OBJECTIVE: To evaluate the combination of two factors: clinical dementia rating sum of boxes scores (CDR-SB) and hippocampal volume (HV) as predictors of conversion from mild cognitive impairment (MCI) to dementia. METHODS: Twenty-eight individuals (9 normal and 19 with MCI) were classified according to their CDR sum of boxes scores into 3 groups. RESULTS: The hippocampal volume was significantly lower in the high-risk group and in those who developed dementia after two years. The rate of conversion was crescent among the three groups. CONCLUSION: We were proposed an additional measurement of the hippocampal volume which may be helpful in the prognosis. However, we noted that the CDR-SB is a method as efficient as neuroimaging to predict dementia with the advantage of being a procedure for low cost and easy implementation, more consistent with public policy.OBJETIVO: Avaliar a combinação de dois fatores: clinical dementia rating sum of boxes scores (CDR-SB) e volume hipocampal (VH) como preditores de conversão de ditúrbio cognitivo leve (DCL) em demência. MÉTODO: Vinte e oito indivíduos (9 normais e 19 com DCL) foram classificados de acordo com a soma dos escores CDR-SB em 3 grupos. RESULTADOS: O volume do hipocampo foi significativamente menor no grupo de alto risco e naqueles que desenvolveram demência depois de dois anos. A taxa de conversão foi crescente entre os três grupos. CONCLUSÃO: Propusemos uma medição adicional do volume do hipocampo que pode ser útil no prognóstico. No entanto, notou-se que a CDR-SB é um método tão eficiente quanto neuroimagem para prever demência com a vantagem de ser um processo de baixo custo e de fácil implementação, mais consistente com a política pública.Universidade Federal de São Paulo (UNIFESP) Department of PsychobiologyUniversidade Federal de São Paulo (UNIFESP) Department of PsychiatryUniversidade Federal de São Paulo (UNIFESP) Department of Preventive MedicineUNIFESP, Department of PsychobiologyUNIFESP, Department of PsychiatryUNIFESP, Department of Preventive MedicineSciEL

Baldaçara, Leonardo

Borgio, João Guilherme Fiorani

Bressan, Rodrigo Affonseca

Jackowski, Andrea Parolin

Lacerda, Acioly Luiz Tavares de

Montaño, Maria Beatriz Marcondes Macedo

Moraes, Walter dos Santos

Ramos, Luiz Roberto

Tufik, Sergio

Arquivos de Neuro-Psiquiatria

OBJECTIVE: To evaluate the combination of two factors: clinical dementia rating sum of boxes scores (CDR-SB) and hippocampal volume (HV) as predictors of conversion from mild cognitive impairment (MCI) to dementia. METHODS: Twenty-eight individuals (9 normal and 19 with MCI) were classified according to their CDR sum of boxes scores into 3 groups. RESULTS: The hippocampal volume was significantly lower in the high-risk group and in those who developed dementia after two years. The rate of conversion was crescent among the three groups. CONCLUSION: We were proposed an additional measurement of the hippocampal volume which may be helpful in the prognosis. However, we noted that the CDR-SB is a method as efficient as neuroimaging to predict dementia with the advantage of being a procedure for low cost and easy implementation, more consistent with public policy

João Guilherme Fiorani Borgio

Leonardo Baldaçara

Walter dos Santos Moraes

Acioly L. T. Lacerda

Maria Beatriz Montaño

Andrea Parolin Jackowski

Sérgio Tufik

Luiz Roberto Ramos

Rodrigo Affonseca Bressan

Directory of Open Access Journals

Hippocampal volume and CDR-SB can predict conversion to dementia in MCI patients

Borgio, João Guilherme Fiorani [UNIFESP]

Baldaçara, Leonardo [UNIFESP]

Moraes, Walter dos Santos [UNIFESP]

Lacerda, Acioly Luiz Tavares de [UNIFESP]

Montaño, Maria Beatriz Marcondes Macedo [UNIFESP]

Jackowski, Andrea Parolin [UNIFESP]

Tufik, Sergio [UNIFESP]

Ramos, Luiz Roberto [UNIFESP]

Bressan, Rodrigo Affonseca [UNIFESP]

Repositório Institucional UNIFESP

839XXXARTICLEHippocampal volume and CDR-SB can predict conversion to dementia in MCI patientsO volume do hipocampo e a soma dos subitens da escala CDR podem predizer a conversão para a demência nos pacientes com comprometimento cognitivo leveJoão Guilherme Fiorani Borgio1,2, Leonardo Baldaçara2, Walter dos Santos Moraes1, Acioly L. T. Lacerda2, Maria Beatriz Montaño3, Andrea Parolin Jackowski2, Sérgio Tufik1, Luiz Roberto Ramos3, Rodrigo Affonseca Bressan2The most relevant challenge in dementia is the early identi-fication of cases that would allow neuroprotective measures to delay or eventually prevent the onset of the illness. Mild cogni-tive impairment (MCI) and cognitive impairment no demen-tia (CIND) represent states of cognitive impairment, estimated by neuropsychological battery tests, with no sufficient crite-ria to meet the diagnosis of dementia1. Despite the high rate of conversion to dementia, it is not know which patients will be demented. Several isolated variables have been evaluated as predictors of conversion but none has demonstrated good ac-curacy2. The use of combined methods to better predict the risk of conversion is being developed in recent years3,4.The identification of predementia states can be done by clinical criteria1 or by semi-structured interviews, as the Clinical Dementia Rating (CDR)5. Its Global Score may be 0=normal, 0.5=questionable dementia (no dementia cogni-tive impairment), 1=mild dementia, 2=moderate dementia and 3=severe dementia5. Individuals with CDR equal to 0.5 have annual conversion rate of 20%6. The CDR sum of boxes scores (CDR-SB) may vary from 0 to 18 and enables a quanti-tative evaluation of impairment. In a five-year study, the an-nual conversion rates to CDR=1 (considered definite demen-tia) were 6.8% to CDR-SB=0, 10% to CDR-SB=0.5, 1 or 1.5 and 35.7% to CDR-SB=2, 2.5 or 37.Universidade Federal de São Paulo (UNIFESP), São Paulo SP, Brazil.1Department of Psychobiology, UNIFESP, São Paulo SP, Brazil;2Department of Psychiatry, UNIFESP, São Paulo SP, Brazil;3Department of Preventive Medicine, UNIFESP, São Paulo SP, Brazil.Correspondence: João Guilherme Fiorani Borgio; Rua Napoleão de Barros 925; 04024-002 São Paulo SP - Brasil; E-mail: joaoborgio@gmail.comConflict of interest: There is no conflict of interest to declare.Received 17 May 2012; Received in final form 26 June 2012; Accepted 03 July 2012ABSTRACTObjective: To evaluate the combination of two factors: clinical dementia rating sum of boxes scores (CDR-SB) and hippocampal volume (HV) as predictors of conversion from mild cognitive impairment (MCI) to dementia. Methods: Twenty-eight individuals (9 normal and 19 with MCI) were classified according to their CDR sum of boxes scores into 3 groups. Results: The hippocampal volume was significantly lower in the high-risk group and in those who developed dementia after two years. The rate of conversion was crescent among the three groups. Conclusion: We were proposed an additional measurement of the hippocampal volume which may be helpful in the prognosis. However, we noted that the CDR-SB is a method as efficient as neuroimaging to predict dementia with the advantage of being a procedure for low cost and easy implementation, more consistent with public policy.Key words: geriatric psychiatry, neuroimage, mild cognitive impairment.RESUMOObjetivo: Avaliar a combinação de dois fatores: clinical dementia rating sum of boxes scores (CDR-SB) e volume hipocampal (VH) como preditores de conversão de ditúrbio cognitivo leve (DCL) em demência. Método: Vinte e oito indivíduos (9 normais e 19 com DCL) foram classificados de acordo com a soma dos escores CDR-SB em 3 grupos. Resultados: O volume do hipocampo foi significativamente menor no grupo de alto risco e naqueles que desenvolveram demência depois de dois anos. A taxa de conversão foi crescente entre os três grupos. Conclusão: Propusemos uma medição adicional do volume do hipocampo que pode ser útil no prognóstico. No entanto, notou-se que a CDR-SB é um método tão eficiente quanto neuroimagem para prever demência com a vantagem de ser um processo de baixo custo e de fácil implementação, mais consistente com a política pública.Palavras-Chave: psiquiatria geriátrica, neuroimagem, distúrbio cognitivo leve.840 Arq Neuropsiquiatr 2012;70(11):839-842Reduction in hippocampal volume (HV), measured by re-gion of interest approach using magnetic resonance imaging (MRI), may be present in patients with MCI8. Longitudinal studies measuring hippocampal atrophy indicate existence of a continuum from normal aging to MCI and dementia spe-cially Alzheimer’s disease (AD)9. Such methodology has been used in a Brazilian setting already10. Nowadays it is pointed as a predictor of conversion to dementia in MCI patients11.The objective of this study was to evaluate the combina-tion of two factors: CDR-SB and HV as predictors of conver-sion from MCI to dementia.METHODSSubjectsThe EPIDOSO study was the first community-based co-hort study with elders in Brazil. It started in 1991, evaluat-ing 1,667 individuals with 65 years and older, living in an ur-ban district, in São Paulo city, whose main objective was to determine predictors of good health outcome12,13. In 1998, 440 individuals, survivors from the original sample, begun following up in the Centro de Estudos do Envelhecimento (CEE). Another study selected, among the CEE sample, those with Mini-Mental Status Examination (MMSE) less than 26 (n=108) and randomly assigned others 48 with MMSE ≥26. The 156 individuals entered a protocol that included CDR-SB, MMSE and Alzheimer’s disease assessment scale-cogni-tive subscale (ADAS-cog)14, which objective was to validate CDR for the diagnosis of dementia in Brazil15. Among that sample, we selected only individuals who had no demen-tia at the initial evaluation (CDR=0 or 0.5), no formal coun-ter indication to underwent MRI and had signed informed consent. Those were then divided into three groups, depend-ing on their CDR-SB. Persons with CDR=0 (thus CDR-SB=0) were called “low-risk” group (LR), those with CDR=0.5 and CDR-SB=0.5, 1 or 1.5 were called “medium-risk” group (MR) and those with CDR=0.5 and CDR-SB=2, 2.5 or 3 were called “high-risk” group (HR).ProceduresIndividuals were submitted to brain MRI, within a max-imum period of four months after the clinical and neuro-psychological evaluation of the former study15. Volumetric MRI scans were performed with a GE 1.5 Tesla Unit (Sigma System, General Electric Medical Systems, Milwaukee, Wisconsin) running version 5.4 software. Head position was standardized16,. A three-dimensional spoiled gradient re-called acquisition in the steady-state pulse sequence was used to obtain 124 contiguous images with slice thickness of 1.5 mm in the coronal plane for region-of-interest mea-sures (echo time=5 milliseconds, repetition time=25 milli-seconds, flip angle=40 degrees, acquisition matrix=256x192, number of excitations=1, field of vision=24 cm). After two years from the baseline, they were re-evaluated with CDR-SB, MMSE and ADAS-cog in order to detect clinical demen-tia (Global score of CDR≤1).The imaging data were analyzed with Brains 2 software, which provides valid and reliable volume measurements of specific structures with a manually operated approach17. Trained and reliable raters, blind to subject information, traced the hippocampus manually using valid protocols18. All volumes were divided by intracranial volume.All data were analyzed with the Statistical Package for the Social Sciences 13.0 for Windows (SPSS, Inc., Chicago, Illinois). The Mann-Whitney test was used for continuous data when comparing two groups and Kruskal-Wallis test for continuous data when comparing three or more groups. Association between the comparison groups and categorical variables was assessed with χ2 test.RESULTSTwenty-eight individuals met the selection crite-ria. The proportion of women was 60.7%, mean age was 81±5.3 years and scholarship with mean 8±3.8 years. The distribution among the groups was: 9 LR, 11 MR and 8 HR. The three groups did not differ in their socio-demographic characteristics (Table 1).No subject had clinical abnormalities on axial proton density and T2-weighted images. Subjects completed  the scan without sedation or significant head movement. The HV was significantly smaller in HG, comparing to LR and MR (Kruskal-Wallis; p<0.001) (Table 1).After two years, no subject from LR, 4 (36.4%) subjects from MR and 7 (87.5%) from HR developed dementia (χ2; p<0.001). Dividing the sample into two groups, those who developed de-mentia (D-group) did not differ in gender, age and years of schol-arship, compared to those who did not (ND-group) (Table  2). The D-group had mean HV smaller than the ND-group two years before the assessment (Mann Whitney; p=0.02).Table 1. Demographic characteristics and results of the three groups and of converters and non-converters.Low-risk (n=9) Medium-risk (n=11) High-risk (n=8) p-valueWomen/Men (% of women) 6/3 (66) 5/6 (45) 6/2 (75) 0.38Age in years (mean±SD) 81.0±5.0 80.0±4.8 82.5±6.6 0.45Years of scholarship (mean ± SD) 8.2±3.5 8.0±4.4 7.6±3.7 0.92HV (% of ICV) 0.283±0.033 0.260±0.037 0.212±0.014 <0.001SD: standard deviation; HV: hippocampal volume; ICV: intracranial volume.841João Guilherme Fiorani Borgio et al. HV, CDR-SB: MCI patientsDISCUSSIONThe HV was smaller in the HR group, suggesting rela-tionship between clinical performance and integrity of hip-pocampus. The individuals who developed dementia had smaller HV at baseline, supporting that it may be a predic-tor of conversion. Those results were expected and are sup-ported by literature19.Although the main outcome, diagnosis of dementia, had not followed the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) crite-ria20, and was made without investigation of its causes. The criterion of CDR=1 is quite sufficient to diagnose dementia, with wide use in recent studies21, as CDR=0.5 for CIND22, and is a valid instrument in our setting15,23.Table 2. Demographic characteristics and results of converters and non-converters.No-dementia (n=17) Dementia (n=11) p-valueWomen/Men (% of women) 11/6 (65) 6/5 (54) 0.59Age in years (mean±SD) 80.8±4.8 81.3±6.3 0.62Years of scholarship (mean±SD) 7.9±3.8 8.0±4.0 0.83HV (% of ICV) 0.266±0.038 0.239±0.039 0.02SD: standard deviation; HV: hippocampal volume; ICV: Intracranial volume.Brain MRI has been more commonly requested by clini-cians to identify causes of dementia24, and CDR is already used in clinical practice in Brazil in order to dispense the an-ticholinesterasic medication25. Thus, a simple modification in the standard evaluation of elders with cognitive complaints may be of great usefulness in predicting those that will con-vert to dementia. We propose an additional measurement of the hippocampal volume which may be helpful in the prog-nosis. However, we noted that the CDR-SB is a method as efficient as neuroimaging to predict dementia with the ad-vantage of being a procedure for low cost and easy imple-mentation, more consistent with public policy.Further studies must evaluate the usefulness of this com-bination in larger samples and the plausibility of combining more biological markers as risk factors to improve the pre-dictive power to identify those who will convert to dementia.1. Petersen RC. Mild cognitive impairment as a diagnostic entity. J Inter Med 2004;256:183-194.2. Boyle PA, Wilson RS, Aggarwal NT, Tang Y, Bennett DA. Mild cognitive impairment: risk of Alzheimer disease and rate of cognitive decline. Neurology 2006;67:441-445.3. Visser PJ. Mild cognitive impairment. In: Pathy J, Sinclair AJ, Morley JE (ed.). Principles and practice of geriatric medicine. 4th ed. Hoboken: John Wiley & Sons, 2006. p. 1-7.4. Borroni B, Premi E, Di Luca M, Padovani A. Combined biomarkers for early Alzheimer disease diagnosis. Curr Med Chem 2007;14:1171-1178.5. Morris JC, Heyman A, Mohs RC, Hughes JP, van Belle G, Fillenbaum G, et al. The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer’s disease. Neurology 1989;39:1159-1165.6. Wang PN, Liu HC, Lin KN. The MCI study in Taiwan. Acta Neurol Taiwanica 2006;15:66-68.7. Morris JC, Storandt M, Miller JP, McKeel DW, Price JL, Rubin EH, et al. Mild cognitive impairment represents early-stage of Alzheimer disease. Arch Neurol 2001;58:397-405.8. Jack CR Jr, Petersen RC, Xu Y, O’Brien PC, Smith GE, Ivnik RJ, et al. Rates of hippocampal atrophy correlate with change in clinical status in aging and AD. Neurology 2000;55:484-489.9. deToledo-Morrell L, Stoub TR, Bulgakova M, Wilson RS, Bennett DA, Leurgans S, et al. MRI-derived entorhinal volume is a good predictor of conversion from MCI to AD. Neurobiol Aging 2004;25:1197-1203.10. Bottino CM, Castro CC, Gomes RL, Buchpiguel CA, Marchetti RL, Neto MR. Volumetric MRI measurements can differentiate Alzheimer’s disease, mild cognitive impairment, and normal aging. Int Psychogeriatr 2002;14:59-72.11. Devanand DP, Pradhaban G, Liu X, Khandji A, De Santi S, Segal S, et al. Hippocampal and entorhinal atrophy in mild cognitive impairment: prediction of Alzheimer disease. Neurology 2007;68:828-836.12. Ramos LR, Toniolo J, Cendoroglo MS, et al. Two-year follow-up study of elderly residents in S. Paulo, Brazil: methodology and preliminary results. Rev Saude Publica 1998;32:397-407.13. Ramos LR, Simoes EJ, Albert MS. Dependence in activities of daily living and cognitive impairment strongly predicted mortality in older urban residents in Brazil: a 2-year follow-up. J Am Geriatr Soc 2001;49:1168-1175.14. Mohs RC, Cohen L. Alzheimer’s Disease Assessment Scale (ADAS). Psychopharmacol Bull 1988;24:627-628.15. Montaño MBMM, Ramos LR. Validade da versão em português da Clinical Dementia Rating. Rev Saude Pública 2005;39:912-917.16. De Bellis MD, Hall J, Boring AM, Frustaci K, Moritz G. A pilot longitudinal study of hippocampal volumes in pediatric maltreatment-related posttraumatic stress disorder. Biol Psychiatry 2001;50:305-309.17. Magnotta VA, Harris G, Andreasen NC, O’Leary DS, Yuh WT, Heckel D. Structural MR image processing using the BRAINS2 toolbox. Comput Med Imaging Graph 2002;26:251-264.18. Schumann CM, Hamstra J, Goodlin-Jones BL, et al. The amygdala is enlarged in children but not adolescents with autism; the hippocampus is enlarged at all ages. J Neurosci 2004;24:6392-6401.19. Tapiola T, Pennanen C, Tapiola M, et al. MRI of hippocampus and entorhinal cortex in mild cognitive impairment: a follow-up study. Neurobiol Aging 2008;29:31-38.20. 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;34:939-944.21. Lim WS, Chin JJ, Lam CK, Lim PP, Sahadevan S. Clinical dementia rating: experience of a multi-racial Asian population. Alzheimer Dis Assoc Disord 2005;19:135-142.References842 Arq Neuropsiquiatr 2012;70(11):839-84222. Lynch CA, Walsh C, Blanco A, et al. The clinical dementia rating sum of box score in mild dementia. Dement Geriatr Cogn Disord 2006;21:40-43.23. Maia AL, 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;64:485-489.24. van der Flier WM, Barkhof F, Scheltens P. Shifting paradigms in dementia: toward stratification of diagnosis and treatment using MRI. Ann N Y Acad Sci 2007;1097:215-224.25. Beltrame A. Protocolos clínicos e diretrizes terapêuticas: medicamentos excepcionais. Brasília: Ministério da Saúde; 2002.

O volume do hipocampo e a soma dos subitens da escala CDR podem predizer a conversão para a demência nos pacientes com comprometimento cognitivo leve

OBJECTIVE: To evaluate the combination of two factors: clinical dementia rating sum of boxes scores (CDR-SB) and hippocampal volume (HV) as predictors of conversion from mild cognitive impairment (MCI) to dementia. METHODS: Twenty-eight individuals (9 normal and 19 with MCI) were classified according to their CDR sum of boxes scores into 3 groups. RESULTS: The hippocampal volume was significantly lower in the high-risk group and in those who developed dementia after two years. The rate of conversion was crescent among the three groups. CONCLUSION: We were proposed an additional measurement of the hippocampal volume which may be helpful in the prognosis. However, we noted that the CDR-SB is a method as efficient as neuroimaging to predict dementia with the advantage of being a procedure for low cost and easy implementation, more consistent with public policy.</jats:p

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http://dx.doi.org/10.1590/S0004-282X2012001100003

O volume do hipocampo e a soma dos subitens da escala CDR podem predizer a conversão para a demência nos pacientes com comprometimento cognitivo leve

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