To identify the nature and prevalence of cognitive and behavioral abnormalities in patients with amyotrophic lateral sclerosis (ALS).
Survey of clinical characteristics.
Multidisciplinary clinic within a university medical center. Patients A volunteer sample of 30 new patients with ALS were recruited consecutively. Of those invited, 23 participants (20 with sporadic ALS and 3 with familial ALS) enrolled. Participants ranged in age from 27 to 80 years (mean age, 56.5 years); the education level ranged from 12 to 21 years (mean education level, 3.5 years of college); and 17 participants (74%) were male.
Neuropsychological tests, neurobehavioral interviews, and structured magnetic resonance imaging.
Patients were classified into subtypes of frontotemporal lobar degeneration (n = 5), suspected Alzheimer disease (n = 1), and subthreshold variants of cognitive impairment (n = 2), behavioral impairment (n = 4), and cognitively and behaviorally normal (n = 11). Five neuropsychological tests, 2 behavioral abnormalities, and right hemisphere gray matter reductions differentiated patients into normal and abnormal groups.
In this sample, a sizable proportion of patients with ALS possess a range of behavioral and cognitive changes that lie on a spectrum of frontotemporal impairment. Right hemisphere atrophy may be a biomarker for cognitive impairment in patients with ALS.
"Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are multisystem neurodegenerative disorders, which have been found highly related, occupying 2 poles of a disease spectrum, with a predominance of motor dysfunction at one end and cognitive symptoms at the other (Clark and Forman, 2006; Neumann et al., 2006). In fact, the 2 disorders have been recognized as representative of a neuropathologic continuum because they share several clinical, genetic, and pathogenetic characteristics (Ling et al., 2013; Lomen-Hoerth et al., 2002; Murphy et al., 2007). Genetic and pathologic analyses have demonstrated that mutations of trans-active response DNA binding protein (TARDBP) of 43 kD (Benajiba et al., 2009), fused in sarcoma/translocated in liposarcoma (FUS/TLS) (Blair et al., 2010), ubiquilin-2 (UBQLN2) (Deng et al., 2011), and c9orf72 (DeJesus-Hernandez et al., 2011; Renton et al., 2011) have a key role in the pathogenesis of the ALS-FTD spectrum. "
[Show abstract][Hide abstract] ABSTRACT: Amyotrophic lateral sclerosis (ALS) and behavioral variant frontotemporal dementia (bvFTD) lie on a clinical, pathologic, and genetic continuum. Neuroimaging techniques have proven to be potentially useful to unravel the shared features of these syndromes. Using resting-state functional magnetic resonance imaging (RS-fMRI), we investigated functional connectivity of brain networks in 15 ALS and 15 bvFTD patients in early stages of disease and 15 healthy controls, looking expressly for connectivity pattern divergence or overlap between the 2 disorders. Compared with controls, we found decreased RS-fMRI signals within sensorimotor, right frontoparietal, salience, and executive networks in both patient groups. Within the default mode network (DMN), divergent connectivity patterns were observed, with RS-fMRI signals in the posterior cingulate cortex enhanced in bvFTD patients and suppressed in ALS patients. Our findings confirm that ALS and bvFTD not only broadly share common RS-fMRI connectivity patterns, probably representing different phenotypical expressions of the same neurodegenerative process, but also differ in the DMN, probably reflecting a different stage of neurodegeneration.
Neurobiology of Aging 06/2014; 36(1). DOI:10.1016/j.neurobiolaging.2014.06.025 · 5.01 Impact Factor
"The dysfunction of higher cognitive abilities, from mild cognitive impairment to frank dementia, is common in ALS (Ringholz et al., 2005), with a prevalence that ranges from 10 to 75% in patients (Miller et al., 2009), mainly involving cognitive and behavioral frontotemporal functions (Strong et al., 2009). In recent years, a growing body of evidence (Neary et al., 2000; Lomen-Hoerth et al., 2003; Rippon et al., 2006; Murphy et al., 2007) has suggested a link between ALS and frontotemporal lobar degeneration (FTLD). Previous studies that assessed subjects at rest (Kew et al., 1993; Abe et al., 1997) or during the performance of executive tasks (Ludolph et al., 1992; Abrahams et al., 1995) reported a significant decrease in frontal lobe activation in non-demented ALS patients who presented cognitive deficits. "
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: A growing body of evidence suggests a link between cognitive and pathological changes in amyotrophic lateral sclerosis (ALS) and in frontotemporal lobar dementia (FTLD). Cognitive deficits have been investigated much less extensively in primary lateral sclerosis (PLS) than in ALS. OBJECTIVE: to investigate bioelectrical activity to Stroop test, assessing frontal function, in ALS, PLS and control groups. METHODS: 32 non-demented ALS patients, 10 non-demented PLS patients and 27 healthy subjects were included. Twenty-nine electroencephalography (EEG) channels with binaural reference were recorded during covert Stroop task performance, involving mental discrimination of the stimuli and not vocal or motor response. Group effects on event related potentials (ERPs) latency were analyzed using statistical multivariate analysis. Topographic analysis was performed using low resolution brain electromagnetic tomography (LORETA). RESULTS: ALS patients committed more errors in the execution of the task but they were not slower, whereas PLS patients did not show reduced accuracy, despite a slowing of reaction times (RTs). The main ERP components were delayed in ALS, but not in PLS, compared with controls. Moreover, RTs speed but not ERP latency correlated with clinical scores. ALS had decreased frontotemporal activity in the P2, P3 and N4 time windows compared to controls. CONCLUSION: These findings suggest a different pattern of psychophysiological involvement in ALS compared with PLS. The former is increasingly recognized to be a multisystems disorder, with a spectrum of executive and behavioural impairments reflecting frontotemporal dysfunction. The latter seems to mainly involve the motor system, with largely spared cognitive functions. Moreover, our results suggest that the covert version of the Stroop task used in the present study, may be useful to assess cognitive state in the very advanced stage of the disease, when other cognitive tasks are not applicable.
"The concept that behavioural impairment in ALS (ALSbi) is rare is no longer supported by clinical evidence . Apathy, disinhibition and poor social monitoring are frequently reported in a subgroup of ALS patients meeting criteria for frontotemporal dementia (FTD) , with a prevalence from 22% to 52%  . In addition, mild to moderate behavioural impairments have also been documented in non-FTD ALS patients . "
[Show abstract][Hide abstract] ABSTRACT: Objective:
The study aims to assess the spectrum of cognitive and behavioural disorders in patients affected by Amyotrophic Lateral Sclerosis (ALS) according to the recent consensus criteria . The study also intends to assess the impact of physical disability on cognitive and behavioural abnormalities.
Detailed neurological, neuropsychological and neurobehavioral evaluations were administered to 23 ALS patients, 11 Lower Motor Neuron Disease (LMND) patients and 39 healthy controls. Strong et al.'s criteria  were applied to diagnose the presence of cognitive/behavioural impairment. Clinical and neuropsychological scores were used for group comparisons and correlation analyses.
In comparison with LMND and controls, a subgroup of ALS patients (∼30%) manifested executive dysfunction, which was severe enough to classify them as cognitively impaired. Action naming difficulties and short-term memory deficits were also observed. Aspontaneity, disorganization and mental rigidity reached clinical relevance in 20% of ALS patients. A small percentage of ALS patients (13%) also had comorbid dementia. The cognitive or behavioural status was not related to the clinical features of ALS.
The use of consensus criteria for cognitive and behavioural impairment and the comparison with the LMND group proved useful in defining the spectrum of non-motor manifestations of ALS.
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