Superagers' brains resist age-related decline, study finds

By Priyanjana Pramanik, MSc.Reviewed by Susha Cheriyedath, M.Sc.May 8 2024

In a recent study published in the Journal of Neuroscience, researchers examined the brain white matter of superagers, i.e., people with exceptional cognitive performance, compared to typical older adults over a period of five years.

Despite no significant differences in overall white matter health, superagers exhibited better microstructure of white matter, particularly in the frontal fibers, suggesting their resistance to age-related cognitive decline.

Study: Superagers resist typical age-related white matter structural changes. Image Credit: oneinchpunch / Shutterstock

Background

Aging is associated with structural and functional changes to the brain and declines in cognitive function. These declines, particularly in episodic memory, are often associated with neurodegenerative conditions such as Alzheimer's disease.

However, a subset of older adults, termed "superagers," maintains robust episodic memory comparable to healthy individuals decades younger, demonstrating how aging is possible without impaired episodic memory. Previous research has indicated that superagers resist age-related changes in gray matter.

Scientists have hypothesized that superagers may also demonstrate preserved white matter integrity, particularly in vulnerable anterior brain regions, challenging the conventional pattern of white matter decline associated with aging.

About the study

This study aimed to understand the neural basis of superagers' exceptional memory by examining the structural integrity of white matter in their brains, which typically deteriorates with age.

The research assessed global white matter health and microstructural properties using diffusion imaging in superagers over 80, comparing them to typical older adults.

The participants were drawn from the Vallecas Project, a longitudinal study of 1213 Caucasian adults in Madrid, Spain. All participants lived in communities, were between 70 and 85 years old, had no psychiatric or neurological conditions, were expected to live for at least four years, and did not require assistance in their daily lives.

Of the people in this cohort, superagers were defined as individuals aged 80 or older with superior episodic memory compared to their age group; specifically, their episodic memory was comparable to an individual two to three decades younger.

MRI data were collected to assess brain white matter health and microstructure. Researchers analyzed white matter volume and lesion volume, while the Fazekas scale was used to quantify white matter hyperintensities.

Diffusion-weighted images were processed, including motion correction and voxel-wise diffusion map calculation. Tract-based spatial statistics (TBSS) were employed for group comparisons of diffusion parameters.

Longitudinal analyses were conducted using linear mixed-effects models to assess changes over time. Statistical analyses incorporated covariates such as age and total intracranial volume, with appropriate corrections for multiple comparisons.

The study employed rigorous methodologies to compare white matter-related structural parameters in superagers with those in typical older adults, offering insights into the neural substrates of exceptional memory aging.

Findings

In the study, 64 superagers and a comparison group of 55 typical older adults were selected from the Vallecas Project cohort, with no significant differences in age or gender between the groups.

Superagers performed better on neuropsychological tests initially, but longitudinal assessments showed no significant differences in cognitive decline rates except for a slower decline in scores on the animal fluency test among superagers.

Cross-sectional comparisons of white matter health revealed no significant differences in total white matter volume, volume of white matter lesions, or Fazekas scores between the two groups.

However, both groups exhibited a high prevalence of white matter lesions, with no significant differences in lesion severity.

Voxel-wise analyses of white matter microstructure indicated higher fractional anisotropy (FA) and lower mean diffusivity (MD) in superagers, particularly in frontal regions.

Longitudinally, superagers showed slower declines in white matter lesion volume than the comparison group, although this difference became nonsignificant after outlier exclusion.

Additionally, superagers exhibited slower declines in MD and FA over time than the comparison group across various white matter tracts, suggesting that white matter microstructure may be linked to resistance to age-related change.

These findings highlight the preserved white matter integrity in superagers, potentially contributing to their exceptional cognitive abilities in comparison with typical older adults.

Conclusions

Overall, the study underscores the importance of white matter health in cognitive aging.

While superagers and adults in the comparison group have similarly healthy white matter based on volumetric and radiological metrics, regional analysis reveals more resilient white matter microstructure among superagers, particularly in anterior brain regions and tracts with protracted maturation.

This suggests a resistance mechanism to age-related changes, possibly explaining the maintenance of memory function in superagers.

However, the authors acknowledge some limitations of the study, including the lack of assessment of other potential protective factors and the cross-sectional design.

Future research is needed to explore the role of vascular health and other cardiovascular risk factors in white matter preservation. Longitudinal studies may shed light on the development of the superaging phenotype and its relationship with structural brain changes.