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Bioenergetic Age Could Predict Alzheimer’s Disease Risk

by Ella

A person’s “bioenergetic age”—a measure of how efficiently their cells generate energy—could be a critical predictor of Alzheimer’s disease risk, according to new research from Weill Cornell Medicine. Published on February 24 in Nature Communications, the study offers promising evidence that maintaining a youthful bioenergetic age could help reduce the likelihood of developing Alzheimer’s, potentially as effectively as current drugs like lecanemab.

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Dr. Jan Krumsiek, senior author of the study and an associate professor at Weill Cornell Medicine, emphasizes the significance of these findings, stating, “That’s quite big because it means some people can lower their risk without the uncertain side effects of current treatments.” The first author of the study, Dr. Matthias Arnold, is the head of the computational neurobiology team at Helmholtz Munich.

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The research addresses a longstanding question in Alzheimer’s research: why do some people show early signs of Alzheimer’s disease, such as issues with brain cell energy production, while others seem unaffected despite similar biological abnormalities? Dr. Krumsiek’s team believes there is a “bioenergetic capacity” that helps protect some individuals by maintaining energy levels in the brain, allowing them to age without experiencing the cognitive decline typical of Alzheimer’s.

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Understanding the Bioenergetic Clock

To explore the link between bioenergetic capacity and Alzheimer’s risk, the researchers turned to acylcarnitines, molecules related to fat and protein metabolism. Acylcarnitines are known to decline as cognitive function worsens, which led the researchers to hypothesize that measuring these molecules could provide insight into an individual’s Alzheimer’s risk.

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Using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a large-scale study aimed at identifying risk factors for Alzheimer’s, Dr. Krumsiek and his colleagues developed a “bioenergetic clock.” This clock compares the bioenergetic age, based on acylcarnitine levels, to a person’s chronological age. The findings revealed that individuals with higher acylcarnitine levels also exhibited more severe Alzheimer’s pathology, cognitive decline, and brain atrophy. These individuals, in turn, had a bioenergetic age that was older than their chronological age.

Bioenergetic Age and Cognitive Decline

The researchers further evaluated cognitive decline using the Mini-Mental State Examination (MMSE), a test commonly used to assess cognitive function. Their findings showed that individuals with lower acylcarnitine levels experienced slower cognitive decline—losing, on average, 0.5 fewer points per year on the MMSE compared to those with higher acylcarnitine levels. Remarkably, this difference in cognitive decline was comparable to the effects seen with the Alzheimer’s drug lecanemab.

The researchers suggest that maintaining lower acylcarnitine levels, and thus a younger bioenergetic age, could be a key strategy for delaying Alzheimer’s onset. The study further highlights the potential of lifestyle interventions—such as adopting a plant-based diet and regular exercise—to help individuals manage acylcarnitine levels and reduce their bioenergetic age.

Lifestyle Interventions and Genetic Background

In addition to identifying the bioenergetic clock, the research team discovered that approximately 30% of participants in the ADNI cohort had an older bioenergetic age despite possessing a favorable genetic background. This subgroup may benefit particularly from early lifestyle interventions aimed at lowering bioenergetic age and potentially delaying or preventing Alzheimer’s onset.

Dr. Krumsiek plans to explore which specific lifestyle changes are most effective at slowing the bioenergetic clock. For example, dietary modifications, such as reducing carbohydrate intake, may help improve metabolic health, though further research is needed to determine the optimal level of carbohydrate restriction.

A Promising Tool for Early Detection

The study also underscores the potential for inexpensive, rapid blood tests to measure acylcarnitine levels, which could provide a valuable tool for identifying individuals at risk of Alzheimer’s. These tests, originally developed to diagnose metabolic and mitochondrial disorders in newborns, could be repurposed for use in older adults, allowing for earlier and more personalized treatment interventions.

“If we can repurpose this technology for older adults,” Dr. Krumsiek said, “that could provide a way to start personalized treatment earlier, helping to slow the disease progression before cognitive symptoms appear.”

Conclusion

The study suggests that bioenergetic age—how efficiently an individual’s cells produce energy—could be a valuable tool for predicting Alzheimer’s disease risk. By monitoring acylcarnitine levels, it may be possible to identify individuals at risk and implement personalized interventions to reduce their bioenergetic age, thus potentially delaying or preventing the onset of Alzheimer’s. This research offers new hope for combating Alzheimer’s disease, moving beyond pharmaceuticals to include lifestyle changes as part of a comprehensive approach to disease prevention.

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