Movement Disorders in Alzheimer’s Disease

  • Sergio E. StarksteinEmail author
  • Marcelo Merello


Movement disorders are a frequent finding in AD and an important issue for differential diagnosis especially with diffuse Lewy body dementia and Creutzfeldt–Jakob disease. Temporal occurrence through the evolution of the disease and severity are crucial for differential diagnosis. In addition, psychiatric complications of AD either itself or due to the use of neuroleptics represent another source of motor symptoms. In this chapter, we will review mainly those movement disorders resulting from the neurodegenerative process.


Alzheimer’s disease Parkinsonism Dystonia Corticobasal syndrome Paratonia 


  1. Anheim M, Hannequin D, Boulay C, et al. Ataxic variant of Alzheimer’s disease caused by Pro117Ala PS1 mutation. J Neurol Neurosurg Psychiatry. 2007;78:1414–5.PubMedCentralPubMedCrossRefGoogle Scholar
  2. Ball JA, Lantos PL, Jackson M, et al. Alien hand sign in association with Alzheimer’s histopathology. J Neurol Neurosurg Psychiatry. 1993;56:1020–3.PubMedCentralPubMedCrossRefGoogle Scholar
  3. Ballard C, McKeith I, Burn D, et al. The UPDRS scale as a means of identifying extrapyramidal signs in patients suffering from dementia with Lewy bodies. Acta Neurol Scand. 1997;96:366–71.PubMedCrossRefGoogle Scholar
  4. Bateman RJ, Xiong C, Benzinger TL, et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med. 2012;367:795–804.PubMedCentralPubMedCrossRefGoogle Scholar
  5. Bennett HP, Corbett AJ, Gaden S, et al. Subcortical vascular disease and functional decline: a 6-year predictor study. J Am Geriatr Soc. 2002;50:1969–77.PubMedCrossRefGoogle Scholar
  6. Boeve BF, Maraganore DM, Parisi JE, et al. Pathologic heterogeneity in clinically diagnosed corticobasal degeneration. Neurology. 1999;53:795–800.PubMedCrossRefGoogle Scholar
  7. Boller F, Lopez OL, Moossy J. Diagnosis of dementia: clinicopathologic correlations. Neurology. 1989;39:76–9.PubMedCrossRefGoogle Scholar
  8. Braak H, Braak E. Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol Aging. 1997;18:351–7.PubMedCrossRefGoogle Scholar
  9. Burkhardt CR, Filley CM, Kleinschmidt-DeMasters BK, et al. Diffuse Lewy body disease and progressive dementia. Neurology. 1988;38:1520–8.PubMedCrossRefGoogle Scholar
  10. Burns A, Luthert P, Levy R, et al. Accuracy of clinical diagnosis of Alzheimer’s disease. BMJ. 1990;301:1026.PubMedCentralPubMedCrossRefGoogle Scholar
  11. Caviness JN. Myoclonus and neurodegenerative disease—what’s in a name? Parkinsonism Relat Disord. 2003;9:185–92.PubMedCrossRefGoogle Scholar
  12. Chand P, Grafman J, Dickson D, et al. Alzheimer’s disease presenting as corticobasal syndrome. Mov Disord. 2006;21:2018–22.PubMedCrossRefGoogle Scholar
  13. Chen J-Y, Stern Y, Sano M, Mayeux R. Cumulative risks of developing extrapyramidal signs, psychosis, or myoclonus in the course of Alzheimer’s disease. Arch Neurol. 1991;48:1141–3.PubMedCrossRefGoogle Scholar
  14. Cummings JL, Dubois B, Molinuevo JL, Scheltens P. International Work Group criteria for the diagnosis of Alzheimer disease. Med Clin North Am. 2013;97:363–8.PubMedCrossRefGoogle Scholar
  15. Doran M, du Plessis DG, Enevoldson TP, et al. Pathological heterogeneity of clinically diagnosed corticobasal degeneration. J Neurol Sci. 2003;216:127–34.PubMedCrossRefGoogle Scholar
  16. Dubois B, Feldman HH, Jacova C, et al. Revising the definition of Alzheimer’s disease: a new lexicon. Lancet Neurol. 2010;9:1118–27.PubMedCrossRefGoogle Scholar
  17. Duker AP, Espay AJ, Wszolek ZK, et al. Atypical motor and behavioral presentations of Alzheimer disease: a case-based approach. Neurologist. 2012;18:266–72.PubMedCrossRefGoogle Scholar
  18. Edler J, Mollenhauer B, Heinemann U, et al. Movement disturbances in the differential diagnosis of Creutzfeldt-Jakob disease. Mov Disord. 2009;24:350–6.PubMedCrossRefGoogle Scholar
  19. Galasko D, Katzman R, Salmon DP, et al. Clinical and neuropathological findings in Lewy body dementias. Brain Cogn. 1996;31:166–75.PubMedCrossRefGoogle Scholar
  20. Gauthier S, Vellas B, Farlow M, et al. Aggressive course of disease in dementia. Alzheimers Dement. 2006;2:210–7.PubMedCrossRefGoogle Scholar
  21. Gilleard CJ, Kellett JM, Coles JA, et al. The St. George’s dementia bed investigation study: a comparison of clinical and pathological diagnosis. Acta Psychiatr Scand. 1992;85:264–9.PubMedCrossRefGoogle Scholar
  22. Gladstone DJ, Black SE. The neurological examination in aging, dementia and cerebrovascular disease. Part 2: motor examination. Geriatr Aging. 2002;5:44–9.Google Scholar
  23. Haan MN, Jagust WJ, Galasko D, Kaye J. Effect of extrapyramidal signs and Lewy bodies on survival in patients with Alzheimer disease. Arch Neurol. 2002;59:588–93.PubMedCrossRefGoogle Scholar
  24. Hobbelen JS, Koopmans RT, Verhey FR, et al. Diagnosing paratonia in the demented elderly: reliability and validity of the Paratonia Assessment Instrument (PAI). Int Psychogeriatr. 2008;20:840–52.PubMedCrossRefGoogle Scholar
  25. Jack Jr CR, Knopman DS, Jaqust WJ, et al. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol. 2010;9:119–28.PubMedCentralPubMedCrossRefGoogle Scholar
  26. Kaur B, Harvey DJ, Decarli CS, et al. Extrapyramidal signs by dementia severity in Alzheimer disease and dementia with Lewy bodies. Alzheimer Dis Assoc Disord. 2013;27(3):226–32.PubMedCrossRefGoogle Scholar
  27. Kauwe JS, Wang J, Chakraverty S, et al. Novel presenilin 1 variant (P117A) causing Alzheimer’s disease in the fourth decade of life. Neurosci Lett. 2008;438:257–9.PubMedCentralPubMedCrossRefGoogle Scholar
  28. Kukull WA, Higdon R, Bowen JD, et al. Dementia and Alzheimer disease incidence: a prospective cohort study. Arch Neurol. 2002;59:1737–46.PubMedCrossRefGoogle Scholar
  29. Lleo A, Rey MJ, Castellvi M, et al. Asymmetric myoclonic parietal syndrome in a patient with Alzheimer’s disease mimicking corticobasal degeneration. Neurologia. 2002;17:223–6.PubMedGoogle Scholar
  30. Louis ED, Klatka LA, Liu Y, Fahn S. Comparison of extrapyramidal features in 31 pathologically confirmed cases of diffuse Lewy body disease and 34 pathologically confirmed cases of Parkinson’s disease. Neurology. 1997;48:376–80.PubMedCrossRefGoogle Scholar
  31. Lowe VJ, Peller PJ, Weigand SD, et al. Application of the National Institute on Aging-Alzheimer’s Association AD criteria to ADNI. Neurology. 2013;80:2130–7.PubMedCrossRefGoogle Scholar
  32. Magnuson TM, Roccaforte WH, Wengel SP, Burke WJ. Medication-induced dystonias in nine patients with dementia. J Neuropsychiatry Clin Neurosci. 2000;12:219–25.PubMedCrossRefGoogle Scholar
  33. McKeith IG, Perry RH, Fairbairn AF, et al. Operational criteria for senile dementia of Lewy body type (SDLT). Psychol Med. 1992;22:911–22.PubMedCrossRefGoogle Scholar
  34. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:263–9.PubMedCentralPubMedCrossRefGoogle Scholar
  35. Merello M, Sabe L, Teson A, et al. Extrapyramidalism in Alzheimer’s disease: prevalence, psychiatric, and neuropsychological correlates. J Neurol Neurosurg Psychiatry. 1994;57:1503–9.PubMedCentralPubMedCrossRefGoogle Scholar
  36. Miyaoka T, Seno H, Yamamori C, et al. Pisa syndrome due to a cholinesterase inhibitor (donepezil): a case report. J Clin Psychiatry. 2001;62:573–4.PubMedCrossRefGoogle Scholar
  37. Morris JC, Drazner M, Fulling K, et al. Clinical and pathological aspects of parkinsonism in Alzheimer’s disease. Arch Neurol. 1989;46:651–7.PubMedCrossRefGoogle Scholar
  38. Murman DL, Kuo SB, Powell MC, Colenda CC. The impact of parkinsonism on costs of care in patients with AD and dementia with Lewy bodies. Neurology. 2003;61:944–9.PubMedCrossRefGoogle Scholar
  39. Park M, Shah RC, Fogg LF, Wyatt JK. Daytime sleepiness in mild Alzheimer’s disease with and without parkinsonian features. Sleep Med. 2011;12:397–402.PubMedCrossRefGoogle Scholar
  40. Pavlis CJ, Kutscher EC, Carnahan RM, et al. Rivastigmine-induced dystonia. Am J Health Syst Pharm. 2007;64:2468–70.PubMedCrossRefGoogle Scholar
  41. Piggott MA, Marshall EF, Thomas N, et al. Striatal dopaminergic markers in dementia with Lewy bodies, Alzheimer’s and Parkinson’s diseases: rostrocaudal distribution. Brain. 1999;122:1449–68.PubMedCrossRefGoogle Scholar
  42. Price JL, Morris JC. Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease. Ann Neurol. 1999;45:358–68.PubMedCrossRefGoogle Scholar
  43. Richards M, Stern Y, Marder K, et al. Relationships between extrapyramidal signs and cognitive function in a community-dwelling cohort of patients with Parkinson’s disease and normal elderly individuals. Ann Neurol. 1993;33:267–74.PubMedCrossRefGoogle Scholar
  44. Richards M, Touchon J, Ledesert B, et al. Mild extrapyramidal signs and functional impairment in ageing. Int J Geriatr Psychiatry. 2002;17:150–3.PubMedCrossRefGoogle Scholar
  45. Risse SC, Raskind MA, Nochlin D, et al. Neuropathological findings in patients with clinical diagnoses of probable Alzheimer’s disease. Am J Psychiatry. 1990;147:168–72.PubMedGoogle Scholar
  46. Rowe CC, Ellis KA, Rimajowa M, et al. Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol Aging. 2010;31:1275–83.PubMedCrossRefGoogle Scholar
  47. Scarmeas N, Albert M, Brandt J, et al. Motor signs predict poor outcomes in Alzheimer disease. Neurology. 2005;64:1696–703.PubMedCentralPubMedCrossRefGoogle Scholar
  48. Sherrington R, Rogaev EI, Liang Y, et al. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer’s disease. Nature. 1995;375:754–60.PubMedCrossRefGoogle Scholar
  49. Shih LC, Vanderhorst VG, Lozano AM, et al. Improvement of pisa syndrome with contralateral pedunculopontine stimulation. Mov Disord. 2013;28:555–6.PubMedCrossRefGoogle Scholar
  50. Shim YS, Roe CM, Buckles VD, Morris JC. Clinicopathologic study of Alzheimer’s disease: Alzheimer mimics. J Alzheimers Dis. 2013;35:799–811.PubMedCentralPubMedGoogle Scholar
  51. Soininen H, Laulumaa V, Helkala EL, et al. Extrapyramidal signs in Alzheimer’s disease: a 3-year follow-up study. J Neural Transm Park Dis Dement Sect. 1992;4:107–19.PubMedCrossRefGoogle Scholar
  52. Spina S, Murrell JR, Huey ED, et al. Corticobasal syndrome associated with the A9D Progranulin mutation. J Neuropathol Exp Neurol. 2007;66:892–900.PubMedCrossRefGoogle Scholar
  53. Starkstein SE, Vazquez S, Merello M, et al. SPECT study of parkinsonism in Alzheimer’s disease. J Neuropsychiatry Clin Neurosci. 1995;7:308–13.PubMedGoogle Scholar
  54. Starkstein SE, Merello M, Brockman S, et al. Apathy predicts more severe parkinsonism in Alzheimer’s disease. Am J Geriatr Psychiatry. 2009;17:291–8.PubMedCrossRefGoogle Scholar
  55. Stern Y, Liu X, Albert M, et al. Modeling the influence of extrapyramidal signs on the progression of Alzheimer’s disease. Arch Neurol. 1996;53:1121–6.PubMedCrossRefGoogle Scholar
  56. Tarawneh R, Holtzman DM. The clinical problem of symptomatic Alzheimer disease and mild cognitive impairment. Cold Spring Harb Perspect Med. 2012;2:1–16.CrossRefGoogle Scholar
  57. Tassorelli C, Furnari A, Buscone S, et al. Pisa syndrome in Parkinson’s disease: clinical, electromyographic, and radiological characterization. Mov Disord. 2012;27:227–35.PubMedCrossRefGoogle Scholar
  58. Thies W, Bleiler L. 2011 Alzheimer’s disease facts and figures. Alzheimers Dement. 2011;7:208–44.PubMedCrossRefGoogle Scholar
  59. Tschampa HJ, Neumann M, Zerr I, et al. Patients with Alzheimer’s disease and dementia with Lewy bodies mistaken for Creutzfeldt-Jakob disease. J Neurol Neurosurg Psychiatry. 2001;71:33–9.PubMedCentralPubMedCrossRefGoogle Scholar
  60. Vaamonde-Gamo J, Flores-Barragan JM, Ibañez R, et al. DaT-SCAN SPECT in the differential diagnosis of dementia with Lewy bodies and Alzheimer’s disease. Rev Neurol. 2005;41:276–9.PubMedGoogle Scholar
  61. Vahia I, Cohen CI, Prehogan A, Memon Z. Prevalence and impact of paratonia in Alzheimer disease in a multiracial sample. Am J Geriatr Psychiatry. 2007;15:351–3.PubMedCrossRefGoogle Scholar
  62. van den Bosch S, Bouckaert F, Peuskens J. Mirtazapine-induced dystonia in a patient with Alzheimer’s disease. Tijdschr Psychiatr. 2006;48:153–7. Dutch.PubMedGoogle Scholar
  63. Vanacore N, Suzzareddu G, Maggini M, et al. Pisa syndrome in a cohort of Alzheimer’s disease patients. Acta Neurol Scand. 2005;111:199–201.PubMedCrossRefGoogle Scholar
  64. Villarejo A, Camacho A, Garcia-Ramos R, et al. Cholinergic-dopaminergic imbalance in Pisa syndrome. Clin Neuropharmacol. 2003;26:119–21.PubMedCrossRefGoogle Scholar
  65. Villegmane VL, Pike KE, Chételat G, et al. Longitudinal assessment of Aβ and cognition in aging and Alzheimer disease. Ann Neurol. 2011;69:181–92.e.CrossRefGoogle Scholar
  66. Wilson RS, Bennett DA, Gilley DW, et al. Progression of Parkinsonian signs in Alzheimer’s disease. Neurology. 2000;54:1284–9.PubMedCrossRefGoogle Scholar
  67. Wisniewski T, Dowjat WK, Buxbaum JD, et al. A novel Polish presenilin-1 mutation (P117L) is associated with familial Alzheimer’s disease and leads to death as early as the age of 28 years. Neuroreport. 1998;9:217–21.PubMedCrossRefGoogle Scholar
  68. Zekanowski C, Styczynska M, Peplonska B, et al. Mutations in presenilin 1, presenilin 2 and amyloid precursor protein genes in patients with early-onset alzheimer’s disease in Poland. Exp Neurol. 2003;184:991–6.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2014

Authors and Affiliations

  1. 1.School of Psychiatry and Clinical NeurosciencesUniversity of Western Australia FremantleFremantleAustralia
  2. 2.Neuroscience Department, Raul Carrea Institute for Neurological Research (FLENI)Universidad Catolica ArgentinaBuenos AiresArgentina

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