Skip to main content
. 2019 Sep 10;13:951. doi: 10.3389/fnins.2019.00951

TABLE 1.

Cognition in ALS.

Authors/Years Number of patients Type of study Outcomes measure Main findings
Abdulla et al., 2014 58 pts / 29 NC CS Neuropsychological assessment Brain MRI Global cognitive dysfunction on executive and verbal memory tests. Smaller right hippocampal volume in pts; left hippocampal volume correlates with verbal episodic memory
Abrahams et al., 2000 2 pts / 25 NC CS Verbal fluency Working memory Verbal fluency impairments result from deficits in the central executive component of working memory
Abrahams et al., 2005 20 pts / 18 NC LS : BL, 6 mo Executive, memory, language, visuospatial functions, behavior, and emotion Verbal fluency remains stable whereas other language abilities decreased overtime
Bock et al., 2017 49 pts LS : BL, 7 mo cognitive-behavioral assessment: ALS-CBS No cognitive change whereas patients develop bi overtime
Braber, 2016 100 pts / 50 NC LS : BL, 3 mo Behavioral and cognitive evaluation Genetic testing No changes over time. C9orf72 repeat expansion has no influence on cognition
Burke et al., 2015 33 pts / 33 CG CS CG burden. Cognitive-behavioral profile of pts Ci and bi (apathy and disinhibition) predict high level of CG burden
Burkhardt et al., 2017 24 pts : 21 : NC LS : BL, 6 mo, 12-18 mo Cognitive assessment with the ECAS and FAB No significant alteration overtime in cognition and behavior
Byrne et al., 2012 191 pts CS Clinical, cognitive, behavioral, and survival data 3T high resolution MRI Screening for C9orf72 mutation. Mutated ALS-pts have lower age of disease onset, more often family history of FTD, more comorbid FTD, distinct pattern of non-motor cortex changes on MRI and shorter survival
Carelli et al., 2018 168 pts CS FAB, MoCA, ECAS BDI, STAI Depression correlates negatively with ECAS and specially with executive functions
Consonni et al., 2013 23 pts / 39 NC CS Standard neuropsychological battery FBI 30%: executive ci, naming and short-term memory deficits; 20%: disorganization and mental rigidity 13%: comorbid dementia.
Dary-Auriol et al., 1997 26 pts / 26 NC CS Global cognition, memory, language, executive functions, MADRS Global but subtle cognitive impairment of all neuropsychological tests with no specific profile
Elamin et al., 2011 139 pts CS Executive function, memory, language, visuospatial function Executive dysfunction and comorbid FTD associated to shorter survival
Elamin et al., 2013 186: BL / 96: 2 assessments / 46: 3 assessments LS : Cognitive assessment Cognitive function declines faster in patients cognitively impaired at BL.
Flaherty et al., 2017 161 pts CS Cognitive-behavioral profile × site of onset and gender relative to emerging FTD Bulbar pts : worse letter fluency; Bulbar females : worse category fluency; females with low oestrogen levels: worse letter fluency
Gillingham et al., 2017 20 pts / 36 NC CS ALS-CFB Executive dysfunction
Gordon et al., 2011 131 pts Cross-sectional Spectrum and clinical associations of ci impairment in ALS Effect of ci on survival 40% ci, 10%FTD Impaired patients: less education, more likely to have bulbar onset. Severe cognitive impairment predicts shorter survival
Govaarts et al., 2016 110 pts CS Behavioral and cognitive evaluation Frontal syndrome correlates negatively to survival
Hervieu-Bègue et al., 2016 15 pts CS Semantic memory 60% of pts have semantic memory impairment
Hu et al., 2013 37 pts / 33 NC CS ALS-BCA and other neuropsychological tests Shorter survival associated to dementia and behavioral impairment
Iwasaki et al., 1990 22 pts / 18 NNMC / 17 NC CS MMSE; immediate and delayed memory tests Pts perform lower than NNMC and NC at MMSE and memory tasks. MMSE and memory correlates negatively to upper limb function
Kamminga et al., 2016 20 ALS pts / 15 ALS-FTD / 27 PNFA / 23 NC CS Syntax comprehension : Test for Reception of Grammar Brain volume by MRI-VBM Syntactic comprehension impaired in 25% of ALS, 92.9% of FTD-ALS, and 81.5% of PNFA Impairment correlates with left peri-insular atrophy
Kasper et al., 2015 98 pts / 70 NC CS Executive cognitive, Executive behavior 70% of ci pts have executive dysfunction (initiation and shifting). Dominant bi is apathy
Kasper et al., 2016 93 pts : 73 NC LS : BL and at three time every 3-6 mo Executive functioning No significant decline
Leslie et al., 2015 17 pts / 19 ALS-FTD, 22 SD / 26 NC CS Assessment of semantic deficits Brain volume by MRI-VBM Significant semantic deficits in ALS and ALS-FTD compared to controls. Severity of semantic deficits varies across clinical phenotypes. Anterior temporal lobe atrophy correlates with semantic deficits
Kilani et al., 2004 18 pts : 19 NC LS : BL, 6 and 12 mo Cognitive function Executive alteration at baseline does not worsen at follow-up
Machts et al., 2018 31 pts and 29 NC CS Brain MRI Reduction of left and right hippocampal volumes in patients’ cornu ammonis field 1 (CA1)
Montuschi et al., 2015 207 pts / 127 NC CS Comprehensive neuropsychological assessment 49.7% cognitively normal, 12.6% ALS with FTD, 19.7% ALS-executive ci, 5.5% ALS-non executive ci, 16% ALS-bi and 6% non-classifiable ci. ALS-FTD older, lower educational level and shorter survival
Murphy J. M. et al., 2007 23 pts CS Neuropsychological, neurobehavioral assessment No impairment: 11 pts; behavioral changes: 4; FTD: 5;other :3 (Alzheimer : 1)
Murphy et al., 2016 274 pts CS Neuropsychological and neurobehavioral assessment : ALS-CBS 54.2% ci, 14.1% bi and 6.5% FTD
Palmieri et al., 2015 260 pts / 134 NC CS Executive function, memory and language. 29% pts have executive ci and 18% non-executive ci; Females have 2-fold risk to have executive ci
Olney et al., 2005 81 pts CS Survival predictors Younger age, limb onset and absence of comorbid FTD predicted higher survival
Phukan et al., 2012 160 pts / 110 NC CS Comprehensive neuropsychological battery 46% no ci; 14% FTD; 21% executive ci; 14% non-executive ci
Poletti et al., 2018 164 BL / 48 at 6 mo / 18 at 12 mo / 5 at 18 mo LS : BL, 6 mo, 12 mo, 24 mo Cognitive and behavioral examination : ECAS No behavioral or cognitive worsening
Raaphorst et al., 2015 26 pts / 21 NC CS Neuropsychological assessment Brain MRI Prose memory impairment correlates to hippocampal volume
Rabkin et al., 2016 247 pts CS Cognition-behavior : CBS Psychological : PHQ 40 % ci, 9% bi, 18% ci and bi, 12 % Major or minor depression; 12% Bi associated with depression
Ringholz et al., 2005 279 pts / 129 NC CS Neuropsychological testing 49% intact; 32% mild ci, 13% moderate ci, 6% severe ci, 15% FTD
Roberts-South et al., 2012 16 pts / 12 NC LS : BL, 6-12-18-24 mo Language testing with standardized tests and analysis of productivity and content No alteration at standardized tests. Impairment of discourse content. Alteration of performances overtime
Robinson et al., 2006 19 pts / 8 CG LS : BL, 6 mo Neuropsychological assessment No change overtime even if some patients develop abnormalities
Schreiber et al., 2005 52 pts LS : BL and each 4 months until 18 mo Executive functions, memory and attentional control. No decline on follow-up
Stojkovic et al., 2016 58 pts LS : BL and yearly Executive function and correlation to survival 49.5 % executive ci and BL executive status might predict survival
Strong et al., 1999 13 pts CS Neuropsychological, language and speech testing Mild impairment in several domains especially when bulbar onset
Strutt et al., 2012 44 pts CS Comprehensive pulmonary (vital capacity) and neuropsychological assessments More respiratory-impairment when clinically significant impairments in frontal-lobe-mediated behaviors. Greater executive functioning deficits in patients with bulbar versus limb onset
Xu et al., 2017 108 pts / 60 NMC CS ACE-III, FAB, ECAS, ALS-FTD-Q, MiND-B 14 to 30% ci on ALS and 3.3 to 11.7 % on NMC. 32 % bi on ALS and 39 % on NMC. Ci and bi influence prognosis
Wei et al., 2016 91 pts CS Neuropsychiatric symptoms and cognition: NPI, ACE-R, FAB Depression 59%, anxiety 41%, lability 26%. NPI correlates with ACE-R but not with FAB
Woolley et al., 2018 294 BL / 134 at follow up LS : BL, 5-18 mo Cognitive and behavioral changes Worsening of behavior but not cognition
Zalonis et al., 2012 48 pts / 47 NC CS Executive function: TMT, SNST, WAIS, WCST Pts worse than NC on TMT, SNST and WAIS Similarities. No difference between bulbar and spinal onset pts

ALS, Amyotrophic Lateral Sclerosis; ACE, Addenbrooke’s Cognitive Examination; ALS-BCA, ALS Brief Cognitive Assessment; ALS-CBS, ALS Cognitive Behavioral Screen; ALS-CFB, ALS-Computerized Frontal Battery; ALS-FTD, ALS-Frontotemporal Dementia; ALS-FTD-Q, ALS-Frontotemporal Dementia Questionnaire; BDI, Beck’s Depression Inventory; Bi, Behavioral Impairment; BL, Baseline; Ci, Cognitive Impairment; CG, Caregiver; Cibi, Cognitive and Behavioral Impairment; CS, Cross-Sectional Study; ECAS, Edinburgh Cognitive and Behavioral ALS Screen; FAB, Frontal Assessment Battery; FTD, Frontotemporal Dementia; LS, Longitudinal Study; MADRS, Montgomery-Asberg Depression Rating Scale; MiND-B, Motor Neuron Disease Behavioral instrument; MMSE, Mini Mental State Examination; MRI, Magnetic Resonance Imaging; NC, Normal Controls; NMC, Controls With Neuromuscular Disease, NNMC, Non Neurological Medical Controls; NPI, Neuropsychiatric Inventory; PHQ, Patient Health Questionnaire; PNFA, Progressive Nonfluent Aphasia; Pt, Patient; SD, Semantic Dementia; STAI, State-Trait Anxiety Inventory; SNST, Stroop Neuropsychological Screening Test; TMT, Trail Making Test; VBM, Voxel-Based Morphometry; WAIS, Similarities Subtest of The Wechsler Adult Intelligence Scale.