Can Biological Aging Clocks Predict Dementia Risk?
Scientists are using patterns of chemical modifications at the DNA level and predicted brain age derived from brain scans to try and predict who is at risk of dementia.
Age is one of the most important risk factors for Alzheimer’s and other dementias. But scientists aren’t sure why some people develop the disease earlier while others, despite having the protein plaques in their brain that define the disease, never develop symptoms.
Biological aging “clocks” might bridge the gap. These clocks use computational algorithms that determine biological aging by looking at the pattern of epigenetic markers – chemical modifications at the DNA level – that affect how genes are turned on or off. Other researchers developed a predicted brain age based on the size of different brain regions and other features observed under an MRI scan.
The latest studies using these predictive algorithms are testing whether they can indicate how fast someone is aging on a cellular level and are at a higher risk of neurodegenerative disease.
Circadian rest-activity rhythms and biological aging
Johns Hopkins researchers Adam Spira and Brion Maher led two recent studies investigating how circadian rest-activity rhythms — the patterns of wakefulness, physical activity, and sleep over the course of 24 hours — and whether they were linked with epigenetic age or other brain imaging outcomes. Previous research suggested that fragmented rhythms, characterized by frequent napping or repeated awakenings at night, may increase the risk of dementia.
The first study led by PhD student Chunyu Liu, published in JAMA Network Open, used a wrist-sensor to track the rest-activity rhythms of middle-aged and older adults for over seven days, and then drew their blood to measure their epigenetic markings. The patterns of these markings are input into a clock algorithm that calculates epigenetic age. There was an association between these rhythms and two of the newer epigenetic aging clock algorithms, noting that sex, race, and ethnicity also played a role.
If validated in future studies, rest-activity rhythms might be used as markers of biological aging that are easy to track. For example, wearable devices could track a person’s activity over the course of the day as well as how long they sleep each night. If the pattern is off, it might present an opportunity for an intervention that targets sleep or physical activity to restore a healthy rest-activity rhythm. More research is needed to understand whether these markers might predict future health risks as well.
The second study, led by PhD student Marc Kaiziu-Lutu and Daniel Callow, an assistant professor, published in Alzheimer’s and Dementia, found that less stable rhythms which involve fragmented sleep and physical activity, were linked to shrinkage of key brain areas in a study looking at more than 340 healthy older adults. Importantly, the study did not track whether they developed dementia.
“I think the main takeaway is that disruptions in daily rest-activity patterns may provide meaningful information about brain health in older adults, even among people who are cognitively unimpaired,” said Callow. “Importantly, this does not mean that disrupted rest-activity patterns cause brain atrophy, but it does suggest that the regularity and stability of daily activity and rest may be an important window into brain health as we age.”
Epigenetic clocks, brain shrinkage, and neurodegenerative disease
Linda McEvoy, a senior investigator at the Kaiser Permanente Washington Health Research Institute.was interested in understanding whether the epigenetic clocks matched up with the predicted brain age measured via an MRI scan. The results were published earlier this year in the journal Aging.
McEvoy and her colleagues used five different epigenetic clocks and two different MRI brain age algorithms from over 1,100 older women. “We hypothesized that epigenetic age might be related to brain age,” McEvoy told Being Patient. In other words, if you appeared older based on the chemical tags on your DNA, then you’d see a similar level of changes via brain scan. But, she said, “We did not find this to be true.”
Only one of the epigenetic clocks, called the AgeAccelGrim2clock, developed to predict risk of death, was associated with patterns of brain changes linked to Alzheimer’s. But it turned out that this link was attributed to smoking — which left a unique imprint on both the epigenetic clock and the brain.
“It suggests that the changes in the brain with age, and with early dementia, reflect biological processes that are not captured by current epigenetic clocks,” said McEvoy.
While researchers feel such aging clocks are promising, more research is needed to validate their ability to predict dementia.
FAQs
Chronological age is defined as your actual age. Biological age is calculated using an algorithm that takes into account the chemical modifications at the DNA level that determine how genes are turned on and off. Some algorithms that predict brain age use MRI scans to see if different brain regions appear younger than your actual age.
Scientists use algorithms that analyze the patterns of epigenetic markers in the DNA or sizes of different regions on an MRI brain scan to predict biological age. The hope is that these clocks could better predict who is at risk of developing dementia, but more research is needed to validate if they’re useful in clinical practice.
Yes. An abnormal circadian rest-activity rhythm, which combines measures of wakefulness, physical activity and sleep, are linked to increases in some biological aging clocks.
