Journal of Neurology

, Volume 253, Issue 3, pp 333–339 | Cite as

Only subtle cognitive deficits in non–bulbar amyotrophic lateral sclerosis patients

  • D. Röttig
  • B. Leplow
  • K. Eger
  • A. C. Ludolph
  • M. Graf
  • S. Zierz


Neuropsychological investigations of amyotrophic sclerosis (ALS) patients revealed considerable discrepancies regarding neurocognitive functions. Some, but not all studies have suggested executive dysfunctioning and memory impairment, and there is a wide range of applied neuropsychological tests and results. In this study, we investigated the neuropsychological performance of 15 non–bulbar ALS patients, 14 patients with neuromuscular symptoms, and 15 healthy controls. To avoid confounding effects of motor disability, performance was assessed using exclusively motor–free tests of frontal lobe functioning (specific memory functions, conditional–associative learning, attention, and executive functions). ALS patients exhibited poorer performance in two conditions (semantic and alternating condition, respectively) of the Verbal Fluency Test, suggesting a subtle executive deficit. No deficits were found in tests of memory, conditionalassociative learning, or attention. Assessed mood status was not related to neuropsychological performance.Verbal memory (CVLT) and verbal fluency (lexical condition) were positively associated with duration of disease. Our results support the view that there are only subtle cognitive deficits in ALS patients and we assume a possible effect of practice on cognitive tasks following reduced daily motor activity.

Key words

amyotrophic lateral sclerosis neuropsychology cognition verbal fluency prefrontal cortex 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Abe K, Fujimura H, Toyooka K, Sakoda S, Yorifuji S, Yanagihara T (1997) Cognitive function in amyotrophic lateral sclerosis. J Neurol Sci 148:95–100CrossRefPubMedGoogle Scholar
  2. 2.
    Abrahams S, Goldstein LH, Al–Chalabi A, Pickering A, Morris RG, Passingham DJ, Leigh PN (1997) Relation between cognitive dysfunction and pseudobulbar palsy in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 62:464–472PubMedGoogle Scholar
  3. 3.
    Abrahams S, Leigh PN, Harvey A, Vythelingum GN, Grisé D, Goldstein LH (2000) Verbal Fluency and executive dysfunction in amyotrophic lateral sclerosis (ALS). Neuropsychologia 38:734–747CrossRefPubMedGoogle Scholar
  4. 4.
    Frank B, Haas J, Heinze H–J, Stark E, Münte TF (1997) Relation of neuropsychological and magnetic resonance findings in amyotrophic lateral sclerosis: evidence for subgroups. Clin Neurol Neurosurg 99:79–86CrossRefPubMedGoogle Scholar
  5. 5.
    Hanagasi HA, Gurvit IH, Ermutlu N, Kaptanoglu G, Karmursel S, Idrisoglu HA, Emre M, Demiralp T (2002) Cognitive impairment in amyotrophic lateral sclerosis: evidence from neuropsychological investigation and event–related potentials. Cogn Brain Res 14:234–244CrossRefGoogle Scholar
  6. 6.
    Paulus KS, Magnano I, Piras MR, Solinas MA, Sau GF, Aiello I (2002) Visual and auditory event–related potentials in sporadic amyotrophic lateral sclerosis. Clin Neurophysiol 113:853–861CrossRefPubMedGoogle Scholar
  7. 7.
    Strong MJ, Grace GM, Orange JB, Leeper HA, Menon RS, Aere C (1999) A prospective study of cognitive impairment in ALS. Neurology 53:1665–1670PubMedGoogle Scholar
  8. 8.
    Chari G, Shaw PJ, Sahgal A (1996) Nonverbal visual attention, but not recognition memory or learning, processes are impaired in motor neuron disease. Neuropsychologia 34:377–385CrossRefPubMedGoogle Scholar
  9. 9.
    Massman PJ, Sims J, Cooke N, Haverkamp LJ, Appel V, Appel SH (1996) Prevalence and correlates of neuropsychological deficits in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 61:450–455PubMedGoogle Scholar
  10. 10.
    Vieregge P, Wauschkuhn B, Heberlein I, Hagenah J, Verleger R (1999) Selective attention in impaired in amyotrophic lateral sclerosis – a study of event–related EEG potentials. Cog Brain Res 8:27–35Google Scholar
  11. 11.
    Abrahams S, Goldstein LH, Lloyd CM, Brooks DJ, Leigh PN (1995) Cognitive deficits in non–demented amyotrophic lateral sclerosis patients: a neuropsychological investigation. J Neurol Sci 129:S54–S55Google Scholar
  12. 12.
    Münte TF, Tröger M, Nusser I, Wieringa BM, Matzke M, Johannes S, Dengler R (1998) Recognition memory deficits in amyotrophic lateral sclerosis assessed with event–related brain potentials. Acta Neurol Scand 98:110–115PubMedGoogle Scholar
  13. 13.
    Abrahams S, Goldstein LH, Kew JJM, Brooks DJ, Lloyd CM, Frith CD, Leigh PN (1996) Frontal lobe dysfunction in amyotrophic lateral sclerosis. A PET study. Brain 119:2105–2120PubMedGoogle Scholar
  14. 14.
    Dary–Auriol M, Ingand P, Bonnaud V, Dumas P, Neau J–P, Gil R (1997) Sclérose latérale amyotrophique et trouble cognitifs. Rev Neurol (Paris) 153:244–250PubMedGoogle Scholar
  15. 15.
    David AS, Gillham MB (1986) Neuropsychological study of motor neuron disease. Psychosomatics 27:441–445PubMedGoogle Scholar
  16. 16.
    Iwasaki Y, Kinoshita M, Ikeda K, Takamiya K, Shiojima T (1990) Cognitive impairment in amyotrophic lateral sclerosis and its relation to motor disabilities. Acta Neurol Scand 81:141–143PubMedGoogle Scholar
  17. 17.
    Kew JJM, Goldstein LH, Leigh PN, Abrahams S, Cosgrave N, Passingham RE, Frackowiak RSJ, Brooks DJ (1993) The relationship between abnormalities of cognitive function and cerebral activation in amyotrophic lateral sclerosis. A neuropsychological and positron emission tomography study. Brain 116:1399–1423PubMedGoogle Scholar
  18. 18.
    Ludolph AC, Langen KJ, Regard M, Herzog H, Kemper B, Kuert T, Böttger IG, Feinendegen L (1992) Frontal lobe function in amyotrophic lateral sclerosis: a neuropsychologic and positron emission tomographic study. Acta Neurol Scand 85:81–89PubMedGoogle Scholar
  19. 19.
    Hartikainen P, Helkala E–L, Soininen H, Riekkinen P (1993) Cognitive and memory deficits in untreated Parkinson’s disease and amyotrophic lateral sclerosis: a comparative study. J Neural Transm 6:127–137Google Scholar
  20. 20.
    Gallassi R, Montagna P, Ciardulli C, Lorusso C, Mussuto V, Stracciari A (1985) Cognitive impairment in motor neuron disease. Acta Neurol Scand 71:480–484PubMedGoogle Scholar
  21. 21.
    Talbot PR, Goulding PJ, Lloyd JL, Snowden JS, Neary D, Testa HJ (1995) Inter–relation between "classic" motor neuron disease and frontotemporal dementia: neuropsychological and single photon emission computed tomography study. J Neurol Neurosurg Psychiatry 58:541–547PubMedGoogle Scholar
  22. 22.
    Loemen–Hoerth C, Murphy J, Henry R, Hillinger M, Chin C, Kramer J, Forshew D (2002) The Frequency of Frontotemporal Lobar Dementia in Amyotrophic Lateral Sclerosis Population: Is Neuropsychological Testing or Neuroimaging more sensitive? Ann Neurol 52:866–867Google Scholar
  23. 23.
    Loemen–Hoerth C, Murphy J, Langmore S, Kramer JH, Olney RK, Miller B (2003) Are amyotrophic lateral sclerosis patients cognitively normal? Neurology 60:1094–1097Google Scholar
  24. 24.
    McCullagh S, Moore M, Gawel M, Feinstein A (1999) Pathological laughing and crying in amyotrophic lateral sclerosis: an association with prefrontal cognitive dysfunction. J Neurol Sci 169:43–48CrossRefPubMedGoogle Scholar
  25. 25.
    Ringholz GM, Mosnik DM, Roebuck TM, McMurray PJ (2002) Rethinking the Cognitive Deficits Associated with Amyotrophic Lateral Sclerosis: Incidence and Subtypes. Ann Neurol Suppl 1:S48–S49Google Scholar
  26. 26.
    Capitani E, Della Salla S, Marchetti C (1994) Is there a cognitive impairment in MND? A survey with longitudinal data. Schweiz Arch Neurol Psychiatr 145:11–13PubMedGoogle Scholar
  27. 27.
    Poloni M, Capitani E, Mazzini L, Ceroni M (1986) Neuropsychological measures in amyotrophic lateral sclerosis and their relationship with CT scan–assessed cerebral atrophy. Acta Neurol Scand 74:257–260PubMedGoogle Scholar
  28. 28.
    Brooks BR (1994) El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommitee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial “Clinical limits of amyotrophic lateral sclerosis”workshop contributors. J Neurol Sci 124:96–107CrossRefPubMedGoogle Scholar
  29. 29.
    Huber W (1983) Aachener Aphasie Test (AAT). Göttingen: HogrefeGoogle Scholar
  30. 30.
    Wittchen HU, Wunderlich U, Gruschwitz S, Zaudig M (1997) Strukturiertes Klinisches Interview für DSV–IV. Achse I Psychiatrische Störungen. Göttingen, Bern, Toronto, Seattle: HogrefeGoogle Scholar
  31. 31.
    Folstein MF, Folstein SE, MacHugh PR (1990) Mini–Mental–Status–Test. Weinheim: Beltz–TestGoogle Scholar
  32. 32.
    Lehrl S (1975) Mehrfachwahl– Wortschatz–Intelligenztest:MWT–B. Balingen: PERIMED–spittaGoogle Scholar
  33. 33.
    Nelson HE, Willison J (1991) National Adult Reading Test (NART) Test Manual. 2 ed. Windsor: NFER–NelsonGoogle Scholar
  34. 34.
    Biehl B, Dangel S, Reiser A (1995) Profile of Mood States (POMS). Weinheim: BeltzGoogle Scholar
  35. 35.
    McGuire D, Garrison L, Armon C, Barohn RJ, Bryan WW, Miller R, Parry GJ, Petajan JH, Ross MA (1997) The Syntex–Synergen ALS/CNTF Study Group. A brief quality–of–life measure for ALS clinical trials based on a subset of items from the sickness impact profile. J Neurol Sci 152:S18–S22CrossRefPubMedGoogle Scholar
  36. 36.
    Smith A (1995) Symbol Digit Modalities Test. Los Angeles:Western Psychological ServicesGoogle Scholar
  37. 37.
    Delis DC, Kramer JH (2000) CVLT: California Verbal Learning Test: Psychological CorporationGoogle Scholar
  38. 38.
    Petrides M (1985) Deficits on conditional– associative–learning tasks after frontal– and temporal–lobe lesions in man. Neuropsychologia 23:601–614CrossRefPubMedGoogle Scholar
  39. 39.
    Petrides M (1990) Nonspatial conditional learning impaired in patients with unilateral frontal but not unilateral temporal lobe excisions. Neuropsychologia 28:137–149CrossRefPubMedGoogle Scholar
  40. 40.
    Baschek I–L, Bredenkamp J, Oehrle B, Wippich W (1977) Bestimmung der Bildhaftigkeit (I), Konkretheit (C) und der Bedeutungshaltigkeit (m') von 800 Substantiven. Z Exp Angew Psychol XXIV:353–396Google Scholar
  41. 41.
    Snodgrass JG, Vanderwart MA (1980) Standardized Set of 260 Pictures: Norms for Name Agree, Image Agreement, Familiarity, and Visual Complexity. J Exp Psychol Mem Cogn 6:174–215Google Scholar
  42. 42.
    Bortz J (1993) Statistik für Sozialwissenschafter. Berlin: SpringerGoogle Scholar
  43. 43.
    Tombaugh TN, Kozak J, Rees L (1998) Normative data for the controlled oral word association test. In: Spreen O, Strauss E (eds) A compendium of neuropsychological tests: administration, norms and commentary. 2 ed. New York: Oxford University PressGoogle Scholar
  44. 44.
    Spreen O, Strauss E (1998) A compendium of neuropsychological tests: administration, norms and commentary. 2 ed. New York: Oxford University PressGoogle Scholar
  45. 45.
    Kilani M, Micallef J, Soubrouillard C, Rey–Lardiller D, Demattei C, Dib M, Philippot P, Ceccaldi M, Pouget J, Blin O (2004) A longitudinal study of the evolution of cognitive function and affective state in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 5:46–54PubMedGoogle Scholar
  46. 46.
    Hartje W, Poeck K (1997) Klinische Neuropsychologie. Stuttgart, New York: ThiemeGoogle Scholar
  47. 47.
    Saletu B, Grünberger J, Anderer P, Linzmayer L (1996) Effects of the Novel Neuroprotective Agent, Riluzole, on Human Brain Function and Behavior: I Double–Blind, Placebo–Controlled EEG Mapping and Psychometric Studies Under Normoxia. Methods Find Exp Clin Pharmacol 18:55–66PubMedGoogle Scholar

Copyright information

© Steinkopff-Verlag 2005

Authors and Affiliations

  • D. Röttig
    • 3
    • 4
  • B. Leplow
    • 3
  • K. Eger
    • 1
  • A. C. Ludolph
    • 2
  • M. Graf
    • 2
  • S. Zierz
    • 1
  1. 1.Department of NeurologyMartin–Luther–University of Halle–WittenbergHalle/SaaleGermany
  2. 2.Department of NeurologyUniversity of UlmUlmGermany
  3. 3.Inst. of PsychologyMartin–Luther–University of Halle–WittenbergHalleGermany
  4. 4.Department of Psychiatry and PsychotherapyMartin–Luther–University of Halle–WittenbergHalle/SaaleGermany

Personalised recommendations