Hostname: page-component-848d4c4894-pjpqr Total loading time: 0 Render date: 2024-07-02T21:34:49.842Z Has data issue: false hasContentIssue false
  • English
  • Français

Clinical progression of moderate-to-severe Alzheimer's disease and caregiver burden: a 12-month multicenter prospective observational study

Published online by Cambridge University Press:  20 September 2010

Luis Agüera-Ortiz ,
Ana Frank-García ,
Pedro Gil  and
Alfonso Moreno
Luis Agüera-Ortiz*
Affiliation:
Department of Psychiatry, University Hospital 12 de Octubre, Madrid, Spain
Ana Frank-García
Affiliation:
Department of Neurology, University Hospital La Paz, Madrid, Spain
Pedro Gil
Affiliation:
Geriatrics Service, Hospital Clínico San Carlos, Madrid, Spain
Alfonso Moreno
Affiliation:
Department of Pharmacology, Hospital Clínico San Carlos, Madrid, Spain
*
Correspondence should be addressed to: Luis Agüera-Ortiz, Department of Psychiatry, University Hospital 12 de Octubre, Edificio de Medicina Comunitaria, Avenida de Córdoba km 5.400, 28041 Madrid, Spain. Phone: +34 91 390 8022; Fax: +34 91 390 8538. Email: laguerao@intersep.org.
Get access Rights & Permissions [Opens in a new window]

Abstract

Background: Prospective studies on the clinical progression of Alzheimer's disease (AD) and its relationship to caregiver burden are needed to improve illness management and use of resources.

Methods: This national, multicenter, observational study evaluated 1235 moderate to severe AD patients under routine care in Spain. Baseline cross-sectional sociodemographic and clinical data, and changes from baseline to month 12 of various neuropsychological tests and clinical ratings, including Blessed Dementia Scale, Mini-mental State Examination (MMSE), Hughes Clinical Dementia Rating sum-of-boxes (CDR-SB), Clinical Global Impression of Change (CGIC) and Zarit Caregiver Burden scales, were recorded and comprehensively analyzed.

Results: Baseline data were in accordance with characteristics consistently reported to influence AD risk regarding anthropometrics, sociocultural features and comorbidities. Significant progressive functional impairments (i.e. in routine activities and essential daily tasks) and cognitive (i.e. MMSE and CDR-SB) impairments were found at month 12. However, patients' behavior and caregivers' burden improved slightly, but significantly, corroborating the major influence of behavioral symptoms on caregivers' distress. Caregivers showed significantly lower burden with patients with higher levels of education and, to a lesser extent, when patients received AD-specific medication. Physicians accurately detected AD clinical evolution as their CGIC ratings significantly correlated with all tests.

Conclusions: These findings reinforce previous AD knowledge and add data on the clinical course of advanced stages of AD. Caregiver burden depended more on patients' behavioral alterations than on their functional or cognitive declines; and it was diminished by their patients having higher levels of education and being treated with AD-specific medications. Research into unexplored factors that might reduce caregiver burden, ultimately benefiting both patients and caregivers, is encouraged.

Keywords

dementianeurodegenerative diseaseneurocognitive disorderclinical coursecognitive impairmentfunctional impairmentbehavioral symptoms
Type
Research Article
Information
International Psychogeriatrics , Volume 22 , Special Issue 8: Focus on prevention in psychogeriatrics , December 2010 , pp. 1265 - 1279
Copyright
Copyright © International Psychogeriatric Association 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Alexopoulos, G. S., Jeste, D. V., Chung, H., Carpenter, D., Ross, R. and Docherty, J. P. (2005). The expert consensus guideline series: treatment of dementia and its behavioral disturbances. Introduction: methods, commentary, and summary. Postgraduate Medicine, Special Issue, 6–22.Google Scholar
Alzheimer's Disease International (2009). World Alzheimer Report 2009. London: Alzheimer's Disease International.Google Scholar
American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Washington, DC: American Psychiatric Association.Google Scholar
Ames, D., Kaduszkiewicz, H., Van Den Bussche, H., Zimmermann, T., Birks, J. and Ashby, D. (2008). For debate: is the evidence for the efficacy of cholinesterase inhibitors in the symptomatic treatment of Alzheimer's disease convincing or not? International Psychogeriatrics, 20, 259–292. doi: 10.1017/S1041610207006680.Google Scholar
Andersen, K. et al. (1999). Gender differences in the incidence of AD and vascular dementia: the EURODEM Studies. EURODEM Incidence Research Group. Neurology, 53, 1992–1997.CrossRefGoogle ScholarPubMed
Andren, S. and Elmstahl, S. (2005). Family caregivers' subjective experiences of satisfaction in dementia care: aspects of burden, subjective health and sense of coherence. Scandinavian Journal of Caring Sciences, 19, 157–168. doi: 10.1111/j.1471-6712.2005.00328.x.Google Scholar
Azad, N. A., Al Bugami, M. and Loy-English, I. (2007). Gender differences in dementia risk factors. Gender Medicine, 4, 120–129. doi: 10.1016/S1550-8579(07)80026-X.CrossRefGoogle ScholarPubMed
Bachner, Y. G. and O'Rourke, N. (2007). Reliability generalization of responses by care providers to the Zarit Burden Interview. Aging and Mental Health, 11, 678–685. doi: 10.1080/13607860701529965.Google Scholar
Bassiony, M. M. and Lyketsos, C. G. (2003). Delusions and hallucinations in Alzheimer's disease: review of the brain decade. Psychosomatics, 44, 388–401.CrossRefGoogle Scholar
Beier, M. T. (2007). Treatment strategies for the behavioral symptoms of Alzheimer's disease: focus on early pharmacologic intervention. Pharmacotherapy, 27, 399–411. doi: 10.1592/phco.27.3.399.Google Scholar
Blessed, G., Tomlinson, B. E. and Roth, M. (1968). The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. British Journal of Psychiatry, 114, 797–811. doi: 10.1192/bjp.114.512.797.Google Scholar
Finkel, S. I., Costa e Silva, J., Cohen, G., Miller, S. and Sartorius, N. (1996). Behavioral and psychological signs and symptoms of dementia: a consensus statement on current knowledge and implications for research and treatment. International Psychogeriatrics, 8 (Suppl. 3), 497–500. doi: 10.1017/S1041610297003943.Google Scholar
Folstein, M. F., Folstein, S. E. and McHugh, P. R. (1975). “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189–198. doi:10.1016/0022-3956(75)90026-6.CrossRefGoogle ScholarPubMed
Fotuhi, M., Hachinski, V. and Whitehouse, P. J. (2009). Changing perspectives regarding late-life dementia. Nature Reviews Neurology, 5, 649–658. doi:10.1038/nrneurol.2009.175.Google Scholar
Germain, S. et al. (2009). Does cognitive impairment influence burden in caregivers of patients with Alzheimer's disease? Journal of Alzheimer's Disease, 17, 105–114. doi:10.3233/JAD-2009-1016.CrossRefGoogle Scholar
Given, C. W., Given, B. A., Stommel, M. and Azzouz, F. (1999). The impact of new demands for assistance on caregiver depression: tests using an inception cohort. The Gerontologist, 39, 76–85. doi:10.1093/geront/39.1.76.CrossRefGoogle Scholar
Hachinski, V. C. et al. (1975). Cerebral blood flow in dementia. Archives of Neurology, 32, 632–637.Google Scholar
Helzer, J. E., Kraemer, H. C., Krueger, R. F., Wittchen, H.-U., Sirovatka, P. J. and Regier, D. A. (2008). Dimensional Approaches in Diagnostic Classification: Refining the Research Agenda for DSM-V. Arlington, VA: American Psychiatric Association.Google Scholar
Hosmer, D. W. and Lemeshow, S. (2000). Applied Logistic Regression. Hoboken, NJ: John Wiley & Sons, Inc.Google Scholar
Hughes, C. P., Berg, L., Danziger, W. L., Coben, L. A. and Martin, R. L. (1982). A new clinical scale for the staging of dementia. British Journal of Psychiatry, 140, 566–572.CrossRefGoogle Scholar
Husted, J. A., Cook, R. J., Farewell, V. T. and Gladman, D. D. (2000). Methods for assessing responsiveness: a critical review and recommendations. Journal of Clinical Epidemiology, 53, 459–468. doi:10.1016/S0895-4356(99)00206-1.CrossRefGoogle Scholar
Jones, R. N., Yang, F. M., Zhang, Y., Kiely, D. K., Marcantonio, E. R. and Inouye, S. K. (2006). Does educational attainment contribute to risk for delirium? A potential role for cognitive reserve. Journals of Gerontology: Series A, Biological Sciences and Medical Sciences, 61, 1307–1311.Google Scholar
Kaufer, D. I. et al. (2000). Validation of the NPI-Q, a brief clinical form of the Neuropsychiatric Inventory. Journal of Neuropsychiatry and Clinical Neurosciences, 12, 233–239.Google Scholar
Kloppenborg, R. P., Van Den Berg, E., Kappelle, L. J. and Biessels, G. J. (2008). Diabetes and other vascular risk factors for dementia: which factor matters most? A systematic review. European Journal of Pharmacology, 585, 97–108. doi: 10.1016/j.ejphar.2008.02.049.Google Scholar
Lobo, A. et al. (1999). Revalidation and standardization of the cognition mini-exam (first Spanish version of the Mini-mental State Examination) in the general geriatric population. Medicina Clínica, 112, 767–774.Google Scholar
Lopez, O. L. et al. (2003). Psychiatric symptoms vary with the severity of dementia in probable Alzheimer's disease. Journal of Neuropsychiatry and Clinical Neurosciences, 15, 346–353.Google Scholar
Lyketsos, C. G. and Lee, H. B. (2004). Diagnosis and treatment of depression in Alzheimer's disease: a practical update for the clinician. Dementia and Geriatric Cognitive Disorders, 17, 55–64. doi: 10.1159/000074277.Google Scholar
Mallows, C. L. (1973). Some comments on Cp. Technometrics, 15, 661–675.Google Scholar
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D. and Stadlan, E. M. (1984). Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology, 34, 939–944.Google Scholar
Moroney, J. T. et al. (1997). Meta-analysis of the Hachinski Ischemic Score in pathologically verified dementias. Neurology, 49, 1096–1105.Google Scholar
Ngandu, T. et al. (2007). Education and dementia: what lies behind the association? Neurology, 69, 1442–1450.CrossRefGoogle Scholar
Oremus, M., Perrault, A., Demers, L. and Wolfson, C. (2000). Review of outcome measurement instruments in Alzheimer's disease drug trials: psychometric properties of global scales. Journal of Geriatric Psychiatry and Neurology, 13, 197–205. doi:10.1177/089198870001300404.CrossRefGoogle ScholarPubMed
Ownby, R. L., Crocco, E., Acevedo, A., John, V. and Loewenstein, D. (2006). Depression and risk for Alzheimer disease: systematic review, meta-analysis, and meta-regression analysis. Archives of General Psychiatry, 63, 530–538.CrossRefGoogle Scholar
Papastavrou, E., Kalokerinou, A., Papacostas, S. S., Tsangari, H. and Sourtzi, P. (2007). Caring for a relative with dementia: family caregiver burden. Journal of Advanced Nursing, 58, 446–457. doi: 10.1111/j.1365-2648.2007.04250.x.Google Scholar
Paradise, M., Cooper, C. and Livingston, G. (2009). Systematic review of the effect of education on survival in Alzheimer's disease. International Psychogeriatrics, 21, 25–32. doi: 10.1017/S1041610208008053.CrossRefGoogle ScholarPubMed
Qiu, C., Kivipelto, M. and von Strauss, E. (2009). Epidemiology of Alzheimer's disease: occurrence, determinants, and strategies toward intervention. Dialogues in Clinical Neuroscience, 11, 111–128.CrossRefGoogle ScholarPubMed
Reynish, E., et al. (2007). The ICTUS Study: A Prospective longitudinal observational study of 1,380 AD patients in Europe. Study design and baseline characteristics of the cohort. Neuroepidemiology, 29, 29–38. doi: 10.1159/000108915.Google Scholar
Rodda, J., Morgan, S. and Walker, Z. (2009). Are cholinesterase inhibitors effective in the management of the behavioral and psychological symptoms of dementia in Alzheimer's disease? A systematic review of randomized, placebo-controlled trials of donepezil, rivastigmine and galantamine. International Psychogeriatrics, 21, 813–824. doi: 10.1017/S1041610209990354.CrossRefGoogle Scholar
Sansoni, J., Vellone, E. and Piras, G. (2004). Anxiety and depression in community-dwelling Italian Alzheimer's disease caregivers. International Journal of Nursing Practice, 10, 93–100. doi: 10.1111/j.1440-172X.2003.00461.x.Google Scholar
Schneider, L. S. and Olin, J. T. (1996). Clinical global impressions in Alzheimer's clinical trials. International Psychogeriatrics, 8, 277–288; discussion 288–290. doi: 10.1017/S1041610296002645.Google Scholar
Sherwood, P. R., Given, C. W., Given, B. A. and von Eye, A. (2005). Caregiver burden and depressive symptoms: analysis of common outcomes in caregivers of elderly patients. Journal of Aging and Health, 17, 125–147. doi: 10.1177/0898264304274179.Google Scholar
Sink, K. M., Covinsky, K. E., Barnes, D. E., Newcomer, R. J. and Yaffe, K. (2006). Caregiver characteristics are associated with neuropsychiatric symptoms of dementia. Journal of the American Geriatrics Society, 54, 796–803. doi: 10.1111/j.1532-5415.2006.00697.x.CrossRefGoogle ScholarPubMed
Takeda, S., Sato, N., Ogihara, T. and Morishita, R. (2008). The renin-angiotensin system, hypertension and cognitive dysfunction in Alzheimer's disease: new therapeutic potential. Frontiers in Bioscience, 13, 2253–2265. doi: 10.2741/2839.CrossRefGoogle Scholar
Temple, V., Jozsvai, E., Konstantareas, M. M. and Hewitt, T. A. (2001). Alzheimer dementia in Down's syndrome: the relevance of cognitive ability. Journal of Intellectual Disability Research, 45, 47–55. doi: 10.1111/j.1365-2788.2001.00299.x.Google Scholar
Weller, R. O., Subash, M., Preston, S. D., Mazanti, I. and Carare, R. O. (2008). Perivascular drainage of amyloid-beta peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer's disease. Brain Pathology (Zurich), 18, 253–266. doi:10.1111/j.1750-3639.2008.00133.x.CrossRefGoogle ScholarPubMed
Wilson, R. S. et al. (2002). Participation in cognitively stimulating activities and risk of incident Alzheimer disease. JAMA, 287, 742–748. doi: 10.1001/jama.287.6.742.Google Scholar
Winblad, B., Jones, R. W., Wirth, Y., Stoffler, A. and Mobius, H. J. (2007). Memantine in moderate to severe Alzheimer's disease: a meta-analysis of randomized clinical trials. Dementia and Geriatric Cognitive Disorders, 24, 20–27. doi: 10.1159/000102568.CrossRefGoogle Scholar
Xu, W., Qiu, C., Gatz, M., Pedersen, N. L., Johansson, B. and Fratiglioni, L. (2009). Mid- and late-life diabetes in relation to the risk of dementia: a population-based twin study. Diabetes, 58, 71–77. doi: 10.2337/db08-0586.Google Scholar
Zarit, S. H., Reever, K. E. and Bach-Peterson, J. (1980). Relatives of the impaired elderly: correlates of feelings of burden. The Gerontologist, 20, 649–655. doi: 10.1093/geront/20.6.649.CrossRefGoogle Scholar