Spectrum of Cognitive Impairment in Korean ALS Patients without Known Genetic Mutations

Abstract

BackgroundCognitive impairment is associated with a negative prognosis in amyotrophic lateral sclerosis (ALS), as well as with clinical specificity. We investigate neuropsychological function in ALS patients without known genetic mutations in a Korean tertiary clinic.MethodsThree hundred and eighteen patients were enrolled in a prospective longitudinal cohort from September 2008 to February 2012. At the time of diagnosis of sporadic ALS, we carried out genetic and comprehensive neuropsychological tests on all patients, and collected demographic and clinical characteristics. Six cognitive domains, namely executive function, attention, language, calculation, visuospatial function and memory were evaluated. ANOVA and t-tests were used to assess differences in clinical characteristics and neuropsychological parameters between sporadic ALS patients. The Kaplan-Meier method and Cox proportional hazard model were used for survival analysis.ResultsOne hundred and sixty-six patients were categorized into five subtypes: normal cognition (ALS pure), cognitive impairment (ALSci), behavioral impairment (ALSbi), frontotemporal dementia (ALS-FTD), and other types of dementia. Seventy patients (70/166, 42.2%) were cognitively or behaviorally impaired. Among the impaired patients, eight (8/166, 4.8%) had FTD-type dementia and one (1/166, 0.6%) was Alzheimer's disease-type. The ALS patients with cognitive impairment (ALSci) and with FTD (ALS-FTD) were more severely impaired in executive function, attention, language and memory than the cognitively intact ALS patients (ALS pure). In a survival analysis, ALSci (β = 1.925, p = 0.025) and ALS-FTD groups (β = 4.150, p = 0.019) tended to have shorter survival than the ALS pure group.ConclusionsAbout half of ALS patients without known genetic variation have cognitive or behavioral impairment. ALS patients with cognitive abnormalities, especially FTD, have a poorer prognosis than those without cognitive impairment. In neuropsychological profiling, executive tasks were effective in identifying cognitive impairment in the ALS patients. It would be useful for clinicians to classify ALS according to neuropsychological profiles, and screen for subtle cognitive impairment.

Amyotrophic lateral sclerosis and motor neuron syndromes in Asia

“…The frequencies with which they occur in Asian patients with ALS are less clear. In a cohort of 166 South Korean patients with sporadic ALS, 42% of patients were found to have behavioural or cognitive dysfunction 77. None carried the C9orf72 repeat expansion, which accounts for the highest proportion of ALS/FTD overlap in the West, suggesting that a different genetic mutation may be responsible 5.…”

Challenges in the Understanding and Treatment of Amyotrophic Lateral Sclerosis/Motor Neuron Disease

“…A quantitative assessment of strength has, in fact, been included in almost every clinical trial of ALS/MND. Multiple measures of strength have been repeatedly utilized in this patient population ranging from classic categorical measurement (manual muscle testing), comprehensive composite measures of strength (Tufts Quantitative Neuromuscular Exam [71,72]) and focused quantitative evaluation of individual muscle groups (hand-held dynamometry [73]). Despite the logic of utilizing strength as a measure of disease activity in a motor neuron disease, the variability between patients with regard to affected regions, baseline strength, and rate of progression has offset the practical utility of strength measurements in clinical trials.…”

Frontotemporal Dysfunction in Amyotrophic Lateral Sclerosis: A Discriminant Function Analysis

“…It is well known that clinical manifestations and specific demographic characteristics such as age at onset can serve as useful predictors [32,33]. However, recent longitudinal studies suggest that cognitive and behavioral decline - though found to be mild and asynchronous with motor decline by some researchers [34,35] - are also evident in a proportion of patients and may be crucial prognostic indices with regard to the course of the disease [34,36,37]. Contemporary research provides indications for a possible biological substrate of the suggested relationship between cognitive/behavioral decline and prognosis.…”

“…Moreover, recent research reports a possible link between specific genetic abnormalities, cognitive and behavioral impairment, and reduced survival [39] . On the basis of such findings demonstrating parallel motor and cognitive decline, along with the latter's possible prognostic value, it has been argued that clinicians should use screening tools to identify subtle cognitive/behavioral deficits and classify ALS patients according to assessment-derived neuropsychological profiles [36]. …”