MRI biomarkers and neuropsychological assessments of hippocampal and parahippocampal regions affected by ALS: A systematic review

Abstract

Background and ObjectiveAmyotrophic lateral sclerosis (ALS) is a progressive motor and extra‐motor neurodegenerative disease. This systematic review aimed to examine MRI biomarkers and neuropsychological assessments of the hippocampal and parahippocampal regions in patients with ALS.MethodsA systematic review was conducted in the Scopus and PubMed databases for studies published between January 2000 and July 2023. The inclusion criteria were (1) MRI studies to assess hippocampal and parahippocampal regions in ALS patients, and (2) studies reporting neuropsychological data in patients with ALS.ResultsA total of 46 studies were included. Structural MRI revealed hippocampal atrophy, especially in ALS‐FTD, involving specific subregions (CA1, dentate gyrus). Disease progression and genetic factors impacted atrophy patterns. Diffusion tensor imaging (DTI) showed increased mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and decreased fractional anisotropy (FA) in the hippocampal tracts and adjacent regions, indicating loss of neuronal and white matter integrity. Functional MRI (fMRI) revealed reduced functional connectivity (FC) between the hippocampus, parahippocampus, and other regions, suggesting disrupted networks. Perfusion MRI showed hypoperfusion in parahippocampal gyri. Magnetic resonance spectroscopy (MRS) found changes in the hippocampus, indicating neuronal loss. Neuropsychological tests showed associations between poorer memory and hippocampal atrophy or connectivity changes. CA1‐2, dentate gyrus, and fimbria atrophy were correlated with worse memory.ConclusionsThe hippocampus and the connected regions are involved in ALS. Hippocampal atrophy disrupted connectivity and metabolite changes correlate with cognitive and functional decline. Specific subregions can be particularly affected. The hippocampus is a potential biomarker for disease monitoring and prognosis.

Volume loss in the left anterior‐superior subunit of the hypothalamus in amyotrophic lateral sclerosis

“…Furthermore, our findings contribute to the increasing body of evidence that ALS is not exclusively a motor neuron disease (MND), but also encompasses non‐motor/extra‐motor symptoms. 2 , 29 , 30 , 31 , 32 , 33 , 34 The absence of significant differences in demographic parameters such as age, sex, and BMI between patients with ALS and HCs in our sample provided a level of homogeneity, allowing for a more precise interpretation of the differences in hypothalamic volumes attributable to ALS pathology rather than confounding demographic variables.…”

“… 1 Amyotrophic lateral sclerosis (ALS) is the third most common neurodegenerative disease globally, after Alzheimer's disease (AD) and Parkinson's disease (PD). 2 , 3 It is characterized by progressive loss of motor neurons, causing focal muscle weakness, rapid muscle wasting, and paralysis. 4 More than 60% of patients die within 3–5 years of diagnosis.…”

Evaluating the bi-directional causal association between temporomandibular disorders and neurodegenerative diseases: a two-sample Mendelian randomisation study

“…Neurodegenerative diseases (NDs) are a group of chronic disorders characterised by the loss of neurons [7]. They mainly include Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) [8][9][10][11]. These conditions can severely damage and debilitate the nervous system, particularly the brain [12].…”