Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We wished to determine whether a screening test battery for cognitive impairment can be given practicably in a busy multidisciplinary ALS clinic, and to assess initial test performance in a sequentially drawn ALS population. We administered a word generation task (letter fluency), the Frontal Behavioral Inventory (FBI), and the Beck Depression Inventory (BDI) to 49 ALS patients and their caregivers during a visit to our ALS clinic. We also computed Clinical Dementia Rating (CDR) scale and ALS Functional Rating Scale (ALSFRS-R) scores for patients. Pearson correlation coefficients and regression analyses assessed associations between outcome measures. The test battery took 30 min to administer. Word generation was associated with the FBI score (r = -0.36, p = 0.01), and time to ALS diagnosis (p = 0.01). Caregiver depressive symptoms (BDI) correlated with the FBI (r = 0.40, p = 0.005) and motor severity (r = -0.47, p<0.01) in patients. CDR scores were associated with behavioral abnormalities and lower ALSFRS-R scores. We concluded that a screen of cognition could be administered during multidisciplinary ALS clinics. Frontostriatal cognitive impairment may be associated with behavioral syndromes and more rapid forms of ALS. Behavioral and motor impairment is associated with depressive symptoms in caregivers. Studies with formal neuropsychological tests are needed to determine the sensitivity and specificity of the screen in ALS.
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PMID:A screening assessment of cognitive impairment in patients with ALS. 1785 14

Although amyotrophic lateral sclerosis and its variants are readily recognised by neurologists, about 10% of patients are misdiagnosed, and delays in diagnosis are common. Prompt diagnosis, sensitive communication of the diagnosis, the involvement of the patient and their family, and a positive care plan are prerequisites for good clinical management. A multidisciplinary, palliative approach can prolong survival and maintain quality of life. Treatment with riluzole improves survival but has a marginal effect on the rate of functional deterioration, whereas non-invasive ventilation prolongs survival and improves or maintains quality of life. In this Review, we discuss the diagnosis, management, and how to cope with impaired function and end of life on the basis of our experience, the opinions of experts, existing guidelines, and clinical trials. We highlight the need for research on the effectiveness of gastrostomy, access to non-invasive ventilation and palliative care, communication between the care team, the patient and his or her family, and recognition of the clinical and social effects of cognitive impairment. We recommend that the plethora of evidence-based guidelines should be compiled into an internationally agreed guideline of best practice.
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PMID:Clinical care of patients with amyotrophic lateral sclerosis. 1788 81

Amyotrophic lateral sclerosis (ALS) is a motor neuron disease that has sporadic and inherited forms. ALS is the most common neurodegenerative disorder of young and middle-aged adults, and few treatments are available. Although the degeneration predominantly affects the motor system, cognitive and behavioural symptoms have been described for over a century, and there is evidence that ALS and frontotemporal dementia overlap clinically, radiologically, pathologically, and genetically. Cognitive decline in ALS is characterised by personality change, irritability, obsessions, poor insight, and pervasive deficits in frontal executive tests. This presentation is consistent with the changes to character, social conduct, and executive function in frontotemporal dementia. We highlight genetic, imaging, and neuropathological evidence that non-motor systems are affected in ALS and explain the importance of recent discoveries. We review studies of cognitive impairment in ALS and common neuropsychological test results. We also provide advice about clinical assessment of frontotemporal dysfunction in patients with ALS, and suggest future research. Understanding of cognitive impairment in ALS will improve care for patients and their families and provide valuable insights into the pathogenesis of neurodegeneration.
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PMID:Cognitive impairment in amyotrophic lateral sclerosis. 1794 53

We aim to investigate the pathological background of mild cognitive impairment (MCI). The most recent 545 cases from the Brain Bank for Aging Research (BBAR) were studied, with a mean age of 80.7 years and male : female ratio of 324 : 221. Cases with clinical dementia rating scale (CDR) 0.5 were retrieved as the best substitute of MCI. CDR was retrospectively determined from clinical charts. Pathological examinations followed the BBAR protocol (JNEN 2004). Post mortem assessment of CDR was possible for 486 cases, and was 0 in 201 cases, 0.5 in 57 cases and 1-3 in 228 cases. CDR 0.5 group was clinicopathologically classified into 33 cases with degenerative changes, nine cases with vascular changes, four cases with combined degenerative and vascular changes, two with hippocampal sclerosis, two with trauma, one with metabolic disease and six with unremarkable changes. The degenerative group was further subclassified into groups with pure and combined pathology. The former consisted of six cases each with Alzheimer change (AC), argyrophilic grain change (AGC) and neurofibrillary tangle predominant change (NFTC), three each with Lewy body disease change without parkinsonism (DLBC) or Parkinson's disease (PDMCI) and one case with progressive supranuclear palsy. The latter consisted of three cases with AC plus AGC, two with AGC plus NFTC and one each with AC plus DLBC, DLBC plus amyotrophic lateral sclerosis and AGC plus DLBC. The pathological backgrounds of patients of class CDR 0.5 were varied and not restricted to AC.
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PMID:Neuropathology of mild cognitive impairment. 1802 80

The deposition of highly phosphorylated microtubule-associated tau protein has been observed in ALS with cognitive impairment (ALSci). In these studies, we have examined whether the expression of two candidate protein kinases for mediating tau hyperphosphorylation (GSK3beta or CDK5) are also altered. The expression of GSK, CDK and p25/p35 was assayed in human frontal, hippocampal, cerebellar, cervical (dorsal and ventral) and lumbar (dorsal and ventral) tissue from neurologically intact control (5), ALS (5) or ALSci (5) patients using RT-PCR, Western blot or immunohistochemistry. To assess GSK-3beta activity, we examined GSK3beta, phospho-GSK3beta and phospho-beta-catenin expression. Expression levels relative to that of beta-actin were compared by ANOVA. The expression of GSK, GSK3beta and phospho-GSK3beta was increased in both ALS and ALSci compared to that of the control. This was accompanied by an increased expression of phospho-beta-catenin. No significant difference between control, ALS or ALSci was observed with respect to the expression of CDK5 or p25/p35. Both GSK3beta and phospho-GSK3beta immunoreactive neurons were mainly located in layer II and layer III in the frontal cortex and in layer II in the hippocampus. This was consistent with the previously described distribution of hyperphosphorylated tau bearing neurons in ALS and ALSci. These data suggest that GSK3beta expression is upregulated in ALS and ALSci and that GSK3beta activation is associated with the intraneuronal deposition of hyperphosphorylated tau protein. This supports the potential role for GSK3beta as a therapeutic target in ALS.
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PMID:Upregulation of GSK3beta expression in frontal and temporal cortex in ALS with cognitive impairment (ALSci). 1822 34

Cognitive impairment in amyotrophic lateral sclerosis (ALS) is correlated with pathologic and radiographic changes in cerebral cortex beyond the motor regions. Clinically, evidence of impairment can be detected in up to 50 percent of patients through direct neuropsychological testing, although frank frontotemporal dementia (FTD) occurs in a limited percentage. Behavioral changes are also common and can be characterized primarily by the presence of increased apathy. Determining the underlying causes of cognitive or behavioral change may be confounded by several disease-related factors, including fatigue, respiratory compromise, depression, and treatment with medications such as riluzole. Studies assessing the evolution and relative risk for cognitive and behavioral impairment in ALS suggest at least two types of patients: those who have clear FTD in whom cognitive decline develops gradually and those who have mild cognitive or behavioral impairments in whom progression either does not occur or is difficult to detect. Limited data suggest that cognition and behavior influence compliance, management, and survival, although this requires further assessment.
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PMID:Cognitive and behavioral impairment in amyotrophic lateral sclerosis. 1862 19

Oxidative stress has been implicated in the progression of a number of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease and amyotrophic lateral sclerosis. We carried out an in-depth study of cognitive impairment and its relationships with oxidative stress markers such as ferric-reducing ability of plasma (FRAP), plasma malondialdehyde and total antioxidative capacity (TAC), as well as cholesterol parameters, in two subsets of subjects, AD patients (n = 59) and a control group of neurologically normal subjects (n = 29), attending the University Hospital Salvador in Santiago, Chile. Cognitive impairment was assessed by a set of neuropsychological tests (Mini-Mental State Examination, Boston Naming Test, Ideomotor Praxia by imitation, Semantic Verbal Fluency of animals or words with initial A, Test of Memory Alteration, Frontal Assessment Battery), while the levels of those oxidative stress markers and cholesterol metabolism parameters were determined according with standard bioassays in fresh plasma samples of the two subgroups of patients. No significant differences were observed when the cholesterol parameters (low-, high-density lipoprotein, total cholesterol) of the AD group were compared with normal controls. Interestingly, a correlation was evidenced when the levels of cognitive impairment were analyzed with respect to the plasma antioxidant capacity (AOC) of patients. In this context, the subset of subjects exhibiting cognitive impairment were divided into two subgroups according with their Global Dementia Scale performance: a subgroup with mild AD and a subgroup with moderate to severe AD. Significant differences in AOC were found between subgroups. The different correlations between cognitive impairment of subgroups of subjects with the oxidative stress profile are discussed in the context of AD pathogenesis.
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PMID:Cognitive impairment and Alzheimer's disease: Links with oxidative stress and cholesterol metabolism. 1904 15

Although amyotrophic lateral sclerosis (ALS) can be associated with cognitive impairment (ALSci) as a reflection of frontotemporal lobar degeneration, the basis of this process is unknown. The observation of neuronal and extraneuronal tau deposition in ALSci in addition to a unique tau phosphorylation at Thr175 has suggested that ALSci can be associated with alterations in tau metabolism. We have examined the association between phosphorylation at Thr175 and tau fibril formation. Both soluble and insoluble tau was purified from control, patients with Alzheimer's disease (AD), ALS without cognitive impairment, and ALSci and the tendency to fibril formation assayed ex vivo using the thioflavin S fluorescence assay. The extent of fibril formation was significantly greater in tau derived from ALSci, with ALS-derived tau being intermediate between control and AD-derived tau. Using both Neuro2A and human embryonic kidney (HEK293T) cells, we expressed full-length tau constructs harboring either a pseudophosphorylation at Thr175 (Thr175-Asp-tau), inhibition of Thr175 phosphorylation (Thr175-Ala-tau) or intact tau (wild-type tau). Both tau fibril formation and cell death were significantly enhanced in the presence of Thr175-Asp-tau, regardless of the tau isoform, suggesting that phosphorylation of Thr175 is associated with tau fibril formation in ALSci.
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PMID:Tau phosphorylation at threonine-175 leads to fibril formation and enhanced cell death: implications for amyotrophic lateral sclerosis with cognitive impairment. 1904 55

Emotional Lability (EL) is a well recognized symptom of cortico-bulbar pathway dysfunction in Motor Neuron Disease/Amyotrophic Lateral Sclerosis (MND/ALS), and is reported to occur in 19-49% of patients. The Emotional Lability Questionnaire (ELQ), is specifically designed to detect EL as reported by MND patients and as observed by their carers. The aims of this study were to 1) validate the Italian version of the ELQ; 2) investigate the relationship between EL and presence of cognitive dysfunction; 3) investigate the relationship between EL and presence of psychopathology. Forty one MND patients, 39 caregivers and respective control groups composed of 39 subjects and 39 partners/friends were tested. The Italian version of the ELQ was found to have good psychometric properties. Seventy-one per cent of patients reported suffering from EL. Correlations were found between bulbar involvement and EL, and between bulbar involvement and low performance on tests of fluid intelligence and working memory. However, the cognitive profile did not correlate with any aspect of EL. The findings suggests that damage to different neurological pathways underlie cognitive change and EL, which supports the concept of MND/ALS as a multisystem disorder. Moreover the outcomes suggest that EL affects patients' everyday life with the increased anxiety and emotional frailty. The findings suggest that those involved in the care of MND patients should be more aware of the effects of EL in the management of the disease.
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PMID:Emotional Lability in MND: Relationship to cognition and psychopathology and impact on caregivers. 1910 49

We aimed to clarify the profile of cognitive impairment in ALS, by meta-analysis of published studies. Criteria for inclusion were: ALS diagnosed according to El Escorial criteria; control group matched for age and education; correction for bias due to motor impairment or dysarthria; no dementia in patients and controls. Effect sizes reflecting a difference in neuropsychological performance between ALS patients and controls were calculated for 12 cognitive domains. The effect of demographic and clinical variables (age, disease duration, site of onset) on cognition was assessed in a moderator analysis. Of 48 eligible articles, 16 studies encompassing 554 ALS patients were included. Significant effect sizes were found for the Mini Mental State Examination (d=0.8), immediate verbal memory (d=0.5), visual memory (d=0.4), fluency (d=0.5), psychomotor speed (d=0.7), language (d=0.5) and executive functioning (d=0.3). The results of the latter three domains are less reliable due to the possibility of publication bias. Psychomotor speed, and to a lesser extent fluency, may have been influenced by motor impairment, despite attempts to correct for motor slowness. In conclusion, the diversity of cognitive problems in ALS seems greater than was previously thought. ALS patients may suffer from cognitive impairment in multiple domains, including memory dysfunction.
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PMID:The cognitive profile of amyotrophic lateral sclerosis: A meta-analysis. 1918 Mar 49


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