Spectrum of cognitive impairment in Korean ALS patients without known genetic mutations

PLoS One. 2014 Feb 3;9(2):e87163. doi: 10.1371/journal.pone.0087163. eCollection 2014.

Abstract

Background: Cognitive 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.

Methods: Three 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.

Results: One 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.

Conclusions: About 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amyotrophic Lateral Sclerosis / diagnosis*
  • Amyotrophic Lateral Sclerosis / ethnology
  • Amyotrophic Lateral Sclerosis / genetics
  • Analysis of Variance
  • Asian Continental Ancestry Group
  • Attention
  • Cognition
  • Cognition Disorders / diagnosis*
  • Cognition Disorders / ethnology
  • Cognition Disorders / genetics
  • Dementia / diagnosis
  • Executive Function
  • Female
  • Frontotemporal Dementia / diagnosis
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Memory
  • Middle Aged
  • Mutation
  • Neuropsychological Tests / statistics & numerical data*
  • Proportional Hazards Models
  • Prospective Studies
  • Republic of Korea

Supplementary concepts

  • Amyotrophic lateral sclerosis 1

Grant support

This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A120182). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.