SciELO - Scientific Electronic Library Online

 
vol.5 issue3Cognitive, functional and behavioral assessment: Alzheimer's diseaseTreatment of Alzheimer's disease in Brazil: I. Cognitive disorders author indexsubject indexarticles search
Home Pagealphabetic serial listing  

Services on Demand

Journal

Article

  • text new page (beta)
  • English (pdf)
  • Article in xml format
  • How to cite this article
  • SciELO Analytics
  • Curriculum ScienTI
  • Automatic translation

Indicators

Related links

Share


Dementia & Neuropsychologia

Print version ISSN 1980-5764

Dement. neuropsychol. vol.5 no.3 São Paulo July/Sept. 2011

http://dx.doi.org/10.1590/S1980-57642011DN05030004 

Views & Reviews

Diagnosis of Alzheimer's disease in Brazil: Supplementary exams

Diagnóstico de doença de Alzheimer no Brasil: exames complementares

Paulo Caramelli 1  

Antonio Lúcio Teixeira 1  

Carlos Alberto Buchpiguel 2  

Hae Won Lee 3  

José Antônio Livramento 4  

Liana Lisboa Fernandez 5  

Renato Anghinah 6  

Group Recommendations in Alzheimer's Disease Vascular DementiaBrazilian Academy of Neurology

1Department of Internal Medicine, School of Medicine, Federal University of Minas Gerais, Belo Horizonte MG, Brazil

2Department of Radiology, School of Medicine, University of São Paulo, São Paulo SP, Brazil

3Institute of Radiology, Hospital das Clínicas, School of Medicine, University of São Paulo and Hospital Sírio-Libanês, São Paulo, SP, Brazil

4Medical Investigation Laboratory (LIM 15), School of Medicine, University of São Paulo, São Paulo SP, Brazil

5Department of Basic Health Sciences, Federal University of Health Sciences Foundation of Porto Alegre, Porto Alegre RS, Brazil

6Referral Center for Cognitive Disorders (CEREDIC), Hospital das Clínicas, School of Medicine, University of São Paulo, São Paulo SP, Brazil

Abstract

This article presents a review of the recommendations on supplementary exams employed for the clinical diagnosis of Alzheimer's disease (AD) in Brazil published in 2005. A systematic assessment of the consensus reached in other countries, and of articles on AD diagnosis in Brazil available on the PUBMED and LILACS medical databases, was carried out. Recommended laboratory exams included complete blood count, serum creatinine, thyroid stimulating hormone (TSH), albumin, hepatic enzymes, Vitamin B12, folic acid, calcium, serological reactions for syphilis and serology for HIV in patients aged younger than 60 years with atypical clinical signs or suggestive symptoms. Structural neuroimaging, computed tomography or - preferably - magnetic resonance exams, are indicated for diagnostic investigation of dementia syndrome to rule out secondary etiologies. Functional neuroimaging exams (SPECT and PET), when available, increase diagnostic reliability and assist in the differential diagnosis of other types of dementia. The cerebrospinal fluid exam is indicated in cases of pre-senile onset dementia with atypical clinical presentation or course, for communicant hydrocephaly, and suspected inflammatory, infectious or prion disease of the central nervous system. Routine electroencephalograms aid the differential diagnosis of dementia syndrome with other conditions which impair cognitive functioning. Genotyping of apolipoprotein E or other susceptibility polymorphisms is not recommended for diagnostic purposes or for assessing the risk of developing the disease. Biomarkers related to the molecular alterations in AD are largely limited to use exclusively in research protocols, but when available can contribute to improving the accuracy of diagnosis of the disease.

Key words: consensus; guidelines; diagnosis; supplementary exams; Alzheimer's disease; Brazil

Resumo

Este artigo apresenta revisão das recomendações sobre os exames complementares empregados para o diagnóstico clínico de doença de Alzheimer (DA) no Brasil, publicadas em 2005. Foram avaliados de modo sistemático consensos elaborados em outros países e artigos sobre o diagnóstico de DA no Brasil disponíveis no PUBMED ou LILACS. Os exames laboratoriais recomendados são hemograma completo, creatinina sérica, hormônio tíreo-estimulante, albumina, enzimas hepáticas, vitamina B12, ácido fólico, cálcio, reações sorológicas para sífilis e, em pacientes com idade inferior a 60 anos, com apresentações clínicas atípicas ou com sintomas sugestivos, sorologia para HIV. Exame de neuroimagem estrutural, tomografia computadorizada ou - preferencialmente - ressonância magnética, é indicado na investigação diagnóstica de síndrome demencial, para exclusão de causas secundárias. Exames de neuroimagem funcional (SPECT e PET), quando disponíveis, aumentam a confiabilidade diagnóstica e auxiliam no diagnóstico diferencial de outras formas de demência. O exame do líquido cefalorraquidiano é preconizado em casos de demência de início pré-senil, com apresentação ou curso clínico atípicos, hidrocefalia comunicante e quando há suspeita de doença inflamatória, infecciosa ou priônica do sistema nervoso central. O eletroencefalograma de rotina auxilia no diagnóstico diferencial de síndrome demencial com outras condições que interferem no funcionamento cognitivo. A genotipagem da apolipoproteína E ou de outros polimorfismos de susceptibilidade não é recomendada com finalidade diagnóstica ou para avaliação de risco de desenvolvimento da doença. Os biomarcadores relacionados às alterações moleculares da DA ainda são de uso quase exclusivo em protocolos de pesquisa, mas quando disponíveis podem contribuir para maior precisão diagnóstica da doença.

Palavras-chave: consenso; diretrizes; diagnóstico; exames complementares; doença de Alzheimer; Brasil

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

References

Knopman DS, DeKosky ST, Cummings JL, et al. Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56:1143-1153. [ Links ]

Nitrini R, Caramelli P, Bottino CM, Damasceno BP, Brucki SM, Anghinah R; Academia Brasileira de Neurologia. Diagnóstico de doença de Alzheimer no Brasil: critérios diagnósticos e exames complementares. Arq Neuropsiquiatr 2005;63:713-719. [ Links ]

Hort J, O'Brien JT, Gainotti G, et al.; EFNS Scientist Panel on Dementia. EFNS guidelines for the diagnosis and management of Alzheimer's disease. Eur J Neurol 2010; 17:1236-1248. [ Links ]

Humpel C, Marksteiner J. Peripheral biomarkers in dementia and Alzheimer's disease. In: Ritsner MS (Ed). The handbook of neuropsychiatric biomarkers, endophenotypes and genes. Volume III: metabolic and peripheral biomarkers. Berlin: Springer; 2009. [ Links ]

Schneider P, Hampel H, Buerger K. Biological marker candidates of Alzheimer's disease in blood, plasma, and serum. CNS Neurosci Ther 2009;15:358-374. [ Links ]

Song F, Poljak A, Smythe GA, Sachdev P. Plasma biomarkers for mild cognitive impairment and Alzheimer's disease. Brain Res Rev 2009;61:69-80. [ Links ]

Locascio JJ, Fukumoto H, Yap L, et al. Plasma amyloid beta-protein and C-reactive protein in relation to the rate of progression of Alzheimer disease. Arch Neurol 2008; 65:776-785. [ Links ]

Ray S, Britschgi M, Herbert C, et al. Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins. Nat Med 2007;13:1359-1362. [ Links ]

O'Bryant SE, Xiao G, Barber R, et al.; Texas Alzheimer's Research Consortium. A serum protein-based algorithm for the detection of Alzheimer disease. Arch Neurol 2010;67: 1077-1081. [ Links ]

Roman GC, Tatemichi TK, Erkinjuntti T, et al. Vascular dementia: diagnostic criteria for research studies: report of the NINDS-AIREN International Workshop. Neurology 1993;43:250-260. [ Links ]

Tschampa HJ, Kallenberg K, Urbach H, et al. MRI in the diagnosis of sporadic Creutzfeldt-Jakob disease: a study on inter-observer agreement. Brain 2005;128:2026-2033. [ Links ]

Collie DA, Sellar RJ, Zeidler M, Colchester AC, Knight R, Will RG. MRI of Creutzfeldt-Jakob disease: imaging features and recommended MRI protocol. Clin Radiol 2001;56: 726-739. [ Links ]

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

Convit A, De Leon MJ, Tarshish C, et al. Specific hippocampal volume reductions in individuals at risk for Alzheimer's disease. Neurobiol Aging 1997;18:131-138. [ Links ]

Jack CR Jr., Petersen RC, Xu YC, et al. Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease. Neurology 1997;49:786-794. [ Links ]

Ball MJ, Fisman M, Hachinski V, et al. A new definition of Alzheimer's disease: a hippocampal dementia. Lancet 1985; 1:14-16. [ Links ]

Fox NC, Warrington EK, Freeborough PA, et al. Presymptomatic hippocampal atrophy in Alzheimer's disease: a longitudinal MRI study. Brain 1996;119:2001-2007. [ Links ]

Laakso MP, Soininen H, Partanen K, et al. MRI of the hippocampus in Alzheimer's disease: sensitivity, specificity, and analysis of the incorrectly classified subjects. Neurobiol Aging 1998;19:23-31. [ Links ]

Scheltens P, Leys D, Barkhof F, et al. Atrophy of medial temporal lobes on MRI in "probable" Alzheimer's disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry 1992;55:967-972. [ Links ]

Visser PJ, Verhey FR, Hofman PA, Scheltens P, Jolles J. Medial temporal lobe atrophy predicts Alzheimer's disease in patients with minor cognitive impairment. J Neurol Neurosurg Psychiatry 2002;72:491-497. [ Links ]

McDonald CR, McEvoy LK, Gharapetian L, et al.; Alzhei­mer's Disease Neuroimaging Initiative. Regional rates of neocortical atrophy from normal aging to early Alzheimer disease. Neurology 2009;73:457-465. [ Links ]

Fox NC, Scahill RI, Crum WR, Rossor MN. Correlation between rates of brain atrophy and cognitive decline in AD. Neurology 1999;52:1687-1689. [ Links ]

Korf ES, Wahlund LO, Visser PJ, Scheltens P. Medial temporal lobe atrophy on MRI predicts dementia in patients with mild cognitive impairment. Neurology 2004;63:94-100. [ Links ]

DeCarli C, Frisoni GB, Clark CM, et al.; Alzheimer's Disease Cooperative Study Group. Qualitative estimates of medial temporal atrophy as a predictor of progression from mild cognitive impairment to dementia. Arch Neurol 2007;64: 108-115. [ Links ]

Duara R, Loewenstein DA, Potter E, et al. Medial temporal lobe atrophy on MRI scans and the diagnosis of Alzheimer disease. Neurology 2008;71:1986-1992. [ Links ]

O'Brien JT. Role of imaging techniques in the diagnosis of dementia. Br J Radiol 2007;80:S71-S77. [ Links ]

Desikan RS, Cabral HJ, Hess CP, et al.; Alzheimer's Disease Neuroimaging Initiative. Automated MRI measures identify individuals with mild cognitive impairment and Alzheimer's disease. Brain. 2009;132:2048-2057. [ Links ]

Frisoni GB, Fox NC, Jack CR Jr, Scheltens P, Thompson PM. The clinical use of structural MRI in Alzheimer disease. Nat Rev Neurol 2010;6:67-77. [ Links ]

Castillo M, Kwock L, Mukherji SK. Clinical applications of proton MR spectroscopy. AJNR Am J Neuroradiol 1996; 17:1-15. [ Links ]

Miller BL. A review of chemical issues in 1H NMR spectroscopy: N-acetyl-L-aspartate, creatine and choline. NMR Biomed 1991;4:47-52. [ Links ]

Shonk TK, Moats RA, Gifford P, et al. Probable Alzheimer disease: diagnosis with proton MR spectroscopy. Radiology 1995;195:65-72. [ Links ]

Moats RA, Ernst T, Shonk TK, Ross BD. Abnormal cerebral metabolite concentrations in patients with probable Alzheimer disease. Magn Reson Med 1994;32:110-115. [ Links ]

Parnetti L, Tarducci R, Presciutti O, et al. Proton magnetic resonance spectroscopy can differentiate Alzheimer's disease from normal aging. Mech Ageing Dev 1997;97:9-14. [ Links ]

Rose SE, de Zubicaray GI, Wang D, et al. A 1H MRS study of probable Alzheimer's disease and normal aging: implications for longitudinal monitoring of dementia progression. Magn Reson Imaging 1999;17:291-299. [ Links ]

Capizzano AA, Schuff N, Amend DL, et al. Subcortical ischemic vascular dementia: assessment with quantitative MR imaging and 1H MR spectroscopy. AJNR Am J Neuroradiol 2000;21:621-630. [ Links ]

Wardlaw JM, Marshall I, Wild J, Dennis MS, Cannon J, Lewis SC. Studies of acute ischemic stroke with proton magnetic resonance spectroscopy: relation between time from onset, neurological deficit, metabolite abnormalities in the infarct, blood flow, and clinical outcome. Stroke 1998; 29:1618-1624. [ Links ]

Lee HW. Evaluation of Azheimer's disease using magnetic resonance spectroscopy: comparation between findings in the posterior cingulate and hippocampi [thesis]. São Paulo: Universidade de São Paulo; 2005. [ Links ]

Kantarci K, Knopman DS, Dickson DW, et al. Alzheimer disease: postmortem neuropathologic correlates of antemortem 1H MR spectroscopy metabolite measurements. Radiology 2008;248:210-220. [ Links ]

Schott JM, Frost C, MacManus DG, Ibrahim F, Waldman AD, Fox NC. Short echo time proton magnetic resonance spectroscopy in Alzheimer's disease: a longitudinal multiple time point study. Brain 2010;133:3315-3322. [ Links ]

Engelhardt E, Moreira DM, Laks J, Cavalcanti JL. Alzheimer's disease and proton magnetic resonance spectroscopy of limbic regions: a suggestion of a clinical-spectroscopic staging. Arq Neuropsiquiatr 2005;63:195-200. [ Links ]

Stebbins GT, Murphy CM. Diffusion tensor imaging in Alzheimer's disease and mild cognitive impairment. Behav Neurol 2009;21:39-49. [ Links ]

Smith CD. Neuroimaging through the course of Alzheimer's disease. J Alzheimers Dis 2010;19:273-290. [ Links ]

Fagan AM, Mintun MA, Mach RH, et al. Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans. Ann Neurol 2006;59:512-519. [ Links ]

Jack CR Jr, Lowe VJ, Weigand SD, et al.; Alzheimer's Disease Neuroimaging Initiative. Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer's disease: implications for sequence of pathological events in Alzheimer's disease. Brain 2009;132:1355-1365. [ Links ]

Aizenstein HJ, Nebes RD, Saxton JA, et al. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol 2008;65:1509-1517. [ Links ]

Jagust W. Positron emission tomography and magnetic resonance imaging in the diagnosis and prediction of dementia. Alzheimers Dement 2006;2:36-42. [ Links ]

Sheline YI, Raichle ME, Snyder AZ, et al. Amyloid plaques disrupt resting state default mode network connectivity in cognitively normal elderly. Biol Psychiatry 2010;67:584-587. [ Links ]

Hampel H, Frank R, Broich K, et al. Biomarkers for Alzhei­mer's disease: academic, industry and regulatory perspectives. Nat Rev Drug Discov 2010;9:560-574. [ Links ]

Silverman DH, Small GW, Chang CY, et al. Positron emission tomography in evaluation of dementia: regional brain metabolism and long-term outcome. JAMA 2001; 286:2120-2127. [ Links ]

Drzezga A, Lautenschlager N, Siebner H, et al. Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer's disease: a PET follow-up study. Eur J Nucl Med Mol Imaging 2003;30:1104-1113. [ Links ]

Terry RD, Masliah E, Salmon DP, et al. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 1991;30:572-580. [ Links ]

Herskovits AZ, Growdon JH. Sharpen that needle. Arch Neurol 2010;67:918-920. [ Links ]

Knopman DS. Tapping into the biology of Alzheimer disease. Neurology 2011;76:496-497. [ Links ]

Machado LR, Livramento JA, Spina-França A. Exame de líquido cefalorraquidiano. In: Mutarelli EG (Ed). Manual de exames complementares em Neurologia. São Paulo: Sarvier; 2006:241-262. [ Links ]

Marra C. CSF: techniques and complications. 55th Annual Meeting American Academy of Neurology . Syllabi on CD-ROM, 2003. [ Links ]

De Meyer G, Shapiro F, Vanderstichele H, et al.; Alzheimer's Disease Neuroimaging Initiative. Diagnosis-independent Alzheimer disease biomarker signature in cognitively normal elderly people. Arch Neurol 2010;67:949-956. [ Links ]

Roe CM, Fagan AM, Williams MM, et al. Improving CSF biomarker accuracy in predicting prevalent and incident Alzheimer disease. Neurology 2011;76:501-510. [ Links ]

Shaw LM, Vanderstichele H, Knapik-Czajka M, et al.; Alzheimer's Disease Neuroimaging Initiative. Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects. Ann Neurol . 2009;65:403-413. [ Links ]

Jack CR Jr, Knopman DS, Jagust WJ, et al. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol 2010;9:119-128. [ Links ]

Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L. Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol 2006; 5:228-234. [ Links ]

Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging and Alzheimer's Association workgroup. Alzheimer's & Dementia 2011 (in press). [ Links ]

Sperling RA, Aisen PS, Beckett , et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging and the Alzheimer's Association workgroup. Alzheimer's & Dementia 2011(in press). [ Links ]

Luccas FJC, Anghinah R, Braga NIO, et al. Recomendações para o registro/interpretação do mapeamento topográfico do eletrencefalograma e potenciais evocados. Parte II: cor­relações clínicas. Arq Neuropsiquiatr 1999;57:132-146. [ Links ]

Sandmann MC, Piana ER, Sousa DS, Bittencourt PRM. Eletrencefalograma digital com mapeamento em demência de Alzheimer e doença de Parkinson. Arq Neuropsiquiatr . 1996;54:50-56. [ Links ]

Lehmann D. Multichannel topography of human alpha EEG fields. Electroencephalogr Clin Neurophysiol 1971;31:439-449. [ Links ]

Duffy FH, Burchfiel JL, Lombroso CT. Brain electrical activity mapping (BEAM): a method for extending the clinical utility of EEG and evoked potential data. Ann Neurol 1979; 5:309-321. [ Links ]

Jelic V, Kowalski J. Evidence-based evaluation of diagnosticaccuracy of resting EEG in dementia and mild cognitive impairment. Clin EEG Neurosci 2009;40:129-142. [ Links ]

Liedorp M, van der Flier WM, Hoogervorst EL,Scheltens P, Stam CJ. Associations between patterns of EEG abnormalities and diagnosis in a large memory clinic cohort. Dement Geriatr Cogn Disord 2009;27:18-23. [ Links ]

Loeches MM, Gil P, Jimenez F, et al. Topographic maps of brain electrical activity in primary degenerative dementia of Alzheimer type and multi-infarct dementia. Biol Psychiatry 1991;29:211-23. [ Links ]

Saletu B, Paulus E, Grunbergerer J. Correlation maps: on the relation of electroencephalographic slow wave activity to computerized tomography and psycopathometric measure­ments in dementia. In: Maurer K. Imaging of brain in psy­chiatry and related fieldsed. Berlin: Springer -Verlag; 1993: 263-265. [ Links ]

Pucci E, Belardinelli N, Cacchiò G, Signorino M, Angeleri F. EEG power spectrum differences in early and late onset forms of Alzheimer's disease. Clin Neurophysiol 1999;110: 621-631. [ Links ]

Dierks T, Perisic I, Frölich L, Ihl R, Maurer K. Topography of the qEEG in dementia of Alzheimer type: relation to severity of dementia. Psychiatry Res 1991;40:181-194. [ Links ]

Leuchter AF, Cook IA, Newton TF, et al. Regional differences in brain electrical activity in dementia: use of spectral power and spectral ratio measures. Electroencephalogr Clin Neurophysiol 1993;87:385-393. [ Links ]

Anderer P, Saletu B, Klöppel B, Semlitsch HV, Werner H. Dis­crimination between demented patients and normals based on topographic EEG slow wave activity: comparison between z statistics, discriminant analysis and artificial neural network classifiers. Electroencephalogr Clin Neurophysiol 1994;91:108-117. [ Links ]

Nielsen T, Montplaisir J, Lassonde M. Decreased interhemi­spheric EEG coherence during sleep in agenesis of the corpus callosum. Eur Neurol 1993;33:173-176. [ Links ]

Leuchter AF, Spar JE, Walter DO, Weiner H. Electroen­cephalographic spectra and coherence in the diagnosis of Alzheimer's-type and multi-infarct dementia. Arch Gen Psychiatry 1987;44:993-998. [ Links ]

Fonseca LC. Demência: eletroencefalo­grama e eletroencefalograma quantitativo. Projeto diretrizes. Associação Médica Brasileira e Conselho Federal de Medicina; 2008. [ Links ]

Miyauchi T, Hagimoto H, Ishii M, et al. Quantitative EEG in patients with presenile and senile dementia of the Alzheimer type. Acta Neurol Scand 1994;89:56-64. [ Links ]

Dierks T, Frolich L, Ihl R, Maurer K. Correlation between cognitive brain function and electrical brain activity in dementia of Alzheimer type. J Neural Transm Gen Sect 1995; 99:55-62. [ Links ]

Goate A, Chartier-Harlin MC, Mullan M, et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 1991;349: 704-706. [ Links ]

Sherrington R, Rogaev EI, Liang Y, et al. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature 1995;375:754-760. [ Links ]

Levy-Lahad E, Wasco W, Poorkaj P, et al. Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Science 1995;269:973-977. [ Links ]

Wattamwar PR, Mathuranath PS. An overview of biomarkers in Alzheimer's disease. Ann Indian Acad Neurol 2010; 13(Suppl 2):S116-S123. [ Links ]

Bertram L, Tanzi RE. The genetic epidemiology of neurodegenerative disease. J Clin Invest 2005;115:1449-1457. [ Links ]

Saunders AM, Strittmatter WJ, Shemechel D, et al. Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. Neurology 1993; 43:1467-1472. [ Links ]

Strittmatter WJ, Saunders AM, Shemechel D, et al. Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci U S A 1993;90:1977-1981. [ Links ]

Patterson C, Feightner JW, Garcia A, Hsiung GY, MacKnight C, Sadovnick AD. Diagnosis and treatment of dementia: 1. Risk assessment and primary prevention of Alzheimer disease. CMAJ 2008;178:548-556. [ Links ]

Andrade FM, Larrandaburu M, Callegari-Jacques SM, Gastaldo G, Hutz MH. Association of apolipoprotein E polymorphism with plasma lipids and Alzheimer's disease in a Southern Brazilian population. Braz J Med Biol Res 2000; 33:529-537. [ Links ]

Schwanke CH, da Cruz IB, Leal NF, Scheibe R, Moriguchi Y, Moriguchi EH. Analysis of association between APOE polymorphism and cardiovascular risk factors in an elderly population with longevity. Arq Bras Cardiol 2002;78:561-579. [ Links ]

Fernandez LL, Scheibe RM. Is MTHFR polymorphism a risk factor for Alzheimer disease like APOE? Arq Neuropsiquiatr 2005;63:1-6. [ Links ]

Souza DR, de Godoy MR, Hotta J, et al. Association of apolipoprotein E polymorphism in late-onset Alzheimer's disease and vascular dementia in Brazilians. Braz J Med Biol Res 2003;36:919-923. [ Links ]

Bahia VS, Kok F, Marie SN, Shinjo SO, Caramelli P, Nitrini R. Polymorphisms of APOE and LRP genes in Brazilian individuals with Alzheimer disease. Alzheimer Dis Assoc Disord 2008;22:61-65. [ Links ]

Bird TD. Genetic aspects of Alzheimer disease. Genet Med 2008;10:231-239. [ Links ]

Bertram L, McQueen MB, Mullin K, Blacker D, Tanzi RE. Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat Genet 2007;39:17-23. [ Links ]

Rogaeva E, Ming Y, Lee JH, et al. The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nat Genet 2007;39:168-177. [ Links ]

Lee JH, Cheng R, Schupf N, et al. The association between genetic variants in SORL1 and Alzheimer disease in an urban multiethnic community-based cohort. Arch Neurol 2007;64:501-506. [ Links ]

Butler AW, Ng NY, Hamshere ML, et al. Meta-analysis of linkage studies for Alzheimer1s disease-a web resource. Neurobiol Aging 2009;30:1037-1047. [ Links ]

Wollmer MA. Cholesterol-related genes in Alzheimer's disease. Biochim Biophys Acta 2010;1801:762-773. [ Links ]

Eschweiler GW, Leyhe T, Klöppel S, Hüll M. New developments in the diagnosis of dementia. Dtsch Arztebl Int 2010; 107:677-683. [ Links ]

Ashida S, Koehly LM, Roberts JS, et al.Disclosing the disclosure: factors associated with communicating the results of genetic susceptibility testing for Alzheimer disease. J Health Commun 2009;14:768-784. [ Links ]

Bekris LM, Yu CE, Bird TD, Tsuang DW. Genetic of Alzheimer disease. J Geriatr Psychiatry Neurol 2010;23:213-227. [ Links ]

Taner NE. Genetics of Alzheimer disease: a centennial review. Neurol Clin 2007;25:611-667. [ Links ]

Ashida S, Koehly LM, Roberts JS, et al. The role of disease preceptors and results sharing in psychological adaptation after genetic susceptibility testing: the REVEAL Study. Eur J Hum Genet 2010;18:1296-1301. [ Links ]

Williamson J, Goldman J, Marder KS. Genetic aspects of Alzheimer disease. Neurologist 2009;15:80-86. [ Links ]

Chung WW, Chen CA, Cupples LA, et al. A new scale measuring psychological impact of genetic susceptibility testing for Alzheimer disease. Alzheimer Dis Assoc Disord 2009;23:50-56. [ Links ]

Received: March 20, 2010; Accepted: June 22, 2011

Disclosure: The authors report no conflicts of interest.

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