Alzheimer Disease and the “Nun Study”

Auguste D. patient of Dr. Alzheimer, who first described the hallmark plaques and tangles of AD.

Auguste D. patient of Dr. Alois Alzheimer, who first described Alzheimer disease.

Every seven seconds somewhere in the world a person is diagnosed with dementia (1), Alzheimer disease (AD) being the commonest form in adults over the age of 65 (2). Few of us therefore can expect to remain untouched in some form by this disease. Many of us may already have an affected friend or family member, and may be concerned about our own potential risk factors. Aside from the holy grail of a potential cure, any studies that identify more accurate predictors of disease or pinpoint factors that lessen the degree of risk, are extremely interesting to those of us who have experienced the devastation of AD within our own families, and who are left wondering about our own or our loved ones’ future health.

Scientists and physicians have been studying AD for over a century. The first described case was a patient, August D., who was treated by Dr. Alois Alzheimer in 1901. Five years later that patient died, and Alzheimer undertook a detailed study of her brain tissue, describing the presence of neurofibrillary tangles and amyloid plaques, the histological hallmarks of AD—and the keys to understanding it. However, even after resolving the structure of plaques and tangles in the 1960s, twenty years would pass before researchers identified the molecules that compose them (3), and even today researchers are still trying to determine what happens first in the onset of AD: The appearance of plaques, the appearance of tangles? Or is there some other, more subtle, event that triggers the pathology?

ADneuronThe genetic and molecular studies of AD are numerous and deep and continue to yield information that may help design an effective treatment or cure for the disease. Equally important, though, are the epidemiology studies that focus on environment and behaviors as risk factors for the disease. One of the most fascinating epidemiological studies is the “Nun Study,” begun in 1986 with volunteers from the School Sisters of Notre Dame convent in Mankato, MN, USA. The pilot study looked at aging in 100 nuns to see if there were any environmental factors that correlated with “successful” aging. In that pilot study, researcher David Snowden, found a clear correlation between educational level and successful aging—in the population studied, higher educational levels correlated with successful aging (physical and mental) and longevity (4).

In 1988 Snowdon presented work from the pilot study, and he was approached by Jim Mortimer from the Minneapolis Veterans Administration Medical Center(4) about designing an Alzheimer disease study using the volunteer nuns. Snowdon received funding for a larger-scale study, and he moved to the University of Kentucky to work with the other members of the Sanders-Brown center there. The “Nun Study” involved 678 volunteer nuns belonging to the order of the School Sisters of Notre Dame. The nuns agreed a take a battery of tests over the course of the study, to open their biographical records and life stories to the researchers, and finally to donate their brains for scientific study after their death (4).

Perhaps the single most important conclusion from the study is that Alzheimer disease is not straight forward. In several cases, pathology studies of brain tissue from the deceased nuns did not correlate with their performance on cognitive function tests. Sometimes the pathologist would score a brain as having signs of extremely advanced AD, only to learn later that the nun herself scored extremely well on all cognitive tests. Other times a brain would show only slight damage associated with AD, and the nun was characterized as exhibiting the signs of advanced cognitive decline and dementia.

The study did provide a hint that people suffering from chronic depression early in life tended to be more likely to show outward signs of AD, even though the actual damage to the brain was minimal (4), and clinicians recognize today that treating depression in AD patients can improve their function. So, there does appear to be a correlation between depression and developing outward symptoms of AD; however, the mechanism behind this relationship is not understood.

Healthy and AD BrainAnother finding from the Nun Study is that participants who had well developed language skills, as demonstrated by analysis of the autobiographies that they wrote as postulates, tended not to develop Alzheimer disease. Autobiographies that could be identified as original and unedited were analyzed for two characteristics: idea density and grammatical complexity. High idea density and to some extent, grammatical complexity, were associated with a decreased likelihood of developing AD (4). Idea density was measured by calculating the number of individual ideas expressed in ten words, and grammatical complexity was measured by rating sentences on a scale of 0 (simple clause) to 7 (complex sentences with embedded grammatical structures and subordination). By the time the researchers finished the analysis, they were able to predict with 80% accuracy from essays written in a woman’s early twenties whether or not she would develop Alzheimer disease at age 80.

With the retirement of Snowdon, the records and tissue samples are back at the University of Minnesota. The data and tissues will be available to researchers around the world, so that researchers and clinicians can continue to learn from these nuns. Additionally, the University of Minnesota has announced that it will begin a second study, with a new group of volunteer nuns, to delve further into the mysteries of Alzheimer disease: Why do some people develop symptoms and not others? Why do some people with advanced brain damage: plaques, tangles and tissue loss, not show any symptoms, while others with minimal brain damage show symptoms of advanced AD?

  1. Thomas, P. and Fenech, M. (2007) A review of genome mutation and Alzheimer disease. Mutagenesis 22, 15–33.
  2. Lovell, M.A. and Markesbery, W.R. (2007). Oxidative DNA damage in mild cognitive impairment and late-stage Alzheimer disease. Nucl. Acid Res. 35, 7497–504.
  3. Goedert, M. and Spillantini, M.G. (2006) A Century of Alzheimer’s Disease. Science 314, 777–780.
  4. Snowdon, D.A. (2001) Aging with Grace. Bantam Books. New York, NY.

Isobel Maciver also contributed to this article.

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Michele Arduengo

Senior Content Developer / Social Media Lead at Promega Corporation
Michele earned her B.A. in biology at Wesleyan College in Macon, GA, and her PhD through the BCDB Program at Emory University in Atlanta, GA. Michele manages the Promega Connections blog. She enjoys leisure reading, writing creative nonfiction and knitting, and the occasional cross-country skiing jaunt.

2 thoughts on “Alzheimer Disease and the “Nun Study”

  1. Dear Michele

    it is a nice article. But I think the most important findings from the nun study you did not mention.
    In Canada, Prof. Pat Mc Gere did not only see the tangles and plaques in the brains of Alzheimer mice. He found microglia that only occur when there is an inflammation. He further followed the idea that Alzheimer might be a disease of inflammation and called all large rheumatic clinics worldwide, asking whether among their patients were also people who have developed Alzheimer’s. Almost Nada.
    In Germany at the University of Goettingen Alzheimer scientists injected mice with the Alzheimer Genes of humans and were successful. They have created Alzheimer mice. Making the connection to Pat Mc gere’s findings, they gave those Alzheimer mice a daily dose of strong anti-inflammatory in their food. Result: after a while these mice changed their behaviour and they could recall again.

    Many Scientists today believe that plaques is not the root cause of the disease. It might be inflammation. The pharmaceuitcal companies do not want to develop an Alzheimer medication that follows those new scientific findings because medications against plaques are patented and highly profitable, according to Prof. Pat Mc Gere.
    For more information on this and film documentaries on all these findings, please go to:
    http://www.nun-study.com

    Kind regards/Lutz

    • Thanks for your additional information. I am aware that the understanding that the relationship between plaques and tangles and the progression of AD is not at all clear, and becomes less so the more we learn. In fact in the Nun Study, a few of the most advanced cases of AD in terms of dementia (as measured behaviorally) were accompanied by only moderate pathology, and one or two of the brains that had rather advanced tissue damage came from individuals that showed no outward signs of dementia before death. These are curious exceptions that would argue that plaques and tangles are not the complete story behind AD. Strokes and other events seemed also to play a major part in the progression of dementia. However, these are small sample sizes. In the majority of the cases examined, pathology at autopsy correlated with dementia. There is much that we do not understand about the molecular progression of AD, I agree.

      That said, for this particular blog, I was more interested in the fact that the original Nun Study represented one of the first thorough epidemiological studies of dementia and aging that could actually follow a population for a long period of time and control for environmental factors such as income, education, access to health care and diet. In my mind the ability to control these factors really elevates this study above many of the others that have been conducted.

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