Microstructural white matter changes underlying cognitive and behavioural impairment in ALS--an in vivo study using DTI.

Elisabeth Kasper,Johannes Prudlo,Stefan Vielhaber,Christina Schuster,Joern Kaufmann,Daniel Bittner,Judith Machts,Reiner Benecke,Stefan Teipel,Christophe Lenglet

doi:10.1371/journal.pone.0114543

Abstract

BackgroundA relevant fraction of patients with amyotrophic lateral sclerosis (ALS) exhibit a fronto-temporal pattern of cognitive and behavioural disturbances with pronounced deficits in executive functioning and cognitive control of behaviour. Structural imaging shows a decline in fronto-temporal brain areas, but most brain imaging studies did not evaluate cognitive status. We investigated microstructural white matter changes underlying cognitive impairment using diffusion tensor imaging (DTI) in a large cohort of ALS patients.MethodsWe assessed 72 non-demented ALS patients and 65 matched healthy control subjects using a comprehensive neuropsychological test battery and DTI. We compared DTI measures of fiber tract integrity using tract-based spatial statistics among ALS patients with and without cognitive impairment and healthy controls. Neuropsychological performance and behavioural measures were correlated with DTI measures.ResultsPatients without cognitive impairment demonstrated white matter changes predominantly in motor tracts, including the corticospinal tract and the body of corpus callosum. Those with impairments (ca. 30%) additionally presented significant white matter alterations in extra-motor regions, particularly the frontal lobe. Executive and memory performance and behavioural measures were correlated with fiber tract integrity in large association tracts.ConclusionIn non-demented cognitively impaired ALS patients, white matter changes measured by DTI are related to disturbances of executive and memory functions, including prefrontal and temporal regions. In a group comparison, DTI is able to observe differences between cognitively unimpaired and impaired ALS patients.

Highlights

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease primarily characterised by a degeneration of upper and lower motor neurons [1]
We investigated microstructural white matter changes underlying cognitive impairment using diffusion tensor imaging (DTI) in a large cohort of ALS patients
In non-demented cognitively impaired ALS patients, white matter changes measured by DTI are related to disturbances of executive and memory functions, including prefrontal and temporal regions

Summary

Introduction

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease primarily characterised by a degeneration of upper and lower motor neurons [1]. Behavioural changes in ALS are characterised by symptoms of apathy [6], and, less frequently, disinhibition and disorganisation [3] In line with these cognitive-behavioural changes, structural brain imaging studies have demonstrated grey matter atrophy [7, 8] and white matter damage [9, 10] in fronto-temporal areas that extend beyond the motor system. A relevant fraction of patients with amyotrophic lateral sclerosis (ALS) exhibit a fronto-temporal pattern of cognitive and behavioural disturbances with pronounced deficits in executive functioning and cognitive control of behaviour. Results: Patients without cognitive impairment demonstrated white matter changes predominantly in motor tracts, including the corticospinal tract and the body of corpus callosum. Executive and memory performance and behavioural measures were correlated with fiber tract integrity in large association tracts

Methods

Results

Conclusion