The Alzheimer’s Mystery: Why Do Some People with “Alzheimer’s Brain” Never Show Symptoms?

It is a little known and greatly mysterious fact that many people whose brains show the classic neuropathological symptoms of Alzheimer’s disease — amyloid plaques and tau tangles — never develop dementia or show any outward signs of having the disease. These people live long and productive lives with no signs of memory loss or any other symptoms of Alzheimer’s dementia; yet these individuals have donated their bodies and brains to science, and it is only upon autopsy of the brain that it is discovered that these people had brains with all the physical signs of full-blown Alzheimer’s disease. Scientists have been studying this mystery for years in an effort to develop a potential cure for the disease based on whatever is going on in the brains of these seemingly extremely unusual individuals.

The Nun Study Began More Than 35 Years Ago 

An experiment that began in 1986, called the Nun Study, is considered by experts on aging to be one of the most innovative efforts to answer questions about who gets Alzheimer’s and why. The study involved 678 nuns, including the Welter sisters, at one convent and six others also in the Sisters of Notre Dame order, in Connecticut, Maryland, Texas, Wisconsin, Missouri, and Illinois. Dr. David Snowdon, an epidemiologist at the University of Kentucky who led the study, and his colleagues, have come up with clues and theories over the years as to why some nuns thrive and others deteriorate so much they lose speech, mobility, and much of their memory. The differences showed up even in nuns with virtually identical backgrounds, even those who are biologically related. Snowdon published his findings in his book on the study called ”Aging with Grace.”

Research Done on the Brains of 15 Deceased Nuns Had Remarkable Findings

According to Dr. Karen Santa Cruz who is currently heading the Nun Study at the University of Minnesota, “(t)he most interesting people to study are the ones with a lot of Alzheimer’s pathology in their brain, but [who] didn’t show any outward sign of memory loss or dementia. Fifteen brains studied so far have shown that a person can have full-blown Alzheimer’s and not suffer any symptoms of dementia.”

One example of a sister who had Alzheimer’s pathology in the brain but never developed Alzheimer’s was Sister Mary. Sister Mary had a vibrant and full life and she lived for over 100 years. Upon her death, analysis of her brain revealed several lesions and other signs of Alzheimer’s that should have caused her to have poor cognition and other health problems. However, she enjoyed reading, knitting, and socializing up until her death. It is thought that her lifelong career as a teacher along with a well-balanced diet and love of reading helped her defy physical and genetic predisposition to dementia.

Sister Mary’s story is a hopeful example of how some diseases can be avoided by lifestyle factors. Other preventative measures put forth by the Nun Study include protecting the head from physical damage (concussions), avoiding tobacco, exercising regularly, and eating a healthy, balanced diet, things they will look more at in a moment.

Are Some Brains More Resilient?

Various studies have shown that approximately 30% of older adults have brains with enough amyloid plaques and/or tau tangles to qualify for an Alzheimer’s diagnosis yet without any symptoms of dementia, according to neuroscientist Timothy Hohman of Vanderbilt University Medical Center, who is leading the largest-ever study to identify genetic explanations for what researchers call “Alzheimer’s resilience.”

“You can have abundant plaques and tangles without having Alzheimer’s disease,” agreed neurologist Rudy Tanzi of Massachusetts General Hospital. “The challenge is to figure out how. If we can, then the goal would be to mimic what these resilient people have with some kind of a drug.”

The National Institute on Aging has funded its Resilience-AD Program, which began in 2017, with $40 million in an effort to identify genetic and other factors that may prevent Alzheimer’s symptoms even in people whose brains clearly have “Alzheimer’s,” and to somehow bottle that resilience. Experimental drugs inspired by discoveries about Alzheimer’s resilience are already moving through clinical trials, and more are in the pipeline.

“Usually, we try to understand why people have a disease,” said the NIA’s Suzana Petanceska, who helps direct its neuroscience programs. “But by looking at these outliers who do not get Alzheimer’s, the idea is to understand the molecular pathways that drive that resilience and harness it to develop therapeutics for the rest of us.”

Some brains apparently somehow compensate for the physical destruction of neurons and synapses caused by amyloid plaques and tau tangles, but scientists and researchers don’t yet understand how or why this happens. The physical damage still happens, but apparently other mechanisms are at work that are somehow preventing the real-life symptoms typically caused by this physical damage.

Some scientists attribute this Alzheimer’s resilience to something they have dubbed “cognitive reserve,” which increases with years of education and learning and refers to redundant brain circuitry that can buffer the effects of losing neurons and synapses to Alzheimer’s. Because more learning promotes denser circuitry and more synapses, the theory is that if the original circuit is lost to Alzheimer’s, the brain can activate the redundant pathways, allowing brains with more cognitive reserve to lose more synapses and neurons to Alzheimer’s pathology without showing cognitive decline.

But this is just one theory, and there are many others, including many resulting from the earlier mentioned Nun Study.

Could healthy lifestyle be the reason for no Alzheimer’s symptoms?

Snowdon and his team in the Nun Study had a wealth of information to conduct their study. They found that studying the risk factors and onset of Alzheimer’s in nuns turned out to be one of the most ideal scenarios for long-term research on disease. Here’s why:

  • The nuns had similar lifestyles, socioeconomic status, access to health care, and social supports.
  • None of these women had ever been married or had children, which gave them each similar risk for certain cancers and other diseases.
  • Several of the nuns had agreed to donate their brains to research after their deaths, which helped the researchers predict which factors influenced cognition throughout the nuns’ lives.
  • Snowdon had access to autobiographies each of the women had written in their 20s, which allowed him to compare cognitive abilities early in life to the women’s present state.

Could more advanced linguistic abilities be the reason for no Alzheimer’s symptoms?

The autobiographies each nun had written upon entering the convent decades earlier were an important part of the study showing that early language ability may be linked to lower risk of Alzheimer’s. Nuns who packed more ideas into the sentences of their early autobiographies were less likely to get Alzheimer’s disease six decades later.

They found that there was a strong positive association between idea density in early life and presence of Alzheimer’s later in life. In fact, 80% of the nuns who lacked early linguistic skills developed Alzheimer’s later in life, while only 10% who had higher linguistic skills developed the disease.

This research suggests that the women who had lower idea density scores had an increased risk for developing dementia and had a lower life expectancy, while nuns with higher scores tended to live a long, dementia-free life.

The association was so direct that Snowdon could predict which nuns might have dementia simply by reading their letters. Many of the women who had high idea density scores had also received secondary education, and in many cases, had earned their master’s degree or had spent several years working as teachers. These findings highlight the importance of higher education and continuous sharpening of cognitive skills throughout life by engaging in reading, writing, and other activities that involve focus and learning.

Could better nutrition be the reason for no Alzheimer’s symptoms?

Although the women in the Nun Study were fed similar foods from the same kitchen, each had their own food preferences, which allowed for some variation in disease pathology.

  • Nutritional analysis revealed that nuns with high amounts of lycopene in their diets had a reduced risk for developing dementia and appeared to age healthily. Lycopene is an antioxidant and the red pigment found in tomatoes and watermelon.
  • Folic acid may help stave off Alzheimer’s disease: Upon analysis, nuns exhibiting Alzheimer’s-like behavior consistently had low levels of folate in their blood. Low folate levels were correlated with atrophy of the neocortex in the brain and a decrease in cognitive abilities. Taking folic acid may be a good way to supplement the folate in your body. Although there is still much research to be done on nutritional factors, it is never too soon to adopt preventative practices, such as consuming folate- and antioxidant-rich foods, to avoid age-related cognitive decline.

Could positive emotional state be the reason for no Alzheimer’s symptoms?

Positive emotional state in early life may contribute to living longer. Experts say “linking positive emotions in the autobiographies to longer life echoes other studies showing that depression increases risk of cardiovascular disease and that people rated as optimists on personality tests were more likely than pessimists to be alive 30 years later.”

Could being unmarried be the reason for no Alzheimer’s symptoms?

Lest you think that being a nun and therefore being unmarried was a factor in some nuns not developing symptoms of Alzheimer’s, a recent study — Associations of Widowhood and Beta Amyloid with Cognitive Decline in Cognitively Unimpaired Older Adults — has shown that widows are more likely to develop symptoms than women who are still married. In February 2020, researchers from Harvard Medical School and Princeton Neuroscience Institute published a study explaining that inflammation might be the key to whether women with physical signs in their brain of Alzheimer’s disease do or do not develop symptoms during their lifetimes. In this study, the researchers compared widows to similar but still-married women with similar high levels of amyloid plaque in their brains. Despite both groups having a relatively equal amount of amyloid plaque in their brain, the still-married women’s cognitive abilities declined only one-third as fast as the cognitive abilities of the widows.

Could lack of stress be the reason for no Alzheimer’s symptoms?

One possible explanation, according to the researchers in the Widowhood study, is that the psychosocial stress of widowhood could trigger inflammation in the brain, just as stress has been shown in numerous studies to trigger inflammation elsewhere in the body. This stress could turn minimally harmful amyloid plaques and tau tangles into feeding grounds for neuron-killing microglia.

Using clusters of brain cells researchers call “Alzheimer’s in a dish,” the biotech company AZTherapies is running a phase three trial with 620 Alzheimer’s patients to see if an old asthma drug called cromolyn can combat this brain inflammation, potentially preventing the disease altogether.

Medicaid Asset Protection

Do you have a loved one who is suffering from Alzheimer’s or another form of dementia? Persons with Alzheimer’s and their families face special legal and financial needs. At the Farr Law Firm, we are dedicated to easing the financial and emotional burden on those suffering from dementia and their loved ones. We help protect a family’s hard-earned assets while maintaining your loved one’s comfort, dignity, and quality of life by ensuring eligibility for critical government benefits such as Medicaid and Veterans Aid and Attendance. Please call us any time to make an appointment for an initial consultation:

Fairfax Alzheimer’s Planning: 703-691-1888
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About Evan H Farr, CELA, CAP

Evan H. Farr is a 4-time Best-Selling author in the field of Elder Law and Estate Planning. In addition to being one of approximately 500 Certified Elder Law Attorneys in the Country, Evan is one of approximately 100 members of the Council of Advanced Practitioners of the National Academy of Elder Law Attorneys and is a Charter Member of the Academy of Special Needs Planners.