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Background Alzheimer disease (AD) patients demonstrate various clinical features reminiscent of children (the retrogenesis model). The Binet test is available for assessing mental development and deterioration. However, neuroimaging correlations remain to be clarified. Although AD patients also manifest social judgment disability, there are few cognitive tests, contrary to so many memory tests. Among the database, we noticed that the Binet test includes the subscale of social judgement using illogical sentences and pictures. The aim of this study is to clarify the neuroimaging correlations for the Binet test, especially for the illogical questions. Methods Forty participants were selected from the database of the Tajiri Project. The Tanaka-Binet test was used to evaluate the mental age and the basic age. The latter is the age level at which the patient can completely accomplish all questions at the immediately lower age level and is used for calculating the mental age. Using the subtests of illogical sentences/pictures, logical judgment abilities were assessed. Using magnetic resonance imaging, we performed four-grade visual evaluation for cortical atrophy. The cerebral metabolic rate for glucose (CMRglc) was measured using an autoradiographic method of 18 F-fluoreodeoxyglucose - positron emission tomography (FDG-PET). Results There was a significant Spearman's correlation between the clinical stage and the basic age. Degree of frontal, temporal and hippocampal atrophy were correlated with the basic age. The entire grey matter and frontal and temporal CMRglc were associated with the basic age. The illogical sentences scores were correlated with the bilateral temporal, hippocampal and the left parieto-temporal CMRglc, whereas the illogical picture scores were correlated with the right parieto-temporal CMRglc. Conclusions We found that frontal and temporal atrophy as well as hypometabolism were associated with the basic age. Regarding the illogical judgment, the current PET data analysis disclosed that there may be a double dissociation between verbal/non-verbal judgments and the left/right parieto-temporal areas.

Background Increasing evidence shows that bilingualism or multilingualism may have beneficial effects on preventing dementia. We performed a cross-sectional, community-based study in Taiwan. Some elders (older than 70 years) in Taiwan can speak Japanese because of the formal Japanese education they received before World War II, when Taiwan was under Japanese rule. After the war, Mandarin Chinese was adopted as the official language of Taiwan. We assessed whether constantly using three languages had an effect on dementia prevalence and cognitive function. Methods We defined multilingualism as the ability to fluently speak Taiwanese (T), Japanese (J), and Mandarin Chinese (C) in daily life. We evaluated the Mini-Mental State Examination and AD8 questionnaire results of 514 community-dwelling people older than 70 years in Taishan, Taiwan. Results Seventy-three of the subjects (14.2%) were multilingual (T, J, C) and 441 (85.8%) were bilingual (T, C). No difference was noted in dementia prevalence between multilingual (6.8%) and bilingual (7.4%) populations, but multilinguals were older than bilinguals (mean age: 79.9 vs 77.3 years). Multilinguals had higher Mini-Mental State Examination scores than bilinguals (mean: 24.6 vs. 22.7). However, after the subjects were stratified into low and high education level groups, the Mini-Mental State Examination difference was found to be significant in only the low education level group. Conclusions Dementia prevalence did not significantly differ between the multilingual (T, J, C) and bilingual (T, C) groups. However, given that the average age of the multilingual group was approximately 2 years older than that of the bilingual group, there may have been minor effects in the multilingual group.

Background The Necker cube is usually used for evaluating the visuoconstructional ability of patients with mild cognitive impairment (MCI) and dementia. However, the Necker cube is often considered a drawing with a visual illusionary perspective. The purpose of this study was to investigate whether Necker cube copying could detect participants with MCI due to dementia. Methods We retrospectively analyzed the database of the 1998 prevalence study that was part of the Tajiri Project (n = 599). Pencil drawings of the Necker cube on A4-sized white paper by non-demented people (Clinical Dementia Rating (CDR) 0 and 0.5, n = 256) were classified into two patterns: non-three-dimension (3-D) and 3-D. Two neuropsychologists assessed Necker cube copying according to the criteria of the classification. After the classification, the database of the 2003 incidence study was used according to the subjects’ conversion to dementia. Results In the prevalence study, among those who made a non-3-D drawing of the Necker cube, there were significantly fewer people in the CDR 0 group than in the CDR 0.5 and CDR 1+ groups; similarly, there were significantly fewer people in the CDR 0.5 group than in the CDR 1 + group (χ2 = 32.6, P CDR 0.5 > CDR 1+, P < 0.001). In the incidence study, among those who made a non-3-D drawing of the Necker cube, there were significantly fewer people in the non-converter group than in the converter group (χ2 = 19.9, P < 0.001). However, there was no significant difference between the non-converter group (n = 21) and the converter group (n = 21) when age, sex, educational levels, and Mini-Mental State Examination scores were controlled (χ2 = 0.0, P = 1.000). Conclusions Our results suggested that Necker cube copying may evaluate visual illusion as well as visuoconstructional ability. The Necker cube may not be an appropriate test to detect participants with MCI due to dementia.

Background Dubois et al. proposed the criteria for prodromal Alzheimer's disease (AD) to detect dementia in its very early stage. Because detection requires magnetic resonance imaging and 18F-fluorodeoxyglucose-positron emission tomography (PET), the prevalence and prognosis have not been fully investigated. Methods Our database included 346 healthy participants (Clinical Dementia Rating (CDR) 0), 119 with questionable dementia (CDR 0.5), and 32 dementia participants (CDR 1+) and was applied to investigate the prevalence of prodromal AD. Forty-four CDR 0.5 participants (37%) were randomly selected to undergo 18F-fluorodeoxyglucose-PET. The same percentage was applied to select 128 CDR 0 and 12 CDR 1 + participants (total: n = 184) to calculate the prevalence. A neuroradiologist classified the PET images in a blinded manner based on the criteria of Silverman et al. Participants were considered to have prodromal AD if they exhibited ‘parietal/temporal +/− frontal hypometabolism’ (PET) with hippocampal atrophy (magnetic resonance imaging). Results Eighteen CDR 0.5 participants (40.9%) met the criteria for prodromal AD, which was a prevalence rate of 9.8% among older adults aged ≥65 years. Thirteen prodromal AD participants (72%) converted to AD during the 5-year follow-up period. Discussion The concept and criteria for prodromal AD are useful for predicting which subjects in a community will convert to AD.

Vascular dementia (VaD) is a condition whereby decreased cerebral perfusion causes cognitive deterioration. We hypothesized that lesions of the anterior nucleus (AN) including the mammillo-thalamic tract cause a decline in the recollection of past episodes/events, and that the left thalamic infarction can cause frontal dysfunction through the “diaschisis.” We investigated 18 VaD cases with only left thalamic infarction. 99m Tc-ECD single photon emission computed tomography (SPECT) was used to assess regional cerebral blood flow (CBF). To test the first hypothesis, the scores on the Cognitive Abilities Screening Instrument (CASI) domain Recent memory or the rating on the Clinical Dementia Rating (CDR) domain Memory were analyzed. To test the second hypothesis, we selected the six regions of interest that correlated with the two measures, i.e., word fluency and/or depressive state, as assessed with the Geriatric Depression Scale (GDS). We found that all patients had amnesia, especially in the AN group, six of the eight patients had scores of 1+ on the CDR Memory scale, and all but one disclosed the CASI domain Recent memory impairment. There were significant correlations between the left anterior cingulate CBF and word fluency scores, and between the right rectal gyrus CBF and GDS scores. We suggest that these observations are due to a remote effect of the thalamic lesion.

Increasing evidence shows that bilingualism or multilingualism may have beneficial effects on preventing dementia. We performed a cross-sectional, community-based study in Taiwan. Some elders (older than 70 years) in Taiwan can speak Japanese because of the formal Japanese education they received before World War II, when Taiwan was under Japanese rule. After the war, Mandarin Chinese was adopted as the official language of Taiwan. We assessed whether constantly using three languages had an effect on dementia prevalence and cognitive function.We defined multilingualism as the ability to fluently speak Taiwanese (T), Japanese (J), and Mandarin Chinese (C) in daily life. We evaluated the Mini-Mental State Examination and AD8 questionnaire results of 514 community-dwelling people older than 70 years in Taishan, Taiwan.Seventy-three of the subjects (14.2%) were multilingual (T, J, C) and 441 (85.8%) were bilingual (T, C). No difference was noted in dementia prevalence between multilingual (6.8%) and bilingual (7.4%) populations, but multilinguals were older than bilinguals (mean age: 79.9 vs 77.3 years). Multilinguals had higher Mini-Mental State Examination scores than bilinguals (mean: 24.6 vs. 22.7). However, after the subjects were stratified into low and high education level groups, the Mini-Mental State Examination difference was found to be significant in only the low education level group.Dementia prevalence did not significantly differ between the multilingual (T, J, C) and bilingual (T, C) groups. However, given that the average age of the multilingual group was approximately 2 years older than that of the bilingual group, there may have been minor effects in the multilingual group.

The relationship of predementia stage with cerebrovascular disease (CVD) has not been fully clarified. Following our Prevalence Study 1998 in Tajiri, Japan, Incidence Study 2003 disclosed that 17.9% of subjects developed vascular dementia (VaD). Some cases developed after stroke (type I), whereas others already met the criteria for subcortical VaD (SVD) despite very mild stage (Clinical Dementia Rating [CDR] 0.5) and progressed to mild stage (CDR 1) (type II). We hypothesized that prognosis of vascular mild cognitive impairment (MCI) included type II VaD or death due to causes associated with vascular risk factors. Prevalence Study 1998 included 497 randomly selected participants, including 346 with a CDR of 0, 119 with a CDR of 0.5, and 32 with a CDR of 1+. The first 2 groups were targeted for Incidence Study 2003. Based on the database, we reanalyzed the ratio of SVD in the subjects with CDR 0.5 and VaD, prognosis with or without CVD, and 2 types of VaD onset. The criteria for SVD were achieved by 67% of those with VaD and by 7% of those with vascular MCI (ie, CDR 0.5). In the CDR 0 group, CVD had no affect on prognosis; however, in the CDR 0.5 group, CVD had an affect on death by cardiovascular disease. The majority of subjects in the CDR 0 and CDR 0.5-CVD (-) groups were classified as type I, whereas all subjects in the CDR 0.5-CVD (+) group were type II. Although vascular MCI is treatable, it may progress to death as well as apparent dementia. Individuals with this "buried under the community" phenomenon of SVD should be targeted for secondary prevention interventions.

Aim: The Clinical Dementia Rating (CDR) is an assessment of dementia severity based on observations of activities of daily living, and a CDR of 0.5 (CDR 0.5) represents questionable dementia. A combination of the Cognitive Abilities Screening Instrument (CASI) and the Trail Making Test (TMT) scores discriminated CDR 0.5 subjects from healthy participants with a high degree of accuracy. We investigated the neurological background of CDR 0.5 subjects by correlating CASI and TMT scores with regional cerebral blood flow (rCBF) as measured by single photon emission computed tomography (SPECT). Methods: From a community-based cohort, 22 CDR 0.5 participants were recruited. CASI and TMT scores, rCBF measure using [123I]-N-isopropyl-p-iodoamphetamine and SPECT were obtained. We evaluated the relationships between the CASI domain scores, between TMT scores and rCBF in a regions-of-interest-based analysis, and voxel-based analysis using Statistical Parametric Mapping 5 software. Results: We found that lower rCBF in the left medial temporal cortex correlated with a decreased CASI domain recent memory score both in the regions-of-interest and statistical parametric mapping analysis. In both the regions-of-interest and statistical parametric mapping analysis, the rCBF in the left prefrontal cortex correlated with CASI domain remote memory and mental manipulation and concentration. Conclusions: Our results indicate that some CDR 0.5 subjects have functional impairments in the medial temporal lobe as well as in the prefrontal cortex, as reflected in the cognitive decline measured by CASI and TMT.

Herein we report the case of a 77-year-old, right-handed man, without dementia, who had a cerebral infarction in the left caudate head that manifested recurrent delusional ideas. He experienced three episodes of delusional ideas; the first two occurred after loss of consciousness and the third after delirium at night. MRI findings of left caudate head infarction were the same for all three episodes. An unstable cerebral perfusion may have caused problems in the cerebral network between the caudate head and cerebral cortex. Decreased cerebral blood flow in the frontal lobe was noted particularly in the second and third episodes, supporting the neurological background of disinhibition of emotional behaviour. Antipsychotic drugs and a small dose of risperidone were effective in controlling the patient's delusional ideas.

Aim: To determine whether impaired instrumental activities of daily living affect conversion from mild cognitive impairment to dementia for subjects in a community. Methods: This is a 7-year retrospective study that followed 226 randomly selected participants from the Prevalence Study 1998 in Tajiri in northern Japan who had Clinical Dementia Rating 0.5. Instrumental activities of daily living levels were assessed with a 21-item questionnaire. We analyzed the scores at baseline between the converters to dementia and non-converters. Results: The converters had lower baseline scores on the ‘bed making’ and ‘mode of transportation’ items compared with the non-converters; the former item was significant after a stepwise logistic regression analysis that excluded age and Mini-Mental State Examination effects. In gender analysis, female converters had lower baseline scores on the ‘bed making’ and ‘cleaning’ items. For male participants, no items were found to have such an effect. Conclusions: We suggest that when individuals with mild cognitive impairment are limited in their performance of instrumental activities of daily living, this is predictive of dementia onset.

In 1997 we examined the prevalence of dementia among the Japanese elderly immigrants living in the Sao Paulo metropolitan area ( n = 166). Herein, we followed up on these subjects for causes of death and dementia incidence. We were able to contact 108 subjects: 54 were already dead. The most common cause of death was cardiac disease. For dementia, 31.6% of the dead subjects were found to have developed dementia before they died, and 20.8% of the living subjects were demented. As for the baseline the clinical dementia rating (CDR), 20.8% of CDR 0 and 50.0% of CDR 0.5 subjects developed dementia in the dead group; whereas in the living group, 23.9% of CDR 0 and 52.6% of CDR 0.5 developed dementia. As a whole, the incidence was 34.2‰ per 1000 person-years. Cardiac disease as the most common cause of death was probably due to the higher prevalence of diabetes mellitus. Compared with the previous study, the lower incidence of dementia from the CDR 0.5 group may have been due to a higher mortality rate. This is the first study on the incidence of dementia in elderly Japanese immigrants in Brazil.

This study verifies the environmental effects on agraphia in mild cognitive impairment and dementia. We compared elderly Japanese subjects living in Japan and Brazil. Methods: We retrospectively analyzed the database of the Prevalence Study 1998 in Tajiri (n=497, Miyagi, Japan) and the Prevalence Study 1997 of elderly Japanese immigrants living in Brazil (n=166, migrated from Japan and living in the São Paulo Metropolitan Area). In three Clinical Dementia Rating (CDR) groups, i.e., CDR 0 (healthy), CDR 0.5 (questionable dementia), and CDR 1+ (dementia) , the Mini-Mental State Examination (MMSE) item of spontaneous writing and the Cognitive Abilities Screening Instrument (CASI) domain of dictation were analyzed with regard to the number of Kanji and Kana characters. Formal errors in characters and pragmatic errors were also analyzed. Results: The immigrants in Brazil wrote similar numbers of Kanji or Kana characters compared to the residents of Japan. In spontaneous writing, the formal Kanji errors were greater in the CDR 1+ group of immigrants. In writing from dictation, all the immigrant CDR groups made more formal errors in Kana than the Japan residents. No significant differences in pragmatic errors were detected between the two groups. Conclusions: Subjects living in Japan use Kanji frequently, and thus the form of written characters was simplified, which might be assessed as mild formal errors. In immigrants, the deterioration in Kanji and Kana writing was partly due to decreased daily usage of the characters. Lower levels of education of immigrants might also be related to the number of Kanji errors. Resumo Este estudo verifica os efeitos do meio ambiente sobre a agrafia em comprometimento cognitivo leve e demência. Nós comparamos indivíduos idosos vivendo no Japão e Brasil. Métodos: Nós, retrospectivamente, analisamos a base de dados do Estudo de Prevalência 1998 em Tajiri (n=497, Miyagi, Japão) e do Estudo de Prevalência 1997 de imigrantes idosos japoneses vivendo no Brasil (n=166, imigrados do Japão e residindo na área metropolitana da cidade de São Paulo). Em três grupos de CDR (Clinical Dementia Rating), isto é, CDR 0 (saudáveis), CDR 0.5 (demência questionável) e CDR1+ (demência), o item de escrita espontânea do Mini-Exame do Estado Mental (MEEM) e o domínio de ditado do Cognitive Abilities Screening Instrument (CASI) foram analisados em relação ao número de caracteres em Kanji e Kana. Erros formais nos caracteres e erros pragmáticos foram também analisados. Resultados: Os imigrantes no Brasil escreveram número similar de caracteres de Kanji e Kana comparados aos residentes no Japão. Na escrita espontânea, os erros formais de Kanji foram maiores no grupo de CDR1+ em imigrantes. Na escrita sob ditado, todos os grupos de CDR de imigrantes fizeram mais erros formais em Kana do que os residentes no Japão. Nenhuma diferença foi encontrada em erros pragmáticos entre os grupos. Conclusões: Sujeitos vivendo no Japão usam Kanji freqüentemente, e então, a forma de caracteres escritos foi simplificada, o que pode ser avaliado como discretos erros formais. Em imigrantes, a deterioração na escrita em Kanji e Kana foi parcialmente devida ao uso diário restrito dos caracteres. Baixos níveis educacionais dos imigrantes podem estar relacionados ao número de erros em Kanji.

Effectiveness of donepezil in slowing the rate of cognitive decline in Alzheimer's disease (AD) has been established. Psychosocial interventions, such as reminiscence therapy and art therapy, are also known to have some clinical effects. However, combined effect of donepezil and psychosocial interventions on cerebral glucose metabolism has not been investigated. A case study using (18F) fluorodeoxyglucose and positron emission tomography revealed that cerebral glucose metabolism in the thalamus and fronto-subcortical network was stimulated after the combined intervention. These areas are considered not to be severely affected by pathological changes in AD. The comprehensive approach of donepezil and psychosocial interventions was judged to be effective for AD patients.

The incidence of dementia and risk factors has not been fully investigated in Japan. Following a prevalence study in 1998, we investigated the incidence and associated factors in the same population in 2003 and 2005. Randomly selected 771 residents in Tajiri were targeted. The final participants included 204 (65.2%) healthy older adults (Clinical Dementia Rating, CDR 0) and 335 (73.1%) people with questionable dementia (CDR 0.5). We analyzed the incidence of dementia and dementing diseases, and possible risk factors. The risk factors included demographics, lifestyle-related factors, vascular risk factors, cognitive functions, and MRI findings. Overall, 3.9% of the CDR 0 and 37.0% of the CDR 0.5 participants developed dementia during the 5-year period, whereas 40.2% of the CDR 0.5 participants developed dementia during the 7-year period. Older adults had a higher incidence. Higher CDR Box scores had a higher incidence. Of the dementing diseases, 60.8% of participants developed Alzheimer' disease (AD), followed by vascular dementia (VaD), 17.9%. Logistic regression analyses showed that age, MMSE, cognitive functions such as recent memory, and generalized atrophy were significant predictors of progression to AD. Similarly, predictive factors for progression to VaD were age, MMSE, cognitive functions such as frontal function, and white matter lesions and cerebrovascular diseases. A comprehensive system including CDR, cognitive tests, and MRI, is recommended in community-based health policy planning.

Background We previously demonstrated a positive correlation with nursing home (NH) replacement and donepezil (DNP) administration on lifetime expectancy after the onset of Alzheimer’s disease (AD). However, the correlation with quality-adjusted life-year (QALY) remains to be elucidated, along with the additional impact of concomitant cerebrovascular disease (CVD). Based upon our recently reported health state utility values, we retrospectively analyzed the correlation with NH replacement and/or DNP administration on QALY and life expectancy in ‘pure’ AD (without CVD) and AD with CVD patients. Methods All outpatients at the Tajiri Clinic from 1999–2012 with available medical records and death certificates were included. The entry criteria were a dementia diagnosis (DSM-IV) and diagnoses of pure AD or AD with CVD (NINCDS-ADRDA), medical treatment for more than 3 months, and follow up to less than 1 year before death. The main outcomes were lifetime expectancy (months between the onset of dementia and death) and QALY. Results We identified 390 subjects, of whom 275 had the diagnosis of dementia that met the entry criteria, including 67 pure AD, 33 AD with CVD, and 110 VaD patients. For the AD patients, 52 had taken DNP and 48 had not received the drug due to treatment prior to the introduction of DNP in 1999 in Japan. For the pure AD group, there were positive correlation between NH and DNP and QALY, as well as lifetime expectancy. As for the AD with CVD group, only a correlation between DNP and lifetime expectancy was noted, with no correlation with QALY. Conclusions We found positive correlations between DNP administration and NH replacement and lifetime expectancy and QALY after the onset of AD. However, concomitant CVD negated such a positive correlation with QALY. The findings suggest that QALY in AD is affected by CVD; thus, indicating the importance of CVD prevention.

The Necker cube is usually used for evaluating the visuoconstructional ability of patients with mild cognitive impairment (MCI) and dementia. However, the Necker cube is often considered a drawing with a visual illusionary perspective. The purpose of this study was to investigate whether Necker cube copying could detect participants with MCI due to dementia.We retrospectively analyzed the database of the 1998 prevalence study that was part of the Tajiri Project (n = 599). Pencil drawings of the Necker cube on A4-sized white paper by non-demented people (Clinical Dementia Rating (CDR) 0 and 0.5, n = 256) were classified into two patterns: non-three-dimension (3-D) and 3-D. Two neuropsychologists assessed Necker cube copying according to the criteria of the classification. After the classification, the database of the 2003 incidence study was used according to the subjects' conversion to dementia.In the prevalence study, among those who made a non-3-D drawing of the Necker cube, there were significantly fewer people in the CDR 0 group than in the CDR 0.5 and CDR 1+ groups; similarly, there were significantly fewer people in the CDR 0.5 group than in the CDR 1 + group (χ(2) = 32.6, P0.001; post-hoc tests using χ(2) tests, CDR 0CDR 0.5CDR 1+, P0.001). In the incidence study, among those who made a non-3-D drawing of the Necker cube, there were significantly fewer people in the non-converter group than in the converter group (χ(2) = 19.9, P0.001). However, there was no significant difference between the non-converter group (n = 21) and the converter group (n = 21) when age, sex, educational levels, and Mini-Mental State Examination scores were controlled (χ(2) = 0.0, P = 1.000).Our results suggested that Necker cube copying may evaluate visual illusion as well as visuoconstructional ability. The Necker cube may not be an appropriate test to detect participants with MCI due to dementia.

Background Cholinesterase inhibitors can delay the progression of Alzheimer’s disease (AD). Several clinical trials of the drug in moderate to severe AD have consistently reported clinically positive effects. A combining effect with psychosocial intervention was reported in mild to moderate AD patients. Since a therapeutic approach or rehabilitation combined with cholinesterase inhibitors for severe AD patients remains controversial, we performed a prospective intervention for patients in Long-Term Care Health Facilities (LTCHF). Methods Two LTCHFs (N1, N2) were enrolled. N1 is a 126-bed facility that does not treat with donepezil but rather with psychosocial intervention (reality orientation and reminiscence). N2 is a 150-bed facility with a 50-bed special dementia unit, in which the physician can prescribe donepezil. On top of the similar psychosocial intervention, rehabilitation is performed in N2. Thirty-two severe AD patients (MMSE

Background: Bilingualism is an area of linguistics that has been investigated in aphasic patients. However, bilingualism and Alzheimer's disease (AD) have not been fully investigated despite the fact that language impairment is a frequent symptom of AD. Brazil has the greatest number of Japanese immigrants and, consequently, there are many bilingual people who are fluent in both Japanese and Portuguese in Brazil. Methods: Using the results from a previous epidemiological survey, we found four AD patients who were fluent in both Japanese and Portuguese before developing AD, and performed the following evaluations in both languages: confrontation naming, oral reading ability, vocabulary comprehension (matching words and drawings), written lexical decision and the Western Aphasia Battery (WAB). Results: All patients demonstrated impaired naming ability in both languages. Oral reading ability was most impaired in the case of Kanji, followed by irregular words in Portuguese. The patients could recognize and pronounce Kana perfectly, and regular Portuguese words almost perfectly. In the severest case, the patient showed disturbed lexical comprehension and lexical decision, especially when faced with Kanji. The WAB classified three patients as having anomic aphasia in both languages, whereas in the severest case the patient was classified as having anomic aphasia in Portuguese and Wernicke aphasia in Japanese. Conclusion: These results may reflect different patterns in language deterioration as AD progresses, with Kanji being more readily affected by the disease than Kana and Portuguese. This is the first study to focus on Japanese–Portuguese bilingualism in AD patients.

Background: We previously examined 42 subjects with Clinical Dementia Rating (CDR) 0.5 with FDG-PET and followed them for 5 years (Int Psychogeriatr 2008). Twenty had converted to Alzheimer’s disease (AD). They had a lower baseline glucose metabolism (CMRglc) in the right cingulate, left parietal/temporal gyrus compared. Dubois et al. (Lancet Neurol 2007) proposed the criteria for "prodromal AD" which needs MRI and FDG-PET findings. Our database can provide information on the prevalence of the condition. Methods: A neuroradiologist classified the PET images blindly to the clinical findings based on the Silverman’s criteria (JAMA 2001): progressive patterns (P1, P2, P3) and non-progressive pattern s (N1, N2, N3). Subjects were considered to have prodromal AD if they showed P1 FDG-PET pattern (Parietal/Temporal +/Frontal hypometabolism) together with hippocampal atrophy as assessed with MRI. Their CDR Memory domains were all 0.5 or 1, showing episodic memory impairment, fulfilling the criteria for "prodromal AD." The prevalence and prognosis of the condition were retrospectively analyzed. Results: Seventeen subjects were diagnosed as prodromal AD, indicating 40.5% among the CDR 0.5 population and 25.0% among the total older adults aged 65 years or older. Twelve out of 17 (70.6%) converted to AD during the 5-year follow up period, which was higher than previously reported ratio (J Neurol Sci 2007) from the total CDR 0.5 population (37.0%). Conclusions: The concept and criteria for "prodromal AD" is useful to predict the converters to AD in a community. A comprehensive system including CDR, cognitive tests, MRI and PET, is recommended in community based health policy planning.

Background:Dementia, depressive state, and physical inactivity, are some of the main topics of geriatric medicine. We previously showed the prevalence of dementia in Tajiri, Miyagi Prefecture, Japan. To investigate the environmental effects, first-generation immigrants are one of the best samples. Brazil is the country with the largest number of Japanese immigrants. Objective:To evaluate the effects of environment on dementia, depressive state, and physical activity, the Tajiri subjects and the elderly Japanese emigrants from Miyagi Prefecture to Brazil were compared. Methods:The total elderly population in Tajiri and that the elderly members of the Miyagi Association in the Sao Paulo metropolitan area in Brazil were compared. All data were gathered using a standardized interview covering physical status, cognitive function (Mini-Mental State Examination, MMSE), and depressive state (Self-reported Depressive Scale, SDS). Dementia and depression were diagnosed based on the DSM-IV. Results:Seventy-six percent of the immigrants perceived their health as being excellent or relatively good, whereas only 56% of Tajiri subjects did so. The percentage of subjects with a history of diabetes mellitus, a lifestyle related disease, was 8.4% in Tajiri and 24.2% in Brazil. In spite of similar prevalences of dementia with slightly different MMSE distributions, the two groups had a different SDS distribution; the immigrants showed lower depressive scores. Conclusion:In spite of environmental changes influencing physical activity and diabetes, cognitive function was not apparently affected. Although the immigrants lives were marked with hardship, their depressive scores were unexpectedly lower than Japanese, probably due to their stronger mental activity.

Background We previously showed the prevalence of dementia in the town of Tajiri (Miyagi Prefecture, Japan), and found it to be 8.0%.The first population-based study on dementia in Brazil (Catanduva) disclosed the prevalence as being 7.1%. To evaluate the effects of environment on development of dementia, elderly Japanese immigrants living in Brazil were examined. Brazil is the country with the largest number of Japanese immigrants. Methods All immigrants aged 65 years and over from Miyagi Prefecture, living in the four cities of the Sao Paulo Metropolitan area were targeted (n = 192). We were able to examine 166 subjects (86.5%). The diagnosis of dementia was based on the DSM-IV with the severity assessed by the CDR (clinical dementia rating) scales. The cognitive ability screening instrument (CASI) was used for neuropsychological assessment. Results Thirteen subjects were diagnosed with dementia, CDR 1–3, the prevalence being 7.8%. Older subjects suffered more from dementia, and, paradoxically, the more highly educated subjects also suffered more. All the CASI items, except for long-term memory and visual construction, significantly deteriorated in the CDR 0.5 group compared with the CDR 0 group. Comments The prevalence of dementia was not thought to be affected by environmental factors. A paradoxically higher rate of dementia in the more educated subjects was probably due to the historical problems of the immigrants. Intact CASI item long-term memory in the CDR 0.5 group indicated that suspected dementia patients could maintain this function. This is the first epidemiological study on dementia in elderly Japanese immigrants in Brazil. Copyright © 2001 John Wiley & Sons, Ltd.

Patients with vascular dementia (VaD) are often isolated, withdrawn from society because of negative symptoms and functional disabilities. The aim of this study was to detect factors associated with social withdrawal in patients with VaD. The participants were 36 institutionalized patients with VaD. Social withdrawal was assessed with the social withdrawal of the Multidimensional Observation Scale for Elderly Subjects (MOSES). Possible explanatory variables were the MOSES items depression and self-care, Cognitive Abilities Screening Instrument (CASI), apathy evaluation scale (AES), and Behavioral Pathology in Alzheimer’s Disease Frequency-Weighted Severity Scale (BEHAVE-ADFW). Multiple regression analyses were conducted for two groups: Analysis 1 was performed in all patients (N = 36) and Analysis 2 was performed in the patients with the ability to move by themselves (i.e., independent walking or independent movement with a cane or a wheelchair; n = 28). In Analysis 1, MOSES item social withdrawal was correlated with AES and MOSES item self-care. In Analysis 2, MOSES item social withdrawal was correlated with AES and CASI domain abstraction and judgment. Decreased social activities of VaD were not related to general cognitive function or depression. Disturbed activities of daily living (ADLs) for self-care may involve decreased frontal lobe function, indicating that comprehensive rehabilitation for both ADL and dementia are needed to improve the social activities of patients with VaD.

cerebral blood flow and altered cerebrovascular reactivity (CVR).Methods: To determine changes in cerebral vascular reactivity in adults over 65 with MCI Subcortical Vascular (MCI -VS) and without MCI -VS.Prospective, case-control. DCL-VS was defined for those subjects with memory complaints and objective cognitive impairment, detected by neuropsychological test. Were obtained data and vascular risk factors. Evaluation of cerebrovascular reactivity in middle cerebral arteries to hypercapnia was measured with transcranial Doppler ultrasonography using the breath-holding index (BHI); pulsatility index (PI) was also recorded.Was considered abnormal, an apnea index of 0.8% (p

Herein we report the case of a 77-year-old, right-handed man, without dementia, who had a cerebral infarction in the left caudate head that manifested recurrent delusional ideas. He experienced three episodes of delusional ideas; the first two occurred after loss of consciousness and the third after delirium at night. MRI findings of left caudate head infarction were the same for all three episodes. An unstable cerebral perfusion may have caused problems in the cerebral network between the caudate head and cerebral cortex. Decreased cerebral blood flow in the frontal lobe was noted particularly in the second and third episodes, supporting the neurological background of disinhibition of emotional behaviour. Antipsychotic drugs and a small dose of risperidone were effective in controlling the patient's delusional ideas.

The Clinical Dementia Rating (CDR) is an assessment of dementia severity based on observations of activities of daily living, and a CDR of 0.5 (CDR 0.5) represents questionable dementia. A combination of the Cognitive Abilities Screening Instrument (CASI) and the Trail Making Test (TMT) scores discriminated CDR 0.5 subjects from healthy participants with a high degree of accuracy. We investigated the neurological background of CDR 0.5 subjects by correlating CASI and TMT scores with regional cerebral blood flow (rCBF) as measured by single photon emission computed tomography (SPECT).From a community-based cohort, 22 CDR 0.5 participants were recruited. CASI and TMT scores, rCBF measure using [(123) I]-N-isopropyl-p-iodoamphetamine and SPECT were obtained. We evaluated the relationships between the CASI domain scores, between TMT scores and rCBF in a regions-of-interest-based analysis, and voxel-based analysis using Statistical Parametric Mapping 5 software.We found that lower rCBF in the left medial temporal cortex correlated with a decreased CASI domain recent memory score both in the regions-of-interest and statistical parametric mapping analysis. In both the regions-of-interest and statistical parametric mapping analysis, the rCBF in the left prefrontal cortex correlated with CASI domain remote memory and mental manipulation and concentration.Our results indicate that some CDR 0.5 subjects have functional impairments in the medial temporal lobe as well as in the prefrontal cortex, as reflected in the cognitive decline measured by CASI and TMT.

A group reminiscence approach (GRA) with reality orientation (RO) is widely used as a psychosocial intervention for dementia. Since clinical effectiveness was reported for the intervention, interest has been directed toward areas of the neuronal network that might be being stimulated. We hypothesized that the frontal lobe associated with social interaction was being stimulated. To test this hypothesis, we studied 24 patients with vascular dementia. In addition to conventional care, a 1-h session of GRA with RO was provided once a week for 3 months in the GRA-RO arm ( n =12). Only supportive care was provided in the control arm ( n =12). Before and after the interventions, cognitive function, depressive state, and social activities were assessed. Since glucose metabolism is associated with brain function, cerebral glucose metabolism was measured by positron emission tomography (PET). Regarding behavioral improvement, 10 patients in the GRA-RO arm showed improvement compared with only two patients in the control arm, a significant difference. PET demonstrated that metabolism in the anterior cingulate was increased in the GRA-RO arm, whereas no significant changes were observed in the control arm. These results suggest that GRA-RO stimulates the anterior cingulate and has a positive effect on social interaction.

Our aim was to investigate the relationships between sleep disturbance and activities of daily living (ADL) and 24-h blood pressure patterns in institutionalized dementia patients. Using 107 institutionalized dementia patients (32 males and 75 females, mean age 76.3 years), patients with a mini mental state examination (MMSE) score

Background The neurologic background of confabulations with reference to delusions or cognitive functions has not been clarified in Alzheimer disease (AD). Methods Confabulations of 41 AD patients and 12 healthy controls were studied using the Modified Confabulation Battery. The mini-mental state examination and Cognitive Abilities Screening Instrument were used for cognitive evaluations. Cerebral atrophy was assessed by voxel-based–morphometry of magnetic resonance imaging and the correlations with confabulations were analyzed by statistical parametric mapping 2. For the relations with delusion, the AD patients were divided into the delusion and nondelusion groups. The single photon emission computed tomography was performed to evaluate cerebral blood flow and the group difference was analyzed by statistical nonparametric mapping 3. Results The AD patients exhibited more confabulations on episodic memory questions compared with semantic questions. The semantic confabulation scores correlated with mini-mental state examination and most Cognitive Abilities Screening Instrument domains scores, and correlated with atrophy in the anterior cingulate, bilateral medial temporal, and right middle temporal gyrus. The delusion group exhibited more episodic confabulations and had lower prefrontal blood flow than the nondelusion group. Conclusions Different mechanisms are involved in confabulations between semantic and episodic memories in AD. Episodic confabulation is affected by delusion related to frontal dysfunction, and semantic confabulation is associated with cognitive dysfunction.

Background: The borderline condition between health and dementia, defined as Clinical Dementia Rating (CDR) 0.5, should be detected for the possible prediction of dementia. Since the CDR requires information from collateral sources, it is difficult to rate people living alone. The aim is to develop a set of tests without collateral information for detecting CDR 0.5 and converters to dementia. Methods: 625 participants were selected from the community; 412 were CDR 0 (healthy), 168 were CDR 0.5 (defined here as mild cognitive impairment; MCI), and were 45 CDR 1+ (dementia). Neuropsychological tests were administered to assess memory, orientation, attention and executive function. We analyzed various combinations of tests by receiver operating characteristic curve and area under the curve (AUC). Among the participants, 497 were randomly selected to be re-examined after 5 years to predict further decline towards dementia. Results: We found that a combination of tests for orientation, memory, attention, executive function, and abstraction and judgment could discriminate subjects with MCI from healthy participants with high accuracy (AUC = 0.83). The predictive accuracy was better than that of the Mini Mental State Examination (AUC = 0.77). The same tests, except orientation, could also predict converters to dementia (AUC = 0.88). Conclusions: We consider that a combination of tests can be helpful for the early detection of individuals with MCI and converters to dementia in the community.

Psychiatric symptoms such as delusions and aggression are frequently observed in patients with Alzheimer's disease (AD), but few studies examined the association of these symptoms with confabulations. We studied 32 AD patients and 10 age- and education-matched healthy older adults. The AD patients were divided into delusion/aggression and non-delusion/non-aggression groups based on their behavioral pathology in AD frequency-weighted severity scale score. Confabulations were assessed using questions about temporality (personal past, orientation, and future planning), and cognitive functions were determined using the mini-mental state examination and the cognitive abilities screening instrument. The AD patients showed confabulations on all types of questions, and their confabulation scores for the past and future were strongly correlated. Cognitive functions were not significantly correlated with confabulation scores for any type of questions. The delusion/aggression group had significantly more confabulations on past and future questions compared to the non-delusion/non-aggression group. These findings suggested that confabulations in remembering the past and planning the future were affected by psychiatric symptoms such as delusion and aggression.

To assess the possible neurological basis of behavioral and psychological symptoms of dementia (BPSD), the relationships between BPSD and cognitive function were evaluated in 40 patients with Alzheimer's disease (AD). BPSD was assessed using the Behavioral Pathology in Alzheimer's Disease Frequency Weighted Severity Scale (BEHAVE-AD-FW) for behavioral symptoms and psychological symptoms separately, and cognitive function was also assessed using the Cognitive Abilities Screening Instrument (CASI). We found that only behavioral symptoms were associated with cognitive function based on the CASI total score and the score for the CASI attention domain. Administration of risperidone, an atypical anti-psychotic drug, for one month, improved the behavioral symptoms and the scores for the CASI attention and orientation domains. Our data suggest that BPSD in AD may reflect two largely independent pathophysiological processes: one associated with behavioral symptoms partly overlapping with attention, and the other associated with psychological symptoms predominantly unrelated to cognitive function.

We have previously evaluated the beneficial effect of the group reminiscence approach (GRA) in patients with vascular dementia (VaD) in respect of cognitive and observed behavioral parameters [1] . Sixty patients who had been diagnosed with VaD were randomly assigned to three arms: a GRA arm, a social contact (SC) arm, and a control arm. A 1-hour session of GRA and SC was held once a week for 3 months with the GRA and SC arms, respectively. Only supportive care was given to those in the control arm. An improvement in cognitive function and behavioral activities was defined as the primary outcome. However, we found that no significant improvements in the main outcome measures had been demonstrated and concluded that these results did not support the hypothesis that GRA is beneficial to patients with VaD. As reported, the dropout ratio was higher in the SC arm (9/20 = 45%) compared with the GRA arm (3/20 = 15%) or the control arm (3/20 = 15%). The participants in the SC arm told us that they had found that the intervention was very boring. In the case of the SC arm, the group was asked during a 50-min session to talk about social issues such as ‘health and disease management’ or ‘hot topics from today’s newspaper’, etc., as well as interests in daily life such as ‘recreational activities in their facilities’ or ‘meals served in their facilities’, etc. The discourse of older adults easily moved to their memories of the past as was the case in the GRA arm, whereas when their talk was blocked off by presenting social topics, participants in the SC arm appeared to be bored. Having assessed emotional ratings in the GRA and SC arms, we could proceed to a secondary analysis. We had assessed 5 ratings: ‘very enjoyable’, ‘enjoyable’, ‘normal’, ‘boring’, and ‘very boring’. In the GRA arm, 13/17 (=76%) answered ‘very enjoyable’ or ‘enjoyable’, whereas in the SC arm, 3/11 (=27%) answered in this way. We thus operationally classified them into two groups: the ‘enjoyable’ group (n = 16, i.e., 13 in the GRA arm plus 3 in the SC Published online: February 28, 2013 E X T R A

The borderline zone condition between normal aging and dementia is a major issue of concern. Although the term mild cognitive impairment (MCI) is popular, its prevalence and neuropsychological features have not been fully investigated. We investigated the prevalence and neuropsychological features for Clinical Dementia Rating (CDR) 0.5 and MCI. For normal aging, the effects of age and educational level on cognitive performance were examined. We examined 1501 older residents (46.8%) in Tajiri 65 years of age and older. They performed the Cognitive Abilities Screening Instrument (CASI). Depressive scores and subjective memory complaints were also evaluated. There was no age effect but an educational effect on cognitive performance in healthy adults. We found the overall prevalence of CDR 0.5 to be 30.2%, whereas that of MCI was only 4.9%. All CASI domains were deteriorated except for long-term memory and visual construction in the CDR 0.5 participants compared with healthy adults, suggesting that CDR 0.5 is similar to very mild Alzheimer disease. Memory complaints' data suggested that it would be better to exclude memory complaints from the MCI criteria. We considered that the concept of CDR 0.5 would be more applicable to community residents rather than that of the MCI.

Behavioral and psychological symptoms of dementia (BPSD), especially aggressiveness, wandering, and sleep disturbance, are a major burden for caregivers. Daily sleep/wake patterns and wandering of institutionalized patients with Alzheimer’s disease (AD) were visually monitored, and 34 patients who manifested wandering were selected and randomly classified into 2 groups: the risperidone group and the nonrisperidone group. After an administration of low-dose risperidone for the risperidone group, the BPSD were reassessed. The binding potentials of dopamine D2 receptor for preadministration and postadministration of risperidone were assessed using positron emission tomography (PET) for 1 case. After the use of risperidone, aggressiveness and wandering were reduced and the nighttime sleeping hours were increased. The PET revealed that the binding potential of dopamine receptor was increased after administration of the drug, associated with improved sleep/wake patterns and behavioral abnormality. Possible serotonergic modulation of dopaminergic function might explain the neurobiological basis of the effect of risperidone.