The Nun Study: Insights from 30 Years of Aging and Dementia Research

Overview

Journal Alzheimers Dement

Specialties Neurology
Psychiatry

Date 2025 Feb 25

PMID 39998266

Authors

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

Affiliations

Soon will be listed here.

Abstract

The Nun Study is an iconic longitudinal study of aging and dementia on a cohort of 678 Catholic nuns from the School Sisters of Notre Dame. Participants consented to undergoing annual neuropsychological assessments, allowing researchers access to convent archives and medical records and post mortem brain donation. This study investigated the associations between epidemiological factors, cognitive function, and brain pathology. By examining published literature that reports on or utilizes Nun Study data, we provide an overview of its methodology and key findings, emphasizing its significant contributions to understanding cognitive impairment and related neuropathologies. Seminal findings on early-life factors affecting cognitive health, clinicopathological correlations, and apparent resistance and resilience to neuropathology are discussed. Decades of Nun Study research have made critical contributions to our understanding of Alzheimer's disease and related dementias and highlight continuing objectives for future research. HIGHLIGHTS: The uniform lifestyles of participants minimized potential confounds of the study. Early-life cognitive ability influenced late-life cognitive outcomes. Some participants with AD pathology did not exhibit dementia. Neuropathological comorbidities were common and increased the risk of dementia.

References

Nelson P, Estus S, Abner E, Parikh I, Malik M, Neltner J . ABCC9 gene polymorphism is associated with hippocampal sclerosis of aging pathology. Acta Neuropathol. 2014; 127(6):825-43. PMC: 4113197. DOI: 10.1007/s00401-014-1282-2. View

Snowdon D, Kemper S, Mortimer J, Greiner L, Wekstein D, Markesbery W . Linguistic ability in early life and cognitive function and Alzheimer's disease in late life. Findings from the Nun Study. JAMA. 1996; 275(7):528-32. View

Morrison-Koechl J, Fearon D, Fernandes M, Tyas S . The Association Between Emotional Expressivity in Autobiographies from Early Adulthood and the Risk of Dementia in the Context of Written Language Skills. J Alzheimers Dis Rep. 2023; 7(1):317-326. PMC: 10200230. DOI: 10.3233/ADR-220106. View

Rabinovici G, Carrillo M, Forman M, DeSanti S, Miller D, Kozauer N . Multiple comorbid neuropathologies in the setting of Alzheimer's disease neuropathology and implications for drug development. Alzheimers Dement (N Y). 2017; 3(1):83-91. PMC: 5651346. DOI: 10.1016/j.trci.2016.09.002. View

Nichols E, Merrick R, Hay S, Himali D, Himali J, Hunter S . The prevalence, correlation, and co-occurrence of neuropathology in old age: harmonisation of 12 measures across six community-based autopsy studies of dementia. Lancet Healthy Longev. 2023; 4(3):e115-e125. PMC: 9977689. DOI: 10.1016/S2666-7568(23)00019-3. View

Guzman M, Judkins A . Digital pathology: a tool for 21st century neuropathology. Brain Pathol. 2009; 19(2):305-16. PMC: 8094780. DOI: 10.1111/j.1750-3639.2009.00264.x. View

McKhann G, Knopman D, Chertkow H, Hyman B, Jack Jr C, Kawas C . The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011; 7(3):263-9. PMC: 3312024. DOI: 10.1016/j.jalz.2011.03.005. View

Greiner P, Snowdon D, Greiner L . The relationship of self-rated function and self-rated health to concurrent functional ability, functional decline, and mortality: findings from the Nun Study. J Gerontol B Psychol Sci Soc Sci. 1996; 51(5):S234-41. DOI: 10.1093/geronb/51b.5.s234. View

Geddes J, Tekirian T, Soultanian N, Ashford J, Davis D, Markesbery W . Comparison of neuropathologic criteria for the diagnosis of Alzheimer's disease. Neurobiol Aging. 1997; 18(4 Suppl):S99-105. DOI: 10.1016/s0197-4580(97)00063-8. View

10.

Greiner P, Snowdon D, Schmitt F . The loss of independence in activities of daily living: the role of low normal cognitive function in elderly nuns. Am J Public Health. 1996; 86(1):62-6. PMC: 1380362. DOI: 10.2105/ajph.86.1.62. View

11.

Khachaturian Z . Diagnosis of Alzheimer's disease. Arch Neurol. 1985; 42(11):1097-105. DOI: 10.1001/archneur.1985.04060100083029. View

12.

Nelson P, Brayne C, Flanagan M, Abner E, Agrawal S, Attems J . Frequency of LATE neuropathologic change across the spectrum of Alzheimer's disease neuropathology: combined data from 13 community-based or population-based autopsy cohorts. Acta Neuropathol. 2022; 144(1):27-44. PMC: 9552938. DOI: 10.1007/s00401-022-02444-1. View

13.

Gearing M, Schneider J, Rebeck G, Hyman B, Mirra S . Alzheimer's disease with and without coexisting Parkinson's disease changes: apolipoprotein E genotype and neuropathologic correlates. Neurology. 1995; 45(11):1985-90. DOI: 10.1212/wnl.45.11.1985. View

14.

Tully C, Snowdon D, Markesbery W . Serum zinc, senile plaques, and neurofibrillary tangles: findings from the Nun Study. Neuroreport. 1995; 6(16):2105-8. DOI: 10.1097/00001756-199511000-00002. View

15.

POTVIN A, Tourtellotte W, DAILEY J, Alberts J, Walker J, Pew R . Simulated activities of daily living examination. Arch Phys Med Rehabil. 1972; 53(10):476-86 passim. View

16.

White L, Edland S, Hemmy L, Montine K, Zarow C, Sonnen J . Neuropathologic comorbidity and cognitive impairment in the Nun and Honolulu-Asia Aging Studies. Neurology. 2016; 86(11):1000-8. PMC: 4799714. DOI: 10.1212/WNL.0000000000002480. View

17.

Morris J, HEYMAN A, Mohs R, Hughes J, van Belle G, Fillenbaum G . The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease. Neurology. 1989; 39(9):1159-65. DOI: 10.1212/wnl.39.9.1159. View

18.

Mirra S, HEYMAN A, McKeel D, SUMI S, Crain B, Brownlee L . The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology. 1991; 41(4):479-86. DOI: 10.1212/wnl.41.4.479. View

19.

Iacono D, Zandi P, Gross M, Markesbery W, Pletnikova O, Rudow G . APOε2 and education in cognitively normal older subjects with high levels of AD pathology at autopsy: findings from the Nun Study. Oncotarget. 2015; 6(16):14082-91. PMC: 4546453. DOI: 10.18632/oncotarget.4118. View

20.

Braak H, Braak E . Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991; 82(4):239-59. DOI: 10.1007/BF00308809. View