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Cognitive intervention in Alzheimer disease

Abstract

Alzheimer disease (AD) is one of the most prevalent chronic medical conditions affecting the elderly population. The effectiveness of approved antidementia drugs, however, is limited—licensed AD medications provide only moderate relief of clinical symptoms. Cognitive intervention is a noninvasive therapy that could aid prevention and treatment of AD. Data suggest that specifically designed cognitive interventions could impart therapeutic benefits to patients with AD that are associated with substantial biological changes within the brain. Moreover, evidence indicates that a combination of pharmacological and non-pharmacological interventions could provide greater relief of clinical symptoms than either intervention given alone. Functional and structural MRI studies have increased our understanding of the underlying neurobiological mechanisms of aging and neurodegeneration, but the use of neuroimaging to investigate the effect of cognitive intervention on the brain remains largely unexplored. This Review provides an overview of the use of cognitive intervention in the healthy elderly population and patients with AD, and summarizes emerging findings that provide evidence for the effectiveness of this approach. Finally, we present recommendations for future research on the use of cognitive interventions in AD and discuss potential effects of this therapy on disease modification.

Key Points

  • No disease-modifying drugs are available for the treatment of Alzheimer disease (AD) and the effectiveness of approved antidementia drugs is still not satisfactory

  • Non-pharmacological interventions could aid the prevention and treatment of AD, and combining pharmacological and non-pharmacological interventions might substantially alleviate the clinical symptoms associated with the disease

  • Neuroimaging studies could further our understanding of the neurobiological mechanisms underlying the effects of cognitive intervention on the brain

  • Health-care professionals must base recommendations concerning the use of cognitive intervention in mild cognitive impairment and AD on robust experimental evidence

  • No standardized intervention programs are currently available for the treatment of the diverse cognitive and functional impairments associated with the different stages of AD

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References

  1. Weyerer, S. & Bickel, H. Epidemiologie Psychischer Erkrankungen im Höheren Lebensalter (Kohlhammer, Stuttgart, 2007).

    Google Scholar 

  2. Omerovic, M., Hampel, H., Teipel, S. J. & Buerger, K. Pharmacological treatment of Alzheimer's dementia: State of the art and current dilemmas. World J. Biol. Psychiatry 9, 69–75 (2008)

    PubMed  Google Scholar 

  3. Angevaren, M., Aufdemkampe, G., Verhaar, H. J., Aleman, A. & Vanhees, L. Physical activity and enhanced fitness to improve cognitive function in older people without known cognitive impairment. Cochrane Database of Systematic Reviews, Issue 3. Art. No.: CD005381. doi: 10.1002/14651858.CD005381.pub3 (2008).

  4. Sitzer, D. I., Twamley, E. W. & Jeste, D. V. Cognitive training in Alzheimer's disease: a meta-analysis of the literature. Acta Psychiatr. Scand. 114, 75–90 (2006).

    CAS  PubMed  Google Scholar 

  5. Knapp, M. et al. Cognitive stimulation therapy for people with dementia: cost-effectiveness analysis. Br. J. Psychiatry 188, 574–580 (2006).

    PubMed  Google Scholar 

  6. Spector, A. et al. Efficacy of an evidence-based cognitive stimulation therapy programme for people with dementia: randomised controlled trial. Br. J. Psychiatry 183, 248–254 (2003).

    PubMed  Google Scholar 

  7. Buonomano, D. V. & Merzenich, M. M. Cortical plasticity: from synapses to maps. Annu. Rev. Neurosci. 21, 149–186 (1998).

    CAS  PubMed  Google Scholar 

  8. Rapoport, S. I. Integrated phylogeny of the primate brain, with special reference to humans and their diseases. Brain Res. Brain Res. Rev. 15, 267–294 (1990).

    CAS  PubMed  Google Scholar 

  9. Finch, C. E. & Sapolsky, R. M. The evolution of Alzheimer disease, the reproductive schedule, and apoE isoforms. Neurobiol. Aging 20, 407–428 (1999).

    CAS  PubMed  Google Scholar 

  10. Palop, J. J., Chin, J. & Mucke, L. A network dysfunction perspective on neurodegenerative diseases. Nature 443, 768–773 (2006).

    CAS  PubMed  Google Scholar 

  11. Valenzuela, M. & Sachdev, P. Can cognitive exercise prevent the onset of dementia? Systematic review of randomized clinical trials with longitudinal follow-up. Am. J. Geriatr. Psychiatry 17, 179–187 (2009).

    PubMed  Google Scholar 

  12. Stern, Y. What is cognitive reserve? Theory and research application of the reserve concept. J. Int. Neuropsychol. Soc. 8, 448–460 (2002).

    PubMed  Google Scholar 

  13. Stern, Y. Cognitive reserve and Alzheimer disease. Alzheimer Dis. Assoc. Disord. 20, 112–117 (2006).

    PubMed  Google Scholar 

  14. Valenzuela, M. J. & Sachdev, P. Brain reserve and dementia: a systematic review. Psychol. Med. 36, 441–454 (2006).

    PubMed  Google Scholar 

  15. Stern, Y. et al. Brain networks associated with cognitive reserve in healthy young and old adults. Cereb. Cortex 15, 394–402 (2005).

    PubMed  Google Scholar 

  16. Oswald, W. D., Rupprecht, R., Gunzelmann, T. & Tritt, K. The SIMA-project: effects of 1 year cognitive and psychomotor training on cognitive abilities of the elderly. Behav. Brain Res. 78, 67–72 (1996).

    CAS  PubMed  Google Scholar 

  17. Rovio, S. et al. Leisure-time physical activity at midlife and the risk of dementia and Alzheimer's disease. Lancet Neurol. 4, 705–711 (2005).

    PubMed  Google Scholar 

  18. Yoshitake, T. et al. Incidence and risk factors of vascular dementia and Alzheimer's disease in a defined elderly Japanese population: the Hisayama Study. Neurology 45, 1161–1168 (1995).

    CAS  PubMed  Google Scholar 

  19. Podewils, L. J. et al. Physical activity, APOE genotype, and dementia risk: findings from the Cardiovascular Health Cognition Study. Am. J. Epidemiol. 161, 639–651 (2005).

    PubMed  Google Scholar 

  20. Laurin, D., Verreault, R., Lindsay, J., MacPherson, K. & Rockwood, K. Physical activity and risk of cognitive impairment and dementia in elderly persons. Arch. Neurol. 58, 498–504 (2001).

    CAS  PubMed  Google Scholar 

  21. Larson, E. B. Physical activity for older adults at risk for Alzheimer disease. JAMA 300, 1077–1079 (2008).

    CAS  PubMed  Google Scholar 

  22. Lautenschlager, N. T. et al. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. JAMA 300, 1027–1037 (2008).

    CAS  PubMed  Google Scholar 

  23. Forbes, D. et al. Physical activity programs for persons with dementia. Cochrane Database of Systematic Reviews, Issue 3. Art. No.: CD006489. doi: 10.1002/14651858.CD006489.pub2 (2008).

  24. Clare, L. & Woods, R. T. Cognitive training and cognitive rehabilitation for people with early-stage Alzheimer's disease: a review. Neuropsychol. Rehabil. 14, 385–401 (2004).

    Google Scholar 

  25. Clare, L., Woods, R. T., Moniz Cook, E. D., Orrell, M. & Spector, A. Cognitive rehabilitation and cognitive training for early-stage Alzheimer's disease and vascular dementia. Cochrane Database of Systematic Reviews, Issue 4. Art. No.: CD003260. doi: 10.1002/14651858.CD003260 (2003).

  26. Grandmaison, E. & Simard, M. A critical review of memory stimulation programs in Alzheimer's disease. J. Neuropsychiatry Clin. Neurosci. 15, 130–144 (2003).

    PubMed  Google Scholar 

  27. Baltes, P. B., Sowarka, D. & Kliegl, R. Cognitive training research on fluid intelligence in old age: what can older adults achieve by themselves? Psychol. Aging 4, 217–221 (1989).

    PubMed  Google Scholar 

  28. Schaie, K. The optimization of cognitive functioning in old age: prediction based on cohort sequentional and longitudinal data. In Successful Aging. Perspectives from the Behavioural Sciences (eds Baltes, P. B. & Baltes, M. M.) 94–117 (Cambridge University Press, Cambridge, 1990).

    Google Scholar 

  29. Owen, A. M. et al. Putting brain training to the test. Nature 465, 775–778 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Ball, K. et al. Effects of cognitive training interventions with older adults: a randomized controlled trial. JAMA 288, 2271–2281 (2002).

    PubMed  PubMed Central  Google Scholar 

  31. Willis, S. L. et al. Long-term effects of cognitive training on everyday functional outcomes in older adults. JAMA 296, 2805–2814 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Belleville, S. Cognitive training for persons with mild cognitive impairment. Int. Psychogeriatr. 20, 57–66 (2008).

    PubMed  Google Scholar 

  33. Petersen, R. C. et al. Current concepts in mild cognitive impairment. Arch. Neurol. 58, 1985–1992 (2001).

    CAS  PubMed  Google Scholar 

  34. Gauthier, S. et al. Mild cognitive impairment. Lancet 367, 1262–1270 (2006).

    PubMed  Google Scholar 

  35. Petersen, R. C. & Morris, J. C. Mild cognitive impairment as a clinical entity and treatment target. Arch. Neurol. 62, 1160–1163 (2005).

    PubMed  Google Scholar 

  36. Mitchell, A. J. & Shiri-Feshki, M. Rate of progression of mild cognitive impairment to dementia—meta-analysis of 41 robust inception cohort studies. Acta Psychiatr. Scand. 119, 252–265 (2009).

    CAS  PubMed  Google Scholar 

  37. Petersen, R. C. et al. Mild cognitive impairment: clinical characterization and outcome. Arch. Neurol. 56, 303–308 (1999).

    CAS  PubMed  Google Scholar 

  38. Olazaran, J. et al. Benefits of cognitive–motor intervention in MCI and mild to moderate Alzheimer disease. Neurology 63, 2348–2353 (2004).

    CAS  PubMed  Google Scholar 

  39. Rozzini, L. et al. Efficacy of cognitive rehabilitation in patients with mild cognitive impairment treated with cholinesterase inhibitors. Int. J. Geriatr. Psychiatry 22, 356–360 (2007).

    PubMed  Google Scholar 

  40. Talassi, E. et al. Effectiveness of a cognitive rehabilitation program in mild dementia (MD) and mild cognitive impairment (MCI): a case control study. Arch. Gerontol. Geriatr. 44 (Suppl. 1), 391–399 (2007).

    PubMed  Google Scholar 

  41. Cipriani, G., Bianchetti, A. & Trabucchi, M. Outcomes of a computer-based cognitive rehabilitation program on Alzheimer's disease patients compared with those on patients affected by mild cognitive impairment. Arch. Gerontol. Geriatr. 43, 327–335 (2006).

    PubMed  Google Scholar 

  42. Troyer, A. K., Murphy, K. J., Anderson, N. D., Moscovitch, M. & Craik, F. I. Changing everyday memory behaviour in amnestic mild cognitive impairment: a randomised controlled trial. Neuropsychol. Rehabil. 18, 65–88 (2008).

    PubMed  Google Scholar 

  43. Kinsella, G. J. et al. Early intervention for mild cognitive impairment: a randomised controlled trial. J. Neurol. Neurosurg. Psychiatry 80, 730–736 (2009).

    CAS  PubMed  Google Scholar 

  44. Bottino, C. M. et al. Cognitive rehabilitation combined with drug treatment in Alzheimer's disease patients: a pilot study. Clin. Rehabil. 19, 861–869 (2005).

    PubMed  Google Scholar 

  45. Requena, C. et al. Effects of cholinergic drugs and cognitive training on dementia. Dement. Geriatr. Cogn. Disord. 18, 50–54 (2004).

    CAS  PubMed  Google Scholar 

  46. Giordano, M. et al. Combination of intensive cognitive rehabilitation and donepezil therapy in Alzheimer's disease (AD). Arch. Gerontol. Geriatr. doi: 10.1016/j.archger.2009.11.008.

    PubMed  Google Scholar 

  47. Spector, A., Orrell, M., Davies, S. & Woods, B. Can reality orientation be rehabilitated? Development and piloting of an evidence-based programme of cognition-based therapies for people with dementia. Neuropsychological Rehabilitation 11, 377–397 (2001).

    Google Scholar 

  48. Loewenstein, D. A., Acevedo, A., Czaja, S. J. & Duara, R. Cognitive rehabilitation of mildly impaired Alzheimer disease patients on cholinesterase inhibitors. Am. J. Geriatr. Psychiatry 12, 395–402 (2004).

    PubMed  Google Scholar 

  49. Requena, C., Maestu, F., Campo, P., Fernandez, A. & Ortiz, T. Effects of cholinergic drugs and cognitive training on dementia: 2-year follow-up. Dement. Geriatr. Cogn. Disord. 22, 339–345 (2006).

    CAS  PubMed  Google Scholar 

  50. Farina, E. et al. Comparing two programs of cognitive training in Alzheimer's disease: a pilot study. Acta Neurol. Scand. 105, 365–371 (2002).

    PubMed  Google Scholar 

  51. Farina, E. et al. Evaluating two group programmes of cognitive training in mild-to-moderate AD: is there any difference between a 'global' stimulation and a 'cognitive-specific' one? Aging Ment. Health 10, 211–218 (2006).

    CAS  PubMed  Google Scholar 

  52. Spector, A., Davies, S., Woods, B. & Orrell, M. Reality orientation for dementia: a systematic review of the evidence of effectiveness from randomized controlled trials. Gerontologist 40, 206–212 (2000).

    CAS  PubMed  Google Scholar 

  53. Belleville, S. et al. Improvement of episodic memory in persons with mild cognitive impairment and healthy older adults: evidence from a cognitive intervention program. Dement. Geriatr. Cogn. Disord. 22, 486–499 (2006).

    PubMed  Google Scholar 

  54. Hall, C. B. et al. Education delays accelerated decline on a memory test in persons who develop dementia. Neurology 69, 1657–1664 (2007).

    CAS  PubMed  Google Scholar 

  55. Kelly, C., Foxe, J. J. & Garavan, H. Patterns of normal human brain plasticity after practice and their implications for neurorehabilitation. Arch. Phys. Med. Rehabil. 87 (Suppl. 2), S20–S29 (2006).

    PubMed  Google Scholar 

  56. Poldrack, R. A. Imaging brain plasticity: conceptual and methodological issues—a theoretical review. Neuroimage 12, 1–13 (2000).

    CAS  PubMed  Google Scholar 

  57. Jansma, J. M., Ramsey, N. F., Slagter, H. A. & Kahn, R. S. Functional anatomical correlates of controlled and automatic processing. J. Cogn. Neurosci. 13, 730–743 (2001).

    CAS  PubMed  Google Scholar 

  58. Sayala, S., Sala, J. B. & Courtney, S. M. Increased neural efficiency with repeated performance of a working memory task is information-type dependent. Cereb. Cortex 16, 609–617 (2006).

    PubMed  Google Scholar 

  59. Hempel, A. et al. Plasticity of cortical activation related to working memory during training. Am. J. Psychiatry 161, 745–747 (2004).

    PubMed  Google Scholar 

  60. Andreasen, N. C. et al. I. PET studies of memory: novel and practiced free recall of complex narratives. Neuroimage 2, 284–295 (1995).

    CAS  PubMed  Google Scholar 

  61. Haier, R. J. et al. Regional glucose metabolic changes after learning a complex visuospatial/motor task: a positron emission tomographic study. Brain Res. 570, 134–143 (1992).

    CAS  PubMed  Google Scholar 

  62. Elbert, T., Pantev, C., Wienbruch, C., Rockstroh, B. & Taub, E. Increased cortical representation of the fingers of the left hand in string players. Science 270, 305–307 (1995).

    CAS  PubMed  Google Scholar 

  63. Olesen, P. J., Westerberg, H. & Klingberg, T. Increased prefrontal and parietal activity after training of working memory. Nat. Neurosci. 7, 75–79 (2004).

    CAS  PubMed  Google Scholar 

  64. Petersen, S. E., van Mier, H., Fiez, J. A. & Raichle, M. E. The effects of practice on the functional anatomy of task performance. Proc. Natl Acad. Sci. USA 95, 853–860 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Wenderoth, N., Debaere, F., Sunaert, S. & Swinnen, S. P. The role of anterior cingulate cortex and precuneus in the coordination of motor behaviour. Eur. J. Neurosci. 22, 235–246 (2005).

    PubMed  Google Scholar 

  66. Seidler, R. D. et al. Cerebellum activation associated with performance change but not motor learning. Science 296, 2043–2046 (2002).

    CAS  PubMed  Google Scholar 

  67. Heiss, W. D., Kessler, J., Mielke, R., Szelies, B. & Herholz, K. Long-term effects of phosphatidylserine, pyritinol, and cognitive training in Alzheimer's disease. A neuropsychological, EEG, and PET investigation. Dementia 5, 88–98 (1994).

    CAS  PubMed  Google Scholar 

  68. Small, G. W. et al. Effects of a 14-day healthy longevity lifestyle program on cognition and brain function. Am. J. Geriatr. Psychiatry 14, 538–545 (2006).

    PubMed  Google Scholar 

  69. Stephan, B. C., Matthews, F. E., McKeith, I. G., Bond, J. & Brayne, C. Early cognitive change in the general population: how do different definitions work? J. Am. Geriatr. Soc. 55, 1534–1540 (2007).

    PubMed  Google Scholar 

  70. Geslani, D. M., Tierney, M. C., Herrmann, N. & Szalai, J. P. Mild cognitive impairment: an operational definition and its conversion rate to Alzheimer's disease. Dement. Geriatr. Cogn. Disord. 19, 383–389 (2005).

    PubMed  Google Scholar 

  71. Blennow, K., Hampel, H., Weiner, M. & Zetterberg, H. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat. Rev. Neurol. 6, 131–144 (2010).

    CAS  PubMed  Google Scholar 

  72. Hampel, H. et al. Biomarkers for Alzheimer's disease: academic, industry and regulatory perspectives. Nat. Rev. Drug Discov. 9, 560–574 (2010).

    CAS  PubMed  Google Scholar 

  73. Dubois, B. et al. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 6, 734–746 (2007).

    PubMed  Google Scholar 

  74. Zetzsche, T., Rujescu, D., Hardy, J. & Hampel, H. Advances and perspectives from genetic research: development of biological markers in Alzheimer's disease. Expert Rev. Mol. Diagn. 10, 667–690 (2010).

    CAS  PubMed  Google Scholar 

  75. Bokde, A. L., Ewers, M. & Hampel, H. Assessing neuronal networks: understanding Alzheimer's disease. Prog. Neurobiol. 89, 125–133 (2009).

    PubMed  Google Scholar 

  76. Wimo, A., Winblad, B., Aguero-Torres, H. & von Strauss, E. The magnitude of dementia occurrence in the world. Alzheimer Dis. Assoc. Disord. 17, 63–67 (2003).

    PubMed  Google Scholar 

  77. Tulving, E. & Thomson, D. M. Encoding specificity and retrieval processes in episodic memory. Psychol. Rev. 80, 352–373 (1973).

    Google Scholar 

  78. Breuil, V., Rotrou, J. D. & Forette, F. Cognitive stimulation of patients with dementia: preliminary results. Int. J. Geriatr. Psychiatry 9, 211–217 (1994).

    Google Scholar 

  79. Wilson, B. A., Evans, J. J., Emslie, H. & Malinek, V. Evaluation of NeuroPage: a new memory aid. J. Neurol. Neurosurg. Psychiatry 63, 113–115 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Wilson, B. Memory rehabilitation in brain-injured people. In Cognitive Neurorehabilitation (eds Stuss, D., Wincour, G. & Robertson, I. H.) 333–346 (Cambridge University Press, Cambridge, 1999).

    Google Scholar 

  81. Landauer, T. & Björk, R. A. Optimum rehearsal patterns and name learning. In Practical Aspects of Memory (eds Gruneberg, M., Morris, E. E. & Sykes, R. N.) 625–632 (Academic Press, London, 1978).

    Google Scholar 

  82. Glisky, E. L., Schacter, D. L. & Tulving, E. Learning and retention of computer-related vocabulary in memory-impaired patients: method of vanishing cues. J. Clin. Exp. Neuropsychol. 8, 292–312 (1986).

    CAS  PubMed  Google Scholar 

  83. Wilson, B., Baddeley, A., Evans, J. & Shiel, A. Errorless learning in the rehabilitation of memory impaired people. Neuropsychol. Rehabil. 4, 307–326 (1994).

    Google Scholar 

  84. Taulbee, L. & Folsom, J. C. Reality orientation for geriatric patients. Hosp. Community Psychiatry 17, 133–135 (1966).

    CAS  PubMed  Google Scholar 

  85. Boylin, W., Gordon, S. K. & Nehrke, M. F. Reminiscence and ego integrity in institutionalized elderly. Gerontologist 16, 118–124 (1976).

    CAS  PubMed  Google Scholar 

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Acknowledgements

Charles P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.

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V. Buschert, A. L. W. Bokde and H. Hampel all researched the data for the article, made substantial contributions to discussions of the content, and contributed equally to writing the article and to reviewing and/or editing of the manuscript before submission.

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Correspondence to Verena Buschert.

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Buschert, V., Bokde, A. & Hampel, H. Cognitive intervention in Alzheimer disease. Nat Rev Neurol 6, 508–517 (2010). https://doi.org/10.1038/nrneurol.2010.113

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