Impact of depressive symptoms on outcome of Alzheimer's disease

Garavello, Anita de Paula Eduardo; Magaldi, Regina Miksian; Paschoal, Sérgio Márcio Pacheco; Jacob Filho, Wilson

doi:10.1590/S1980-57642010DN40400015

Abstract

There is no consensus in the medical literature about the impact of depressive symptoms on the evolution of Alzheimer's disease (AD). Objective: To compare the evolution of AD patients, with and without depressive symptoms, in terms of cognition, functionality and caregiver stress. Methods: The study entailed 2 stages: an initial retrospective stage involving review of medical charts of patients with mild and moderate AD. Patients were divided according to the presence or absence of depressive symptoms, defined by medical interview and questions on depressed mood from the CAMDEX (Cambridge Examination for Mental Disorders of the Elderly) and Neuropsychiatric Inventory (NPI). Twenty-nine patients were evaluated, 37.9% with depression (Group D+) and 62.1% without depression (Group D-). The groups were compared regarding demographic and medical characteristics, cognitive and functional performance, presence of apathy as a separate symptom, and caregiver stress, using standardized tests and questionnaires. In the second transversal step, the same tools were reapplied after 2 to 4 years of follow-up, and evolution for the two groups was compared. Results: The two groups were highly homogeneous in demographic and clinic characteristics, as well as in length of follow-up, and presented no significant difference in cognitive or functional evaluation at the time of diagnoses or after follow-up. Only caregiver stress was greater in Group D+ at the two time points (p<0.001). Conclusions: No differences in the evolution of AD patients with or without depressive symptoms were evident. Nevertheless, these symptoms were associated to emotional burden of caregivers.

Key words:
Alzheimer's disease; depression; cognition; caregiver

Resumo

Não há consenso na literatura sobre o impacto dos sintomas depressivos na evolução da doença de Alzheimer (DA). Objetivo: Comparar a evolução de pacientes com DA, com e sem sintomas depressivos, quanto à cognição, à funcionalidade e estresse do cuidador. Métodos: O estudo incluiu duas etapas: a primeira retrospectiva, com revisão de prontuários de pacientes com DA leve e moderada, divididos conforme presença ou ausência de sintomas depressivos, definidas por anamnese e questões referentes a humor deprimido do CAMDEX (Cambridge Examination for Mental Disorders of the Elderly) e Interrogatório Neuro-psiquiátrico (INP). Foram avaliados 29 pacientes, 37,9% com (D+) e 62,1% sem depressão (D-). Os grupos foram comparados quanto a variáveis demográficas, clínicas e quanto ao desempenho cognitivo, funcionalidade, presença de apatia do paciente e estresse do cuidador, através de questionários e testes padronizados. Na segunda etapa, transversal, foram reaplicados os mesmos instrumentos após 2 a 4 anos de acompanhamento, comparando-se a evolução nos dois grupos. Resultados: Os grupos, homogêneos segundo variáveis demográficas, clínicas e tempo de evolução, não apresentaram diferença significante nos testes cognitivos e na avaliação funcional, no momento do diagnóstico, e ao longo da evolução. Quanto ao estresse do cuidador, foi maior no grupo D+ nos dois momentos (p<0,001). Conclusões: Não se constatou diferença na evolução de pacientes com DA com ou sem sintomas depressivos. No entanto, tais sintomas se relacionaram a maior sobrecarga emocional do cuidador, no momento do diagnóstico e na evolução.

Palavras-chave:
doença de Alzheimer; depressão; cognição; cuidador

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References

Levy ML, Cummings JL, Fairbanks LA, et al. Longitudinal assessment of symptoms of depression, agitation, and psychosis in 181 patients with Alzheimer's disease. Am J Psychiatry 1996;153:1438-1443.
Olin JT, Katz IR, Meyers BS, et al. Provisional diagnostic criteria for depression of Alzheimer disease. Am J Psychiatry 2002;10:129-141.
Zweig, RM, Ross CA, Hedreen JC, et al. The neuropathology of aminergic nuclei in Alzheimer's disease. Ann Neurol 1988; 24:233-242.
Zweig RM, Ross CA, Hedreen JC, et al. Neuropathology of aminergic nuclei in Alzheimer's disease. Prog Clin Biol Res 1989;317:353-365.
Zubenko GS, Moosy J, Kopp U. Neurochemical correlates of major depression in primary dementia. Arch Neurol 1990; 47:209-214.
Zubenko GS. Biological correlates of clinical heterogeneity in primary dementia. Neuropsychopharmacology 1992;6:77-93.
Forstl H, Burns A, Luthert P, et al. Clinical and neuropathological correlates of depression in Alzheimer's disease. Psychol Med 1992;22:877-884.
Zubenko GS, Zubenko WN, McPherson S, et al. A collaborative study of the emergence and clinical features of the major depressive syndrome of Alzheimer's disease. Am J Psychiatry 2003;160:857-866.
Chemerinski E, Petracca G, Sabe L, Kremer J, Starkstein S. The specificity of depressive symptoms in patients with Alzheimer's disease. Am J Psychiatry 2001;158:68-72.
Holtzer R, Scarmeas N, Wegesin DJ, et al. Depressive symptoms in Alzheimer's disease: natural course and temporal relation to function and cognitive status. J Am Geriatr 2005; 53:2083-2089.
Starkstein S, Mizrabi R, Garau L. Specificity of symptoms of depression in Alzheimer disease. Am J Geriatr Psychiatry 2005;13:802-807.
Beeson R, Deutsch SH, Farran C, Neundorfer M. Loneliness and depression in caregivers of persons with Alzheimer's disease or related disorders. Issues Ment Health Nurs 2000; 21:779-806.
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of the Department of Health and Human Services Task Force on Alzheimer's disease. Neurology 1984;34:939-94.
Spitzer RL, Williams JBW, Gibbon M, First MB. The Structured Clinical Interview for DSM-III-R (SCID), I: history, rationale and description. Arch Gen Psychiatry 1992;49:624-629.
Lopez OL, Becker JT, Sweet RA, et al. Psychiatric symptoms vary with the severity of dementia in probable Alzheimer's disease. J Neuropsychiatry Clin Neurosci 2003;15:346-353.
Roth M, Tym BK, Mauntjoy CQ, et al. CAMDEX: a standardized instrument for the diagnosis of mental disorders in the elderly with special reference to the early detection of dementia. Br J Psychiatry 1986;149:698-709.
Bottino CMC, Stoppe AJ, Scalco AZ, Ferreira RCR, Hototian R, Scalco MZ. Validade e confiabilidade da versão brasileira do CAMDEX. Arq Neuropsiquiatr 2001;59(Supl 3):20.
Cummings JL, Mega M, Gray K, et al. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994;44:2308-2314.
Nitrini R, Lefèvre BH, Mathias SC, et al. Neuropsychological tests of simple application for diagnosing dementia. Arq Neuropsiquiatr 1994;52:457-465.
Nitrini R, Caramelli P, Herrera, et al. Performance of illiterate and literate nondemented elderly subjects in two tests of long-term memory. J Int Neuropsychol Society 2004;10:634-638.
Brucki SMD, Nitrini R, Caramelli P, Bertolucci PHF, Okamoto, IH. Normas sugeridas para o uso do Mini-Exame do Estado Mental no Brasil. Arq Neuropsiquiatr 2003;61:777-781.
Folstein MF, Folstein SE, McHugh PR. Mini Mental State: A practical method for grading the cognitive state of patients for the clinician. J Psychiatry Res 1975;12:189-198.
Pfeffer RI, Kurosaki TT, Harrah CH, et al. Measurement of functional activities in older adults in the community. J Gerontol 1982;37:323-329.
Scazufca M. Brazilian version of the Burden Interview scale for the assessment of burden of care in carers of people with mental illnesses. Rev Bras Psiquiatr 2002;24:12-17.
Franch JV, Olmo JG, Pousa SL, et al. Comparison of different clinical diagnostic criteria for depression in Alzheimer disease. Am J Geriatr Psychiatry 2006;14:589-597.
Holthoff V, Baumann B, Kalbe E, et al. Regional cerebral metabolism in early Alzheimer's disease with clinically significant apathy or depression. Biol Psychiatry 2005;57:412-421.
Craig D, Mirakhur A, Hart DJ, McIlroy SP, Passmore AP. A cross-sectional study of neuropsychiatric symptoms in 435 patients with Alzheimer's disease. Am J Geriatr Psychiatry 2005;13:460-468.
De Ronchi D, Bellini F, Berardi D, Serretti A, Ferrari B, Dalmonte E. Cognitive status, depressive symptoms, and health status as predictors of functional disability among elderly persons with low-to-moderate education: The Faenza Community Aging Study. Am J Geriatr Psychiatry 2005;13:672-685.
Kales HC, Chen P, Blow FC, Welsh DE, Mellow AM. Rates of clinical depression diagnosis, functional impairment, and nursing home placement in coexisting dementia and depression. Am J Geriatr Psychiatry 2005;13:441-449.
Lyketsos C, DelCampo L, Steinberg M, et al. Treating depression in Alzheimer disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction: the DIADS. Arch Gen Psychiatry 2003;60:737-746.
Landes AM, Sperry SD, Strauss ME. Prevalence of apathy, dysphoria and depression in relation to dementia severity in Alzheimer's disease. J Neuropsychiatry Clin Neurosci 2005; 17:342-349.
Hurt C, Bhattacharyya S, Burns A, et al. Patient and caregiver perspectives of quality of life in dementia. An investigation of the relationship to behavioural and psychological symptoms in dementia. Dement Geriatr Cogn Disord 2008;26:138-146.
Schulz R, McGinnis KA, Zhang S, et al. Dementia patient suffering and caregiver depression. Alzheimer Dis Assoc Disord 2008;22:170-176.

Publication Dates

Publication in this collection
Oct-Dec 2010

History

Received
18 Apr 2010
Accepted
11 Sept 2010

This is an open-access article distributed under the terms of the Creative Commons Attribution License

[1] Levy ML, Cummings JL, Fairbanks LA, et al. Longitudinal assessment of symptoms of depression, agitation, and psychosis in 181 patients with Alzheimer's disease. Am J Psychiatry 1996;153:1438-1443.

[2] Olin JT, Katz IR, Meyers BS, et al. Provisional diagnostic criteria for depression of Alzheimer disease. Am J Psychiatry 2002;10:129-141.

[3] Zweig, RM, Ross CA, Hedreen JC, et al. The neuropathology of aminergic nuclei in Alzheimer's disease. Ann Neurol 1988; 24:233-242.

[4] Zweig RM, Ross CA, Hedreen JC, et al. Neuropathology of aminergic nuclei in Alzheimer's disease. Prog Clin Biol Res 1989;317:353-365.

[5] Zubenko GS, Moosy J, Kopp U. Neurochemical correlates of major depression in primary dementia. Arch Neurol 1990; 47:209-214.

[6] Zubenko GS. Biological correlates of clinical heterogeneity in primary dementia. Neuropsychopharmacology 1992;6:77-93.

[7] Forstl H, Burns A, Luthert P, et al. Clinical and neuropathological correlates of depression in Alzheimer's disease. Psychol Med 1992;22:877-884.

[8] Zubenko GS, Zubenko WN, McPherson S, et al. A collaborative study of the emergence and clinical features of the major depressive syndrome of Alzheimer's disease. Am J Psychiatry 2003;160:857-866.

[9] Chemerinski E, Petracca G, Sabe L, Kremer J, Starkstein S. The specificity of depressive symptoms in patients with Alzheimer's disease. Am J Psychiatry 2001;158:68-72.

[10] Holtzer R, Scarmeas N, Wegesin DJ, et al. Depressive symptoms in Alzheimer's disease: natural course and temporal relation to function and cognitive status. J Am Geriatr 2005; 53:2083-2089.

[11] Starkstein S, Mizrabi R, Garau L. Specificity of symptoms of depression in Alzheimer disease. Am J Geriatr Psychiatry 2005;13:802-807.

[12] Beeson R, Deutsch SH, Farran C, Neundorfer M. Loneliness and depression in caregivers of persons with Alzheimer's disease or related disorders. Issues Ment Health Nurs 2000; 21:779-806.

[13] McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of the Department of Health and Human Services Task Force on Alzheimer's disease. Neurology 1984;34:939-94.

[14] Spitzer RL, Williams JBW, Gibbon M, First MB. The Structured Clinical Interview for DSM-III-R (SCID), I: history, rationale and description. Arch Gen Psychiatry 1992;49:624-629.

[15] Lopez OL, Becker JT, Sweet RA, et al. Psychiatric symptoms vary with the severity of dementia in probable Alzheimer's disease. J Neuropsychiatry Clin Neurosci 2003;15:346-353.

[16] Roth M, Tym BK, Mauntjoy CQ, et al. CAMDEX: a standardized instrument for the diagnosis of mental disorders in the elderly with special reference to the early detection of dementia. Br J Psychiatry 1986;149:698-709.

[17] Bottino CMC, Stoppe AJ, Scalco AZ, Ferreira RCR, Hototian R, Scalco MZ. Validade e confiabilidade da versão brasileira do CAMDEX. Arq Neuropsiquiatr 2001;59(Supl 3):20.

[18] Cummings JL, Mega M, Gray K, et al. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994;44:2308-2314.

[19] Nitrini R, Lefèvre BH, Mathias SC, et al. Neuropsychological tests of simple application for diagnosing dementia. Arq Neuropsiquiatr 1994;52:457-465.

[20] Nitrini R, Caramelli P, Herrera, et al. Performance of illiterate and literate nondemented elderly subjects in two tests of long-term memory. J Int Neuropsychol Society 2004;10:634-638.

[21] Brucki SMD, Nitrini R, Caramelli P, Bertolucci PHF, Okamoto, IH. Normas sugeridas para o uso do Mini-Exame do Estado Mental no Brasil. Arq Neuropsiquiatr 2003;61:777-781.

[22] Folstein MF, Folstein SE, McHugh PR. Mini Mental State: A practical method for grading the cognitive state of patients for the clinician. J Psychiatry Res 1975;12:189-198.

[23] Pfeffer RI, Kurosaki TT, Harrah CH, et al. Measurement of functional activities in older adults in the community. J Gerontol 1982;37:323-329.

[24] Scazufca M. Brazilian version of the Burden Interview scale for the assessment of burden of care in carers of people with mental illnesses. Rev Bras Psiquiatr 2002;24:12-17.

[25] Franch JV, Olmo JG, Pousa SL, et al. Comparison of different clinical diagnostic criteria for depression in Alzheimer disease. Am J Geriatr Psychiatry 2006;14:589-597.

[26] Holthoff V, Baumann B, Kalbe E, et al. Regional cerebral metabolism in early Alzheimer's disease with clinically significant apathy or depression. Biol Psychiatry 2005;57:412-421.

[27] Craig D, Mirakhur A, Hart DJ, McIlroy SP, Passmore AP. A cross-sectional study of neuropsychiatric symptoms in 435 patients with Alzheimer's disease. Am J Geriatr Psychiatry 2005;13:460-468.

[28] De Ronchi D, Bellini F, Berardi D, Serretti A, Ferrari B, Dalmonte E. Cognitive status, depressive symptoms, and health status as predictors of functional disability among elderly persons with low-to-moderate education: The Faenza Community Aging Study. Am J Geriatr Psychiatry 2005;13:672-685.

[29] Kales HC, Chen P, Blow FC, Welsh DE, Mellow AM. Rates of clinical depression diagnosis, functional impairment, and nursing home placement in coexisting dementia and depression. Am J Geriatr Psychiatry 2005;13:441-449.

[30] Lyketsos C, DelCampo L, Steinberg M, et al. Treating depression in Alzheimer disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction: the DIADS. Arch Gen Psychiatry 2003;60:737-746.

[31] Landes AM, Sperry SD, Strauss ME. Prevalence of apathy, dysphoria and depression in relation to dementia severity in Alzheimer's disease. J Neuropsychiatry Clin Neurosci 2005; 17:342-349.

[32] Hurt C, Bhattacharyya S, Burns A, et al. Patient and caregiver perspectives of quality of life in dementia. An investigation of the relationship to behavioural and psychological symptoms in dementia. Dement Geriatr Cogn Disord 2008;26:138-146.

[33] Schulz R, McGinnis KA, Zhang S, et al. Dementia patient suffering and caregiver depression. Alzheimer Dis Assoc Disord 2008;22:170-176.

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