A large-scale international study involving more than 10,000 MRI scans and more than 13,000 memory tests on 3,700 cognitively healthy adults from 13 independent projects showed that age-related memory loss is associated with widespread structural changes in several brain regions.
The analysis showed that brain volume loss and memory decline are non-linearly related; as long as structural changes remain moderate, memory can be maintained at a stable level. However, as the rate of atrophy increases, cognitive decline accelerates disproportionately and progresses more rapidly, particularly in old age.
As the researchers predicted, the strongest connections were found in the hippocampus, the brain region crucial for memory formation and retention. However, the changes are not limited to this area. Significant connectivity was also found in numerous cortical and deep brain structures, suggesting that the impairment affects entire neural networks. Thus, memory loss reflects not just a failure in one region, but rather a general state of the brain.
The researchers emphasized that the discovered patterns cannot be explained solely by known genetic risk factors for Alzheimer's disease, such as the APOE ε4 variant, as people who do not carry these genetic traits also showed structural changes accompanied by memory impairment.
This suggests that normal brain aging cannot be reduced to a simple model that identifies "one gene or one disease," because age-related memory loss reflects the cumulative biological decline of the brain over decades. The hippocampus plays an important role, but it is part of a broader network encompassing the entire brain.
