White matter in the brains of super-aged people is more resistant to aging and cognitive decline

As we age, the brain undergoes structural and functional changes that can lead to a decline in cognitive abilities, particularly episodic memory. These declines are often associated with neurodegenerative diseases such as Alzheimer's disease. However, a unique group of older adults known as "superagers" are immune to this trend, maintaining strong episodic memory comparable to much younger healthy individuals.

Previous research has shown that superagers are able to resist typical age-related changes in the gray matter of the brain. In a new study published in The Journal of Neuroscience, scientists analyzed the white matter of super-agers over a five-year period, comparing them with typical older adults.

Although there were no significant differences in the overall health of their white matter, superadgers had better microstructure in some white matter fibers, especially in the frontal region. This finding indicates their ability to resist the cognitive decline typically associated with aging.

Comparison of the brains of superagers and typical older people

The study included 64 superadults and 55 typical older adults from the Vallecas Project cohort, a longitudinal study of 1,213 Caucasian adults in Madrid, Spain. The researchers collected MRI data to assess brain white matter and microstructure, focusing on white matter volume, lesion volume, and quantification of white matter hyperintensity using the Fazekas scale.

Diffusion-weighted images were processed, including motion correction and calculation of a voxel-by-voxel diffusion map. Superagers initially performed better on cognitive tests, but both groups showed similar rates of cognitive decline over time, with the exception of slower decline in one particular test (animal verbal fluency) for Superagers.

Superagers experience slower white matter decline

When considering white matter status, there were no significant differences between groups in terms of total white matter volume, white matter lesions, or severity of lesions. Both groups had a high prevalence of white matter lesions with similar levels of severity. However, detailed analysis of white matter microstructure showed that superaders had higher fractional anisotropy and lower mean diffusivity in some brain regions, especially frontal regions.

The study's first author, Marta Garo, PhD, a neuroscientist from the Laboratory of Clinical Neuroscience, Center for Biomedical Technologies, Polytechnic University of Madrid, Spain, explained the key findings.

Garo said that “the study showed better preservation of white matter microstructure over time in Super Agers compared with a control group of older adults with normal memory for their age.”

“This can be interpreted to mean that superagers can avoid the normal age-related changes that occur in white matter microstructure, which is why we say in the title that superagers resist the typical age-related structural changes in white matter,” she added.

“The Superager paradigm shows how an older person can age naturally with excellent memory. This is important when we are trying to combat pathological memory decline, because studying the brains of super-agers will help us understand which brain structures are important for good memory as we age. Identification of these structures could potentially help in the development of brain stimulation methods,” Garo noted.

What contributes to cognitive decline?

Dr. Paul Psychogios, a board-certified medical geneticist and associate director of the Providence Clinical Genetics and Genomics Program in Burbank, California, who was not involved in this study, commented: “This is a significant study that complements the authors' previous research on the importance of gray matter changes for brain health and superaging."

“It provides detailed insight into how the brain protects against age-related memory loss and ultimately the development of dementia, highlighting, among other factors, the important role of vascular health in a different aging process than previously described,” Psychogios explained.

Dr Ben Raine, a neuroscientist and science communicator who was also not involved in the study, said: “This is an interesting and useful study,” not least because “there is enormous interest and utility in understanding why some people age gracefully, while others are more prone to cognitive decline."

How to maintain brain health as you age?

Garo noted that “in a previous study, using the same cohort of superagers, we examined what lifestyle and medical factors distinguished superagers from a control group of older adults with normal memory for their age.”

“We found that Super Agers had better mobility, better mental health, fewer problems with glucose levels and hypertension, and a greater interest in music,” she said.

However, Garo cautioned that “we cannot say that controlling for all of these factors will help you become a super athlete, as we cannot infer cause and effect from this study.”

“However, these results indicate that good mental and physical health, as well as having hobbies, can promote healthy aging,” she added.

Rain agreed, listing several tips for healthy aging, including:

• maintaining good sleep hygiene
• regular exercise
• social interaction
• mental exercises.

"Sleep and exercise are proven pillars of brain health, but social interaction doesn't get enough attention," Raine said. “As we age, we spend more time alone, and isolation is bad for the brain. Spending time with other people is a great way to exercise and protect your brain.”

“Mental exercise is important because it is a stimulus that supports brain function. If you lie in bed for weeks at a time, your leg muscles will atrophy from lack of use. The brain is similar, especially in old age. There is a saying in neuroscience: “use it or lose it.” — Ben Rein, MD

"Participating in cognitive activities and challenges—like reading, puzzles, hobbies—trains pathways in your brain that may otherwise be vulnerable to atrophy," he explained. "When these pathways are trained, the brain is more likely to retain them... And here we can see a direct connection to the study."

“Those who use their brains more often, especially for high-level cognitive tasks, are more likely to show greater white matter integrity. Activating certain circuits literally preserves their structure,” Raine said.

The neuroscientist concluded that “of course there are many other important influences on these superaggers (genetics, lifestyle, etc.), but the brain is like a muscle: the more you use it, the stronger it will be and the more resilient it will be.” will lead to atrophy.”