated with dementia in younger women under 60 years of age.
Forced breathing volume was associated with lower ischemic stroke and dementia risk, whereas elevated erythrocyte count was associated with PD and dementia risk.
In sensitivity analyses, eliminating individuals diagnosed with a neurological disorder within five years of their biological age assessment generally showed smaller effect sizes but showed the same direction of effect, maintaining significant associations with vascular and all-cause dementia, ischemic stroke, and phenoage.
Overall, the study results showed that biological aging was associated with an increased risk of several age-related neurological diseases, with ischemic stroke, vascular-type dementia, and dementia of any cause having the highest effect sizes. Changes in biological age may reduce the risk of dementia and stroke.
Controlling for critical variables in disease-specific modeling (including smoking history and diabetes, hypertension, and dyslipidemia), strong associations persisted, demonstrating that these biological age indicators are relevant beyond simple cardiovascular risk estimation.