Signs of Alzheimer’s at an Early Age

Scientists studying Alzheimer’s disease are increasingly finding clues that the brain begins to deteriorate years before a person shows symptoms of dementia.

Now, research on a large extended family of 5,000 people in Colombia with a genetically driven form of Alzheimer’s has found evidence that the precursors of the disease begin even earlier than previously thought and that this early brain deterioration occurs in more ways than has been documented before.

The studies, published this month in the journal Lancet Neurology, found that the brains of people destined to develop Alzheimer’s clearly show changes at least 20 years before they have any cognitive impairment. In the Colombian family, researchers saw these changes in people ages 18 to 26; on average, members of this family develop symptoms of mild cognitive impairment at 45 and of dementia at 53.

These brain changes occur earlier than the first signs of plaques made from a protein called beta amyloid, a hallmark of Alzheimer’s. Researchers detected higher-than-normal levels of amyloid in the spinal fluid of these young adults. And they identified indications that brain areas known to be affected by Alzheimer’s may be smaller than in those who do not have the Alzheimer’s gene.

The Colombian family suffers from a rare form of Alzheimer’s that is caused by a genetic mutation; it strikes about a third of its members in midlife. Because the family is so large and researchers can identify who will get the disease, studying the family provides an unusual opportunity to learn about Alzheimer’s causes and pathology.

Researchers, led by Dr. Eric Reiman of the Banner Alzheimer’s Institute in Phoenix, and in Colombia by Dr. Francisco Lopera, a neurologist at the University of Antioquia, recently conducted a clinical trial to test a drug on family members before they develop symptoms, to see if early brain changes can be halted or slowed.

In one of the Lancet Neurology studies, researchers examined 44 relatives between ages 18 to 26. Twenty had the mutation that causes Alzheimer’s. The cerebrospinal fluid of those with the mutation contained more amyloid than that of relatives without it. This was striking because researchers know that when people develop amyloid plaques amyloid levels in their spinal fluid are lower than normal.

So, the high level of amyloid fluid in the Colombian family supports a hypothesis about a difference between the beginning phases of genetic early-onset Alzheimer’s and the more common late-onset Alzheimer’s. The difference may be that early-onset Alzheimer’s involves an overproduction of amyloid, while late onset involves a problem clearing amyloid from the brain.

In the second study, brain imaging was used to look for amyloid plaques in 50 people ages 20 to 56. Plaques occurred at an average age of 28, more than 15 years before cognitive impairment would be expected and two decades before dementia.

The study also found that amyloid plaques increased steadily until about age 37, after which the brain did not seem to gain many more plaques. Blennow said that while researchers know that amyloid plaques plateau when people already have dementia, they did not know that the plateau appears to occur years before.

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