The Characteristics of Cognitive Impairment in ALS Patients Depend on the Lateralization of Motor Damage

(1) Background: Cognitive features of patients with amyotrophic lateral sclerosis (ALS) have never been specifically analyzed according to the lateralization of motor impairment. In the present study we investigated the cognitive performances of ALS patients to describe the relationship between motor and cognitive dysfunction, according to site and side of disease onset. (2) Methods: Six-hundred and nine ALS patients underwent a comprehensive neuropsychological evaluation at diagnosis in Turin ALS Centre Tests included—mini-mental state examination (MMSE), frontal assessment battery (FAB), trail-making test A/B (TMT A-B), digit span forward and backward (digit span FW/digit span BW), letter fluency test (FAS), category fluency test (CAT), Rey auditory verbal learning test (RAVLT), Babcock story recall test (BSRT), Rey-Osterrieth complex figure test (ROCFT), Wisconsin card sorting test (WCST), Raven’s coloured progressive matrices (CPM47). Cognitive performances of patients, grouped by side and site of onset, were statistically compared using z-scores, as appropriate. (3) Results: Bulbar patients and bilateral spinal onset patients (Sbil) were generally characterized by lower cognitive performances in most neuropsychological tests, when compared to patients with lateralized onset (right-side spinal onset, Sri and left-side spinal onset, Sle). Digit span backward and visual memory task (ROCFT) median z-scores were significantly higher, reflecting a better cognitive performance, in Sri patients when compared to bulbar/Sbil patients, while verbal memory tasks (RAVLT and BRST) resulted in significantly higher scores in Sle patients. Our results are in keeping with hemispheric functional lateralization of language and visuospatial abilities. (4) Conclusions: In ALS patients, as in other neurodegenerative diseases, we found a direct relationship between lateralized motor and cognitive features.

[1]  A. Chiò,et al.  Decline of cognitive and behavioral functions in amyotrophic lateral sclerosis: a longitudinal study , 2020, Amyotrophic lateral sclerosis & frontotemporal degeneration.

[2]  J. Kassubek,et al.  Imaging in amyotrophic lateral sclerosis: MRI and PET. , 2019, Current opinion in neurology.

[3]  A. Chiò,et al.  Cognitive impairment across ALS clinical stages in a population-based cohort , 2019, Neurology.

[4]  A. Chiò,et al.  Validation of the revised classification of cognitive and behavioural impairment in ALS , 2019, Journal of Neurology, Neurosurgery, and Psychiatry.

[5]  D. Mantini,et al.  Neural signatures of Trail Making Test performance: Evidence from lesion-mapping and neuroimaging studies , 2018, Neuropsychologia.

[6]  Adriano Chiò,et al.  Secular Trends of Amyotrophic Lateral Sclerosis: The Piemonte and Valle d’Aosta Register , 2017, JAMA neurology.

[7]  G. Rouleau,et al.  Clinical Spectrum of Amyotrophic Lateral Sclerosis (ALS). , 2017, Cold Spring Harbor perspectives in medicine.

[8]  R. Lemon,et al.  Cortical influences drive amyotrophic lateral sclerosis , 2017, Journal of Neurology, Neurosurgery, and Psychiatry.

[9]  H. Levin,et al.  Memory-related white matter tract integrity in amyotrophic lateral sclerosis: an advanced neuroimaging and neuropsychological study , 2017, Neurobiology of Aging.

[10]  T. Hortobágyi,et al.  Amyotrophic lateral sclerosis - frontotemporal spectrum disorder (ALS-FTSD): Revised diagnostic criteria , 2017, Amyotrophic lateral sclerosis & frontotemporal degeneration.

[11]  G. Deuschl,et al.  MDS clinical diagnostic criteria for Parkinson's disease , 2015, Movement disorders : official journal of the Movement Disorder Society.

[12]  J. Janszky,et al.  Visuospatial impairment in Parkinson's disease: The role of laterality , 2015, Laterality.

[13]  M. Filippi,et al.  Neuroimaging in amyotrophic lateral sclerosis: insights into structural and functional changes , 2014, The Lancet Neurology.

[14]  M. Kiernan,et al.  Study of motor asymmetry in ALS indicates an effect of limb dominance on onset and spread of weakness, and an important role for upper motor neurons , 2014, Amyotrophic lateral sclerosis & frontotemporal degeneration.

[15]  U. Bonuccelli,et al.  The relationship between motor symptom lateralization and cognitive performance in newly diagnosed drug-naïve patients with Parkinson's disease , 2013, Journal of clinical and experimental neuropsychology.

[16]  B. D. de Jong,et al.  Handedness correlates with the dominant Parkinson side: A systematic review and meta‐analysis , 2012, Movement disorders : official journal of the Movement Disorder Society.

[17]  L. Goldstein,et al.  The anatomy of cognitive impairment in amyotrophic lateral sclerosis: More than frontal lobe dysfunction , 2012, Cortex.

[18]  Sarah E. MacPherson,et al.  Evidence of Social Understanding Impairment in Patients with Amyotrophic Lateral Sclerosis , 2011, PloS one.

[19]  Nick C Fox,et al.  Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. , 2011, Brain : a journal of neurology.

[20]  O. Hardiman,et al.  The syndrome of cognitive impairment in amyotrophic lateral sclerosis: a population-based study , 2011, Journal of Neurology, Neurosurgery & Psychiatry.

[21]  A. Chiò,et al.  Phenotypic heterogeneity of amyotrophic lateral sclerosis: a population based study , 2011, Journal of Neurology, Neurosurgery & Psychiatry.

[22]  A Al-Chalabi,et al.  Concordance between site of onset and limb dominance in amyotrophic lateral sclerosis , 2010, Journal of Neurology, Neurosurgery & Psychiatry.

[23]  A. Aleman,et al.  Repetitive Transcranial Magnetic Stimulation over the Right Dorsolateral Prefrontal Cortex Disrupts Digit Span Task Performance , 2008, Neuropsychobiology.

[24]  J. Ravits,et al.  Focality of upper and lower motor neuron degeneration at the clinical onset of ALS , 2007, Neurology.

[25]  D. Bowers,et al.  Laterality, region, and type of motor dysfunction correlate with cognitive impairment in Parkinson's disease , 2007, Movement disorders : official journal of the Movement Disorder Society.

[26]  Andreas Meyer-Lindenberg,et al.  Shared and distinct neurophysiological components of the digits forward and backward tasks as revealed by functional neuroimaging , 2004, Neuropsychologia.

[27]  G. Hammond,et al.  Correlates of human handedness in primary motor cortex: a review and hypothesis , 2002, Neuroscience & Biobehavioral Reviews.

[28]  D. Neary,et al.  Cognitive change in motor neurone disease/amyotrophic lateral sclerosis (MND/ALS) , 2000, Journal of the Neurological Sciences.

[29]  J. Rothwell,et al.  Human handedness and asymmetry of the motor cortical silent period , 1999, Experimental Brain Research.

[30]  L. Goldstein,et al.  A positron emission tomography study of frontal lobe function (verbal fluency) in amyotrophic lateral sclerosis , 1995, Journal of the Neurological Sciences.

[31]  I. Litvan,et al.  Long-duration Parkinson's disease: role of lateralization of motor features. , 2013, Parkinsonism & related disorders.

[32]  A. Ludolph,et al.  Amyotrophic lateral sclerosis. , 2012, Current opinion in neurology.