Automatic MRI volumetry in asymptomatic cases at risk for normal pressure hydrocephalus

Sven Haller; Marie-Louise Montandon; Cristelle Rodriguez; François R Herrmann; Panteleimon Giannakopoulos

doi:10.3389/fnagi.2023.1242158

Automatic MRI volumetry in asymptomatic cases at risk for normal pressure hydrocephalus

Front Aging Neurosci. 2023 Nov 3:15:1242158. doi: 10.3389/fnagi.2023.1242158. eCollection 2023.

Authors

Sven Haller^{1

2

3

4}, Marie-Louise Montandon⁵, Cristelle Rodriguez⁶, François R Herrmann⁵, Panteleimon Giannakopoulos^{6

7}

Affiliations

¹ CIMC - Centre d'Imagerie Médicale de Cornavin, Geneva, Switzerland.
² Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden.
³ Faculty of Medicine, University of Geneva, Geneva, Switzerland.
⁴ Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
⁵ Department of Rehabilitation and Geriatrics, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
⁶ Division of Institutional Measures, Medical Direction, Geneva University Hospitals, Geneva, Switzerland.
⁷ Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Abstract

The occurrence of significant Alzheimer's disease (AD) pathology was described in approximately 30% of normal pressure hydrocephalus (NPH) cases, leading to the distinction between neurodegenerative and idiopathic forms of this disorder. Whether or not there is a specific MRI signature of NPH remains a matter of debate. The present study focuses on asymptomatic cases at risk for NPH as defined with automatic machine learning tools and combines automatic MRI assessment of cortical and white matter volumetry, risk of AD (AD-RAI), and brain age gap estimation (BrainAge). Our hypothesis was that brain aging and AD process-independent volumetric changes occur in asymptomatic NPH-positive cases. We explored the volumetric changes in normal aging-sensitive (entorhinal cortex and parahippocampal gyrus/PHG) and AD-signature areas (hippocampus), four control cortical areas (frontal, parietal, occipital, and temporal), and cerebral and cerebellar white matter in 30 asymptomatic cases at risk for NPH (NPH probability >30) compared to 30 NPH-negative cases (NPH probability <5) with preserved cognition. In univariate regression models, NPH positivity was associated with decreased volumes in the hippocampus, parahippocampal gyrus (PHG), and entorhinal cortex bilaterally. The strongest negative association was found in the left hippocampus that persisted when adjusting for AD-RAI and Brain Age values. A combined model including the three parameters explained 36.5% of the variance, left hippocampal volumes, and BrainAge values, which remained independent predictors of the NPH status. Bilateral PHG and entorhinal cortex volumes were negatively associated with NPH-positive status in univariate models but this relationship did not persist when adjusting for BrainAge, the latter remaining the only predictor of the NPH status. We also found a negative association between bilateral cerebral and cerebellar white matter volumes and NPH status that persisted after controlling for AD-RAI or Brain Age values, explaining between 50 and 65% of its variance. These observations support the idea that in cases at risk for NPH, as defined by support vector machine assessment of NPH-related MRI markers, brain aging-related and brain aging and AD-independent volumetric changes coexist. The latter concerns volume loss in restricted hippocampal and white matter areas that could be considered as the MRI signature of idiopathic forms of NPH.

Keywords: Alzheimer; MRI markers; brain aging; hippocampus; normal pressure hydrocephalus; vector machine assessment; white matter.

Grants and funding

This research was carried out with the help of an unrestricted grant from the Association Suisse pour la Recherche sur Alzheimer, an unrestricted grant from the Schmidheiny Foundation, and the Swiss National Foundation (grant nos. 320030-169390, and 320030_169876).