You Asked, We Answered

Review questions from Mayo Clinic Study of Aging participants and answers from study experts.

Are our unique population results being extrapolated to similar but less extensive population studies?

Source: Michelle M. Mielke, Ph.D.

Yes, our findings on topics including risk factors, blood and cerebrospinal fluid biomarkers, and neuroimaging generally extrapolate to clinical populations and other studies that are not population based.

However, studies of purely clinical populations do not fully extrapolate to our population-based study, especially when trying to develop risk scores for the development and progression of Alzheimer's disease and dementia. That is why it is important to develop risk scores and establish the role of biomarkers for community use in a population-based study such as the Mayo Clinic Study of Aging.

How does data gathered here compare with data gathered in other major research institutions?

Source: David S. Knopman, M.D.

The Mayo Clinic Study of Aging is really unique. We are conducting the only study in the world that meets high standards as an epidemiologically valid study that is also able to do large volumes of magnetic resonance and positron emission tomography (PET) scans.

No other epidemiological study in the U.S. or Canada does anything with brain scanning in healthy older adults. Johns Hopkins, Harvard and University of California, San Francisco, which are the other places in the U.S. that do PET imaging, do it on a much smaller scale in only select individuals. So for many reasons, the Mayo Clinic Study of Aging is unique.

What is a clinical diagnosis versus a biological diagnosis?

Source: Bradley F. Boeve, M.D.

A biological diagnosis reveals the actual underlying disorder causing a person's symptoms; examples include Alzheimer's disease, Lewy body disease and other diseases.

But because it is difficult to make a diagnosis with 100% certainty in the vast majority of individuals, clinicians use the patient's history and examination along with a battery of tests — blood tests, neuropsychological assessment, brain scans, and the like — to determine the clinical diagnosis. Examples of clinical diagnoses include mild cognitive impairment, Alzheimer's dementia, dementia with Lewy bodies and frontotemporal dementia. The clinical diagnoses can then provide strategies for management and prognosis.

Based on the clinical diagnosis, and sometimes special tests, clinicians can often suggest the biological diagnosis with a certainty of approximately 70% to 90%, but this is not a perfect science. In other words, in patients who have typical features and findings to give a clinical diagnosis of Alzheimer's dementia, most — but not all — will have an underlying biological diagnosis of Alzheimer's disease causing their symptoms.

As more potent therapies are tested, we want to be sure that we are treating the right biological disorder. This is why research is so important. Investigators want to develop the ability to determine the biological diagnosis as definitively as possible — particularly as therapies are developed and tested to positively affect key proteins that cause diseases. In Alzheimer's disease, the key proteins are beta-amyloid and tau.

What kind of cosmetic or visual effects will be present on a family member who donates their brain for research?

Source: Kris A. Johnson, R.N.

Obtaining the brain tissue needed during autopsy should leave no disfigurement. The incision is in the back of the head and would require close inspection to be seen.

Can you clarify how imaging tests such as MRI and PET are different or similar?

Source: Clifford R. Jack, Jr., M.D.

Here is a brief explanation: MRI reveals things about the anatomy of the brain, such as the presence of small or large strokes or whether certain areas of the brain are shrunken due to the effects of a degenerative disease.

PET scans show deposits of abnormal proteins in the brain, where they are located and how dense they are. The two primary proteins deposits we are able to identify are amyloid plaques and tau tangles. Separate PET scans are needed for each of these, and that is why we ask volunteers to do two PET scans in the same day — one for identifying plaques and one for identifying tangles.

What are the benefits of the Mediterranean diet? What about plant-based diets or others? Is there research showing the benefits of those as well?

Source: Mayo Clinic Patient Education: Mediterranean Diet (PDF)

The Mediterranean diet is more than a "diet." It is a heart-healthy eating plan. For most people, what is good for your heart is good for your brain — and the rest of your body, too.

The Mediterranean diet is shown to reduce the risk of cancer, heart disease, neurological diseases and diabetes. In addition, it may improve the well-being of those with depression. Studies have also shown a reduction in:

  • Arthritis
  • Childhood asthma
  • Dementia
  • Erectile dysfunction and female sexual dysfunction
  • Frailty
  • Macular degeneration in people 60 years of age and older
  • Metabolic syndrome

What gender differences are being seen in the data collected as a part of the Mayo Clinic Study of Aging?

Source: Michelle M. Mielke, Ph.D.

Examining sex and gender differences in the development and progression of Alzheimer's disease is a hot topic in the field and an area of active investigation in the Mayo Clinic Study of Aging.

Findings to date

In the Mayo Clinic Study of Aging, similar to several other population-based studies, men are more likely to have cognitive impairment than are women. However, among people with cognitive impairment, women tend to progress faster to a diagnosis of dementia. We are currently trying to understand why this is.

In terms of brain changes, we do not see any differences in women versus men for brain levels of amyloid and tau, the two hallmark pathological characteristics of Alzheimer's disease. However, we are seeing some differences when examining vascular-related brain changes.

The brain is composed of gray matter, which is made up of the brain cells, and white matter, which is made up of the axons that help the brain cells communicate. We tend to see more white matter changes with age in women but more small bleeds around blood vessels in men. We do not currently know what this means for risk of dementia and what is causing these differences between men and women.

With regard to risk factors for memory changes, we also see some differences between women and men. Although both women and men with less than 12 years of education, memory concerns, stroke and atrial fibrillation have the same risk of developing memory impairment, specific risk factors are more pronounced for women. These include being a current smoker, having hypertension and having high cholesterol. Among men, obesity, never having married and being widowed are risk factors.

Ongoing research

Some of our ongoing research aims to understand how certain factors specific to women or to men increase the risk of dementia.

Among women, we are examining whether pregnancies with high blood pressure, the removal of ovaries before natural menopause or the use of hormone therapies affect the brain. Among men, we are examining whether prostate cancer or certain types of chemotherapy used for treatment affect the brain and increase the risk of dementia.

Is it worth finding out whether a patient who has some memory issues has Alzheimer's or dementia? Should such a patient request any certain or specific testing be done when making an appointment?

Source: Hugo Botha, M.D., Ch.B.

There is a lot to unpack in this excellent question!

First, it's important to be clear with the terminology, which can be confusing. There are some terms we use in neurology that serve as markers of the severity of a patient's cognitive or behavioral problems.

For example, if a patient has no concerns and no problems in day-to-day life, that person is "cognitively unimpaired." If the patient feels that memory or thinking has changed, but it's not impacting daily life and cognitive testing results are good, we may give a diagnosis of "subjective cognitive impairment."

If things are a bit more severe, such that the patient notices memory or thinking challenges during the more difficult aspects of daily life — for example, at work — and we find evidence for cognitive changes on testing, we may give a diagnosis of "mild cognitive impairment."

Finally, if things are bad enough that the cognitive or behavioral impairment is limiting the patient's day-to-day functioning and we find more severe impairment on testing, we may diagnose the patient with "dementia."

However, these terms do not specify the cause of the problem. Someone may have dementia from several strokes, or mild cognitive impairment from a traumatic brain injury.

This brings us to the second important point: Memory loss can be the result of non-neurologic diseases — such as vitamin or hormone deficiencies — reversible neurological conditions — for example, seizures — or neurodegenerative diseases such as Alzheimer's disease. It's important to establish the cause, because in some cases there are specific treatments that can reverse or slow the cause of memory loss.

Even among the degenerative diseases, it's worthwhile to get the most specific diagnosis possible. Alzheimer's disease refers to a particular disease process in the brain, with specific changes on brain-imaging markers, spinal fluid tests and pathology — although the last one can only really be assessed at autopsy.

There are other degenerative diseases that can cause identical symptoms, so we have to rely on special tests to figure out if someone may in fact have Alzheimer's disease. But some of these non-Alzheimer's degenerative diseases may not respond to medicines we use in Alzheimer's disease, or they may have other medicines that can help with symptoms, and generally the disease course can be very different.

The final important point raised by the question pertains to testing. Yes, there are specific tests that can be helpful.

An internist or general neurologist can evaluate for common medical diseases that may impact cognition, such as sleep apnea or vitamin or hormone deficiencies. This includes a detailed physical and neurological examination.

We recommend that patients with memory or cognitive concerns undergo formal neuropsychological testing unless it's clear from testing in the office that they will struggle significantly on formal testing. This is the best way to discern normal aging versus a disease process.

If cognitive impairment is confirmed and no clear cause is found on routine testing, a brain MRI should be done. This may reveal shrinkage of the brain, old strokes or brain bleeds. Depending on what is found, a consultation with a behavioral neurologist may be recommended, along with further testing.

The road to an accurate diagnosis can be long and frustrating, but it doesn't have to be. Mayo Clinic has an excellent book on Alzheimer's disease and related dementias that can serve as a guide through the process and important educational resource, with a new edition released in late 2020.

What questions should I be asking at my appointment?

Source: Mohamed Elminawy, M.B., B.Ch.

Research participants are the most valuable part of the Mayo Clinic Study of Aging. They are often very inquisitive about what we do. Typically, during a research visit, the participants go through an exhaustive list of tests and questions from researchers. One of our goals is to address any of their concerns as well. To this end, we always welcome any questions directed to us.

We at the Mayo Clinic Study of Aging firmly believe that proactive engagement will have a positive impact on the patient's overall experience. Examples of what we love to be asked include:

  • What are some of the latest discoveries in the field of aging and dementia?
  • What are the best available services that I can use to maintain my brain health?
  • How does my family history of dementia affect my risk of developing a similar condition?
  • Is there anything I can do to improve my memory?

Staff members in the Alzheimer's Disease Research Center and the Mayo Clinic Study of Aging are well trained, with extensive expertise, and are ready to answer all of your questions. We're equipped with a lot of resources, and we have many programs that we'd like to see our participants using more.

Are tau and amyloid proteins always present in the brain or do they develop over time?

Source: David T. Jones, M.D.

Tau and beta-amyloid proteins are necessary for the normal functioning of the brain and they are always present, but their exact role in normal brain function is an area of active scientific study.

However, with increasing age these proteins change into new forms that are not present in early life. The abnormal "clumped" forms of these proteins that appear later in life are the ones that are associated with Alzheimer's disease physiology.