Looking for early signs of Alzheimer’s

By the time memory loss shows up, the disease is well under way. Researchers are finding ways that may reveal brain changes sooner.

For a long time, memory loss was seen as the telltale sign of Alzheimer's disease. While this is certainly the most common symptom, it may not be the best way to identify the disease in its early stages.

"A major problem of Alzheimer's diagnosis, and ultimately effective treatment, is that by the time the first clinical symptoms appear, irreversible damage to the brain has already occurred," says Dr. Seth Gale, a neurologist with Harvard-affiliated Brigham and Women's Hospital. "It is now believed that Alzheimer's-related changes begin in the brain at least a decade before any symptoms emerge."

The goal for researchers and clinicians now is to move away from looking only at individual symptoms or one or two test results, and instead to find and use several approaches in a consolidated effort to identify Alzheimer's at an earlier point.

Why early detection?

While there is no cure for Alzheimer's, early detection makes it possible for people to participate in clinical trials to test the latest therapies. Also, taking FDA-approved medications and adopting brain-healthy behaviors like aerobic exercise and social stimulation can help people with early-stage disease improve their emotional health and shore up their cognitive performance in everyday activities. "Knowledge is power, and early detection can give people more time and opportunity to think about their future and plan what they may need," says Dr. Gale.

Some of these diagnostic techniques for Alzheimer's are still being explored, but here is a summary of the ones that are both regularly used in practice or show the most promise.

Blood tests

Researchers are close to developing blood tests that can predict the onset of Alzheimer's symptoms by measuring certain proteins linked with the disease.

In a 2014 study in Alzheimer's & Dementia, scientists tested 1,100 people with mild cognitive impairment and, based on levels of 10 proteins, were able to identify 87% of those who would later be diagnosed with dementia.

In another related study, published online Sept. 6, 2016, by Journal of Alzheimer's Disease, researchers looked at blood work from 292 people with early signs of memory impairment and found that those who progressed to Alzheimer's showed changes in certain proteins in the immune system that did not appear in those who did not develop the disease. High levels of these proteins are known to drive inflammation, both in the brain and the body, and have been linked with brain diseases.

Cognitive testing

People on Medicare are eligible for an annual wellness visit, which includes an evaluation of cognitive impairment. The screening tests are short questionnaires that assess mental skills, such as memory, attention, language, and visuospatial perception (the ability to process and interpret visual information about where objects are in space).

How effective these or other tests are for identifying or predicting early Alzheimer's is unknown — a 2014 report in Annals of Internal Medicine found inconclusive evidence — but Dr. Gale believes that such tests are often good for identifying problems that need to be further explored. "Cognitive screening tests allow doctors to recognize an emerging memory problem that may not always be apparent from what patients, or their family, report in the doctor's office," he says.

Further cognitive testing in the form of a neuropsychological evaluation — which typically requires a doctor's referral — or testing by a neurologist at a specialized memory center can enable a primary care doctor to confirm a suspicion of early-onset Alzheimer's. "This also can help detect subtle declines that a doctor might want to follow more closely," says Dr. Gale.

PET scans

A positron emission tomography (PET) scan detects radioactive tracers in a special dye that is injected into a vein in your arm. The movement of the tracers in the brain can highlight a change in the way brain cells process energy, which suggests Alzheimer's in certain patients. Newer tracers can also show a buildup of amyloid protein plaques and tangled or twisted tau proteins in the brain, both of which occur with Alzheimer's.

"Research is still being conducted to determine what amount of plaques and tangles indicates a risk of developing Alzheimer's symptoms or having the disease itself," says Dr. Gale. "But PET tracers are the closest means yet that researchers and doctors have for identifying these protein clumps in living patients."

Research published March 2, 2016, in the journal Neuron showed that PET scans also can help track Alzheimer's progression. Scientists looked at 53 adults ages 20 to 90, about half of whom were diagnosed with probable Alzheimer's. Using PET scans, the researchers found that with advancing age, more tau protein accumulated in the medial temporal lobe, which is home to the hippocampus and the brain's memory center.

The downside to PET scans is cost. Medicare and private insurance sometimes cover an older type of PET that looks only at how brain cells process energy. Newer PET scans, which show the buildup of plaques and tangles, are quite expensive. They can range from $4,500 to $6,000, and Medicare has not yet agreed to cover them. "All of these PET tests are now only done in certain circumstances, and ordered by neurologists to help make a diagnosis," says Dr. Gale.

MRI scans

Magnetic resonance imaging (MRI) can't find plaque buildup, but it helps spot patterns of tissue loss that are different from those seen in normal aging. MRI can also identify other reasons for cognitive changes, like small, silent strokes. By themselves, MRI scans are not sufficient for an Alzheimer's diagnosis, but often their results can be added to other information, like cognitive testing and specific symptoms, to help with a suspected diagnosis. Medicare and most insurers cover doctor-ordered MRI.

Depression

It is not clear if depression increases your chances of getting Alzheimer's, but research suggests the onset of depression in older age may be an early sign of the disease. A study reported at the Society of Nuclear Medicine and Molecular Imaging's 2014 Annual Meeting found that late-life depression was a predictive factor in the development of Alzheimer's symptoms. Researchers looked at 371 patients with mild cognitive impairment who underwent PET and MRI scans. The results showed that those who had depressive symptoms had higher amyloid protein buildup in their brains than those who were not depressed.

Behavior changes

Initial research has shown an association between sudden neuropsychiatric symptoms — such as anxiety, apathy, irritability, and restlessness — and the progression of Alzheimer's disease. "Observational studies have found that people with these behavior changes are more likely to develop cognitive issues," says Dr. Gale. "It may be that these changes are a reflection of early development of plaques and tangles, but this is not entirely clear. Still, it's a good idea to have symptoms like these checked out by your doctor."

Family history

People with a first-degree relative — such as a parent or sibling — with Alzheimer's are more likely to develop the disease, according to the Alzheimer's Association. "This doesn't mean you will get Alzheimer's, but it puts you at a higher risk, and you should be more aware of the early signs and symptoms," says Dr. Gale.

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