Older biological age linked to increased dementia risk

Key takeaways:

• Those who developed dementia tended to be male, alcohol/tobacco users and APOE e4 positive.
• Gray matter volume, cortical size and thickness mediated links between biological age and dementia.

Among a large cohort of older dementia-free adults, older biological age was linked to an increased risk for dementia with brain structures impacting these associations, according to research published in Neurology.

“The study bridges the disconnect between fundamental aging biology and dementia prevention among middle-aged and elderly populations by establishing biological age metrics as actionable targets,” Zengli Yu, PhD, professor and director of the School of Public Health at Zhengzhou University, China, told Healio. “Moreover, it delves into the fundamental neurobiological processes that potentially underlie this association.”

As prior research is limited regarding the links between and the mechanisms that guide biological aging and dementia, Yu and colleagues sought to investigate these relationships through a prospective longitudinal study.

The researchers searched the U.K. Biobank between 2006 and 2010 to yield records of more than 280,000 dementia-free adults (mean age, 56.8 years; 54.6% women), for whom biological aging was evaluated from clinical traits via the Klemera-Doubal method biological age (KDM-BA) and PhenoAge algorithms.

Assessments for dementia were made by analyzing patient records and primary care data, then followed up from a battery of baseline examinations until onset of dementia, death, end of the study period or loss to attrition, whichever came first.

Genetic risk of dementia was assessed using the apolipoprotein E (APOE) e4 genotype and polygenic risk scores from two datasets, one of which comprised 488,000 individuals in the U.K. Biobank.

Structural MRI data for all participants were analyzed to determine potential roles of certain brain structures (gray matter volume [GMV], cortical mean thickness and surface area), as links between biological age and dementia were evaluated via mediation analysis.

Over a median follow-up of roughly 14 years, 4,770 cases of dementia were recorded, with an average chronological age at baseline of 65 years. Conversely, according to a release related to the study, those who remained dementia-free had an average baseline chronological age of 57 years. One algorithm placed the average biological age of those with dementia as 55 years compared with 45 for those without.

Those who developed dementia during follow up tended to be older and male, used alcohol and/or tobacco and were APOE e4 positive.

The researchers also reported that each standard deviation increase in KDM-BA and PhenoAge accelerations was associated with a 14% (HR = 1.14; 95% CI: 1.10–1.18) and 15% (HR = 1.15; 95% CI: 1.12–1.19) higher incidence of dementia, respectively.

Yu and colleagues also reported that APOE e4 carriers and those with the highest PhenoAge accelerations had the highest risk for dementia (HR = 4.20, 95% CI: 3.69–4.78) compared with those with non-APOE e4 and lowest PhenoAge accelerations.

Finally, GMV, cortical mean thickness and cortical surface were partial mediators for the association between biological age accelerations and dementia, in the range of 6.64% to 17.98%.

“The findings of this study have the potential to enhance public awareness of the health risks linked to advanced biological aging,” Yu told Healio. “It offers clinically actionable evidence that decelerating biological aging processes could substantially reduce dementia incidence, offering a novel preventive strategy complementary to existing cognitive-focused interventions.

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For more information:

Zengli Yu, PhD, can be reached at zly@zzu.edu.cn.