Cognitive function in bulbar– and spinal–onset amyotrophic lateral sclerosis

Abstract

We performed a longitudinal study of frontal and temporal lobe functions in patients with amyotrophic lateral sclerosis (ALS) and compared the evolution of cognitive performance with that of motor deficits in patients with spinal and bulbar-onset of the disease. Fifty two patients suffering from sporadic ALS according to the El Escorial criteria were examined; 37 patients had a spinal, 15 a bulbar onset of the disease. The data profile included examinations at entry (E1), every four months at follow-up (E2, E3, E4) and after 18 months (E5), if possible. Neuropsychological testing covered the domains of executive functions, memory and attentional control. ALS patients showed executive dysfunctions that were most prominently represented by deficits of non-verbal and verbal fluency and concept formation. Memory-related deficits were also present but less expressed. The same held true for phasic and tonic alertness and divided attention. In contrast to motor functions declining concomitantly with disease progression, cognitive deficits appeared in early disease, were essentially present at initial testing and did not substantially decline on follow-up. A subgroup analysis revealed that bulbar-onset ALS patients performed consistently poorer in many cognitive tests than spinal-onset ones with special reference to verbal and non-verbal fluency and interference control. This subgroup difference persisted or even increased throughout follow-up. We conclude that there is a fronto-temporal pattern of cognitive dysfunction in ALS expressing itself early in the course of the disease and mainly with bulbar forms. The cognitive deficits do not progress in synchrony with motor decline, but distinctly more slowly. We suggest that cognitive dysfunctions reflect functional and possibly morphological deficits outside the primary motor system that is specific for the nature and evolution of the disease and might also give clues to etiopathogenesis.

Screening for cognitive and behavioural impairment in patients with amyotrophic lateral sclerosis: frequency of abnormality and effect on survival

“…There have been attempts to determine whether clinical features are correlated with the presence of cognitive and behavioral testing. Some studies have found cognitive impairment to be more common in people with bulbar onset than limb onset of ALS [32]. However, other studies suggest that site of onset has no influence on the presence of cognitive impairment [33][34][35].…”

Degeneration of the Human Nervous System and Magnetic Resonance Neuroimaging

“…There is increasing evidence that not only do 2-5% of ALS patients present an ALS/dementia complex but also that patients with classical ALS without obvious clinical evidence of cognitive deficits may have subtle changes in frontal cortical function (Ludolph et al, 1992;Kew et al, 1993b;Lulé et al, 2005;Lomen-Hoerth et al, 2002). The cognitive impairment has been reported as more pronounced in ALS patients with a bulbar onset compared to patients with spinal onset (Abrahams et al, 1997;Strong et al, 1999;Lomen-Hoerth et al, 2002;Schreiber et al, 2005) and is also evident in patients with primary lateral sclerosis (PLS; Piquard et al, 2006). Longitudinal investigation of ALS patients (up to 18 months) revealed that cognitive dysfunction in ALS occurred early in the disease course and that the cognitive deficits may not progress in synchrony with motor decline, but distinctly more slowly (Schreiber et al, 2005).…”

“…The cognitive impairment has been reported as more pronounced in ALS patients with a bulbar onset compared to patients with spinal onset (Abrahams et al, 1997;Strong et al, 1999;Lomen-Hoerth et al, 2002;Schreiber et al, 2005) and is also evident in patients with primary lateral sclerosis (PLS; Piquard et al, 2006). Longitudinal investigation of ALS patients (up to 18 months) revealed that cognitive dysfunction in ALS occurred early in the disease course and that the cognitive deficits may not progress in synchrony with motor decline, but distinctly more slowly (Schreiber et al, 2005). Functional imaging studies confirm hypoperfusion in the resting state in the frontal cortex in ALS with or without cognitive deficits (Ludolph et al, 1992;Anzai et al, 1990;Tanaka et al, 1993).…”

Neuroimaging Advances in Amyotrophic Lateral Sclerosis

“…32,33 Cognitive impairment has been reported as more pronounced in ALS patients with a bulbar onset compared with patients with spinal onset. [34][35][36][37] Longitudinal investigation of ALS patients revealed that cognitive dysfunction in ALS occurred early in the disease course and that the cognitive deficits may not progress in synchrony with motor decline, but may occur distinctly more slowly. 37 Functional neuroimaging has supported the clinical findings of frontal cortical involvement not only in patients with an ALS/dementia complex but also in patients with ALS and subclinical cognitive impairment: hypoperfusion in the frontal cortex in ALS with or without cognitive deficits measured with PET 32 and fMRI 38 and association of reduced frontal executive function and reduced activity in fronto-parietal areas measured with PET.…”