Clinicopathological correlates of Alzheimer's disease in a general autopsy series from Brazil

Grinberg, Lea Tenenholz; Ferretti, Renata Eloah de Lucena; Leite, Renata E.P.; Farfel, Jose Marcelo; Pacheco, Silmara P.; Alho, Ana Teresa Di Lorenzo; Grisoli, Renata P.; Matos, Heidy T.M.; Moreira, Eliza G.; Balbino, Erika S.; Oliveira, Katia C.; Rosemberg, Sergio; Carvalho, Heráclito Barbosa; Pasquallucci, Carlos Augusto G.; Saldiva, Paulo Hilario N.; Jacob-Filho, Wilson; Nitrini, Ricardo

doi:10.1590/S1980-57642008DN10400005

Abstract

The current neuropathological staging models of Alzheimer's disease (AD) have been developed within the last 20 years. Nevertheless, they were mostly tested on Caucasians of Northern European ancestry or on Asians. Objective: To verify which of the accepted neuropathologic criteria best discriminates AD from normal aging in a well characterized Brazilian clinicopathological series. Methods: A random sample consisting of 89 subjects belonging to the Brazilian Brain Bank of the Aging Brain Study were clinically and neuropathologically fully assessed using immunohistochemistry. Clinical and functional statuses were assessed by interviewing a reliable informant. The Clinical dementia rating scale (CDR) was compared to Braak and Braak stage, the consortium to establish a registry for Alzheimer's disease (CERAD) score and NIA-Reagan (National Institute of Aging - Reagan Institute) score. Subjects with a neuropathologic diagnosis other then AD were excluded (n=27). Results: The CDR score distribution for the 62 selected subjects was as follows: CDR0=39, CDR0.5=9, CDR³1=14. There were no differences regarding age, gender and education among the groups. CDR score correlated best with the CERAD score (r=0.5303; p<0.001) . Braak and Braak stage was significantly higher in subjects with higher CDR. Correlation of the NIA-Reagan criteria was partially disrupted because a large proportion of subjects did not fit any of its categories. Conclusions: In this series, CERAD criteria better correlated with the CDR groups. Consistent with earlier studies, some cognitively normal subjects have AD neuropathological diagnosis.

Key words:
Alzheimer's disease; dementia; diagnostic criteria; neuropathological criteria; brain bank

Resumo

Os modelos de estadiamento neuropatológico da doença de Alzheimer (DA) têm sido desenvolvidos nos últimos 20 anos. Entretanto, têm sido quase exclusivamente testados em caucasianos de ascendência norte-européia ou em asiáticos. Objetivos: verificar quais dos critérios neuropatológicos discrimina melhor entre a DA e o envelhecimento normal em uma casuística clinicopatológica brasileira bem caracterizada. Métodos: uma amostra aleatória de 89 casos do Banco Brasileiro de Encéfalos do Estudo de Envelhecimento Cerebral foi submetida à avaliação neuropatológica completa com imunohistoquímica. As condições clínicas e funcionais foram avaliadas mediante entrevista com informante confiável. Os escores na Clinical Dementia Rating Scale (CDR) foram comparados com os escores dos estágios de Braak e Braak, do CERAD (Consortium to Establish a Registry for Alzheimer's Disease) e do consórcio NIA-Reagan (National Institute of Aging-Reagan Institute). Casos com diagnósticos neuropatológicos diferentes de DA foram excluídos (n=27). Resultados: Os 62 casos foram classificados em: CDR0=39, CDR0,5=9, CDR³1=14. Não havia diferenças quanto a idade, gênero e escolaridade entre os grupos. Os escores no CERAD correlacionaram-se melhor com os do CDR (r=0,5303; p<0,001). Os escores nos estágios de Braak e Braak foram significativamente mais elevados nos casos com CDR mais altos. A correlação do CDR com os escores dos critérios NIA-Reagan foi parcialmente rompida porque grande proporção de casos não se enquadrava em nenhuma das categorias diagnósticas destes critérios. Conclusões: Nesta casuística, os critérios do CERAD correlacionam-se melhor com os do CDR. Como observado por outros estudos, alguns casos de indivíduos cognitivamente normais, preencheram critérios neuropatológicos para o diagnóstico de DA.

Palavras-chave:
doença de Alzheimer; demência; critérios diagnósticos; critérios neuropatológicos; banco de encéfalos; banco de cérebros

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References

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Ferri CP, Prince M, Brayne C, et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005;366:2112-2117.
²
Mirra SS, Heyman A, McKeel D, et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology 1991;41:479-486.
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Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991;82:239-259.
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The National Institute on Aging and Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer's Disease. Consensus recommendations for the postmortem diagnosis of Alzheimer's disease. Neurobiol Aging 1997;18:S1-S2.
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Bancher C, Jellinger K, Lassmann H, Fischer P, Leblhuber F. Correlations between mental state and quantitative neuropathology in the Vienna longitudinal study on dementia. Eur Arch Psychiat Clin Neurosci 1996;246:137-146.
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Berg L, McKeel DW, Miller JP, et al. Clinicopathologic studies in cognitively healthy aging and Alzheimer disease: Relation of histologic markers to dementia severity, age, sex, and apolipoprotein E genotype. Arch Neurol 1998;55:326-335.
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Giannakopoulos P, Gold G, Kovari E, et al. Assessing the cognitive impact of Alzheimer disease pathology and vascular burden in the aging brain: the Geneva experience. Acta Neuropathol 2007;113:1-12.
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Froehlich TE, Bogardus ST, Jr., Inouye SK. Dementia and race: are there differences between African Americans and Caucasians? J Am Geriatr Soc 2001;49:477-484.
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Grinberg LT, Ferretti RE, Farfel JM, et al. Brain bank of the Brazilian aging brain study group - a milestone reached and more than 1,600 collected brains. Cell Tissue Bank 2007;8:151-162.
¹⁰
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.
¹¹
Nitrini R, Caramelli P, Bottino CM, Damasceno BP, Brucki SM, Anghinah R. Diagnosis of Alzheimer's disease in Brazil: diagnostic criteria and auxiliary tests. Recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology. Arq Neuropsiquiatr 2005;63:713-719.
¹²
Neary D, Snowden JS, Gustafson L et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology. 1998;51:1546-1554.
¹³
McKeith IG, Dickson DW, Lowe J et al. Diagnosis and management of dementia with Lewy bodies - Third report of the DLB consortium. Neurology. 2005;65:1863-1872.
¹⁴
Morris JC. The clinical dementia rating (CDR): current version and scoring rules. Neurology. 1993;43:2412-2414.
¹⁵
McKeel DW, Price JL, Miller JP, et al. Neuropathologic criteria for diagnosing Alzheimer disease in persons with pure dementia of Alzheimer type. J Neuropathol Exp Neurol 2004;63:1028-1037.
¹⁶
McKeel DW, Ball MJ, Price JL, et al. Interlaboratory histopathologic assessment of Alzheimer neuropathology: different methodologies yield comparable diagnostic results. Alz Dis Assoc Disorder 1993;7:136-151.
¹⁷
Grober E, Dickson D, Sliwinski MJ, et al. Memory and mental status correlates of modified Braak staging. Neurobiol Aging 1999;20:573-579.
¹⁸
Arriagada PV, Growdon JH, Hedley-Whyte ET, Hyman BT. Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease. Neurology 1992;42:631-639.
¹⁹
Bierer LM, Hof PR, Purohit DP, et al. Neocortical neurofibrillary tangles correlate with dementia severity in Alzheimer's disease. Arch Neurol 1995;52:81-88.
²⁰
Nagy Z, Esiri MM, Jobst KA et al. Relative roles of plaques and tangles in the dementia of Alzheimer's disease: correlations using three sets of neuropathological criteria. Dementia 1995;6:21-31.
²¹
Geddes JW, Tekirian TL, Soultanian NS, Ashford JW, Davis DG, Markesbery WR. Comparison of neuropathologic criteria for the diagnosis of Alzheimer's disease. Neurobiol Aging 1997;18:S99-S105.
²²
Braak H, Braak E, Ohm T, Bohl J. Alzheimer's disease: mismatch between amyloid plaques and neuritic plaques. Neurosci Lett 1989;103:24-28.
²³
Morris JC, Storandt M, McKeel DW, et al. Cerebral amyloid deposition and diffuse plaques in ''normal'' aging: evidence for presymptomatic and very mild Alzheimer's disease. Neurology 1996;46:707-719.
²⁴
Crystal H, Dickson D, Fuld P, et al. Clinico-pathologic studies in dementia nondemented subjects with pathologically confirmed Alzheimer's disease. Neurology 1988;38:1682-1687.
²⁵
Jorm AF, Jacomb PA. The informant questionnaire on cognitive decline in the elderly (IQCODE): Socio-demographic correlates, reliability, validity and some norms. Psychol Med 1989;19:1015-1022
²⁶
Bustamante SE, Bottino CM, Lopes MA, et al. Combined instruments on the evaluation of dementia in the elderly: preliminary results. Arq Neuropsiquiatr 2003;61:601-606.
²⁷
Isella V, Villa L, Russo A, et al. Discriminative and predictive power of an informant report in mild cognitive impairment. J Neurol Neurosurg Psychiatry 2006;77:166-171.

Publication Dates

Publication in this collection
Oct-Dec 2007

History

Received
11 Oct 2007
Reviewed
28 Oct 2007
Accepted
27 Nov 2007

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

[1] ¹
Ferri CP, Prince M, Brayne C, et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005;366:2112-2117.

[2] ²
Mirra SS, Heyman A, McKeel D, et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology 1991;41:479-486.

[3] ³
Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991;82:239-259.

[4] ⁴
The National Institute on Aging and Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer's Disease. Consensus recommendations for the postmortem diagnosis of Alzheimer's disease. Neurobiol Aging 1997;18:S1-S2.

[5] ⁵
Bancher C, Jellinger K, Lassmann H, Fischer P, Leblhuber F. Correlations between mental state and quantitative neuropathology in the Vienna longitudinal study on dementia. Eur Arch Psychiat Clin Neurosci 1996;246:137-146.

[6] ⁶
Berg L, McKeel DW, Miller JP, et al. Clinicopathologic studies in cognitively healthy aging and Alzheimer disease: Relation of histologic markers to dementia severity, age, sex, and apolipoprotein E genotype. Arch Neurol 1998;55:326-335.

[7] ⁷
Giannakopoulos P, Gold G, Kovari E, et al. Assessing the cognitive impact of Alzheimer disease pathology and vascular burden in the aging brain: the Geneva experience. Acta Neuropathol 2007;113:1-12.

[8] ⁸
Froehlich TE, Bogardus ST, Jr., Inouye SK. Dementia and race: are there differences between African Americans and Caucasians? J Am Geriatr Soc 2001;49:477-484.

[9] ⁹
Grinberg LT, Ferretti RE, Farfel JM, et al. Brain bank of the Brazilian aging brain study group - a milestone reached and more than 1,600 collected brains. Cell Tissue Bank 2007;8:151-162.

[10] ¹⁰
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.

[11] ¹¹
Nitrini R, Caramelli P, Bottino CM, Damasceno BP, Brucki SM, Anghinah R. Diagnosis of Alzheimer's disease in Brazil: diagnostic criteria and auxiliary tests. Recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology. Arq Neuropsiquiatr 2005;63:713-719.

[12] ¹²
Neary D, Snowden JS, Gustafson L et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology. 1998;51:1546-1554.

[13] ¹³
McKeith IG, Dickson DW, Lowe J et al. Diagnosis and management of dementia with Lewy bodies - Third report of the DLB consortium. Neurology. 2005;65:1863-1872.

[14] ¹⁴
Morris JC. The clinical dementia rating (CDR): current version and scoring rules. Neurology. 1993;43:2412-2414.

[15] ¹⁵
McKeel DW, Price JL, Miller JP, et al. Neuropathologic criteria for diagnosing Alzheimer disease in persons with pure dementia of Alzheimer type. J Neuropathol Exp Neurol 2004;63:1028-1037.

[16] ¹⁶
McKeel DW, Ball MJ, Price JL, et al. Interlaboratory histopathologic assessment of Alzheimer neuropathology: different methodologies yield comparable diagnostic results. Alz Dis Assoc Disorder 1993;7:136-151.

[17] ¹⁷
Grober E, Dickson D, Sliwinski MJ, et al. Memory and mental status correlates of modified Braak staging. Neurobiol Aging 1999;20:573-579.

[18] ¹⁸
Arriagada PV, Growdon JH, Hedley-Whyte ET, Hyman BT. Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease. Neurology 1992;42:631-639.

[19] ¹⁹
Bierer LM, Hof PR, Purohit DP, et al. Neocortical neurofibrillary tangles correlate with dementia severity in Alzheimer's disease. Arch Neurol 1995;52:81-88.

[20] ²⁰
Nagy Z, Esiri MM, Jobst KA et al. Relative roles of plaques and tangles in the dementia of Alzheimer's disease: correlations using three sets of neuropathological criteria. Dementia 1995;6:21-31.

[21] ²¹
Geddes JW, Tekirian TL, Soultanian NS, Ashford JW, Davis DG, Markesbery WR. Comparison of neuropathologic criteria for the diagnosis of Alzheimer's disease. Neurobiol Aging 1997;18:S99-S105.

[22] ²²
Braak H, Braak E, Ohm T, Bohl J. Alzheimer's disease: mismatch between amyloid plaques and neuritic plaques. Neurosci Lett 1989;103:24-28.

[23] ²³
Morris JC, Storandt M, McKeel DW, et al. Cerebral amyloid deposition and diffuse plaques in ''normal'' aging: evidence for presymptomatic and very mild Alzheimer's disease. Neurology 1996;46:707-719.

[24] ²⁴
Crystal H, Dickson D, Fuld P, et al. Clinico-pathologic studies in dementia nondemented subjects with pathologically confirmed Alzheimer's disease. Neurology 1988;38:1682-1687.

[25] ²⁵
Jorm AF, Jacomb PA. The informant questionnaire on cognitive decline in the elderly (IQCODE): Socio-demographic correlates, reliability, validity and some norms. Psychol Med 1989;19:1015-1022

[26] ²⁶
Bustamante SE, Bottino CM, Lopes MA, et al. Combined instruments on the evaluation of dementia in the elderly: preliminary results. Arq Neuropsiquiatr 2003;61:601-606.

[27] ²⁷
Isella V, Villa L, Russo A, et al. Discriminative and predictive power of an informant report in mild cognitive impairment. J Neurol Neurosurg Psychiatry 2006;77:166-171.

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