Cognitive phenotypes of sequential staging in amyotrophic lateral sclerosis

Area of Science:

• Neuroscience
• Neurology
• Radiology

Background:

• Amyotrophic lateral sclerosis (ALS) is characterized by the progressive spread of TDP-43 pathology in the brain.
• Diffusion tensor imaging (DTI) using magnetic resonance imaging (MRI) can visualize this pathological spread.
• Cognitive deficits are observed in some ALS patients and may serve as in vivo markers of disease progression.

Purpose of the Study:

• To investigate the association between MRI-based markers of TDP-43 pathology spread and cognitive deficits in ALS patients.
• To develop and validate a Cognitive-Staging system based on executive function, disinhibited behavior, and memory deficits.
• To assess the congruency and diagnostic accuracy of Cognitive-Staging compared to MRI-Staging.

Main Methods:

• 139 ALS patients underwent DTI MRI and the Edinburgh Cognitive and Behavioural ALS screen (ECAS).
• Cognitive functions (executive function, disinhibited behavior, memory) were selected for staging based on their association with brain regions affected by TDP-43 pathology.
• Receiver Operating Characteristic (ROC) curve analyses defined cut-off scores for cognitive staging (stages 2-4).

Main Results:

• 55% of patients (77/139) met criteria for Cognitive-Staging (stages 2-4) based on performance in executive function, memory, or disinhibited behavior.
• Significant correlations were found between DTI parameters and the cognitive profiles of patients across MRI stages 2-4.
• High congruency was observed between MRI-Staging and Cognitive-Staging, with high specificity for executive function (Stage 2) and disinhibited behavior (Stage 3), and moderate specificity for memory (Stage 4).

Conclusions:

• Cognitive impairment in ALS follows specific patterns that can be reliably used for Cognitive-Staging.
• Cognitive-Staging demonstrates high specificity and sensitivity in reflecting the pattern of cerebral changes seen on MRI in ALS.
• Cognitive screening provides a rapid, accessible, and informative clinical tool for assessing brain function in ALS patients.