# Regional brain volume changes in Hakim’s disease versus Alzheimer’s and mild cognitive impairment

## TL;DR

This study compares brain volume changes in Hakim’s disease, Alzheimer’s disease, and mild cognitive impairment to better understand their distinct patterns and underlying mechanisms.

## Contribution

The study identifies disease-specific brain volume changes in Hakim’s disease using an AI-based segmentation tool and compares them with Alzheimer’s disease and mild cognitive impairment.

## Key findings

- Hakim’s disease shows reduced volume in the supramarginal and paracentral gyri compared to healthy controls.
- Alzheimer’s disease is marked by hippocampal and temporal lobe atrophy, especially in the entorhinal cortex and fusiform gyrus.
- Mild cognitive impairment in older adults shows brain volume ratios similar to healthy controls.

## Abstract

Idiopathic normal-pressure hydrocephalus (Hakim’s disease) is characterized by ventricular enlargement and disproportionately enlarged subarachnoid space hydrocephalus, leading to localized brain deformation. Differentiating regional brain volume changes in Hakim’s disease from those in Alzheimer’s disease, Hakim’s disease with Alzheimer’s disease, and mild cognitive impairment provides insights into disease-specific mechanisms. This study aimed to identify disease-specific patterns of brain volume changes in Hakim’s disease, Alzheimer’s disease, Hakim’s disease with Alzheimer’s disease, and mild cognitive impairment and compare them with those in cognitively healthy individuals using an advanced artificial intelligence-based brain segmentation tool.

The study included 970 participants, comprising 52 patients with Hakim’s disease, 256 with Alzheimer’s disease, 25 with Hakim’s disease with Alzheimer’s disease, 163 with mild cognitive impairment, and 474 healthy controls. The intracranial spaces were segmented into 100 brain and 7 CSF subregions from 3D T1-weighted MRIs using brain subregion analysis. The volume ratios of these regions were compared among the groups using Glass’s Δ, referencing 400 healthy controls aged ≥50 years. Hakim’s disease exhibited significant volume reduction in the supramarginal gyrus of the parietal lobe and the paracentral gyrus of the frontal lobe. Alzheimer’s disease exhibited prominent volume loss in the hippocampus and temporal lobe, particularly in the entorhinal cortex, fusiform gyrus, and inferior temporal gyrus. Hakim’s disease with Alzheimer’s disease showed significant volume reductions in the supramarginal gyrus of the parietal lobe, similar to Hakim’s disease, whereas temporal lobe volumes were relatively preserved compared with those in Alzheimer’s disease. Patients with mild cognitive impairment aged ≥70 years had comparable regional brain volume ratios with healthy controls in the same age group. The Hakim’s disease and Hakim’s disease with Alzheimer’s disease groups were characterized by volume reductions in the frontal and parietal lobes caused by disproportionately enlarged subarachnoid space hydrocephalus-related compression compared with temporal lobe atrophy observed in the Alzheimer’s disease group. These disease-specific morphological changes highlight the need for longitudinal studies to clarify the causes of compression and atrophy.

Yamada et al. used a deep learning model to automatically segment 3D T1-weighted MRI images into 100 detailed brain subregions and 7 CSF subregions, discovering that the volume ratios of the supramarginal gyrus and paracentral gyrus were smaller in patients with Hakim's disease (idiopathic normal-pressure hydrocephalus) compared to healthy controls.

Graphical Abstract