SAN ANTONIO, Feb. 26, 2025 – Catholic nuns don't make a habit of participating in long-term studies on aging and dementia, but one notable exception has yielded critical insights into cognitive resilience, neuropathology and aging-related disorders.
Researchers at The University of Texas Health Science Center at San Antonio (UT Health San Antonio) published a study analyzing more than 30 years of aging and dementia patterns of 678 nuns from the School Sisters of Notre Dame enrolled in the aptly named Nun Study, conceived by epidemiologist and neurology professor David A. Snowdon, PhD, in 1986.
It now is housed at UT Health San Antonio's Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases , under the direction of Margaret Flanagan, MD, tenured associate professor of pathology and laboratory medicine.
Among takeaways from this latest analysis: Some individuals showed resilience to cognitive decline despite an Alzheimer's diagnosis, indicating unknown protective mechanisms at work, and that early-life linguistic ability and grammatical complexity correlated with a lower risk of impairment in later life.
Also, advanced digital pathology techniques and artificial intelligence are reshaping the study of Alzheimer's and related dementias. It all portends advancement for preventive intervention in cognitive decline.
"By leveraging this unique cohort of Catholic nuns with homogeneous lifestyles and rigorous longitudinal assessments, the study has clarified key factors influencing dementia risk and protection," Flanagan said. "The work underscores the need for multilayered comprehensive approaches that account for multiple pathologies in dementia research and highlights the promise of AI-driven neuropathology."
Flanagan is senior author of the study titled, "The Nun Study: Insights from 30 years of aging and dementia research," published Feb. 26 by Alzheimer's & Dementia: The Journal of the Alzheimer's Association. Other authors also are with the Biggs Institute and the departments of pathology or neurology at UT Health San Antonio. First author of the study is MD/PhD student Kyra Clarke.
One of the most significant
The new Nun Study analysis describes "one of the most significant longitudinal aging and dementia studies."
Snowdon founded the initiative while at the University of Minnesota and then later took it with him to the University of Kentucky. With his retirement in 2008, the study returned to the University of Minnesota. The study briefly moved again to Northwestern University in 2021 when Flanagan was there, and then to UT Health San Antonio.
Cloistered and homogenous, the cohort of American nuns 75 years of age or older at the School Sisters of Notre Dame, a worldwide institute of Roman Catholic sisters, proved ideal for study, minimizing variables like smoking or differences in access to health care that may have confounded similar research.
While all 678 participants now have passed away, the study remains alive and vibrant at the Biggs Institute, with research currently being performed on donated brain autopsy material and the extensive data collected during the nuns' lives, Flanagan said.
The participants consented to undergoing annual neuropsychological assessments, allowing researchers access to convent archives and medical records, plus the post-mortem brain donation. The new study investigated the associations between epidemiological factors, cognitive function and brain pathology.
Among the findings:
- Cognitive resilience and neuropathology : The study identifies factors contributing to cognitive resilience despite the presence of Alzheimer's pathology. Some individuals exhibited high neuropathological burden but remained cognitively intact, indicating unknown protective mechanisms.
- APOE genotypes and dementia risk: The article discusses the role of APOE e4 and e2 in Alzheimer's risk and cognitive preservation. The Apolipoprotein E (APOE) gene plays a role in the metabolism of fats in the brain. APOE e4 is a risk gene that increases the likelihood of developing Alzheimer's disease. APOE e2 is a protective gene that may reduce the risk.
- Early-life predictors of cognitive health: The relationship between early-life linguistic ability and later-life cognitive function is a major finding. High idea density and grammatical complexity in young adulthood correlated with a lower risk of cognitive impairment in later life.
- Comorbid neuropathologies and dementia risk: The study emphasizes that most cases of dementia involve mixed pathologies, including LATE, HS-A and vascular pathology, rather than pure Alzheimer's disease. LATE refers to Limbic-predominant age-related TDP-43 encephalopathy, a type of dementia that affects people as they age. It is often caused by abnormal clumps of a protein called TDP-43 in the brain. HS-A, or hippocampal sclerosis of aging, is damage in the hippocampus that happens with age, affecting memory. LATE and HS-A are underrecognized but impactful. LATE is distinct from Alzheimer's disease but frequently co-exists with it. HS-A is a major contributor to dementia in the oldest-old. The presence of these multiple brain pathologies suggest that multi-targeted therapeutic strategies may be necessary.
- Advancements in digital pathology: The study highlights how digital spatial profiling and machine learning are revolutionizing neuropathological assessments today. Digital pathology and AI are reshaping neuropathology research. Whole slide imaging, spatial transcriptomics and machine-learning models are providing novel insights into brain pathology and paving the way for precision diagnostics.
"The findings from the Nun Study have significantly advanced our understanding of Alzheimer's disease and related disorder neuropathologies," Flanagan said. "As all the studies comprehensively described in this review have indicated, there is still a need for ongoing investigation into the multifactorial nature of cognitive decline, particularly in aging populations.
"However, we also highlight promising opportunities for biomarker development and providing us with the opportunity to identify and delineate potential targets for preventive intervention in cognitive decline," she said.
Separately, Flanagan, a native of Ireland who completed her medical training at Trinity College Dublin, recently was highlighted by the Women in Medicine in Ireland Network . Each Sunday, it chooses "another great female medic, past or present," and acknowledges "their contribution to medicine in Ireland," according to its website. The initiative posted an article highlighting her roles at UT Health San Antonio.
Last year, she received a $100,000 Rising STARs award from the University of Texas Board of Regents to advance research relating to Alzheimer's Disease and other neurodegenerative diseases.
UT Health San Antonio is a world-class research university, ranking at the top 5% among institutions globally for clinical medicine according to U.S. News & World Report. It is No. 12 in the world among universities for the impact of its discoveries – in normalized citation impact, which compares the number of citations its research receives per paper to the average for similar published work, a recognized core measure of research impact.
The Nun Study: Insights from 30 years of aging and dementia research
Kyra M. Clarke, Shahroo Etemadmoghadam, Benjamin Danner, Cole Corbett, Ali Ghaseminejad-Bandpey, Matthew Dopler, Julie Parker-Garza, Mohammad Alhneif, Sahana Babu, Oluwaseun B. Ogunbona, Angelique D. Gonzalez, Arash Salardini, Margaret E. Flanagan
First published: Feb. 26, 2025, Alzheimer's & Dementia: The Journal of the Alzheimer's Association
Link to full study: https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.14626
The University of Texas Health Science Center at San Antonio (UT Health San Antonio), a primary driver of San Antonio's $44.1 billion health care and biosciences sector, is the largest academic research institution in South Texas with an annual research portfolio of more than $436 million. Driving substantial economic impact with its six professional schools, a diverse workforce of more than 9,400, an annual expense budget of $1.67 billion and clinical practices that provide 2.5 million patient visits each year, UT Health San Antonio plans continued growth over the next five years and anticipates adding more than 1,500 higher-wage jobs to serve San Antonio, Bexar County and the South Texas region. To learn about the many ways "We make lives better®," visit UTHealthSA.org .
The Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases is dedicated to providing comprehensive dementia care while advancing treatment through clinical trials and research. The Biggs Institute is a National Institute on Aging (NIA)-designated Alzheimer's Disease Research Center (ADRC). In addition to patient care and research, the Biggs Institute partners with the School of Nursing at UT Health Science Center San Antonio to offer the Caring for the Caregiver program.
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