Login to MyKarger

New to MyKarger? Click here to sign up.

Login with Facebook

Forgot Password? Reset your password

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login (Shibboleth)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Table of Contents
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 psherida@caregroup.harvard.edu


  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.