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Vol. 24, No. 2, 2007
Issue release date: July 2007
Section title: Original Research Article
Free Access
Dement Geriatr Cogn Disord 2007;24:125–137

The Role of Higher-Level Cognitive Function in Gait: Executive Dysfunction Contributes to Fall Risk in Alzheimer’s Disease

Sheridan P.L.a, b · Hausdorff J.M.b, c
aBehavioral Neurology Division, Department of Neurology, Beth Israel Deaconess Medical Center, and bDivision on Aging, Harvard Medical School, Boston, Mass., USA; cMovement Disorders Unit, Tel-Aviv Sourasky Medical Center; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
email Corresponding Author

Pamela Sheridan, MD, MMSc

Behavioral Neurology, Beth Israel Deaconess Medical Center

330 Brookline Avenue

Boston, MA 02215 (USA)

Tel. +1 617 667 0483, Fax +1 617 667 7981, E-Mail


  1. Jellinger KA: The neuropathological diagnosis of Alzheimer’s disease. J Neural Transm Suppl 1998;53:97–118.
  2. Braak H, Braak E: Diagnostic criteria for neuropathologic assessment of Alzheimer’s disease. Neurobiol Aging 1997;8:S85–S88.
    External Resources
  3. Dietz V: Neurophysiology of gait disorders: present and future applications. Electroencephal Clin Neurophysiol 1997;103:333–355.
  4. Shik ML, Orlovsky GN: Neurophysiology of locomotor automatism. Physiol Rev 1976;36:465–501.
  5. Imamura T, et al: Fall-related injuries in dementia with Lewy bodies (DLB) and Alzheimer’s disease. Eur J Neurol 2000;7:77–79.
  6. Morris JC, Rubin EH, Morris EJ, Mandel SA: Senile dementia of the Alzheimer’s type: an important risk factor for serious falls. J Gerontol 1987;42:412–417.
  7. Koutsavlis AT, Wolfson C: Elements of mobility as predictors of survival in elderly patients with dementia: findings from the Canadian Study of Health and Aging. Chronic Dis Can 2000;21:93–103.
  8. Weller I, Schatzker J: Hip fractures and Alzheimer’s disease in elderly institutionalized Canadians. Ann Epidemiol 2004;14:319–324.
  9. Buchner DM, Larson EB: Falls and fractures in patients with Alzheimer-type dementia. JAMA 1987;257:1492–1495.
  10. Nakamura T, Meguro K, Sasaki H: Relationship between falls and stride length variability in senile dementia of the Alzheimer type. Gerontology 1996;42:108–113.
  11. Camicioli R, Howieson D, Lehman S, Kaye J: Talking while walking: the effect of a dual task in aging and Alzheimer’s disease. Neurology 1997;48:955–958.
  12. Sheridan P, Solomont J, Kowall N, Hausdorff JM: Influence of executive function on locomotor function: divided attention increases gait variability in Alzheimer’s disease. J Am Geriatr Soc 2003;51:1633–1637.
  13. O’Keeffe ST, et al: Gait disturbance in Alzheimer’s disease: a clinical study. Age Ageing 1996;25:313–316.
  14. Visser H: Gait and balance in senile dementia of Alzheimer’s type. Age Ageing 1983;12:296–301.
  15. Kluger A, et al: Patterns of motor impairment in normal aging, mild cognitive decline, and early Alzheimer’s disease. J Gerontol B Psychol Sci Soc Sci 1997;52:28–39.
  16. Beloozerova IN, Sirota MG: Cortically controlled gait adjustments in the cat. Ann NY Acad Sci 1998;16:860:550–553.
    External Resources
  17. Willingham D: A neuropsychological theory of motor skill learning. Psychol Rev 1998;105:558–584.
  18. Christensen LO, Johannsen P, Sinkjaer T, et al: Cerebral activation during bicycle movements in man. Exp Brain Res 2000;135:66–72.
  19. Fukuyama H, Ouchi Y, Matsuzaki S, Nagahama Y, et al: Brain functional activity during gait in normal subjects: a SPECT study. Neurosci Lett 1997;228:183–186.
  20. Malouin F, Richards CL, Jackson PL, Dumas F, Doyon J: Brain activations during motor imagery of locomotor related tasks: a PET study. Hum Brain Mapp 2003;19:47–62.
  21. Hikosaka O, Nakamura K, Sakai K, Nakahara H: Central mechanisms of motor skill learning. Curr Opin Neurobiol 2002;12:217–222.
  22. Jahanshahi M, et al: Self-initiated versus externally triggered movements. I. An investigation using measurement of regional cerebral blood flow with PET and movement-related potentials in normal and Parkinson’s disease subjects. Brain 1995;118:913–933.
  23. Jueptner M, Frith CD, Brooks DJ, et al: Anatomy of motor learning. II. Subcortical structures and learning by trial and error. J Neurophysiol 1997;77:1325–1337.
  24. Passingham RE: Attention to action. Philos Trans R Soc Lond B Biol Sci 1996;351:1473–1479.
  25. Jueptner M, et al: Anatomy of motor learning. I. Frontal cortex and attention to action. J Neurophysiol 1997;77:113–1324.
  26. Johansen-Berg H, Matthews PM: Attention to movement modulates activity in sensori-motor areas, including primary motor cortex. Exp Brain Res 2002;142:13–24.
  27. Jahanshahi M, Frith CD: Willed action and its impairments. Cognitive Neuropsychol 1998;15:483–533.
  28. de Jong BM, van Zomeren AH, Willemsen ATM, Paans AMJ: Brain activity related to serial cognitive performance resembles circuitry of higher order motor control. Exp Brain Res 1996;109:136–140.
  29. Badgaiyan RD: Executive control, willed actions, and non-conscious processing. Hum Brain Mapp 2000;9:38–41.
  30. Gopher D: Attention control: explorations of the work of an executive controller. Brain Res Cogn Brain Res 1996;5:23–38.
  31. D’Esposito M, Ballard D, Zarahn E, Aguirre GK: The role of prefrontal cortex in sensory memory and motor preparation: an event-related fMRI study. Neuroimage 2000;11:400–408.
  32. Rowe J, Friston K, Frackowiak R, Passingham R: Neuroimage 2002;17:988–998.
  33. Criado JM, de la Fuente A, Heredia M, Riolobos AS, Yajeya J: Electrophysiological study of prefrontal neurones of cats during a motor task. Pflügers Arch 1997;434:91–96.
  34. Knight RT: Contribution of human hippocampal region to novelty detection. Nature 1996;383:256–259.
  35. Tesche CD, Karhu J: Theta oscillations index human hippocampal activation during a working memory task. Proc Natl Acad Sci USA 2000;97:919–924.
  36. Sinnamon HM: Hippocampal theta activity related to elicitation and inhibition of approach locomotion. Behav Brain Res 2005;160:236–249.
  37. Song EY, Kim YB, Kim YH, Jung MW: Role of active movement in place specific firing of hippocampal neurons. Hippocampus 2005;15:8–17.
  38. Zarahn E, Rakitin B, Abela D, et al: Positive evidence against human hippocampal involvement in working memory maintenance of familiar stimuli. Cereb Cortex 2005;15:303–316.
  39. Adams RL, Parsons OA: Neuropsychology for Clinical Practice: Etiology, Assessment, and Treatment of Common Neurologic Disorders. Washington, American Psychological Association, 2003.
  40. Fuster JM: Synopsis of function and dysfunction of the frontal lobe. Acta Psychiatr Scand 1999;395(suppl):51–57.
    External Resources
  41. Perry RJ, Hodges JR: Attention and executive deficits in Alzheimer’s disease. A critical review. Brain 1999;122:383–404.
  42. Shallice T, Burgess P: The domain of supervisory processes and temporal organization of behaviour. Philos Trans R Soc Lond B Biol Sci 1996;351:1405–1411.
  43. Shallice T: From neuropsychology to mental structure. Cambridge, Cambridge University Press, 1988.
  44. Neville H, Bavelier D: Human brain plasticity: evidence from sensory deprivation and altered language experience. Prog Brain Res 2002;138:177–188.
  45. Bavelier D, Neville HJ: Cross-modal plasticity: where and how? Nat Rev Neurosci 2002;3:443–452.
  46. Theoret H, Merabet L, Pascual-Leone A: Behavioral and neuroplastic changes in the blind: evidence for functionally relevant cross-modal interactions. J Physiol (Paris) 2004;98:221–233.
  47. Hulette CM, et al: Neuropathological and neuropsychological changes in ‘normal’ aging: evidence for preclinical Alzheimer disease in cognitively normal individuals. J. Neuropathol Exp Neurol 1998;57:1168–1174.
  48. Foldi NS, Lobosco JJ, Schaefer LA: The effect of attentional dysfunction in Alzheimer’s disease: theoretical and practical implications. Semin Speech Lang 2002;23:139–150.
  49. Lafleche G, Albert MS: Executive function deficit in mild Alzheimer’s disease. Neuropsychology 1995;9:313–320.
    External Resources
  50. Binetti G, et al: Executive dysfunction in early Alzheimer’s disease. J Neurol Neurosurg Psychiatry 1996;60:91–93.
  51. Albert MS: Cognitive and neurobiologic markers of early Alzheimer disease. Proc Natl Acad Sci USA 1996;93:13547–13551.
  52. Baddeley AD, Baddeley HA, Bucks RS, Wilcock GK: Attentional control in Alzheimer’s disease. Brain 2001;124:1492–1508.
  53. Perry RJ, Watson P, Hodges JR: The nature and staging of attention dysfunction in early (minimal and mild) Alzheimer’s disease: relationship to episodic and semantic memory impairment. Neuropsychologia 2000;38:252–271.
  54. Baddeley A, Logie R, Bressi S, et al: Dementia and working memory. Q J Exp Psychol A 1986;38:603–618.
  55. Baddeley A, Della Sala S, Spinnler H: The two-component hypothesis of memory deficit in Alzheimer’s disease. J Clin Exp Neuropsychol 1991;13:372–380.
  56. Baddeley AD: Working memory. Oxford, Oxford University Press, 1986.
  57. Grober E, Sliwinski MJ: Dual-task performance in demented and nondemented elderly. J Clin Exp Neuropsychol 1991;13:667–676.
  58. Della Sala S, Baddeley A, Papagno C, Spinnler H: Dual-task paradigm: a means to examine the central executive. Ann NY Acad Sci 1995;769:161–171.
  59. Baddeley AD, Bressi S, Della Sala S, Logie R, Spinnler H: The decline of working memory in Alzheimer’s disease. A longitudinal study. Brain 1991;114:2521–2542.
  60. Suva D, Favre I, Kraftsik R, et al: Primary motor cortex involvement in Alzheimer disease. J Neuropathol Exp Neurol 1999;58:1125–1134.
  61. Golaz J, Bouras C, Hof PR: Motor cortex involvement in presenile dementia: report of a case. J Geriatr Psychiatry Neurol 1992;5:85–92.
  62. Ferreri F, Pauri F, Pasqualetti P, et al: Motor cortex excitability in Alzheimer’s disease: a transcranial magnetic stimulation study. Ann Neurol 2003;53:102–108.
  63. Di Lazzaro V, Oliviero A, Pilato F, et al: Motor cortex hyperexcitability to transcranial magnetic stimulation in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2004;75:555–559.
  64. Alagona G, Ferri R, Pennisi G, et al: Motor cortex excitability in Alzheimer’s disease and in subcortical ischemic vascular dementia. Neurosci Lett 2004;362:95–98.
  65. Rossor MN, et al: Progressive frontal gait disturbance with atypical Alzheimer’s disease and corticobasal degeneration. J Neurol Neurosurg Psychiatry 1999;67:345–352.
  66. Alexander NB: Postural control in older adults. J Am Geriatr Soc1994;42:93–108.
  67. Alexander NB, et al: Maintenance of balance, gait patterns, and obstacle clearance in Alzheimer’s disease. Neurology 1995;45:908–914.
  68. Nutt JG, Marsden CD, Thompson PD: Human walking and higher-level gait disorders, particularly in the elderly. Neurology 1993;43:268–279.
  69. Tanaka A, Okuzumi H, Kobayashi I: Gait disturbance of patients with vascular and Alzheimer-type dementias. Percept Mot Skills 1995;80:735–738.
  70. Ott BR, Ellias SA, Lannon MC: Quantitative assessment of movement in Alzheimer’s disease. J Geriatr Psychiatry Neurol 1995;8:71–75.
  71. Korczyn AD: The underdiagnosis of the vascular contribution to dementia. J Neurol Sci 2005;229–230:3–6.
  72. Tian J, Shi J, Bailey K, Mann DM: Relationships between arteriosclerosis,cerebral amyloid angiopathy and myelin loss from cerebral cortical white matter in Alzheimer’s disease. Neuropathol Appl Neurobiol 2004;30:45–56.
    External Resources
  73. Capizzano AA, Acion L, Bekinschtein T, et al: White matter hyperintensities are significantly associated with cortical atrophy in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2004;75:822–827.
  74. Sitoh YY, Sitoh YY, Sahadevan S: Clinical significance of cerebral white matter lesions in older Asians with suspected dementia. Age Ageing 2004;33:65–71.
    External Resources
  75. Kono I, Mori S, Nakajima K, et al: Do white matter changes have clinical significance in Alzheimer’s disease? Gerontology 2004;50:242–246.
  76. van Gijn J: Leukoaraiosis and vascular dementia. Neurology 1998;51(suppl 3):S3–S8.
  77. Pohjasvaara T, Mantyla R, Ylikoski R, et al: Comparison of different clinical criteria (DSM-III, ADDTC, ICD-10, NINDS-ARIEN, DSM-IV) for the diagnosis of vascular dementia. Stroke 2000;31:2952–2957.
  78. Kuller LH, Lopez OL, Jagust WJ, et al: Determinants of vascular dementia in the Cardiovascular Health Cognition Study. Neurology 2005;64:1548–1552.
  79. Wolfson L, Wei X, Hall CB, et al: Accrual of MRI white matter abnormalities in elderly with normal and impaired mobility. J Neurol Sci 2005;232:23–27.
  80. Wolfson L: Gait and balance dysfunction: a model of the interaction of age and disease. Neuroscientist 2001;7:178–183.
  81. Franssen EH, Souren LE, Torossian CL, Reisberg B: Equilibrium and limb coordination in mild cognitive impairment and mild Alzheimer’s disease. J Am Geriatr Soc 1999;47:463–469.
  82. Scarmeas N, Albert M, Brandt J, et al: Motor signs predict poor outcomes in Alzheimer’s disease. Neurology 2005;64:1696–1703.
  83. Zadikoff C, Lang AE: Apraxia in movement disorders: a review. Brain 2005 Jun 1; [Epub ahead of print].
  84. Della Sala S, Spinnler H, Venneri A: Walking difficulties in patients with Alzheimer’s disease might originate from gait apraxia. J Neurol Neurosurg Psychiatry 2004;75:196–201.
  85. Stevens JA, Olson S: Reducing falls and resulting hip fractures among older women. MMWR Morb Mortal Wkly Rep 2000;49:1–12.
  86. Baloh RW, Ying SH, Jacobson KM: A longitudinal study of gait and balance dysfunction in normal older people. Arch Neurol 2003;60:835–839.
  87. Hausdorff JM, Rios D, Edelberg HK: Gait variability and fall risk in community-living older adults: a 1-year prospective study. Arch Phys Med Rehabil 2001;82:1050–1056.
  88. Hausdorff JM, Edelberg HK, Mitchell SL, et al: Increased gait unsteadiness in community-dwelling elderly fallers. Arch Phys Med Rehabil 1997;78:278–283.
  89. Maki BE: Gait changes in older adults: predictors of falls or indicators of fear. J Am Geriatr Soc 1997;45:313–320.
  90. Azizah MG, Lajoie Y, Teasdale N: Step length variability at gait initiation in elderly fallers and non-fallers, and young adults. Gerontology 2003;49:21–26.
  91. Lundin-Olsson L, Nyberg L, Gustafson Y: ‘Stops walking when talking’ as a predictor of falls in elderly people. Lancet 1997;349:617.
  92. Lundin-Olsson L, Nyberg L, Gustafson Y: Attention, frailty, and falls: the effect of a manual task on basic mobility. J Am Geriatr Soc 1998;46:758–761.
  93. Becker JT, et al: Compensatory reallocation of brain resources supporting verbal episodic memory in Alzheimer’s disease. Neurology 1996;46:692–700.
  94. Furey ML, et al: Cholinergic stimulation alters performance and task-specific regional cerebral blood flow during working memory. Proc Natl Acad Sci USA 1997;94:6512–6516.
  95. Verghese J, et al: Abnormality of gait as a predictor of non-Alzheimer’s dementia. N Engl J Med 2002;347:1761–1768.
  96. Waite LM, Grayson DA, Piguet O, et al: Gait slowing as a predictor of incident dementia: 6-year longitudinal data from the Sydney Older Persons Study. J Neurol Sci 2005;229–230:89–93.
  97. Shaw FE, Bond J, Richardson DA, et al: Multifactorial intervention after a fall in older people with cognitive impairment and dementia presenting to the accident and emergency department: a randomised controlled trial. BMJ 2003;326:1–6.
  98. Ray WA, Taylor JA, Meador KG, et al: A randomized trial of a consultation service to reduce falls in nursing homes. JAMA 1997;278:557–562.
  99. Mulrow CD, Gerety MB, Kanten D, et al: A randomized trial of physical rehabilitation for very frail nursing home residents. JAMA 1994;271:519–524.
  100. Teri L, Gibbons LE, McCurry SM, et al: Exercise plus behavioral management in patients with Alzheimer disease: a randomized controlled trial. JAMA 2003;290:2015–2022.
  101. Robertson MC, Campbell AJ, Gardner MM, et al: Preventing injuries in older people by preventing falls: a meta-analysis of individual-level data. J Am Geriatr Soc 2002;50:905–911.
  102. Barnett A, Smith B, Lord SR, et al: Community-based group exercise improves balance and reduces falls in at-risk older people: a randomised controlled trial. Age Ageing 2003;32:407–414.
  103. Wallace AE, Koford LL, West AN: Double-blind, placebo controlled trial of methylphenidate in older, depressed, medically ill patients. Am J Psychiatry 1995;152:929–931.
  104. Kittur S, Hauser P: Improvement of sleep and behavior by methylphenidate in Alzheimer’s disease. Am J Psychiatry 1999;156:1116–1117.
  105. Leonard BE, McCartan D, White J, King DJ: Methylphenidate: a review of its neuropharmacological, neuropsychological and adverse clinical effects. Hum Psychopharmacol 2004;19:151–180.
  106. Camicioli R, Lea E, Nutt JG, Sexton G, Oken BS: Methylphenidate increases the motor effects of L-Dopa in Parkinson’s disease: a pilot study. Clin Neuropharmacol 2001;24:208–213.
  107. White HK, Levin ED: Chronic four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer’s disease. Psychopharmacology 1999;84:158–165.
    External Resources
  108. Minkeviciene R, Bannerjee P, Tanila H: Memantine improves spatial learning in a transgenic mouse model of Alzheimer’s disease. J Pharmacol Exp Ther 2004;311:677–682.
  109. Rowland LM, Astur RS, Jung RE, et al: Selective cognitive impairments associated with NMDA receptor blockade in humans. Neuropsychopharmacology 2005;30:633–639.