原 著 MMSE J 1 2 3 Key words : MMSE J ADNI MMSE J 2006 Japanese Altzheimer s Disease Neuroimaging Initiative J ADNI 313 2010 J ADNI 2 145 6 JADNI 2010 2012 3 J ADNI 2014 3 105 68 37 2014 6 20 2010 2014 6 3 2014 10 129 4 http://www.geocities.jp/shinjitunodentatu/daisannsyaiin.html J ADNI 2016 1 J ADNI http://humandbs.biosciencedbc.jp/hum0043 v1 JADNI 2010 MMSE J JADNI 2010 313 MMSE J 23/24 23 24 /MCI National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer s Disease and Related Disorders Association NINCDS/ADRDA the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition DSM IV 313 54 8 MRI 4 3 1 251 MMSE J 23/24 100 7 0.86 0.89 0.80 0.94 MMSE J /MCI AD NINCDS/ADRDA DSM IV. MMSE J MMSE J MMSE J ROC 1 J ADNI PI 2 3 168 Japanese Journal of Cognitive Neuroscience
100 7 23/24 23/24 24/25 2010 6 142 142 23 4 2 1 1 115 MMSE J MMSE J 6 100 7 0.80 0.74 MMSE J MMSE J 100 7 100 7 MMSE J MMSE J ADNI MCI AD 1 16.5% Petersen et al. 2010 ADNI 1 29.0% 64/221 2013 2 ADNI ADNI Mini Mental State Examination MMSE Marshall F. Folstein Susan E. Folstein Paul R. McHugh 1975 Folstein et al. 1975 2006 MMSE J 2006 2006 Altzheimer s Disease Neuroimaging Initiative ADNI J ADNI MMSE MMSE MMSE MMSE J ADNI JADNI 2008 2010 7 313 MMSE J JADNI 2010 MMSE J 2012 2 1 2012 2012 3 J ADNI JADNI 2012 8 2014 3 105 2014 6 20 2010 JADNI 2010 Vol. 18 No. 3 4 2016 169
2014 6 3 1 1 2014 6 20 J ADNI 2014 105 68 37 2010 J ADNI 5 J ADNI 2014 10 129 105 105 24 129 2014 12 27 1 14 2015 5 3 23 2015 3 4 1 5 2015 4 7 13 2015 7 8 19 2 2015 8 8 5 PI J ADNI 8 2014 12 2015 8 2015 11 2 JADNI 2015 11 4 http://www.geocities.jp/shinjitunodentatu/daisannsyaiin. html J ADNI 2016 1 J ADNI http://humandbs.biosciencedbc.jp/ hum0043 v1 J ADNI 2014 J ADNI JADNI 2010 MMSE J Mini 170 Japanese Journal of Cognitive Neuroscience
Mental LLC, Inc. MMSE Psychological Assessment Resources Inc. MMSE MMSE MMSE J MMSE 100 7 100 7 world back spelling MMSE / 2 100 7 world back spelling 100 7 100 7 world back spelling MMSE J 3 J ADNI MMSE J / J ADNI I. 1. 2010 J ADNI 2010 J ADNI 313 MMSE J MMSE J J ADNI 6 142 MMSE J MMSE J 2010 313 142 129 129 MCI 5 GDS J 2 1 123 123 2 2 123 1 GDS J 4 WMS R J 1 2 GDS J 6 WMS R J 1 3 MMSE J 2 WMS R J B 1 24 4 MMSE J 1 5 WMS R J WMS R 9 1 1 GDS J 1 6 WMS R J 9 1 12 7 WMS R J B 4 8 WMS R J B 2 9 WMS R J 42 10 WMS R J 4 11 CDR J 18 12 8 13 4 14 6 15 12 PET 1 16 3 123 121 2 12 24 6 12 18 24 36 2010 6 142 6 MMSE J Vol. 18 No. 3 4 2016 171
6 2010 313 142 123 2. 251 MMSE J J ADNI 2010 J ADNI 313 313 54 123 54 313 GDS J 10 1 2 MRI 2 7 3 8 313 313 251 251 2008 8 2010 2 MMSE J 100 7 2 100 7 100 7 version 2 100 7 backward repetition version 251 3 1 MMSE J 2 100 7 3 MMSE J 23/24 100 7 23/24 Receiver Operating Characteristic Analysis ROC 1 MMSE J JADNI 2010 MMSE J MMSE J 313 t Tukey 251 313 t Wilcoxon rank sum test Kruskal Wallis test Tukey Bonferroni Wilcoxon rank sum test 2 100 7 100 7 100 7 26.43 SD 3.34 26.62 SD 3.08 100 7 5% p=0.049, Wilcoxon signed rank test 100 7 3 MMSE J 23/24 MMSE 23/24 23 MMSE J 23/24 NL MCI AD MMSE J Probable AD 172 Japanese Journal of Cognitive Neuroscience
NINCDS/ADRDA McKhann et al. 1984 DSM IV NL MCI AD 89 MCI 127 AD 35 MMSE J MMSE J 23 24 23/24 NL/ MCI AD 4 Receiver Operating Characteristic Analysis ROC MMSE J Receiver Operating Characteristic Analysis ROC MCI AD NINCDS/ADRDA DSM IV NL MCI AD 5 MMSE J 10 100 7 Cronbach s alpha reliability coefficient Cronbach 3. 115 2010 JADNI 2010 JADNI 6 142 142 23 123 23 142 7 2 6 1 6 1 4 142 142 115 115 2008 8 2010 2 115 57 MCI 46 AD 12 115 110 251 115 2008 8 2010 2 JADNI 2010 MMSE J 100 7 115 MMSE J 100 7 100 7 MMSE J 30 1 2010 ADNI NL MCI AD NINCDS/ADRADA DSM IV MMSE CDR GDS NL/MCI AD MMSE J 23/24 CDR J 115 3 Vol. 18 No. 3 4 2016 173
1 MMSE J MMSE J 142 MMSE J JADNI 2010 t F Tukey 142 115 115 t Wilcoxon rank sum test Kruskal Wallis test Tukey Bonferroni Wilcoxon rank sum test 2 100 7 100 7 MMSE 100 7 back spelling 100 7 2 100 7 Wilcoxon signed rank test 3 MMSE J 115 MMSE J 6 4 MMSE J 10 Cronbach II. 1. 251 MMSE J JADNI 2010 313 251 NL 89 MCI 127 AD 35 1 MMSE J 107 2010 MMSE J J ADNI 2010 t Tukey : 107 7 MMSE J Table 1 p=0.63 100 7 p=0.20 : 16 8 15 : p=0.004 t 100 7 : p= 0.006 t : 3 F p<0.0001 Tukey 60 64 65 74 65 74 75 p<0.0001 JADNI 2010 2010 Table 2 t 103.85 3.56 313 251 t Wilcoxon rank sum test Kruskal Wallis test Tukey Bonferroni Wilcoxon rank sum test Table 2 Wilcoxon rank sum test Kruskal Wallis test Bonferroni Wilcoxon rank sum test : : p=0.88 100 7 : p=0.23, Wilcoxon rank sum test : 100 7 174 Japanese Journal of Cognitive Neuroscience
16 8 15 p=0.001 100 7 p=0.003, Wilcoxon rank sum test : p<0.0001, Kruskal Wallis test Bonferroni 60 64 65 74 p<0.001 65 74 75 p<0.001 t Tukey Table 1 Table 2 MMSE J Table 3 16 χ 2 =22.939, df=2, p<0.0001, Chi squared test Wilcoxon rank sum test Kruskal Wallis test : 60 64 16 8 15 p=0.013, Wilcoxon rank sum test MMSE J 8 15 p<.0001, Kruskal Wallis test 16 p=0.0012, Kruskal Wallis test 100 7 : 100 7 Wilcoxon rank sum test Table 3 Kruskal Wallis test 8 15 p=0.0003 16 p=0.0012 100 7 Table 1. Means and SDs of MMSE J scores for 251 subjects by Demogaraphic Characteristics Sex Male Female N 107 144 p value Backward repetition version M SD 26.73 2.88 26.54 3.18 0.63 Serial 7s version M SD 26.74 3.17 26.20 3.39 0.20 Years of Education 16 y 8 15 y p value N 71 180 Backward repetition version M SD 27.49 2.95 26.28 3.03 0.004 Serial 7s version M SD 27.34 2.94 26.07 3.37 0.006 Age 60 64 y 65 74 y 75 y N 48 123 80 p value** Backward repetition version M SD 27.65 3.20 27.20 2.80 25.11 2.80 <.0001 > > Serial 7s version M SD 27.31 3.85 26.96 3.01 25.09 2.97 <.0001 > > t test, ANOVA Multiple comparison by Tukey s method. p<0.001 Vol. 18 No. 3 4 2016 175
Table 2. Means and SDs of MMSE J scores for 251 subjects by Demogaraphic Characteristics Sex Male Female N 107 144 p value Backward repetition version M SD 26.73 2.88 26.54 3.18 0.88 Serial 7s version M SD 26.74 3.17 26.20 3.39 0.23 Years of Education 16 y 8 15 y p value N 71 180 Backward repetition version M SD 27.49 2.95 26.28 3.03 0.001 Serial 7s version M SD 27.34 2.94 26.07 3.37 0.003 Age 60 64 y 65 74 y 75 y N 48 123 80 p value Backward repetition version M SD 27.65 3.20 27.20 2.80 25.11 2.80 <.0001 > > Serial 7s version M SD 27.31 3.85 26.96 3.01 25.09 2.97 <.0001 > > Wilcoxon rank sum test, Kruskal Wallis test Multiple comparison by Wilcoxon rank sum test with Bonferroni correction. p<.001 Table 3. Contingency table by Age and Years of Education for 251 subjects Years of Education Age 8 15 y 16 y Total 60 64 y 22 26 48 65 74 y 90 33 123 75 y 68 12 171 Total 180 71 251 χ 2 test p<.0001 2 100 7 100 7 5% p=0.049, Wilcoxon signed rank test 100 7 3 MMSE J MMSE J 23/24 NL+MCI AD 2 MMSE J MMSE J 24 23 2 100 7 0.86 0.89 0.80 0.94 100 7 0.87 0.89 0.88 0.92 4 ROC 251 ROC NL/MCI AD MMSE J 100 7 : ROC 100 7 23/24 0.86 0.89 24/25 0.91 0.81 23/24 0.86 0.89 24/25 176 Japanese Journal of Cognitive Neuroscience
0.91 0.81 : ROC 24/25 0.86 0.86 23/24 0.80 0.94 23/24 0.80 0.94 24/25 0.86 0.85 5 MMSE J Cronbach Cronbach 0.43 100 7 0.53 MMSE J 100 7 MMSE J 2. 115 JADNI 6 142 115 NL 57 MCI 46 AD 12 1 MMSE J MMSE J JADNI 2010 t F Tukey Table 4 : 100 7 MMSE J t p=0.73 100 7 p=0.24 : t p=0.013 100 7 p=0.023 : : p<0.0001 100 7 : p<0.002 F Tukey p=0.0004 100 7 p<0.0001 Table 4. Means and SDs of MMSE J scores by Demogaraphic Characteristics for 115 subjects Sex Male Female N 51 64 p value Backward repetition version M SD 27.37 2.63 27.20 2.66 0.73 Serial 7s version M SD 27.39 2.84 26.73 3.05 0.24 Years of Education 16 y 8 15 y p value N 39 76 Backward repetition version M SD 28.13 2.34 27.90 2.37 0.013 Serial 7s version M SD 27.90 2.69 26.58 3.15 0.023 Age 60 64 y 65 74 y 75 y N 25 53 37 p value Backward repetition version M SD 28.16 2.37 27.96 2.37 25.70 2.71 <.0001 > > Serial 7s version M SD 28.00 2.94 27.51 2.46 25.68 3.22 0.002 t test, ANOVA Multiple comparison by Tukey s method. p<0.001 > > Vol. 18 No. 3 4 2016 177
Table 5. Means and SDs of MMSE J scores for 115 subjects by Demogaraphic Characteristics Sex Male Female N 51 64 p value Backward repetition version M SD 27.37 2.63 27.20 2.66 0.90 Serial 7s version M SD 27.39 2.84 26.73 3.05 0.25 Years of Education 16y 8 15y p value N 39 76 Backward repetition version M SD 28.13 2.34 27.90 2.37 0.013 Serial 7s version M SD 27.90 2.69 26.58 3.15 0.029 Age 60 64y 65 74y 75y N 25 53 37 p value Backward repetition version M SD 28.16 2.37 27.96 2.37 25.7 2.71 <.0001 > > Serial 7s version M SD 28.00 2.94 27.51 2.46 25.68 3.22 <.002 > > Wilcoxon rank sum test, Kruskal Wallis test Multiple comparison by Wilcoxon rank sum test with Bonferroni correction. p<.0001 Multiple comparison by Wilcoxon rank sum test with Bonferroni correction. p<.01 115 t Wilcoxon rank sum test Kruskal Wallis test Tukey Bonferroni Wilcoxon rank sum test Table 4 : 100 7 MMSE J Wilcoxon rank sum test p=0.90 100 7 p=0.25 : Wilcoxon rank sum test p=0.013 100 7 p=0.029 : Kruskal Wallis test p< 0.0001 100 7 p<0.002 Bonferroni Wilcoxon rank sum test p<0.01 100 7 p<0.01 t Tukey Table 4 Table 5 MMSE J Table 6 χ 2 =14.55, df=2, p=0.0007, Chi squared test Wilcoxon rank sum test Kruskal Wallis test : 60 64 16 8 15 p=0.008, Wilcoxon rank sum test 8 15 p=0.0009, Kruskal Wallis test 16 p= 178 Japanese Journal of Cognitive Neuroscience
Table 6. Contingency table by Age and Years of Education for 115 subjects Age 8 15y 16 y Total 60 64 y 15 10 25 65 74 y 19 34 53 75 y 5 32 78 Total 39 76 115 χ 2 test p=.0007 4 MMSE J Cronbach 0.40 100 7 0.52 MMSE J 100 7 0.029, Kruskal Wallis test 100 7 : 100 7 Wilcoxon rank sum test Table 6 8 15 p=0.0003, Kruskal Wallis test 16 p=0.0012, Kruskal Wallis test 100 7 2 100 7 6 100 7 : p=0.13 6 : p=0.8, Wilcoxon signed rank test 100 7 251 115 3 MMSE J MMSE J 6 test retest 100 7 0.80 95% 0.72 0.85, t=13.94, df=113, p<0.0001 0.74 95% 0.65 0.81, t=11.72, df=113, p< 0.0001 III. 1. MMSE J CDR J WMS R GDS J 4 NL MCI AD MMSE MCI AD NL MCI AD MMSE ADNI MMSE NL MCI 30 24 AD 26 20 MMSE MMSE MMSE 23/24 MMSE ADNI MMSE 30 24 NL MCI 26 20 AD /MCI AD 23 24 MMSE J Vol. 18 No. 3 4 2016 179
251 MMSE J 2 24 23 100 7 0.86 0.89 0.88 0.94 MMSE J Tombaugh and McIntyre 1992 23/24 0.87 MMSE J 2. MMSE J test retest 0.74 95% 0.65 0.81, t=11.72, df=113, p<0.0001 100 7 0.80 95% 0.65 0.81, t=13.94, df=113, p<0.0001 MMSE test retest 0.79 0.98 Stuss et al. 1996 MMSE J 100 7 3. 100 7 100 7 100 7 100 7 100 7 back spelling 100 7 100 7 back spelling 4. JADNI MCI AD MCI AD 9.6% ADNI MCI AD 1 16.5% Petersen et al. 2010 ADNI 1 29.0% 64/221 2013 2 MCI AD MCI 2 ADNI 1 ADNI ADNI MMSE J MMSE J MMSE MMSE J Psychological Assessment Resources Inc. 180 Japanese Journal of Cognitive Neuroscience
MMSE MMSE J 2 Psychological Assessment Resources Inc. 1 Folstein MF, Folstein SE, McHugh PR. 1975 Mini Mental State : A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research 12, 189 198. 2 JADNI 2010 MMSE J : A preliminary report. 12 3 4, 186 190. 3 2012 MMSE J : 4 2014 J ADNI 2014, 6, 24. http:// www.u tokyo.ac.jp/public/public01_260624_j.html 5 J ADNI 2014 2014 12 19 http://www.u tokyo.ac.jp/ja/administration/code ofconduct/pdf/20141222/f file 1 2.pdf 6 2015 2015 1 14 http://www.geocities.jp/shinjitunodentatu/daisannsya iin.html 7 J ADNI 2015 2015 3 23 http://www.geocities.jp/shinjitunodentatu/daisannsya iin.html 8 2015 2015 4 1 2015 4 1 http://www.geocities.jp/shinj itunodentatu/daisannsyaiin.html 9 2015 J ADNI 2015 7 13 http:// www.geocities.jp/shinjitunodentatu/daisannsyaiin.html 10 J ADNI 2015 2 2015 8 19 http://www.geocities.jp/shinjitunodentatu/daisannsya iin.html 11 2015 JADNI 2015 11 2 http://www.geocities.jp/ shinjitunodentatu/daisannsyaiin.html 12 2016 JADNI http://humandbs.biosciencedbc.jp/hum00 43 v1 13 McKhann G, et al. 1984 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 34, 939 944. 14 Tombaugh TN, McIntyre NJ. 1992 The Mini Mental State Examination : A comprehensive review. Journal of the American Geriatrics Society 40 9, 922 935. 15 Stuss DT, et al. 1996 Do long tests yield a more accurate diagnosis of dementia than short tests? A comparison of 5 neuropsychological tests. Archives of Neurology 53 10, 1033 1039. 16 Petersen RC, Aisen PS, Beckett LA, Donohue MC, Gamst AC, et al. 2010 Alzheimer s Disease Neuroimaging Initiative ADNI : clinical characterization. Neurology 74 1, 201 209. 17 2013 JADNI 2013 Vol. 18 No. 3 4 2016 181
Reexamination of the Validity and Reliability of the Japanese Version of the Mini Mental State Examination MMSE J Morihiro Sugishita 1, Isao Hemmi 2, Tomoko Takeuchi 3 1 Tokyo Metropolitan University, Tokyo, Japan, J ADNI Psychology Core PI 2 Japanese Red Cross College of Nursing, Tokyo, Japan 3 Tsukuba University, Tsukuba, Japan Key words : MMSE, MMSE J, ADNI, dementia, validity, reliability The criterion based validity of the Japanese version of the Mini Mental State Examination MMSE J Sugishita 2006 was preliminarily evaluated in 2010 Sugishita, Hemmi and JADNI 2010 based on data from 313 subjects who participated in the Japanese Alzheimer s Disease Neuroimaging Initiative J ADNI. Test retest reliability was also preliminarily examined in 145 subjects in J ADNI who were tested twice. The second testing was performed 6 months after the first Sugishita, Hemmi and JADNI 2010. However, in March, 2012, an employee of a pharmaceutical company reported that the J ADNI data for some subjects had been falsified. In March, 2014, Drs. Sugishita, M and Asada,T reported a total of 105 cases with confirmed or suspected falsification of data or protocol violation 68 cases by Sugishita and 37 cases by Asad to the Special Investigative Committee of the University of Tokyo. In June 20, 2014, the Committee confirmed that data had been inappropriately modified by inappropriate persons. The authors Sugishita & Hemmi of the 2010 paper Sugishita, Hemmi and JADNI 2010 then proposed to withdraw and revise the paper. The editorial board of the Japanese Journal of Cognitive Neuroscience accepted the proposal on June 3, 2014. In October 2014, 129 cases with confirmed or suspected falsification of data or protocol violation were reported to the Third Party Panel of the University of Tokyo. The Third Party Panel examined all 129 subjects and found no falsification of data or protocol violations. However, the four written refutations by Dr. M. Sugishita argued against the criticism of the Third Party Panel and it became clear that the Third Party Panel had made errors in judgment cf. http://www.geocities.jp/shinjitunodentatu/daisannsyaiin.html. Consequently, it is necessary to exclude the subjects with falsification of data or protocol violation from the J ADNI data. However, Dr. T. Iwatsubo the J ADNI principal investigator disclosed under limitations the uncorrected J ADNI data to researchers through the Japan Science and Technology Information Aggregator, Electronic J STAGE in January 2016 http://humandbs.biosciencedbc.jp/hum0043 v1. Therefore, the aim of the present study was to reexamine the validity and reliability of the MMSE J after excluding cases with confirmed or suspected falsification of data or protocol violations. In our previous study Sugishita, Hemmi and JADNI 2010, the criterion based validity of the cut off score of 23/24 for dementia was evaluated in 313 subjects and compared with a medical doctor s classification of the same subjects into two groups a Normal/Mild Cognitive Impairment MCI group and an Alzheimer s Disease AD group based on the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer s Disease and Related Disorders Association NINCDS/ADRDA and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition DSM IV. In the present study, after excluding 54 subjects with confirmed or suspected falsification of data or protocol violations and 8 subjects with other various reasons 4 with brain MRI abnormality, 3 with low educational level, and 1 with an abnormally high depression scale score, criterion based validity was evaluated in 251 subjects. Criterion based validity was found to be excellent and almost the same as that in our previous study the serial 7s version : sensitivity 0.86, 182 Japanese Journal of Cognitive Neuroscience
specificity 0.89, the backward repetition version : sensitivity 0.80, specificity 0.94. The proximal cut off score for dementia were newly evaluated against the external criteria, namely, the classification the Normal/MCI group and the AD group by the medical doctor based on NINCDS/ADRDA and DSM IV criteria. However, the MMSE J was sometimes tested before the classification of the medical doctor. The medical doctor sometimes knows the MMSE J score, which influence the classification of the medical doctor. Receiver Operating Characteristic Analysis showed that the proximal cut off score for dementia was 23/24 in the serial 7 version, and 23/24 or 24/25 in the backward repetition version. In the previous study, test retest reliability was evaluated in the 142 subjects who were tested twice namely, at screening and at 6 months after screening. In the present study, after excluding 23 cases with confirmed or suspected falsification of data or protocol violations and 4 subjects with other various reasons 2 with low educational level, 1 with suspected brain tumor and 1 with insufficient data, test retest reliability was evaluated in 115 subjects. To assess the test retest reliability of the MMSE J, the Pearson correlation coefficients were calculated. Test retest reliability was found to be excellent 0.74 for the backward repetition version ; 0.80 for the serial 7s version which are almost the same as those of the previous study. The criterion based validity and test retest reliability of the present study were excellent, which indicates that the MMSE J is a clinically applicable screening instrument for dementia. The results of the present study also showed that the backward repetition version had higher scores than the serial 7 version, which means that the former is easier than the latter. In both the present and previous studies, the criterion based validity and the proximal cut off score for dementia were evaluated against external criteria not completely independent from the MMSE J score. In a future study, criterion based validity and the proximal cut off score for dementia should be examined against the external criteria independent from the MMSE J score. US ADNI data showed that the conversion rate of the amnestic type of the MCI to the AD was 16.5% one year after the first examination. However, the J ADNI data revealed that the conversion rate one year and two years after the first examination was extremely high, that is, 29% Asada 2013, which suggests that the J ADNI data is dubious. In a future study whether the extremely high conversion rates are due to a falsification of data, protocol violation or other causes need to be elucidated. As long as these problems remain, it appears that the J ADNI data should not be used for research purposes. Vol. 18 No. 3 4 2016 183