Micro-strokes mimic Alzheimer’s Disease

SAN DIEGO — In the mid-20th century, senior citizens suffering from hopelessly muddled thinking were generally described as having hardening of the arteries. Today, they are characterized as having Alzheimer’s disease. But a new study suggests the disease accounts for only about half the cases of dementia. Many instead trace to a previously unappreciated source: microscopic losses of blood flow in the brain.

These cause small infarcts — regions that die when starved of blood — explains University of Washington pathologist Thomas Montine. The dead brain segments, caused by some as-yet-undiagnosed disease that targets the body’s smallest vessels, “are too small to see with your eye,” he says, or even with advanced imaging technologies. The smaller-than-a-pin-prick areas of dead tissue emerge “only when you’re dissecting the brain,” he reported April 6 in San Diego at the annual Experimental Biology meeting.

“Under the microscope, they look like any other stroke,” he said, “just much, much smaller.”

A small number of them would probably go unnoticed. However, a lifetime’s accumulation in areas of the brain that affect cognition create a slowly developing loss of memory and reasoning ability. “It looks more like a dementia syndrome than a stroke,” Montine says. And because the memory problems reflect cell death, it’s irreversible with drugs or any other therapy.

Montine’s group made the discovery while studying the brains from elderly participants who had been in an ongoing Adult Changes in Thought study in the Seattle area. At the time of their recruitment, the 3,400 men and women enrolled to date had to be at least 65 years old, mentally healthy and members of a local health maintenance organization.

The recruits are representative of the general local population, with one-third eventually developing dementia. Every two years they received free health and psychological exams. They are also encouraged to donate their brains to science when they die; so far about one in five has agreed to do so.

Montine and his colleagues have been probing the donated organs, some 300 brains to date. Among those from dementia patients, 45 percent showed evidence of Alzheimer’s disease. Another 10 percent exhibited a hallmark of Parkinson’s and related neurological conditions called Lewy body disease. These conditions are characterized by abnormal accumulations of a particular protein, alpha-synuclein.

But the “big surprise,” Montine says, was the discovery that 33 percent of people who had dementia at death showed no neurological symptoms other than the micro infarcts. The same magnitude of this unusual vascular disease, he says, has been witnessed in only one other major group — participants of the Honolulu Asian American Study. But these were all men, a large number of them smokers and all of Japanese descent. The unusual share of microvascular brain disease in that population was attributed to those factors — and was not expected to represent what would occur in the general U.S. population. Especially, Montine adds, in people who all had ready access to affordable health care.

Whether this microvascular damage occurred throughout the body or only in the brain is unknown, Montine says, because only the brains were available for study. What triggered the microvascular disease also remains unknown, though Montine has an idea. “We’re sure suspicious about diabetes and hypertension,” he says. “And I can tell you that we have some preliminary results that support that.”

Right now, when dementia begins to develop, doctors and drug companies often target such patients for treatment with Alzheimer’s medicines. “Our data,” says Montine, “suggest that such drugs will not work in about half of the cases — simply because the dementia is due to other causes.”

The potentially good news, he says, is that if diabetes or high blood pressure does foster microvascular dementia, there are plenty of good medicines available to treat those diseases. Targeting at-risk individuals with early treatment might slow or halt the progression of dementia in a large share of the population.