Spectrum of cognitive impairment in Korean ALS patients without known genetic mutations.
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.
Department of Neurology, College of Medicine, Hanyang University, Seoul, Republic of Korea.
Seong-il
SI
Oh
Department of Neurology, College of Medicine, Hanyang University, Seoul, Republic of Korea.
Aram
A
Park
Department of Neurology, College of Medicine, Hanyang University, Seoul, Republic of Korea.
Hee-Jin
HJ
Kim
Department of Neurology, College of Medicine, Hanyang University, Seoul, Republic of Korea.
Ki-Wook
KW
Oh
Department of Neurology, College of Medicine, Hanyang University, Seoul, Republic of Korea.
Hojin
H
Choi
Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan, University School of Medicine, Seoul, Republic of Korea.
Min-Jung
MJ
Kwon
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Chang-Seok
CS
Ki
Department of Neurology, College of Medicine, Hanyang University, Seoul, Republic of Korea.
Hee-Tae
HT
Kim
Department of Neurology, College of Medicine, Hanyang University, Seoul, Republic of Korea.
Seung Hyun
SH
Kim
D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics; D000704:Analysis of Variance; D044466:Asian People; D001288:Attention; D003071:Cognition; D003072:Cognition Disorders / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics; D003704:Dementia / Q000175:diagnosis; D056344:Executive Function; D005260:Female; D057180:Frontotemporal Dementia / Q000175:diagnosis; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008568:Memory; D008875:Middle Aged; D009154:Mutation; D009483:Neuropsychological Tests / Q000706:statistics & numerical data*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D056910:Republic of Korea