Apathy in Alzheimer's disease: Contribution to a clinical view on progression of dementia

Stella, Florindo; Andrade, Larissa Pires de; Vital, Thays Martins; Coelho, Flávia Gomes de Melo; Nascimento, Carla Manuela Crispim; Hernández, Salma Stephany Soleman

doi:10.1590/S1980-57642010DN40300007

Abstract

In addition to cognitive impairment, apathy is increasingly recognized as an important neuropsychiatric syndrome in Alzheimer's disease (AD).

Aims:

To identify the relationship between dementia severity and apathy levels, and to discuss the association of this condition with other psychopathological manifestations in AD patients.

Methods:

This study involved 15 AD patients (mean age: 77 years; schooling: 4.9 years), with mild, moderate and severe dementia, living in Rio Claro SP, Brazil. Procedures included evaluation of cognitive status by the Mini-Mental State Examination, Clinical Dementia Rating, and Global Deterioration Scale. Apathy syndrome was assessed by the Apathy Evaluation Scale and Neuropsychiatric Inventory (NPI-apathy domain). Other psychopathological manifestations such as depression were also considered.

Results:

Patients with more severe dementia presented higher levels of apathy, reinforcing the hypothesis that apathy severity aggravates as the disease progresses. Using the Spearman coefficient correlation an association was identified between the MMSE and Apathy Evaluation Scale (r=0.63; p=0.01), and also between the MMSE and NPI-apathy domain (r=0.81; p=0.01). Associations were also found between the Global Deterioration Scale and Apathy Evaluation Scale (r=0.58; p=0.02), and between the Global Deterioration Scale and NPI-apathy domain (r=0.81; p=0.01).

Conclusions:

Apathy is a distinct syndrome among patients with AD and increases with global deterioration.

Key words:
apathy; Alzheimer's disease; disease progression

Resumo

A apatia tem sido reconhecida como uma importante síndrome na doença de Alzheimer (DA), além do comprometimento cognitivo.

Objetivo:

Avaliar a relação entre gravidade da demência e níveis de apatia e discutir a associação de apatia com outras manifestações psicopatológicas em pacientes com DA.

Sujeitos:

15 pacientes com DA com demência leve, moderada e avançada, residentes em Rio Claro SP, Brasil.

Métodos:

Avaliação do status cognitivo por meio do Mini-Exame do Estado Mental, Escore Clínico de Demência e Escala de Deterioração Global. A avaliação da apatia incluiu a Escala de Avaliação de Apatia e o Inventário Neuropsiquiátrico (NPI-domínio apatia). Depressão também foi aferida.

Resultados:

Os pacientes com demência avançada apresentaram níveis mais elevados de apatia, o que reforça a hipótese de que ela se agrava na medida em que a doença progride. Por meio do coeficiente de correlação de Spearman, verificou-se associação do Mini-Exame do Estado Mental com a Escala de Avaliação de Apatia (r=0,63; p=0,01) e com o NPI-domínio apatia (r=0,81; p=0,01); também se constatou associação da Escala de Deterioração Global com a Escala de Avaliação de Apatia (r=0,58; p=0,02) e com o NPI-domínio apatia (r=0,81; p=0,01).

Conclusões:

A apatia é uma síndrome distinta em pacientes com DA e que se agrava com a deterioração global imposta pela doença.

Palavras-chave:
apatia; doença de Alzheimer; progressão da doença

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References

Lyketsos CG. Neuropsychiatric symptoms (behavioral and psychological symptoms of dementia) and the development of dementia treatments. Int Psychogeriatr 2007;19:409-420.
Cummings JL, Mackell J, Kaufer D. Behavioral effects of current Alzheimer's disease treatments: a descriptive review. Alzheimer Dement 2008;4:49-60.
Gauthier S, Vellas B, Farlow M, Burn D. Aggressive course of disease in dementia. Alzheimer Dement 2006;2:210-217.
Aalten P, Verhey FR, Boziki M, et al. Neuropsychiatric syndromes in dementia. Results from the European Alzheimer Disease Consortium: part I. Dement Geriatr Cogn Disord 2007;24:457-463.
Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994;44:2308-2314.
Robert P, Onyike CU, Leentjens AF, et al. Proposed diagnostic criteria for apathy in Alzheimer's disease and other neuropsychiatric disorders. Eur Psychiatry 2009;24:98-104.
Onyike CU, Sheppard JM, Tschanz JT, et al. Epidemiology of apathy in older adults: the Cache County Study. Am J Geriatr Psychiatry 2007;15:365-375.
Drijgers RL, Aalten P, Winogrodzka A, Verhey FR, Leentjens AF. Pharmacological treatment of apathy in neurodegenerative diseases: a systematic review. Dement Geriatr Cogn Disord 2009;28:13-22.
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 Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984;34:939-944.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR 4th Ed. Text Revised), Washington DC: American Psychiatric Association, 2000.
Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 1993;43:2412-2414.
Maia ALG, Godinho C, Ferreira ED, et al. Aplicação da versão brasileira da Escala de Avaliação Clínica da Demência (Clinical Dementia Rating - CDR) em amostras de pacientes com demência. Arq Neuropsiquiatr 2006;64:485-489.
Folstein MF, Folstein SE, McHugh PR. "Mini-mental state": a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-198.
Brucki SM, Nitrini R, Caramelli P, Bertolucci PH, Okamoto IH. Suggestions for utilization of the mini-mental state examination in Brazil. Arq Neuropsiquiatr 2003;61:777-781.
Camozzato AL, Kochhann R, Simeoni C, et al. Reliability of the Brazilian Portuguese version of the Neuropsychiatric Inventory (NPI) for patients with Alzheimer's disease and their caregivers. Int Psychogeriatr 2008;20:383-393.
Marin RS, Biedrzycki RC, Firinciogullari S. Reliability and validity of the Apathy Evaluation Scale. Psychiatry Res 1991;38:143-162.
Guimarães HC, Fialho PPA, Carvalho VA, Santos EL, Caramelli P. Brazilian caregiver version of the Apathy Scale. Dement Neuropsychol 2009;3:321-326.
Reisberg B, Ferris SH, de Leon MJ, Crook T. The Global Deterioration Scale for assessment of primary degenerative dementia. Am J Psychiatry 1982;139:1136-1139.
Alexopoulos GS, Abrams RC, Young RC, Shamoian CA. Cornell Scale for Depression in Dementia. Biol Psychiatry 1988; 23:271-284.
Carthery-Goulart MT, Areza-Fegyveres R, Schultz RR, et al. Brazilian version of the Cornell depression scale in dementia. Arq Neuropsiquiatr 2007;65:912-915.
Tagariello P, Girardi P, Amore M. Depression and apathy in dementia: same syndrome or different constructs? A critical review. Arch Gerontol Geriatr 2009;49:246-249.
Turró-Garriga O, López-Pousa S, Vilalta-Franch J, Turón-Estrada A, Pericot-Nierga I, Lozano-Gallego M, Hernández-Ferràndiz M, Soler-Cors O, Planas-Pujol X, Monserrat-Vila S, Garre-Olmo J. A longitudinal study of apathy in patients with Alzheimer's disease. Rev Neurol 2009;48:7-13.
Starkstein SE, Jorge R, Mizrahi R, Robinson RG. A prospective longitudinal study of apathy in Alzheimer's disease. J Neurol Neurosurg Psychiatry 2006;77:8-11.
Levy ML, Cummings JL, Fairbanks LA, et al. Apathy is not depression. J Neuropsychiatry Clin Neurosci 1988;10:314-319.
Holthoff VA, Beuthien-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.
Levy R, Dubois B. Apathy and the functional anatomy of the prefrontal cortex-basal ganglia circuits. Cereb Cortex 2006;16: 916-928.
Lugaresi A, Montagna P, Morreale A, Gallassi R. 'Psychic akinesia' following carbon monoxide poisoning. Eur Neurol 1990;30:167-169.
Kumral E, Bayulkem G, Evyapan D, Yunten N. Spectrum of anterior cerebral artery territory infarction: clinical and MRI findings. Eur J Neurol 2002;9:615-624.
MacDonald AW, Cohen JD, Stenger VA, Carter CS. Dissociating the role of the dorsolateral prefrontal and anterior cingulate cortex in cognitive control. Science 2000;288(5472):1835-1838.
Benoit M, Koulibaly PM, Migneco O, Darcourt J, Pringuey DJ, Robert PH. Brain perfusion in Alzheimer's disease with and without apathy: a SPECT study with statistical parametric mapping analysis. Psychiatry Res 2002;114:103-111.
Cohen JD, Botvinick M, Carter CS. Anterior cingulate and prefrontal cortex: who's in control? Nat Neurosci 2000;3: 421-423.
Esposito F, Rochat L, Van der Linden ACJ, et al. Apathy and executive dysfunction in Alzheimer disease. Alzheimer Dis Assoc Disord 2010;24:131-137.
Guimarães HC, Levy R, Teixeira AL, Beato RG, Caramelli P. Neurobiology of apathy in Alzheimer's disease. Arq Neuropsiquiatr 2008;66:436-443.

Publication Dates

Publication in this collection
Jul-Sep 2010

History

Received
28 May 2010
Accepted
04 July 2010

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

[1] Lyketsos CG. Neuropsychiatric symptoms (behavioral and psychological symptoms of dementia) and the development of dementia treatments. Int Psychogeriatr 2007;19:409-420.

[2] Cummings JL, Mackell J, Kaufer D. Behavioral effects of current Alzheimer's disease treatments: a descriptive review. Alzheimer Dement 2008;4:49-60.

[3] Gauthier S, Vellas B, Farlow M, Burn D. Aggressive course of disease in dementia. Alzheimer Dement 2006;2:210-217.

[4] Aalten P, Verhey FR, Boziki M, et al. Neuropsychiatric syndromes in dementia. Results from the European Alzheimer Disease Consortium: part I. Dement Geriatr Cogn Disord 2007;24:457-463.

[5] Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994;44:2308-2314.

[6] Robert P, Onyike CU, Leentjens AF, et al. Proposed diagnostic criteria for apathy in Alzheimer's disease and other neuropsychiatric disorders. Eur Psychiatry 2009;24:98-104.

[7] Onyike CU, Sheppard JM, Tschanz JT, et al. Epidemiology of apathy in older adults: the Cache County Study. Am J Geriatr Psychiatry 2007;15:365-375.

[8] Drijgers RL, Aalten P, Winogrodzka A, Verhey FR, Leentjens AF. Pharmacological treatment of apathy in neurodegenerative diseases: a systematic review. Dement Geriatr Cogn Disord 2009;28:13-22.

[9] 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 Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984;34:939-944.

[10] American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR 4th Ed. Text Revised), Washington DC: American Psychiatric Association, 2000.

[11] Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 1993;43:2412-2414.

[12] Maia ALG, Godinho C, Ferreira ED, et al. Aplicação da versão brasileira da Escala de Avaliação Clínica da Demência (Clinical Dementia Rating - CDR) em amostras de pacientes com demência. Arq Neuropsiquiatr 2006;64:485-489.

[13] Folstein MF, Folstein SE, McHugh PR. "Mini-mental state": a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-198.

[14] Brucki SM, Nitrini R, Caramelli P, Bertolucci PH, Okamoto IH. Suggestions for utilization of the mini-mental state examination in Brazil. Arq Neuropsiquiatr 2003;61:777-781.

[15] Camozzato AL, Kochhann R, Simeoni C, et al. Reliability of the Brazilian Portuguese version of the Neuropsychiatric Inventory (NPI) for patients with Alzheimer's disease and their caregivers. Int Psychogeriatr 2008;20:383-393.

[16] Marin RS, Biedrzycki RC, Firinciogullari S. Reliability and validity of the Apathy Evaluation Scale. Psychiatry Res 1991;38:143-162.

[17] Guimarães HC, Fialho PPA, Carvalho VA, Santos EL, Caramelli P. Brazilian caregiver version of the Apathy Scale. Dement Neuropsychol 2009;3:321-326.

[18] Reisberg B, Ferris SH, de Leon MJ, Crook T. The Global Deterioration Scale for assessment of primary degenerative dementia. Am J Psychiatry 1982;139:1136-1139.

[19] Alexopoulos GS, Abrams RC, Young RC, Shamoian CA. Cornell Scale for Depression in Dementia. Biol Psychiatry 1988; 23:271-284.

[20] Carthery-Goulart MT, Areza-Fegyveres R, Schultz RR, et al. Brazilian version of the Cornell depression scale in dementia. Arq Neuropsiquiatr 2007;65:912-915.

[21] Tagariello P, Girardi P, Amore M. Depression and apathy in dementia: same syndrome or different constructs? A critical review. Arch Gerontol Geriatr 2009;49:246-249.

[22] Turró-Garriga O, López-Pousa S, Vilalta-Franch J, Turón-Estrada A, Pericot-Nierga I, Lozano-Gallego M, Hernández-Ferràndiz M, Soler-Cors O, Planas-Pujol X, Monserrat-Vila S, Garre-Olmo J. A longitudinal study of apathy in patients with Alzheimer's disease. Rev Neurol 2009;48:7-13.

[23] Starkstein SE, Jorge R, Mizrahi R, Robinson RG. A prospective longitudinal study of apathy in Alzheimer's disease. J Neurol Neurosurg Psychiatry 2006;77:8-11.

[24] Levy ML, Cummings JL, Fairbanks LA, et al. Apathy is not depression. J Neuropsychiatry Clin Neurosci 1988;10:314-319.

[25] Holthoff VA, Beuthien-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.

[26] Levy R, Dubois B. Apathy and the functional anatomy of the prefrontal cortex-basal ganglia circuits. Cereb Cortex 2006;16: 916-928.

[27] Lugaresi A, Montagna P, Morreale A, Gallassi R. 'Psychic akinesia' following carbon monoxide poisoning. Eur Neurol 1990;30:167-169.

[28] Kumral E, Bayulkem G, Evyapan D, Yunten N. Spectrum of anterior cerebral artery territory infarction: clinical and MRI findings. Eur J Neurol 2002;9:615-624.

[29] MacDonald AW, Cohen JD, Stenger VA, Carter CS. Dissociating the role of the dorsolateral prefrontal and anterior cingulate cortex in cognitive control. Science 2000;288(5472):1835-1838.

[30] Benoit M, Koulibaly PM, Migneco O, Darcourt J, Pringuey DJ, Robert PH. Brain perfusion in Alzheimer's disease with and without apathy: a SPECT study with statistical parametric mapping analysis. Psychiatry Res 2002;114:103-111.

[31] Cohen JD, Botvinick M, Carter CS. Anterior cingulate and prefrontal cortex: who's in control? Nat Neurosci 2000;3: 421-423.

[32] Esposito F, Rochat L, Van der Linden ACJ, et al. Apathy and executive dysfunction in Alzheimer disease. Alzheimer Dis Assoc Disord 2010;24:131-137.

[33] Guimarães HC, Levy R, Teixeira AL, Beato RG, Caramelli P. Neurobiology of apathy in Alzheimer's disease. Arq Neuropsiquiatr 2008;66:436-443.

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