Re-defining Alzheimer’s disease—maybe

Alzheimer’s disease is characterized by abnormal protein deposits in the brain. It begins with an asymptomatic phase and progresses—if the person lives long enough—to mild cognitive impairment and, eventually, a level of impairment that interferes with the daily process of living.

Researchers have developed two types of tests to diagnose Alzheimer’s before symptoms appear: blood tests that identify biomarkers, and genetic tests that identify the problematic genes. The tests show the full spectrum of the disease, beginning with the seeds of pathology deep inside the brain and ending with dementia.

Biomarker tests. A blood test can detect changes in the brain that predict Alzheimer’s disease up to 15 years before the first symptoms emerge.

Genetic tests: Genetic tests can identify a group of susceptibility genes—APOE—indicating an increased likelihood of developing Alzheimer’s disease by age 85. If you have a single copy of the APOE e4 gene, you are two to three times more likely than the general population to get Alzheimer’s by age 85. If you have two copies, you are 12 times more likely to develop the disease.  

Several groups are working to develop guidelines for diagnosing Alzheimer’s. It’s controversial. The working groups disagree on the word “diagnosis” when referring to the results of the blood test. Some prefer the word “risk,” believing that people should not be diagnosed with the disease based on biomarkers alone.

About drugs and treatment:

• Two drugs have been shown to reduce the disease progression by 27 percent, although their effectiveness in the later stages of the disease or in asymptomatic people, is unproven. The drugs cost $26,000 to $32,000 a year, with side effects that include a risk of swelling and bleeding in the brain.
• There are currently no treatments for those who have the biomarkers but not the symptoms.
• New guidelines discourage routine testing of asymptomatic people except in the context of research. But clinical trials of Alzheimer’s drugs are under way for treating people whose blood tests for the disease are positive. If such drugs prove successful, pre-symptomatic testing may become routine.  

About conflicting evidence:

• A substantial number of the people diagnosed with Alzheimer’s—based on blood and genetic tests—will die without ever having exhibited signs of dementia.
• Postmortem studies have found that up to 30 percent of people who received a clinical diagnosis of Alzheimer’s disease did not have the characteristic plaques and tangles in their brains.
• Many people have the plaques and tangles—as shown in postmortem dissections—but not dementia. In a famous study of 678 nuns, ages 75 to 107, postmortem dissections showed that the brains of many of the nuns had all the plaques and tangles of Alzheimer’s disease, but that their owners had shown no signs of dementia when they were alive. In fact, in 80% of the cases the pathology, as revealed in their brains, did not concur with the symptoms seen during life.

Something else is going on here. 

By the way, 23andMe gives you the choice of not looking at the results of the APOE gene test. I gathered up the courage, looked and got the following message: "Constance, you do not have the ε4 variant we tested." Whew!

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