Dementia, Drugs, and DNA

By Deborah Westover, MSN, RN, CNL, CNRN & Rachel Westman, MS, CGC

Dementia is a generic term commonly used to describe a decline in a person’s cognitive functioning, such as changes in their memory, judgment, or reasoning. Dementia is an umbrella term, meaning it covers a broad category of disorders that affect the brain. Dementia can be caused by vascular changes (most common in those who have had a stroke), Lewy bodies disease, Parkinson’s disease, frontotemporal degeneration, head injuries, and others; however, Alzheimer’s disease is the most common cause, accounting for about 60 to 80% of cases.

It is estimated that over 6 million Americans are living with Alzheimer’s disease.  About 1 in 9 people over the age 65 have Alzheimer’s disease. Also, certain populations such as older Black and Hispanic Americans are more likely to develop the disease.  By 2030 one of the largest population demographics, those born in mid to late 1940s to early 1960s, will all be over the age of 65–this means we have an aging population. Since age is one of the primary risk factors for Alzheimer’s disease, the number and proportion of cases is continually growing. 

Due to how common Alzheimer’s disease is, many individuals have personal experience caring for someone who is, or was, affected. It is estimated around 83% of those supporting and helping people with Alzheimer’s disease are family members, friends, or other unpaid caregivers. The impact can be great on caregivers and family members, leaving many to ask questions about what they can do to help reduce their own chances of developing the disease:

  • What steps can I take to reduce my own risk? 
  •  Are there treatments or medications that can be taken to prevent, lower the chance, or slow down the onset of disease? 
  • Is there testing available to help identify if I am at a higher risk for the disease?
  • Is there testing available which may determine early signs or stages of disease, not yet recognized?
  • What are my options?

In our digital world, it is easy to turn to the internet and start asking these questions; however, the variety of information and potential answers is vast.

Over the last several years, there have been many advances in the care and treatment of those with Alzheimer’s disease, as well as for those at risk. More and more companies are taking advantage of the opportunity to market their tests directly to consumers. One example is the role of APOE testing. In previous posts we discuss the role of genetics and genetic testing with Alzheimer’s disease (see “The Limits of Limitless” and “Alzheimer’s Disease and Genetics”), including the role of the gene APOE and important considerations before testing for one’s own APOE status.

The focus on testing for the APOE gene has drastically grown due to recent approval of the medication lecanemab (Leqembi). This is a medication that is approved by the FDA as a treatment, not a cure, for those with early stages of Alzheimer’s disease. This treatment has not been approved for asymptomatic individuals (those considered at risk but who have no symptoms) or for those with moderate or advanced disease. Studies suggest that lecanemab may help slow progression of disease. However, there can be side effects including ARIA (amyloid-related imaging abnormalities) that can cause small spots of brain bleeding and/or swelling. Individuals who develop ARIA may or may not present with symptoms, but can increase the risk for future small bleeds or swelling. As a part of the clinical trials, it was found that those who carry one (heterozygous) or two (homozygous) APOE e4 alleles are at an increased risk for ARIA. For this reason, the FDA is encouraging testing for APOE status before initiating treatment.

One article published in Reuters in April 2023 details: “In the four months ahead of U.S. approval of Leqembi in January, APOE4 testing among people over 55 who visited a doctor within the last 30 days increased 125%. From September 2022 to January 2023, the rate averaged 1.4 tests per 100,000 patients, compared with 0.6 tests per 100,000 patients in the same period a year earlier, the analysis by Seattle-based Truveta found.” 

The recommendation to receive testing is understandable, since the hope is to help reduce the risk of complications from lecanemab (Leqembi) for those with early stages of disease who may receive treatment. However, there are likely limitations in accessing testing, including the coverage of testing by insurance and gaps in available appropriate follow-up care and counseling of individuals, and subsequently their families, who are undergoing APOE testing.  Many clinics and centers are not set-up to provide genetic counseling for everyone undergoing testing.

Due to the increased appeal in assessing one’s own risk for Alzheimer’s disease, direct to consumer marketing of testing options has grown beyond just APOE testing. For example, “AD-Detect” is a test that was released this summer by Quest and can be patient initiated (does not require a visit with a provider). This test involves measuring two blood-based biomarkers (beta amyloid 42 and beta amyloid 40). On Quest’s website the company states the test, “may help to detect the risk of Alzheimer’s disease before severe mental decline” by measuring the ratio of the biomarkers. In an article published by WIRED last month (August 2023) regarding this testing: “Quest’s medical director of neurology, said the test was 89 percent accurate at identifying people with elevated levels of amyloid in the brain and 71 percent accurate at ruling out those who did not have elevated amyloid, based on data the company presented at the 2022 Alzheimer’s Association International Conference.”

It is important to note, this testing is merely measuring a person’s possible risk of disease and is not diagnostic of Alzheimer’s disease. There is a lack of data available regarding whether this testing can predict whether someone will develop disease. As quoted by MedPage Today, Rebecca Edelmayer, PhD, the senior director of scientific engagement with the Alzheimer’s Association, “as a result, it is unclear what the results of this test may mean about your Alzheimer’s risk or your health status,” and “there is a lack of data to support the broad use of these tests tests in primary care settings, let alone individually by consumers at home.” The diagnosis of Alzheimer’s disease is based on a combination of evaluations including brain imaging, other lab studies, possible neuropsychological evaluation, and the review of a person’s medical history. Individuals who opt to undergo such testing may be left with more questions than answers without a more complete assessment.

What are your best options?

With all the information that is available at your fingertips, it is always important to consult with your primary care provider, especially before opting for lab-based testing (genetic or non-genetic based testing).

While we cannot change our genetics, we can control the modifiable risk factors for the disease, such as following a brain health lifestyle, protecting yourself from head injuries, not using tobacco, or avoiding excessive alcohol consumption. A brain healthy lifestyle includes eating a healthy diet, staying socially active, and regularly exercising. Examples of brain healthy diets include the Mediterranean, DASH (Dietary Approaches to Stop Hypertension), and MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay).

If interested, get involved in clinical research trials to develop better treatments and find ways to prevent the disease. The Alzheimer’s Association has a wonderful tool called “TrialMatch” that will connect you to active clinical trials that are recruiting individuals living with Alzheimer’s disease, caregivers, or healthy volunteers – TrialMatch.

Lastly, pull information from trusted resources, such as the following:

Genetic counseling for Alzheimer’s disease involves a review of your personal health and family history so that we may provide a more personalized assessment of your risk. A genetic counselor can answer questions and discuss the potential risks, benefits, and limitations of genetic testing that is currently available, and can help put any testing you have already had into context.If you have questions about Alzheimer’s disease and your family, consider scheduling an appointment with one of our board certified genetic counselors.