People with an older biological age than their chronological age may be more at risk for dementia. (© svetazi - stock.adobe.com)
In a nutshell
- People whose biological age exceeds their chronological age face up to 35% higher risk of developing dementia, independent of other known risk factors.
- Accelerated biological aging is associated with widespread reductions in brain structure, such as decreased gray matter volume and cortical thickness, which may contribute to increased dementia risk.
- Genetic factors, particularly the APOE ε4 gene, interact with biological aging to further elevate dementia risk, while lifestyle factors may help slow down biological aging, potentially reducing dementia risk.
ZHENGZHOU, China — Growing old is inevitable, but some people age faster than others on a biological level. Researchers from China say that accelerated biological aging might significantly increase your risk of developing dementia.
Researchers found that people whose bodies were aging faster than their chronological age had up to 35% higher risk of developing dementia, independent of other known risk factors. This biological aging process appears to work by causing widespread changes in brain structure, potentially opening new pathways for early intervention.
The research, published in Neurology, followed nearly 281,000 UK residents for over 13 years, making it one of the largest studies on the relationship between biological aging and dementia risk.
What Is Biological Age and Why Does It Matter?
Unlike your chronological age, the number of candles on your birthday cake, biological age reflects how quickly your body is actually aging at a cellular and systemic level. Scientists can calculate this by looking at biomarkers in your blood and other clinical measurements.
For this research, scientists used two different biological age calculations. The first method, called KDM-BA, combines measurements including lung function, blood pressure, cholesterol, kidney function, and inflammation markers. The second, called PhenoAge, uses nine blood chemistry values including glucose levels, immune cell counts, and inflammation markers.
When your biological age exceeds your chronological age, scientists call this “accelerated aging.” About 16% of participants showed accelerated aging using the KDM-BA method, while 32% showed acceleration with the PhenoAge calculation.
How Accelerated Aging Impacts Dementia Risk
During the study period, 4,770 participants developed dementia. When researchers compared the lowest and highest quartiles of biological aging, they found those with the most accelerated aging had a significantly higher dementia risk.
For every increase in the rate of biological aging, dementia risk went up by 14% for those measured with KDM-BA and 15% for those measured with PhenoAge.
The researchers performed brain MRIs on a subset of participants and discovered that accelerated biological aging was associated with widespread reductions in brain structure.
People with advanced biological age showed decreased gray matter volume across numerous brain regions, reduced cortical thickness, and smaller surface areas. Statistical analysis revealed these brain changes explained between 6.6% and 18% of the relationship between biological aging and dementia.
Genes, Demographics, and Combined Risk Factors
The study also examined how genetic risk factors interact with biological aging. Carriers of the APOE ε4 gene variant, the strongest known genetic risk factor for dementia, who also had the highest PhenoAge acceleration had more than four times the dementia risk compared to non-carriers with the lowest biological age acceleration.
The negative effects of KDM-BA accelerations were more pronounced in people under age 65, while PhenoAge acceleration seemed to have a stronger impact on those over 65 and individuals with higher body mass index.
Slowing down biological aging could potentially help prevent dementia. While no proven methods exist to reverse biological aging completely, previous research indicates that lifestyle factors like diet, exercise, stress management, and adequate sleep may influence the rate of biological aging.
Many age-related diseases share common underlying risk factors. By targeting these fundamental aging processes, scientists might potentially address multiple conditions simultaneously.
This research could change how we view dementia risk. Rather than focusing solely on chronological age as an inevitable risk factor, more research on how to slow down biological aging could eventually lead to new interventions and prevention strategies for dementia.
Paper Summary
Methodology
The researchers used data from the UK Biobank, a massive prospective longitudinal study of over 500,000 adults aged 37-73 years recruited between 2006 and 2010. After excluding participants with missing data or pre-existing dementia, they analyzed 280,918 participants over a median follow-up of 13.58 years. Biological age was calculated using two separate algorithms: the Klemera-Doubal method (KDM-BA) based on 9 clinical parameters including lung function and blood chemistry, and the PhenoAge algorithm based on 9 blood biomarkers. Brain structure was assessed using MRI scans measuring gray matter volume, cortical thickness, and surface area. Dementia cases were identified through hospital records and primary care data using ICD-10 codes.
Results
During follow-up, 4,770 participants developed dementia. Each standard deviation increase in KDM-BA and PhenoAge biological age acceleration was associated with 14% and 15% higher dementia risk, respectively. Participants in the highest quartile of KDM-BA acceleration had 35% increased dementia risk compared to the lowest quartile. For PhenoAge, the highest quartile had 32% increased risk. Carriers of the APOE ε4 gene with the highest PhenoAge acceleration had 4.2 times higher dementia risk compared to non-carriers with the lowest biological age acceleration. Brain imaging analyses showed accelerated biological aging was associated with widespread reductions in brain structure, and these changes mediated 6.64-17.98% of the relationship between biological age acceleration and dementia.
Limitations
The researchers acknowledge several limitations. First, they used the date of dementia diagnosis rather than initial onset, which means participants might have been in a prodromal stage at baseline. Second, UK Biobank participants tend to be more health-conscious than the general population, potentially underestimating dementia prevalence. Third, the study population consisted primarily of middle-aged and older White British individuals, limiting generalizability to other ethnicities and age groups. Finally, they lacked measurements at multiple time points, making it difficult to assess the impact of changes in biological aging over time.
Funding/Disclosures
The study was supported by Major Projects of Collaborative Innovation of Zhengzhou, Special Major Public Welfare Project of Henan Province, and Key Project of Science and Technology of Henan Province. The authors reported no relevant disclosures or conflicts of interest.
Publication Information
The study titled “Associations of Accelerated Biological Aging With Dementia and the Mediation Role of Brain Structure: Findings From a Longitudinal Study” was published in Neurology (Volume 104, Number 10) on May 27, 2025. The lead authors were Yacong Bo and Liuqiao Sun from Zhengzhou University, China, with corresponding authors Xin Zhao, Zengli Yu, and Zhengbin Wang.
