Prospective Study Hints at Age-Related Memory Advantages for Rural Dwellers

Elderly rural dwellers may have small to moderate memory advantages over their counterparts who live in urban areas. So suggests an initial characterization of cognitive aging in a rural community cohort outside of Las Vegas, Nevada, reported by Cleveland Clinic researchers.

Published in Frontiers in Dementia, findings from the longitudinal cohort study suggest the possibility that late-life rural living may promote cognitive resilience in some individuals. However, additional prospective research is needed to understand factors that influence aging outcomes for older adults living in rural areas, who are underrepresented in studies of Alzheimer’s disease and related dementias.

“Based on earlier retrospective studies, we hypothesized that people living and aging in a rural community would have much worse outcomes than people living in an urban community,” says first author Justin B. Miller, PhD, a staff neuropsychologist at Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas. “We were surprised to find that people who live in a rural community might actually fare better in terms of memory.”

Study design in brief

The study’s cohort included individuals aged ≥50 years who currently live in a nonmetropolitan area in the broader Desert Southwest Region surrounding Las Vegas. They are being followed by researchers with the Nevada Exploratory Alzheimer’s Disease Research Center (NVeADRC). One of only four National Institute on Aging-funded Exploratory Alzheimer’s Disease Research Centers, NVeADRC was established under a grant to the Cleveland Clinic Lou Ruvo Center for Brain Health.

“We’re in a unique position to systematically and prospectively study aging in people who live outside of metropolitan areas because the geography of southern Nevada is rural to frontier,” says Dr. Miller. “We’re seeking funding to expand our project to be multistate so we can perform large-scale research on factors that differentiate urban and rural dwellers.”

Dr. Miller and his team compared their rural-dwelling cohort to urban-dwelling older adults living in Las Vegas followed by Cleveland Clinic’s Center for Neurodegeneration and Translational Neuroscience (CNTN). The NVeADRC and CNTN protocols have been aligned as much as possible and have many common data elements.

Enrollment through NVeADRC began in February 2021; the CNTN cohort dates to 2016. Both cohorts are ongoing. The researchers are collecting demographic data from both cohorts and assessing participants with a primary battery of neuropsychological tests that includes verbal and nonverbal learning and memory, language, attention, executive functions and other abilities.

“We’re also testing a comprehensive panel of biomarkers, including levels of beta amyloid and tau in plasma and markers of inflammation in serum, as well as performing structural brain imaging,” Dr. Miller notes. “With additional funding, we hope to incorporate amyloid positron emission tomography into our project.”

Teasing out differences between rural and urban dwellers

The initial analysis was focused solely on understanding differences between urban (n = 129) and rural dwellers (n = 81) in memory functioning, with stratification by cognitive impairment as follows:

• Impaired rural
• Impaired urban
• Unimpaired rural
• Unimpaired urban

Analysis of variance was used to identify differences in demographics such as age, education and premorbid intelligence. Chi-square testing was used for categorical variables such as sex, race and ethnicity. Secondary analyses were performed to explore the relationship between the Area Deprivation Index (ADI) in the two cohorts combined and each cohort independently.

Study participants were mostly non-Hispanic (96.3% of rural dwellers and 91.5% of urban dwellers) and white (90% and 90%, respectively). Women made up 63% of the rural-dwelling cohort and 46.5% of the urban-dwelling cohort. The cohorts were comparable in mean age (70.7 years for rural dwellers and 71.5 years for urban dwellers) and mean years of education.

Key findings included the following:

• Neuropsychological testing revealed that just over half of the rural dwellers (51.9%) were cognitively unimpaired, compared with 44.1% of the urban dwellers.
• Rural dwellers demonstrated superior verbal memory compared with their urban counterparts on primary measures of learning, recall and recognition, with overall comparisons showing small to medium effects.
• No differences in nonverbal memory or overall clinical status were seen between the two cohorts.

After stratification by cognitive impairment, rural-urban differences were larger among unimpaired individuals. Within-group comparisons showed that the magnitude of impairment between cognitively normal and impaired participants was greater in the rural than in the urban cohort.

“The difference in delayed recall between the normal and impaired groups among rural dwellers was almost double that observed among urban dwellers,” Dr. Miller observes. “Once an individual begins to experience mental impairment, it appears to have a larger impact if they live in a rural area than in an urban area.”

Among individuals with cognitive impairment, comparison of demographic characteristics between the two cohorts revealed only two significant differences: educational level, which was significantly lower in the rural cohort, and neighborhood deprivation, with more rural than urban dwellers living in severely disadvantaged neighborhoods.

Monitoring will continue

The investigators note that their findings underscore the complexity of factors that underlie the effects that geography may have on cognitive aging. “Further prospective research is essential to better understand the factors that influence aging outcomes in rural dwellers and other understudied populations,” Dr. Miller concludes. “Our continuing work at the NVeADRC aims to provide some of these needed insights.”