TABLE 1.
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.