By Nancy Tannler
In the April Brain Awareness lecture series, Oregon Health Sciences University (OHSU) presented an online talk titled, “Is prevention of Alzheimer’s disease possible?” Dr. Aimee Pierce, associate professor of neurology and Director of Clinical Care and Therapeutics in the Layton Aging and Alzheimer’s Disease Center, spoke about the most current information available on Alzheimer’s disease (AD). The event was moderated and supported by Helmi Lutsep and Kate Stout.
According to Dr. Pierce, the two strongest factors of AD-related dementias (ADRD) are aging and genetics. The likelihood is increased by ethnicity; in African Americans, there is a 14 percent chance; Hispanic, 12 percent; non-Hispanic white, 10 percent.
AD is one form of dementia; others are Parkinson’s, frontal temporal lobar degeneration, vascular dementia and dementia with the Lewy bodies.
Dr. Pierce’s statistics state that there are approximately six million people living with AD. These numbers are expected to rise to nearly 14 million by 2060 and the likelihood of contracting AD doubles in frequency every five years after the age of 60.
With normal aging, Dr. Pierce said there are certain cognitive changes that occur such as attention, word finding and short-term memory that can be compensated by daily living activities. Dementia, however, is not a normal part of aging. When there are serious problems with language, memory loss, judgment and reasoning–in other words complex and daily activities–this is serious.
Scientists first discovered Alzheimer’s in 1906. Until recently, most of the research to cure the disease has been disappointing. There are three pathologies that are assessed when treating AD–cerebral atrophy, amyloid plagues and neurofibrillary tangles.
Dr. Pierce said neuroscientists have come up with ways to test people to determine the stages of the disease and they can even tell pre-symptomatic people if they have it. The tests are PET scans, cerebrospinal fluid and blood tests. Unfortunately, Medicare does not cover the cost of these tests or the available medicines.
The biomarkers they are looking for are amyloid plaques and tau tangles. Amyloid plaques are misfolded proteins that develop in the spaces between nerve cells and begin in the areas of the brain concerned with memory. Tau tangles detach from microtubules and stick to other tau molecules that eventually form tangles, thus harming the synaptic communication between neurons.
“Over the years, many clinical trials targeting amyloids had negative responses, until 2021,” Dr. Pierce said, “when the FDA approved aducanumab.” After 18 months of investigational treatment, patients had noticeably less amyloid plague in their brains.
In January 2023, lecanemab came on the market. It may moderately slow mild cognitive decline and reduce amyloid plaques in patients with early AD.
“Studies to prevent tau tangles are being developed in the form of antibodies and vaccines,” said Dr. Pierce. The approach is to prevent microtubule-binding (hyperphosphorylation) of tau and stabilize these fragments in neurons and reduce their growth.
Most people have developed active immunities over their lifetime that will prevent them from developing AD. Passive immunity, like antibodies received from mother’s milk or medicine, however, has no effect.
Scientists also know more about the risk factor genes. In one percent of all cases there is a mutation to one of three genes that causes very early onset–30s, 40s, 50s. For the other 99 percent there are several genes that have been identified as AD markers. The most common is APOE, a lipid transport protein. The risk of having this gene increases three-fold if a parent has AD–which is stronger in the maternal than paternal family history. You can also carry this gene and never get AD.
What neuroscientists have discovered will make a difference in early detection and intervention in AD. Amyloid accumulates in the brain a decade or more before memory loss symptoms show up.
“Think about what happens in cancer, atherosclerosis, osteoporosis…if we wait to treat until after symptoms appear,” said Dr. Pierce. “Intervention prior to dementia (widespread irreversible brain cell loss) may likely have a better chance of changing the course of the disease.”
AD is exacerbated by inflammation, not unlike other diseases of modern society. Lifestyle and environment are important. Dr. Pierce recommends a healthy Mediterranean diet, controlling diabetes and hypertension, getting a good night’s sleep, protecting your brain (wear a helmet), keeping your mind active and getting regular exercise.
OHSU is doing a clinical study aimed at enrolling 1,400 older adults with normal memory loss and intermediate or elevated amyloid levels. They will do an initial screening based on blood test for amyloid. Participants will receive an amyloid PET brain scan and be given an anti-amyloid antibody–lecanemab–every two to four weeks for four years. To learn more, visit aheadstudy.org.