The brain reveals key differences between Alzheimer’s and another form of cognitive decline

A recent analysis highlights structural differences in the brain between Alzheimer’s disease and another form of cognitive decline known as suspected non-Alzheimer’s pathology. The latter is characterized by an abnormal accumulation of the tau protein in the absence of beta-amyloid deposits, a protein often associated with Alzheimer’s. Researchers examined more than twelve hundred participants to understand how these two conditions affect the volume of the hippocampus, a brain region essential for memory and learning.

The results show that individuals with Alzheimer’s disease have a significantly reduced total hippocampal volume compared to other groups. More specifically, atrophy affects the posterior part of this structure more, while the anterior part appears relatively preserved. This disparity creates an imbalance between the anterior and posterior volumes, a phenomenon less pronounced in individuals with non-Alzheimer’s pathology or without markers of decline.

In people without markers of disease, as well as in those with non-Alzheimer’s pathology, the volume of the hippocampus decreases gradually with age. In contrast, in Alzheimer’s patients, this reduction seems less influenced by natural aging, suggesting that the disease accelerates atrophy independently of age. Researchers also observed that the volumes of the different parts of the hippocampus are linked to cognitive performance, neuropsychiatric symptoms, and levels of dependence in daily activities.

Biological markers in the cerebrospinal fluid, such as tau and beta-amyloid proteins, play a key role in these observations. In Alzheimer’s patients, reduced hippocampal volumes correlated with abnormal levels of these proteins, confirming their involvement in cognitive degradation. In contrast, in individuals with non-Alzheimer’s pathology, only tau concentrations appeared associated with localized atrophy, particularly in the posterior and intermediate parts of the hippocampus.

A notable finding is that the ratio between the anterior and posterior volumes of the hippocampus could help distinguish between the two conditions, particularly in people under sixty years old. This ratio shows a moderate ability to differentiate Alzheimer’s patients from others, although this distinction becomes less clear with age.

Finally, the study emphasizes that hippocampal atrophy, particularly in its posterior part, is not only an indicator of the current severity of the disease but could also predict the future progression of symptoms. These findings reinforce the idea that the hippocampus does not degrade uniformly and that its different parts play distinct roles in cognitive disorders.

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DOI: https://doi.org/10.1007/s00234-026-04061-1

Title: Differential atrophy along the longitudinal axis of the hippocampus in Alzheimer’s disease and suspected non-Alzheimer’s disease pathophysiology (SNAP)

Journal: Neuroradiology

Publisher: Springer Science and Business Media LLC

Authors: Torcato Meira; Rafaela Morais-Ribeiro; Tiago Jesus; Marcelo Dias; Ana Coelho; Tiago Gil Oliveira