Association between dysarthria and cognitive impairment in ALS: A prospective study

Abstract

Several studies have demonstrated impaired cognition in amyotrophic lateral sclerosis (ALS) patients, but it has been difficult to identify risk factors for this impairment. An association between cognitive changes and bulbar site of onset or dysarthria has been suggested, but the findings are variable. We tested for both associations in a large cohort of ALS patients. At the time of diagnosis of sporadic ALS, all patients (n=355) in this prospective study underwent comprehensive neuropsychological testing. In addition, a subset of 175 patients underwent a detailed assessment of dysarthria, which was quantified using the Appel ALS Score (AALSS). ALS patients with bulbar site of onset performed significantly worse than limb onset patients on a few timed ((VSAT-time, p<0.05), (Stroop Color, p<0.05), (Stroop Word, p<0.05)) tests of frontal lobe functions, but the significance could not be replicated when motor impairment was accommodated into the tests ((VSAT-errors, p=0.73), (Stroop interference, p=0.08)). ALS patients with dysarthria performed significantly worse than non-dysarthrics on multiple timed ((BD, p<0.05), (VSAT-time, p<0.05), (Stroop Color, p<0.05), (Stroop Word, p<0.05), (Trails A, p<0.05), (Trails B, p<0.05)) neuropsychological tests, and the significance was maintained when motor impairment was accommodated into one of these tests (Stroop interference, p<0.05). Additionally, dysarthrics performed significantly worse on two untimed measures of cognition ((Similarities, p<0.05), (Rey Copy, p<0.05)). Cognitive functioning in ALS does not associate with the site of onset and has a moderate association with dysarthria.

The neuropathological signature of bulbar-onset ALS: A systematic review

“…The involvement of speech and language processing areas in bulbar ALS has been previously suggested by studies that reported language impairments, in ALS that were related to either bulbar-onset disease (15, 60, 61), or to the degree of bulbar motor decline (2, 6, 16, 54, 62), independent of dementia and motor disabilities. These observations, along with our analysis, suggest a potential co-development of aphasia and bulbar motor symptoms, which, from a pathophysiological perspective, may be directly related to the pattern of disease propagation within the brain.…”

“…This latter finding remains disputed, however (18, 19). Two hypotheses have been proposed regarding the association between motor and extramotor abnormalities in ALS, in relation to the disease subtype: 1) it has been suggested that the site of symptom onset may be related to the burden of extra motor impairments, with bulbar-onset ALS showing a unique neurodegenerative profile associated with specific and concomitant extramotor impairments (1, 6, 13–15, 20–22); and 2) the presence of bulbar motor dysfunction, regardless of site of onset, may be associated with extramotor impairments (6, 7, 16, 17). Neither of the two hypotheses has been investigated neuropathologically in cadaveric brain tissue.…”

Prospective memory tasks: a more sensitive method for screening cognitive impairment in ALS?

“…The association between cognitive changes and bulbar onset has been suggested by some studies [29,30], but still under controversial [31]. The relative small sample size of bulbar onset group maybe one of the reason of our negative result.…”

Clinical and Radiological Markers of Extra-Motor Deficits in Amyotrophic Lateral Sclerosis

“…However, not all neuropsychology studies corroborate these findings ( 34 , 38 , 39 , 45 , 46 , 54 – 56 ). Several studies have specifically evaluated mental set shifting ability in ALS using the Trail Making Test; most of them identifying considerable dysfunction ( 37 , 42 , 47 , 55 , 57 ), while others have not captured such deficits ( 58 , 59 ). Response inhibition and attentional control are typically examined by the Stroop test, and are often impaired in ALS ( 11 , 27 , 35 – 37 , 51 , 53 , 57 , 60 ), but unaffected cohorts have also been reported ( 39 , 40 , 44 , 49 ).…”