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 or a-beta, a hallmark of Alzheimer’s. Researchers detected higher-than-normal levels of amyloid in the spinal fluid of these young adults. They found suggestions that memory-encoding parts of the brain were already working harder than in normal brains. 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.