A newer approach to improve diagnosis and treatment of Alzheimer’s disease involves what is called “precision medicine.” This means taking into consideration a patient’s genes, environment, and lifestyle in order to customize treatment. Dr. Howard Fillitt suggests that research on biomarker blood tests and monoclonal antibody drugs can help primary care physicians to better understand a patient’s symptoms and prescribe treatment for each person’s actual needs.

Blood tests measure fragments of various Alzheimer’s proteins that have entered the bloodstream from the brain. The best biomarkers indicate whether a person has Alzheimer’s pathology, beta-amyloid plaques and tau tangles, in the brain.  The use of blood tests is less invasive and costs less than a lumbar puncture or an amyloid PET scan. It could result in Alzheimer’s diagnoses being done faster and earlier so a patient can begin receiving appropriate treatment sooner. However, as of this writing, none of these tests have been FDA approved, nor are they standardized, according to Dr. Nicholas Ashton, neurologist and senior director of Banner Health’s Research Blood-Based Biomarker Program.

Monoclonal antibody drugs (called “mab” drugs) are used for the treatment of many diseases, including cancer. Some mab drugs are considered immunotherapies, because they help the immune system recognize and destroy certain target cells. In Alzheimer’s treatment this technology is used to seek out beta-amyloid protein cells, one of this disease’s most common pathological traits. These Alzheimer’s anti-amyloid mab drugs are the disease’s first disease-modifying drugs, because they work to prevent the buildup of these amyloid plaques in the brain. Two of these drugs are Leqembi, which attaches to beta-amyloid before it forms plaques, and Kisunla, which attaches to beta-amyloid once it has formed the plaque. Kisunla is for people in the earliest stages, when symptoms are still mild. Research has shown that the earlier in their course of disease that the participants received the drug, the more improvement they experienced in the trials. This highlights the need for more accurate and accessible diagnostic tools so that Alzheimer’s can be caught earlier, ideally before symptoms even appear. And it is important to note that Kisunla is not a cure, but a drug that might help slow the progression of Alzheimer’s disease. 

If drugs are able to remove the plaques in people who are already diagnosed with mild cognitive impairment or mild dementia, Dr. Fillitt believes the progression of Alzheimer’s disease can be slowed down by about 30 or 35 percent. If people in the community are screened with blood tests, and the tests reveal that they have an elevated p tau, that means that they’re cooking the disease, but they don’t have symptoms.  A brain scan can confirm the diagnosis, and then they can be put on these drugs that remove the plaques in the pre-clinical stage of the disease, hopefully delaying the onset of symptoms.

The goal is tocombine lifestyle management with drug treatment in the same way as it is done in heart disease. The FINGER study has shown that managing five risk factors – exercise, socialization, cognitive stimulation, and management of diabetes and hypertension- you can delay the onset or slow the rate of cognitive decline in aging people and in people with mild cognitive impairment. FINGER is being replicated in about 62 countries around the world, so it’s a very powerful prevention model.

According to Dr. Fillitt, if we could delay the onset of symptoms from Alzheimer’s disease by just five years, it might reduce the number of cases of Alzheimer’s by 50 percent, since the average age of onset of dementia or symptoms from Alzheimer’s is about 75 and the average age of death is about 80. Most 80-year-olds would value having an extra year recognizing their grandchildren and being able to function independently. Precision medicine could allow people to get an extra year or so of stability before progressing to the next stage of the disease and needing much more caregiving. 

With precision medicine the role of primary care is to determine who needs to be referred to a specialist for further evaluation; this can often be done with a 10-minute cognitive assessment. If that assessment reveals cognitive impairment, the next step is to determine its cause. It could be the result of too many medications, lack of restorative sleep, depression, B-12 deficiency, sleep apnea, or other causes. Once those are ruled out, the next step is to determine if it is Alzheimer’s, so the primary physician will probably refer his/her patient to a neurologist.

It must also be noted that not everyone with plaques and even tangles in the brain has cognitive impairment. Some 95-year-olds were robust and still working when they died, and while the autopsy revealed that their brains are filled with plaques, they had no cognitive impairment while alive. That is why doing a cognitive assessment is so important as part of the workup to see if people have symptoms. Since many of these drugs come with risks and potentially serious side effects, patients need to discuss with their physicians whether or not to take them.