When the memory flickers out

Facts, faces, experiences: Our brain’s capacity to learn new things, store the memories and summon them up on demand is a marvel. Yet we take it all for granted until the skills start to crumble in those we love, or in ourselves.

What goes awry in the brain to make this happen?

Dementia is a collection of problems with thinking, learning and memory that are bad enough to interfere with daily living. And it doesn’t have a single origin. A variety of events, singly or together, can damage or kill brain cells, or interfere with how they talk to one another, and thus cause the condition.

By far the most common cause in older adults is Alzheimer’s disease, which accounts for 60% to 80% of dementia cases, according to the Alzheimer’s Assn. in Chicago. An additional 10% or so of cases are caused by damage to the blood vessels in the brain, or cerebrovascular disease.

Scientists still don’t fully understand Alzheimer’s, though they’ve seen lots of changes in the brains of people who have it. Abnormal versions of normal body proteins build up inside and outside brain cells, for example. And the brain becomes inflamed.

But the specific things that set off the disease and influence how it progresses are something of a mystery, says Heather Snyder, senior director of medical and scientific operations at the Alzheimer’s Assn.

The most agreed-upon theory starts with snippets of brain protein called amyloid-beta. These clump together in the spaces between brain cells to form ugly lesions called plaques.

Amyloid-beta then seems to cause another protein — this time, one inside brain cells — to go bad, says Dr. Helena Chui, director of the Alzheimer Disease Research Center at the USC Keck School of Medicine. This protein, tau, normally helps brain cells transport nutrients from one end of the cell to the other. When tau sticks together in another kind of lesion called a tangle, the nutrient flow is disrupted, and the brain cells sicken.

In their weakened state, they don’t communicate properly. This causes the difficulty in thinking that manifests as dementia. Eventually, brain cells die and the brain shrinks faster than it normally does in an aging person. Alzheimer’s disease almost always gets worse over time.

The main risk factor for Alzheimer’s is unavoidable — getting older. One in 10 people over age 65 will develop it, Snyder says; for those who reach 85 or older, the rate rises to 1 in 3.

Genes also make a big contribution. In a few cases, a single gene variant passed from parent to child makes Alzheimer’s all but inevitable. But for the vast majority of people who get the disease, the cause is uncertain. Other genes might contribute, but their effects are weaker, and there are more than two dozen that could be involved.

“They increase your risk, but they are not guaranteeing that you’ll develop the disease,” Snyder says.

The most powerful of these risk genes is Apolipoprotein E, or APOE. Its regular job in the body is to direct the manufacture of a protein involved in moving fats around. The undesirable version is known as APOE-e4, and one bad copy will raise a person’s risk of Alzheimer’s by perhaps three or four times, says Dr. Paul Aisen, director of the Alzheimer’s Therapeutic Research Institute of USC in San Diego. Two copies of APOE-e4 (one from each parent) raises the risk by more than 10 times.

Dementia caused by cerebrovascular disease is different. A stroke or other blockage in the vessels cuts off blood supply to parts of the brain, killing the cells in the area. If that happens to a brain region involved in memory, thinking or learning, dementia will result.

Maintaining a healthy heart and blood vessel system can help stave off this kind of dementia. Don’t smoke, Snyder says. Managing conditions such as obesity, hypertension and diabetes also helps.

A number of activities seem to reduce the risk for dementia. A trial of more than 2,500 older adults at risk for dementia tested whether interventions such as a tailored diet, an exercise program, brain training and close monitoring of risk factors for vascular disease would make people less likely to wind up with the condition.

After just two years, the participants who received the interventions had higher scores on memory and thinking tests than the participants who just followed regular health advice. The results were reported in 2015 in the journal Lancet.

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