Brain white matter in superagers is more resistant to aging and cognitive impairment

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

Previous studies have shown that super-aged people are able to resist typical age-related changes in the brain's gray matter. In a new study published in The Journal of Neuroscience, scientists analyzed the white matter of super-aged people over five years, comparing them to typical older adults.

Although there were no significant differences in the overall health of their white matter, superagers had better microstructure in some white matter fibers, particularly in the frontal region. This finding suggests that they may be able to resist the cognitive decline typically associated with aging.

Comparing the Brains of Super-Agers and Typical Older People

The study included 64 super-aged and 55 typical older adults from the Vallecas Project cohort, a long-term study of 1,213 Caucasian adults in Madrid, Spain. The researchers collected MRI data to assess the brain's white matter and microstructure, with a focus on white matter volume, lesion volume, and quantification of white matter hyperintensities using the Fazekas scale.

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

Superadders experience slower white matter decline

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

First author of the study, Marta Garo, PhD, a neurobiologist in the Laboratory of Clinical Neuroscience, Center for Biomedical Technology, Polytechnic University of Madrid, Spain, explained the key findings.

Garo said "the study showed better preservation of white matter microstructure over time in superagers compared to a control group of older adults with normal memory for their age."

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

"The superager paradigm shows how an older person can age naturally with excellent memory. This is important when we try to combat pathological memory decline, because studying the brains of superagers will help us understand which brain structures are important for good memory as we age. Identifying these structures could potentially help develop brain stimulation techniques," Garo said.

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 the study, commented: “This is a significant study that complements the authors’ previous research on the importance of gray matter changes in brain health and superaging.”

"It provides detailed insight into the mechanisms by which the brain is protected from age-related memory loss and ultimately the development of dementia, revealing, among other factors, the important role of vascular health in a different aging process than previously described," explained Psychogios.

Dr Ben Raine, a neuroscientist and science communicator who was also not involved in the study, said: "This is interesting and useful research," not least because "there is huge 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 super-agers, we examined what lifestyle and medical factors differentiate super-agers 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 can't say that controlling for all of these factors will help you become a superager, as we can't draw any causal conclusions from this study."

"However, these results suggest that good mental and physical health, as well as having hobbies, may contribute to healthy aging," she added.

Raine agreed, listing several recommendations 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 maintains brain function. If you lie in bed for weeks, your leg muscles will atrophy from lack of use. The brain is similar, especially as you get older. There is a saying in neuroscience: ‘use it or lose it.’” — Ben Raine, MD

“Engaging in cognitive activities and challenges — like reading, puzzles, hobbies — trains pathways in your brain that might otherwise be vulnerable to atrophy,” he explained. “When those pathways are trained, the brain is more likely to preserve them… and that’s where we can see a direct connection to the study.”

"Those who use their brains more, 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 super-agers (genetics, lifestyle, etc.), but the brain is like a muscle: the more you use it, the stronger it will be and the more resistant it will be to atrophy."