Biomarkers at midlife may predict cognitive decline

By Staff 9 Min Read

  • Researchers report that cognitive functioning in midlife might provide insights to brain health later in life.
  • They say that staying physically healthy by adopting lifestyle habits such as not smoking, exercising regularly, eating properly, and participating in social activities can improve brain health.
  • They note that keeping the cardiorespiratory system healthy is essential to brain health.

Cognitive function and health in midlife – ages 40 to 65 – might provide clues to brain health later in life, according to a review published today in the journal Trends in Neuroscience.

In their findings, researchers suggest that midlife is understudied and that more research should focus on this period in people’s lives.

During midlife, the brain undergoes significant molecular, cellular, and structural changes associated with cognitive decline, processes that accelerate during midlife.

Researchers say these individual changes could explain why cognitive aging varies from person to person.

During midlife, there can also be changes in the volume of structures within the brain. For example, the hippocampus, which is responsible for memory and learning, could shrink, altering those abilities.

“Two robust findings concerning the ‘middle-aging’ brain is the accelerating shrinkage of the hippocampus (a brain area critical for memory) and reduction in the volume of white matter (the connections between brain cells and brain areas), Yvonne Nolan, a professor of anatomy and neuroscience at the University of College Cork in Ireland and an author of the study, and Sebastian Dohm-Hanse, a PhD student at the university and an author of the study, told Medical News Today in a joint statement.

Experts say that exploring changes in brain health in midlife and screening for risks of future cognitive decline could allow for earlier detection and treatment of diseases such as dementia.

Earlier treatment could also be more effective and give rise to additional approaches and treatment options.

“As the global population continues to age, there is a greater emphasis on optimization and primary prevention of brain health in the fields of geroscience and longevity,” said Dr. Mike Gorenchtein, a geriatrician at Northwell Lenox Hill Hospital in New York who was not involved in the study.

“A better understanding of these neurophysiologic pathways can potentially enhance screening and diagnosis of the initial stages of cognitive decline (before development of dementia), expand our knowledge of lifestyle interventions to optimize brain health, and pave the way for novel therapeutics for dementia,” Gorenchtein told Medical News Today.

Lifestyle factors, such as tobacco smoking, alcohol consumption, and diet, have been associated with brain aging.

Evidence suggests that changes in other parts of the body could predict brain health and function.

For example, the review notes that during midlife, changes in gait, reaction time, memory, white matter integrity, and neuroinflammation can accelerate. Experts say all of these could be tied to cognitive function in later years.

“This research is refreshing and empowers providers and their patients to take charge of brain health earlier rather than later,” said Shannel Kassis Elhelou, PsyD, a geropsychology and neuropsychology fellow at Pacific Neuroscience Institute’s Brain Wellness and Lifestyle Programs in California who was not involved in the study.

“Research on brain health in midlife is invaluable because it sheds light on critical factors influencing cognitive function and overall well-being during this pivotal stage of life,” Elhelou told Medical News Today. “Continued research in this area can lead to the development of targeted interventions and public health initiatives aimed at promoting optimal brain health.”

“Brain health in midlife can provide valuable insights to brain health later in life,” Elhelou added. “There is a growing body of research linking lifestyle choices and overall health to cognitive functioning in late life. Lifestyle habits developed during midlife, such as maintaining a healthy diet, exercise, sleep, stress management, and engaging in cognitively stimulating activities, can have long-term effects on brain health. Additional research has found factors associated with learning, such as higher levels of educational attainment and more complex occupations with a lower risk for cognitive decline.”

Exercise could aid in healthy cognitive aging, according to experts.

“Physical exercise during middle age has been found to slow the shrinking of the hippocampus and improve white matter connections,” Nolan and Dohm-Hanse shared with Medical News Today. “Running exercise, in particular, is beneficial for brain plasticity, especially as seen in animal studies. For instance, it is well known to increase the production of new brain cells in the hippocampus, which is critical for proper memory function. Improvements in memory have been found in both animals and humans following prolonged aerobic exercise.”

However, the researchers think that further research is still needed.

“Large meta-analyses of human exercise interventions, at least in the adult lifespan, have found mixed results concerning effects on cognitive function,” they said. “However, this could be because exercise intervention studies tend to be conducted very differently, so finding an average health-promoting effect among all studies is difficult, especially considering the changes that occur in brain structure and function throughout the lifespan.”

The relationship between exercise and cognitive health isn’t clear-cut.

For example, the researchers mention that a 2023 review of 24 meta-analyses found the effect of exercise on cognition was inconclusive and there was possible publication bias.

However, Nolan and Dohm-Hanse noted that “a physically active lifestyle should be promoted as it is known to have many beneficial effects throughout the body.”

“Future research with standardized designs will likely come to support that it is as good for the brain and mind as for the rest of the body,” they added.

“It is without doubt that midlife offers the opportunity for true proactive primary prevention, although there is no universally accepted biomarker to stratify the risk of dementia in fully cognitively intact middle-aged individuals,” Elhelou says. “Midlife brain health can indeed, along with other important physiologic parameters, provide clues on projected cognitive health and overall health span, with many of these metrics still modifiable with lifestyle and (if indicated) treatment.”

The study authors note that the biological aging of organs in the body influences other organs’ aging. For example, the aging of the heart and lungs can affect the brain’s aging rate.

“If the cardiorespiratory system is in poor shape, it is likely that this will be detrimental to the brain – aging it faster, according to Nolan and Dohm-Hanse. “The health of the brain is intimately coupled to the health of the rest of the body, especially via the systemic circulation, so maintaining healthy blood pressure through physical activity, limiting alcohol intake and a healthy diet rich in fiber, omega-3 fatty acids and phytochemicals is important for healthy brain aging.”

“There is also some evidence to suggest that staying cognitively and socially active during the transition from middle to older age is beneficial for healthy brain aging,” they continued. “People who self-report spending a lot of time with friends and family and engaging in physical and mental activity tend to experience better mental and cognitive health. There is also evidence to suggest that a sense of purpose in life, such as deriving meaning from activities like work, volunteering, spiritual engagement, or creative activities, is linked with positive brain health outcomes.”

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