New research from Weill Cornell Medicine suggests that a person’s “bioenergetic age” – a measure of how efficiently their cells generate energy – could play a significant role in predicting Alzheimer’s disease risk. Published on February 24 in Nature Communications, the study indicates that adopting a healthy lifestyle could reverse the bioenergetic clock, helping to prevent or delay Alzheimer’s in ways comparable to new treatments like lecanemab.
“What’s significant here is that some individuals can reduce their Alzheimer’s risk without facing the uncertain side effects of current treatments,” said Dr. Jan Krumsiek, senior author of the study and an associate professor at Weill Cornell Medicine. The study’s first author, Dr. Matthias Arnold, heads the computational neurobiology team at Helmholtz Munich.
One of the earliest signs of Alzheimer’s is the brain’s inability to efficiently metabolize glucose, a key energy source. However, some people remain asymptomatic for years despite this energy dysfunction. This delay suggests the existence of a “bioenergetic capacity,” allowing these individuals to maintain higher energy levels, thus protecting their cognitive function longer.
Dr. Krumsiek explains that those with this protective bioenergetic capacity can often remain unusually healthy into old age, without the cognitive declines that typically accompany aging.
Unlocking the Bioenergetic Clock
To understand how bioenergetic age affects Alzheimer’s, the researchers focused on acylcarnitines—molecules linked to cognition and the metabolism of fats and proteins. By examining data from the Alzheimer’s Disease Neuroimaging Initiative, the team found that acylcarnitine levels in the blood could predict who was at risk for Alzheimer’s. Higher levels were associated with more severe disease progression, cognitive decline, and brain atrophy, while lower levels indicated slower cognitive decline.
Participants with lower acylcarnitine levels experienced a cognitive decline of about 0.5 points less per year on the mini-mental state examination, a common Alzheimer’s test. This difference in decline was comparable to the effects of lecanemab, a drug currently in use for treating Alzheimer’s.
Genetics and Lifestyle Interventions
While genetic factors largely determine the rate at which the bioenergetic clock ticks forward, Dr. Krumsiek notes that lifestyle choices such as eating a plant-based diet and exercising can lower acylcarnitine levels, leading to a younger bioenergetic age.
The researchers also identified a subgroup of participants with a favorable genetic background but older bioenergetic age. These individuals could potentially benefit more from early lifestyle changes aimed at lowering their bioenergetic age, helping delay or prevent Alzheimer’s onset.
Future Directions
Dr. Krumsiek plans to investigate which lifestyle interventions are most effective at reducing bioenergetic age. One promising approach is a low-carb diet, which may support metabolic health. However, further research is needed to determine the exact amount of carbohydrate restriction necessary for optimal benefit.
In addition, the study highlights the potential of using acylcarnitine blood tests—a tool initially developed for diagnosing metabolic disorders in newborns—as a low-cost, rapid method to assess bioenergetic age in older adults. This could pave the way for early, personalized interventions to delay or prevent Alzheimer’s.
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