Researchers see changes linked to the disease in subjects ages 3 to 20 years old

Changes in the brain associated with Alzheimer’s disease can be seen as early as childhood in people with a heightened genetic risk, according to a study published Wednesday in the journal Neurology.

Research on Alzheimer’s has largely focused on the characteristic proteins that build up in the brain in old age, but experimental drugs meant to target those symptoms have been disappointing. One relatively new theory is that the mind-robbing disease is actually a developmental disorder that begins much earlier in life.

The new study “very significantly extends that” hypothesis, said Rebecca Knickmeyer, a developmental cognitive neuroscientist at the University of North Carolina at Chapel Hill, who wasn’t involved in the research.

Alzheimer’s is the most common form of dementia among the elderly. Symptoms may start with mild memory loss. In later stages, patients might have trouble speaking, reading and writing.

For the study, scientists tapped a dataset of 1,187 healthy children and young adults ranging in age from 3 to 20 years old for whom brain-imaging and cognitive-testing data were available. The youngsters also had been tested for variants of a gene associated with Alzheimer’s risk, known as apolipoprotein E, or the APOE gene. Each person has two copies of the APOE gene, one inherited from each parent.

The team found that in some people with at least one copy of the so-called e4 variant—the version most associated with heightened Alzheimer’s risk—the size of the hippocampus was significantly smaller than in other young people in the study. The hippocampus is the seahorse-shaped brain region involved in memory formation.

Certain regions of the cerebral cortex involved in tasks like object recognition and decision-making also were among the smallest in people with at least one copy of the e4 variant.

These kinds of changes in brain structure are often “thought to be a result of Alzheimer’s disease,” said Linda Chang, the director of the Neuroscience and MRI Research program at the University of Hawaii in Manoa and the study’s lead author. But they “might be present already in childhood.”

The scientists also examined cognitive-test scores of the young people and found that children with a small hippocampus fared worst on certain memory tests, especially those with two copies of the e4 variant.

The correlation between test scores and genetic traits was inconsistent. For instance, the lowest scores on attention tests were from children with thicker cortices who had one e4 and one e2 variant, a trait thought to be protective against Alzheimer’s. The researchers said this suggests the need to test more children who carry e2, the least-common version of the APOE gene, to see how it affects brain function.

The results, wrote Dr. Knickmeyer in an editorial that accompanies the study, “do not have immediate implications” clinically. But, they are part of a growing body of work that suggests Alzheimer’s is a developmental condition and provide a road map for future research. Studies that follow children through adolescence and into adulthood will be necessary to evaluate brain development in more detail, she said. Here, each child was tested only at one point in their young life.