Researchers from the Mark and Mary Stevens Neuroimaging and Informatics Institute (Stevens INI) at the Keck School of Medicine of USC have found that two distinct types of brain tissue work together to support cognition in older adults, and that the health of the brain's short-range wiring may help soften the cognitive effects of gray matter loss.

The study, published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, analyzed brain scans and cognitive assessments from 459 community-dwelling adults age 60 and older across India. It is among the first studies to examine the brain's superficial white matter in a community-based population from a low- and middle-income country.

Superficial white matter is a thin layer of nerve fibers immediately beneath the brain's outer gray matter. These short, curved fibers act like local roads, carrying signals between nearby areas of the cerebral cortex. Gray matter, by comparison, contains many of the brain cells that process information.

Gray matter and superficial white matter are physically close and may play different roles: gray matter processes information, while superficial white matter helps nearby brain regions communicate. Our findings suggest that cognitive health depends not only on how much gray matter is preserved, but also on the condition of the wiring that connects it."

Yingxu Liu, PhD, postdoctoral scholar, Stevens INI and first author of the study

A closer look at the brain's local connections

The researchers used an advanced form of diffusion MRI, which measures how water moves through brain tissue, to assess microscopic features of superficial white matter. They focused on measures that reflect neurite density, the small projections that allow nerve cells to send and receive signals, and the amount of freely moving water around them. Lower neurite density or more free water can indicate tissue disruption associated with processes such as loss of myelin, inflammation, or swelling.

Participants also completed tests of language, memory, executive function, and visuospatial ability. The team found that healthier superficial white matter was most consistently associated with stronger language skills. The clearest links appeared in frontotemporal areas involved in recognizing words, speaking fluently, and holding language information in mind.

Gray matter atrophy measures remained the strongest overall predictors of cognition. However, the relationship between gray matter and cognitive performance depended in part on superficial white matter: when this local wiring showed poorer integrity, gray matter loss was more strongly tied to worse language performance and cognitive impairment. When superficial white matter was healthier, those associations were weaker.

"The findings point to superficial white matter as a possible source of resilience," said Leon Aksman, PhD, assistant professor of research neurology at the Stevens INI and senior author of the study. "Two people with a similar degree of gray matter loss may not experience the same cognitive effects if the local connections surrounding that gray matter differ in health. Following participants over time will be essential to test whether preserving these connections can help maintain cognition."

Broadening the picture of brain aging

The data came from the Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India, known as LASI-DAD. More than half of the broader LASI-DAD sample has low literacy, and roughly 60% live in rural communities, groups that have rarely been represented in neuroimaging research.

In the present analysis, the relationship between superficial white matter and language was stronger among participants who could not read or read incorrectly, had no formal education, or lived in rural areas. The study does not show that these social conditions directly caused brain changes. Rather, the findings highlight how lifelong social, educational, health, and environmental experiences may intersect with brain aging.

Because the study captured one point in time, the researchers cannot determine whether changes in superficial white matter precede gray matter loss or cognitive decline. Future long-term studies will examine how these tissues change together and how vascular health, inflammation, Alzheimer's-related proteins, and other factors contribute.

"A fuller understanding of brain aging requires research that reflects the world's social, cultural, and geographic diversity," said Arthur W. Toga, PhD, director of the Stevens INI and Provost Professor at USC. "By studying an underrepresented population and looking beyond gray matter alone, this work brings us closer to identifying the biological and social factors that may protect cognition across the lifespan."

Source:

Journal reference: