Top

Published in:

01-02-2011 | Review Article

Dementia and cognitive impairment in amyotrophic lateral sclerosis: a review

Authors: Maria Teresa Giordana, Patrizia Ferrero, Silvia Grifoni, Alessia Pellerino, Andrea Naldi, Anna Montuschi

Published in: Neurological Sciences | Issue 1/2011

Abstract

Amyotrophic lateral sclerosis (ALS) is generally considered to be a paradigm of pure motor neuron disorder; nevertheless, the possible occurrence of cognitive impairment up to a frank dementia in patients affected by ALS is recognized. The appraisal of the cognitive impairment in ALS patients is crucial not only to the therapeutic trials of this incurable disease, but also to the planning of care, compliance to interventions, the end-of-life decisions. The cognitive/behavioral changes of ALS patients are consistent with frontotemporal dysfunctions; the overlap of neuropathological features of ALS and frontotemporal lobe degeneration (FTLD) supports, in addition, the putative spectrum of ALS and FTD. In the present review, the pertinent clinical, genetic, neuropathological, neuropsychological and neuroimaging data of the literature are comprehensively and critically discussed. The distinct and overlapping features of ALS and FTD are pointed out, as well as the undisclosed questions deserving additional studies.

Murphy J, Henry R, Lomen-Hoert C (2006) Identification and categorization of frontotemporal dementia impairment in ALS. In: Strong MJ (ed) Dementia and motor neuron disease. Informa UK Ltd, Abingdon, pp 59–66

Strong MJ, Grace GM, Freedman M et al (2009) Consensus criteria for the diagnosis of frontotemporal cognitive and behavioural syndromes in amyotrophic lateral sclerosis. Amyotroph Lateral Scler 10:131–146CrossRefPubMed

Neumann M, Sampathu DM, Kwong LK et al (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314:130–133CrossRefPubMed

Arai T, Hasegawa M, Akiyama H et al (2006) TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun 351:602–611CrossRefPubMed

Mackenzie IR, Feldman HH (2005) Ubiquitin immunohistochemistry suggests classic motor neuron disease, motor neuron disease with dementia, and frontotemporal dementia of the motor neuron disease type represent a clinicopathologic spectrum. J Neuropathol Exp Neurol 64:730–739CrossRefPubMed

Lillo P, Hodges JR (2009) Frontotemporal dementia and motor neuron disease: overlapping clinic-pathologic disorders. J Clin Neurosci 16:1131–1135CrossRefPubMed

Geser F, VM-Y Lee, Trojanowski JQ (2010) Amyotrophic lateral sclerosis and frontotemporal lobar degeneration: a spectrum of TDP-43 proteinopathies. Neuropathology 30:103–112CrossRefPubMed

Neumann M, Kwong LK, Sampathu DM et al (2007) TDP-43 proteinopathy in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Arch Neurol 64:1388–1394CrossRefPubMed

Mackenzie IRA (2007) The neuropathology of FTD associated with ALS. Alzheimer Dis Assoc Disord 21:44–49CrossRef

10.

Ringholz GM, Appel SH, Bradshaw M et al (2005) Prevalence and patterns of cognitive impairment in sporadic ALS. Neurology 65:586–590CrossRefPubMed

11.

Hamilton RL, Bowser R (2004) Alzheimer disease pathology in amyotrophic lateral sclerosis. Acta Neuropathol 107:515–522CrossRefPubMed

12.

Lomen-Hoerth C, Anderson T, Miller B (2002) The overlap of amyotrophic lateral sclerosis and frontotemporal dementia. Neurology 59:1077–1079CrossRefPubMed

13.

Kertesz A, Blair M, McMonagle P et al (2007) The diagnosis and course of frontotemporal dementia. Alzheimer Dis Assoc Disord 21:155–163CrossRefPubMed

14.

Neary D, Snowden JS, Gustafson L et al (1998) Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 51:1546–1554PubMed

15.

Hodges JR, Davies RR, Xuereb JH et al (2004) Clinicopathological correlates in frontotemporal dementia. Ann Neurol 56:399–406CrossRefPubMed

16.

Knopman DS, Boeve BF, Parisi JE et al (2005) Antemortem diagnosis of frontotemporal lobar degeneration. Ann Neurol 57:480–488CrossRefPubMed

17.

Mackenzie IR, Feldman H (2003) The relationship between extramotor ubiquitin-immunoreactive neuronal inclusions and dementia in motor neuron disease. Acta Neuropathol 105:98–102PubMed

18.

Hodges JR, Davies R, Xuereb J et al (2003) Survival in frontotemporal dementia. Neurology 61:349–354PubMed

19.

Hu W, Seelar H, Josephs K (2009) Clinical and survival profiles of patients with frontotemporal dementia and motor neuron disease. Neurology 72 (Suppl 3) P09.163

20.

Mc Clusky L, Elman L, Libon D (2009) ALS-dementia in a large population of patients with ALS and FTD. Neurology 72 (Suppl 3) S45.007

21.

Magistrello M, Rota E, Caglio M (2009) The diagnosis of FTD-ALS: a longitudinal study in a specialized dementia unit. Neurol Sci 9:S266

22.

Caselli RJ, Windebank AJ, Petersen RC et al (1993) Rapidly progressive aphasic dementia and motor neuron disease. Ann Neurol 33:200–207CrossRefPubMed

23.

Tsuchiya K, Ikeda K, Haga et al (2001) Atypical amyotrophic lateral sclerosis with dementia mimicking frontal Pick’sdisease: a report of an autopsy case with a clinical course of 15 years. Acta Neuropathol. 101:625–630PubMed

24.

Olney RK, Murphy J, Forshew D et al (2005) The effects of executive and behavioral dysfunction on the course of ALS. Neurology 65:1774–1777CrossRefPubMed

25.

Raaphorst J, De Visser M, Linssen WH, De Haan RJ, Schmand B (2009) The cognitive profile of amyotrophic lateral sclerosis: a meta-analysis. Amyotroph Lateral Scler 29:1–13CrossRef

26.

Grossman AB, Woolley-Levine S, Bradley WG, Miller RG (2007) Detecting neurobehavioral changes in amyotrophic lateral sclerosis. Amyotroph Lateral Scler 8:56–61CrossRefPubMed

27.

Gibbons ZC, Richardson A, Neary D, Snowden JS (2008) Behaviour in amyotrophic lateral sclerosis. Amyotroph Lateral Scler 9:67–74CrossRefPubMed

28.

Lomen-Hoerth C, Murphy J, Langmore S et al (2003) Are amyotrophic lateral sclerosis patients cognitively normal? Neurology 60:1094–1097PubMed

29.

Rakowicz WP, Hodges JR (1998) Dementia and aphasia in motor neuron disease: an underrecognised association? J Neurol Neurosurg Psychiatry 65:881–889CrossRefPubMed

30.

Murphy JM, Henry RG, Langmore S et al (2007) Continuum of frontal lobe impairment in amyotrophic lateral sclerosis. Arch Neurol 64:530–534CrossRefPubMed

31.

Phukan J, Pender NP, Hardiman O (2007) Cognitive impairment in amyotrophic lateral sclerosis. Lancet Neurol 6:994–1003CrossRefPubMed

32.

Bak TH, Hodges JR (2004) The effects of motor neurone disease on language: further evidence. Brain Lang 89:354–361CrossRefPubMed

33.

Doran M, Xuereb J, Odges JR (1995) Rapidly progressive aphasia with bulbar motor neurone disease: a clinical and neuropsycological study. Behav Neurol 8:169–180

34.

Tsuchiya K, Ozawa E, Fukushima J et al (2000) Rapidly progressive aphasia and motor neuron disease: a clinical, radiological, and pathological study of an autopsy case with circumscribed lobar atrophy. Acta Neuropathol 99:81–87CrossRefPubMed

35.

Duffy JR, Peach RK, Strand EA (2007) Progressive apraxia of speech as a sign of motor neuron disease. Am J Speech Lang Pathol 16:198–208CrossRefPubMed

36.

Rippon GA, Scarmeas N, Gordon PH et al (2006) An observational study of cognitive impairment in amyotrophic lateral sclerosis. Arch Neurol 63:345–352CrossRefPubMed

37.

Abrahams S, Goldstein LH, Al-Chalabi A et al (1997) Relation between cognitive dysfunction and pseudobulbar palsy in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 62:464–472CrossRefPubMed

38.

Robinson KM, Lacey SC, Grugan P et al (2006) Cognitive functioning in sporadic amyotrophic lateral sclerosis: a six month longitudinal study. JNNP 77:668–670

39.

Strong MJ, Grace GM, Orange JB et al (1999) A prospective study of cognitive impairment in ALS. Neurology 53:1665–1670PubMed

40.

Abrahams S, Leigh PN, Goldstein LH (2005) Cognitive change in ALS: a prospective study. Neurology 64:1222–1226PubMed

41.

Schreiber H, Gaigalat T, Wiedemuth-Catrinescu U et al (2005) Cognitive function in bulbar- and spinal-onset amyotrophic lateral sclerosis. A longitudinal study in 52 patients. J Neurol 252:772–781CrossRefPubMed

42.

Hosler BA, Siddique T, Sapp PC et al (2000) Linkage of familial amyotrophic lateral sclerosis with frontotemporal dementia to chromosome 9q21–q22. JAMA 284:1664–1669CrossRefPubMed

43.

Vance C, Al-Chalabi A, Ruddy D et al (2006) Familial amyotrophic lateral sclerosis with frontotemporal dementia is linked to a locus on chromosome 9p13.2–21.3. Brain 129:868–876CrossRefPubMed

44.

Valdmanis PN, Dupre N, Bouchard JP et al (2007) Three families with amyotrophic lateral sclerosis and frontotemporal dementia with evidence of linkage to chromosome 9p. Arch Neurol 64:240–245CrossRefPubMed

45.

Le Ber I, Camuzat A, Berger E et al (2009) Chromosome 9p-linked families with fronto-temporal dementia associated with motor neuron disease. Neurology 72:1669–1676CrossRefPubMed

46.

Boxer A, Mackenzie R, Boeve BF et al (2010) Clinical, neuroimaging and neuropathological features of a new chromosome 9p-linked FTD-ALS family. J Neurol Neurosurg Psychiatry. doi:10.1136/jnnp.2009.204081

47.

Gellera C, Colombrita C, Ticozzi N et al (2008) Identification of new ANG gene mutations in a large cohort of Italian patients with amyotrophic lateral sclerosis. Neurogenetics 9:33–40CrossRefPubMed

48.

Wicks P, Abrahams S, Papps B et al (2009) SOD1 and cognitive dysfunction in familial amyotrophic lateral sclerosis. J Neurol 256:234–241CrossRefPubMed

49.

Belzil VV, Valdmanis PN, Dion PA et al (2009) Mutations in FUS cause FALS and SALS in French and French Canadian populations. Neurology 73:1176–1179CrossRefPubMed

50.

Chio A, Restagno G, Brunetti M et al (2009) Two Italian kindreds with familial amyotrophic lateral sclerosis due to FUS mutation. Neurobiol Aging 30:1272–1275CrossRefPubMed

51.

Kwiatkowski TJ Jr, Bosco DA, Leclerc AL et al (2009) Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323:1205–1208CrossRefPubMed

52.

Vance C, Rogelj B, Hortobagyi T et al (2009) Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323:1208–1211CrossRefPubMed

53.

Kirby J, Goodall EF, Smith W et al (2009) Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis. Neurogenetics doi 101007/s10048-009-0218-9

54.

Baker M, Mackenzie IR, Pickering-Brown SM et al (2006) Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature 442:916–919CrossRefPubMed

55.

Pickering-Brown SM, Rollinson S, Du Plessis D et al (2008) Frequency and clinical characteristics of progranulin mutation carriers in the Manchester frontotemporal lobar degeneration cohort: comparison with patients with MAPT and no known mutations. Brain 131:721–731CrossRefPubMed

56.

Yu CE, Bird TD, Bekris LM et al (2010) The spectrum of mutations in progranulin: a collaborative study screening 545 cases of neurodegeneration. Arch Neurol 67:161–170CrossRefPubMed

57.

Gitcho MA, Bigio EH, Mishra M et al (2009) TARDBP 3’-UTR variant in autopsy-confirmed frontotemporal lobar degeneration with TDP-43 proteinopathy. Acta Neuropathol 118:633–645CrossRefPubMed

58.

Gallone S, Giordana MT, Scarpini E et al (2009) Absence of TARDBP gene mutations in an Italian series of patients with frontotemporal lobar degeneration. Dement Geriatr Cogn Disord 28:239–243CrossRefPubMed

59.

Mackenzie IRA, Neumann M, Bigio EH et al (2010) Nomenclature and nosology for neuropathologic subtypes of frontotemporal lobar degeneration: an update. Acta Neuropathol 119:1–4CrossRefPubMed

60.

Cairns NJ, Neumann M, Bigio EH et al (2007) TDP-43 in familial and sporadic frontotemporal lobar degeneration with ubiquitin inclusions. Am J Pathol 171:227–240CrossRefPubMed

61.

Wilson CM, Grace GM, Munots D, He BP, Strong MJ (2001) Cognitive impairment in sporadic ALS: a pathological continuum underlying a multisystem disorder. Neurology 57:651–657PubMed

62.

Mackenzie IR, Bigio EH, Ince PG et al (2007) Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations. Ann Neurol 61:427–434CrossRefPubMed

63.

Liscic RM, Grinberg LT, Zidar J, Gitcho MA, Cairns NJ (2008) ALS and FTLD: two faces of TDP-43 proteinopathy. Eur J Neurol 15:772–780CrossRefPubMed

64.

Giordana MT, Piccinini M, Grifoni S et al (2010) TDP-43 redistribution is an early event in amyotrophic lateral sclerosis. Brain Pathol 20:351–360CrossRefPubMed

65.

Josephs KA, Parisi JE, Knopman DS et al (2006) Clinically undetected motor neuron disease in pathologically proven frontotemporal lobar degeneration with motor neuron disease. Arch Neurol 63:506–512CrossRefPubMed

66.

Brandmeir NJ, Geser F, Kwong LK et al (2007) Severe subcortical TDP-43 pathology in sporadic frontotemporal lobar degeneration with motor neuron disease. Acta Neuropathol 115:147–149CrossRef

67.

Kawashima T, Doh-ura K, Kikuchi H et al (2001) Cognitive dysfunction in patients with amyotrophic lateral sclerosis is associated with spherical or crescent-shaped ubiquitinated intraneuronal inclusions in the parahippocampal gyrus and amygdala but not in the neostriatum. Acta Neuropathol 102:467–472PubMed

68.

Kato S, Hayashi H, Yagishita A (1993) Involvement of the frontotemporal lobe and limbic system in amyotrophic lateral sclerosis: as assessed by serial computed tomography and magnetic resonance imaging. J Neurol Sci 116:52–58CrossRefPubMed

69.

Frank B, Haas J, Heinze HJ et al (1997) Relation of neuropsychological and magnetic resonance findings in amyotrophic lateral sclerosis: evidence for subgroups. Clin Neurol Neurosurg 99:79–86CrossRefPubMed

70.

Pioro EP (2006) Neuroimaging in ALS and ALS with frontotemporal dementia In: Strong MJ (ed) Dementia and motor neuron disease. Informa UK Ltd, Abingdon, pp 107–131

71.

Lulè D, Ludolph AC, Kassubek J (2009) MRI-based functional neuroimaging in ALS: an update. Amyotroph Lateral Scler 10:258–268CrossRefPubMed

72.

Kew JJ, Goldstein LH, Leigh PN et al (1993) The relationship between abnormalities of cognitive function and cerebral activation in amyotrophic lateral sclerosis. A neuropsychological and positron emission tomography study. Brain 116:1399–1423CrossRefPubMed

73.

Abrahams S, Goldstein LH, Kew JJ et al (1996) Frontal lobe dysfunction in amyotrophic lateral sclerosis. A PET study. Brain 119:2105–2120CrossRefPubMed

74.

Talbot PR, Goulding PJ, Lloyd JJ et al (1995) Inter-relation between “classic” motor neuron disease and frontotemporaldementia: neuropsychological and single photon emission computed tomography study. J Neurol Neurosurg Psychiatry 58:541–547CrossRefPubMed

75.

Snowden J, Neary D, Mann D (2007) Frontotemporal lobar degeneration: clinical and pathological relationships. Acta Neuropathol 114:31–38CrossRefPubMed

76.

Chang JL, Lomen-Hoerth C, Murphy J et al (2005) A voxel-based morphometry study of patterns of brain atrophy in ALS and ALS/FTLD. Neurology 65:75–80CrossRefPubMed

77.

Whitwell JL, Jack CR Jr, Senjem ML, Josephs KA (2006) Patterns of atrophy in pathologically confirmed FTLD with and without motor neuron degeneration. Neurology 66:102–104CrossRefPubMed

78.

Nishihira Y, Tan C-H, Onodera O et al (2008) Sporadic amyotrophic lateral sclerosis: two pathological patterns shown by analysis of distribution of TDP-43-immunoreactive neuronal and glial cytoplasmic inclusions. Acta Neuropathol 116:169–182CrossRefPubMed

79.

Jeong Y, Park KC, Cho SS et al (2005) Pattern of glucose hypometabolism in frontotemporal dementia with motor neuron disease. Neurology 64:734–736PubMed

80.

Neary D, Snowden JS, Mann DM et al (1990) Frontal lobe dementia and motor neuron disease. J Neurol Neurosurg Psychiatry 53:23–32CrossRefPubMed

81.

Ishikawa T, Morita M, Nakano I (2007) Brain perfusion imaging in amyotrophic lateral sclerosis with dementia. Brain Nerve 10:1093–1098

82.

Abe K, Fujimura H, Toyooka K et al (1993) Single-photon emission computed tomographic investigation of patients with motor neuron disease. Neurology 43:1569–1573PubMed

83.

Abrahams S, Goldstein LH, Simmons A et al (2004) Word retrieval in amyotrophic lateral sclerosis: a functional magnetic resonance imaging study. Brain 127:1507–1517CrossRefPubMed

84.

Wooley SC, York MK, Moore DH et al (2010) Detecting frontotemporal dysfunction in ALS: utility of the ALS Cognitive Behavioral Screen (ALS-CBS^TM). Amyotroph Lateral Scler 11:303–311CrossRef

85.

Lillo P, Garcin B, Hornberger M et al (2010) Neurobehavioral features in frontotemporal dementia with amyotrophic lateral sclerosis. Arch Neurol 67:826–830CrossRefPubMed

Title: Dementia and cognitive impairment in amyotrophic lateral sclerosis: a review
Authors: Maria Teresa Giordana
Patrizia Ferrero
Silvia Grifoni
Alessia Pellerino
Andrea Naldi
Anna Montuschi
Publication date: 01-02-2011
Publisher: Springer Milan
Published in: Neurological Sciences / Issue 1/2011
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-010-0439-6

At a glance: The STEP trials

Springer Medicine

Dementia and cognitive impairment in amyotrophic lateral sclerosis: a review

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2011

The usefulness of albumin-adjusted ischemia-modified albumin index as early detecting marker for ischemic stroke

Pretreatment with a novel aquaporin 4 inhibitor, TGN-020, significantly reduces ischemic cerebral edema

Speech-induced primary lingual dystonia: a rare focal dystonia

Clock T3111C and Per2 C111G SNPs do not influence circadian rhythmicity in healthy Italian population

A case of mixed type of paroxysmal dyskinesia: is there an overlap between two clinical categories of paroxysmal dyskinesia?

A case of strictly unilateral migraine without aura transformed in an episodic hemicrania continua