Cognition, function, and prevalent dementia in centenarians and near-centenarians: An individual participant data (IPD) meta-analysis of 18 studies.

INTRODUCTION: There are limited data on prevalence of dementia in centenarians and near-centenarians (C/NC), its determinants, and whether the risk of dementia continues to rise beyond 100. METHODS: Participant-level data were obtained from 18 community-based studies (N = 4427) in 11 countries that included individuals ≥95 years. A harmonization protocol was applied to cognitive and functional impairments, and a meta-analysis was performed. RESULTS: The mean age was 98.3 years (SD = 2.67); 79% were women. After adjusting for age, sex, and education, dementia prevalence was 53.2% in women and 45.5% in men, with risk continuing to increase with age. Education (OR 0.95;0.92-0.98) was protective, as was hypertension (odds ratio [OR] 0.51;0.35-0.74) in five studies. Dementia was not associated with diabetes, vision and hearing impairments, smoking, and body mass index (BMI). DISCUSSION: Among the exceptional old, dementia prevalence remains higher in the older participants. Education was protective against dementia, but other factors for dementia-free survival in C/NC remain to be understood.

Mental and Physical Self-Awareness of Alzheimer Patients: Decreased Awareness of Amnesia and Increased Fear of Falling Compared to Views of Families: The Tajiri and Wakuya Projects.

INTRODUCTION: The purpose of this study is to examine self-awareness of patients with Alzheimer disease (AD) regarding forgetfulness and physical status, with the goal of further psychological understanding of these patients. METHODS: The 255 subjects included 33 healthy volunteers and 48 patients with mild cognitive impairment who were elderly community residents selected from the 2017 Wakuya Project and 174 consecutive outpatients with AD at the Tajiri Clinic. Test data were selected from a pooled database. Results from the Mini-Mental State Examination, Clinical Dementia Rating (CDR), Short Falls Efficacy Scale International (FES), and Everyday Memory Checklist (EMC) were used in the study. FES and EMC data were also obtained from family members for comparison. RESULTS: EMC scores in the AD groups (mild to moderate and moderate to severe) were significantly higher (more complaining memory impairment) than those in the CDR 0 (healthy) group and significantly lower (less self-awareness for memory impairment) than the corresponding EMC scores of families of the subjects. In contrast, FES scores of the AD groups did not differ significantly from those of the CDR 0 group, and these scores were higher (more fear of falling) than those of family members. Additionally, family-FES scores of the AD groups were higher than those of the CDR 0 and 0.5 groups. CONCLUSION: The results showed an evidence of the heterogeneity of awareness, an emotional response (concern or fear, FES), and a cognitive appraisal of function (EMC). These may be explained whereby awareness of/fear of falling increases with AD due to a preserved emotional awareness, whereas awareness of cognitive impairment is impaired due to memory deficits.

Does parity matter in women's risk of dementia? A COSMIC collaboration cohort study.

BACKGROUND: Dementia shows sex difference in its epidemiology. Childbirth, a distinctive experience of women, is associated with the risk for various diseases. However, its association with the risk of dementia in women has rarely been studied. METHODS: We harmonized and pooled baseline data from 11 population-based cohorts from 11 countries over 3 continents, including 14,792 women aged 60 years or older. We investigated the association between parity and the risk of dementia using logistic regression models that adjusted for age, educational level, hypertension, diabetes mellitus, and cohort, with additional analyses by region and dementia subtype. RESULTS: Across all cohorts, grand multiparous (5 or more childbirths) women had a 47% greater risk of dementia than primiparous (1 childbirth) women (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.10-1.94), while nulliparous (no childbirth) women and women with 2 to 4 childbirths showed a comparable dementia risk to primiparous women. However, there were differences associated with region and dementia subtype. Compared to women with 1 to 4 childbirths, grand multiparous women showed a higher risk of dementia in Europe (OR = 2.99, 95% CI = 1.38-6.47) and Latin America (OR = 1.49, 95% CI = 1.04-2.12), while nulliparous women showed a higher dementia risk in Asia (OR = 2.15, 95% CI = 1.33-3.47). Grand multiparity was associated with 6.9-fold higher risk of vascular dementia in Europe (OR = 6.86, 95% CI = 1.81-26.08), whereas nulliparity was associated with a higher risk of Alzheimer disease (OR = 1.91, 95% CI 1.07-3.39) and non-Alzheimer non-vascular dementia (OR = 3.47, 95% CI = 1.44-8.35) in Asia. CONCLUSION: Parity is associated with women's risk of dementia, though this is not uniform across regions and dementia subtypes.

Alzheimer's deterioration in intellectual and neurobiological staging supports the retrogenesis model: a double dissociation between verbal/non-verbal judgments and the left/right parieto-temporal glucose metabolism. A retrospective data analysis from the Tajiri Project.

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.

Can dementia patients live in a community? A case of a patient in trouble with the law.

We experienced a case involving a 67-year-old man with Alzheimer's disease who exhibited criminal behaviour. Although his behaviour improved after admission to a long-term care facility, he was not able to return to his home because he was suspected of theft. At 62 years of age, he developed slowly progressive memory loss and had difficulty managing money. He was diagnosed with Alzheimer's disease and began taking galantamine. He was placed in police custody after he had tried to take another person's fuel tank early one morning. However, he was not charged with theft because he did not remember his actions. Because it was difficult for his sister to constantly monitor him, he was admitted to a long-term care facility. He displayed high emotional insecurity and continually asked when he could return home. His physical function was good, enabling him to perform various activities alone, but he experienced the delusion of theft during these activities. He appealed the decision prohibiting him from going home. However, the staff suggested that he would exhibit problematic behaviours at home, and it was decided that he should not live at home. After living at the long-term care facility for 3 years, he died of acute cardiac infarction. When a person goes to jail for committing a crime, that person can return to society after completing a jail term. That was not the case with this man with Alzheimer's disease. As such, guidelines and standards to evaluate the criminal responsibility of dementia patients need to be established.

Language background in early life may be related to neuropsychiatry symptoms in patients with Alzheimer disease.

BACKGROUND: The relationship between early life experience and the occurrence of neuropsychiatry symptoms (NPSs) in patients with Alzheimer disease (AD) is unclear. METHODS: From 2012 to 2014, we prospectively recruited 250 patients with probable AD from the memory clinic of Taipei Veterans General Hospital. All patients underwent standard assessments, including brain magnetic resonance imaging or computed tomography, neuropsychological tests, neuropsychiatry inventory (NPI-Q) and related blood tests. A linear regression analysis was performed to investigate the relationship between NPSs and age, gender, disease severity, depression, language background (with or without Japanese education). RESULTS: Among the 250 participants, 113 (45.2%) were women. Their average age was 82.6 years. Of all the participants, 93 (37.2%) had received formal Japanese education, whereas 157 (62.8%) did not receive Japanese education. The participants with Japanese education were slightly younger (83.1 ± 3.6 vs. 81.4 ± 3.4, P = 0.006), with a higher proportion of them were women (30.5% vs. 69.8%, P < 0.001) and fewer years of total education (10.8 ± 4.5 vs. 7.7 ± 3.2, P < 0.001), compared to the participants without Japanese education. NPI-Q scores significantly differed between the two groups (15.8 vs. 24.1, P = 0.024). Both disease severity and language background predicted NPI-Q scores. CONCLUSIONS: Language background in early life may be related to NPSs in patients with AD, and this effect is more significant in patients with a lower education level than in those with a higher education level. More NPSs may be the result of negative effects on dominant language or early life experiences.

Speaking one more language in early life has only minor effects on cognition in Taiwanese with low education level: the Taishan Project.

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.

Impact of Alzheimer's Disease in Nine Asian Countries.

BACKGROUND: Asia will soon have the majority of demented patients in the world. OBJECTIVE: To assess dementia using a uniform data system to update the current status of dementia in Asia. METHODS: A uniformed data set was administered in Taiwan, China, Hong Kong, Korea, Japan, Philippines, Thailand, Singapore, and Indonesia to gather data with regard to Alzheimer's disease (AD) and its related issues for these countries. RESULTS: In total, 2,370 AD patients and their caregivers were recruited from 2011 to 2014. The demographic characteristics of these patients and the relationships between patients and caregivers were different among individuals in these countries (p < 0.001). Of note, the family history for having dementia was 8.2% for females in contrast to 3.2% for males. CONCLUSION: Our study highlighted the differences in dementia assessment and care in developing versus developed countries. Greater effort with regard to studying dementia, especially in developing countries, is necessary.

Singing can improve speech function in aphasics associated with intact right basal ganglia and preserve right temporal glucose metabolism: Implications for singing therapy indication.

Clinically, we know that some aphasic patients can sing well despite their speech disturbances. Herein, we report 10 patients with non-fluent aphasia, of which half of the patients improved their speech function after singing training. We studied ten patients with non-fluent aphasia complaining of difficulty finding words. All had lesions in the left basal ganglia or temporal lobe. They selected the melodies they knew well, but which they could not sing. We made a new lyric with a familiar melody using words they could not name. The singing training using these new lyrics was performed for 30 minutes once a week for 10 weeks. Before and after the training, their speech functions were assessed by language tests. At baseline, 6 of them received positron emission tomography to evaluate glucose metabolism. Five patients exhibited improvements after intervention; all but one exhibited intact right basal ganglia and left temporal lobes, but all exhibited left basal ganglia lesions. Among them, three subjects exhibited preserved glucose metabolism in the right temporal lobe. We considered that patients who exhibit intact right basal ganglia and left temporal lobes, together with preserved right hemispheric glucose metabolism, might be an indication of the effectiveness of singing therapy.

Necker cube copying may not be appropriate as an examination of dementia: reanalysis from the Tajiri Project.

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 (χ(2) = 32.6, P < 0.001; post-hoc tests using χ(2) tests, CDR 0 > 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 (χ(2) = 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 (χ(2) = 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.

Prevalence and prognosis of prodromal Alzheimer's disease as assessed by magnetic resonance imaging and 18F-fluorodeoxyglucose-positron emission tomography in a community: reanalysis from the Osaki-Tajiri Project.

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 (18) F-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 (18) F-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.

Disturbed social recognition and impaired risk judgement in older residents with mild cognitive impairment after the Great East Japan Earthquake of 2011: the Tome Project.

AIM: After the Great East Japan Earthquake of 2011, we investigated the safety of residents in the affected communities. Most of the people requiring help were elderly and had previously been assessed as Clinical Dementia Rating (CDR) 0.5 (i.e. as having mild cognitive impairment (MCI)). We examined how well they understood the television news and whether they could make appropriate decisions. METHODS: This community-based study of dementia and difficulties following a disaster started in Tome, northern Japan. The subjects were 188 randomly selected older residents who underwent CDR, blood tests, magnetic resonance imaging, and cognitive tests, including an original visual risk cognition task. They were shown NHK news broadcasts from the day of the earthquake to determine whether they could understand the content. RESULTS: Neither the CDR 0 (healthy) nor the CDR 0.5 (MCI) subjects fully understood the television news. Some subjects did not recognize the danger of aftershocks and engaged in risky behaviour. CDR 0.5 subjects who exhibited such behaviour scored lower on the visual risk cognition task. CONCLUSIONS: It is noteworthy that television news is difficult to understand, even for healthy older adults. We found that MCI subjects had particular difficulties due to the disaster and suggest that risk cognition could be evaluated using visually presented materials.

Lifetime expectancy and quality-adjusted life-year in Alzheimer's disease with and without cerebrovascular disease: effects of nursing home replacement and donepezil administration--a retrospective analysis in the Tajiri Project.

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.

Alzheimer's disease patients institutionalized in group homes run by long-term care insurance exhibit fewer symptoms of behavioural problems as evaluated by the Behavioural Pathology in Alzheimer's Disease Rating Scale.

BACKGROUND: The behavioural and psychological symptoms of dementia (BPSD) caused by Alzheimer's disease (AD) can burden caregivers. Group homes (GH), small nursing homes, for the elderly with dementia are institutions commonly run by the public long-term care insurance system in Japan. The purpose of this study was to compare the prevalence of BPSD of AD, as evaluated by the Behavioural Pathology in Alzheimer's Disease Rating Scale, between GH patients and community residents. METHODS: A total of 74 patients with AD were enrolled: 37 were patients institutionalized in GH (Hachinski score < 5) and 37 were demographic-matched community residents undergoing treatment at the Osaki-Tajiri SKIP Center. There were no significant differences in mean age (81.4 vs 81.1 years, P = 0.816), mean educational level (7.7 vs 8.0 years, P = 0.497), sex (women/men: 30/7 vs 30/7, P = 1.000) and mean Mini-Mental State Examination scores (14.1 vs 14.1, P = 0.950) between the two groups. Care level (range: 0.5-5.0, slight to bedridden), activities of daily living care level (range: 1-7, almost normal to severe), and the presence or absence BPSD based on the domains of the Behavioural Pathology in Alzheimer's Disease Rating Scale were compared. RESULTS: GH patients had a significantly higher care level (P < 0.05) and activities of daily living care level (P < 0.05) but had fewer symptoms of BPSD (P < 0.05) than community residents. When the activities of daily living care level was controlled, GH patients had significantly fewer symptoms than community residents in Aggressiveness (21% vs 50%; χ2 = 4.5, P = 0.035), Affective disturbances (13% vs 42%; χ2 = 5.1, P = 0.023), and Anxieties and phobias (4% vs 46%; χ2 = 11.1, P = 0.001). CONCLUSIONS: GH run by the long-term care insurance system appear to be effective in improving environmental factors for moderate AD patients and reducing Aggressiveness, Affective disturbances, and Anxieties and phobias.

[Reliability and validity of the Japanese version of the AD8].

AIM: The AD8 is a brief, sensitive informant interview tool for detecting dementia. However, there are no reports of a Japanese version of the AD8. Our aim was to establish the reliability and validity of the AD8 for screening for dementia in older adults 75 years of age or older in Japan. METHODS: We acquired the author's permission to translate the AD8 from English to Japanese. A total of 572 community residents 75 years of age or older living in Kurihara, Northern Japan agreed to participate in this study. Of these participants, 214 scored a Clinical Dementia Rating (CDR) of 0 (healthy), 289 scored a CDR of 0.5 (mild cognitive impairment) and 69 scored a CDR of 1 or above (dementia). Analysis 1. Reliability of the Japanese version of the AD8. Analysis 2. Validity of the AD8: Receiver operating characteristic (ROC) curve for nondemented (CDR 0+0.5) vs. demented (CDR 1 or above) individuals. RESULTS: For the Japanese version of the AD8, the Cronbach' s coefficient alpha was 0.88 and the Guttman's split half method coefficient was 0.85. For the patients with CDR values of 0+0.5 vs. 1 or above, the area under the ROC curve was 0.89 (p<0.0001) and the cut-off score was 1/2, with a sensitivity of 88.4% and specificity of 68.4%. CONCLUSIONS: We established the reliability and validity of the Japanese version of the AD8 for screening for dementia in older adults 75 years of age or older in the community.

'Residence is not home' is a particular type of delusion associated with cognitive decline of Alzheimer's disease.

BACKGROUND: Although delusion is one of the common symptoms of Alzheimer's disease (AD), the association between cognitive deficits and delusions remains unclear. Considering the heterogeneity of delusion, the correlation may depend upon the type of the delusion. METHODS: 142 consecutive first-visit AD outpatients of the Tajiri Clinic (Osaki, Miyagi, Japan) were enrolled in the study. Psychological data included the Mini-Mental State Examination (MMSE), the Cognitive Abilities Screening Instrument (CASI) and the Frequency-Weighted Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD-FW). Correlations to cognitive deficits for each category of delusional content were evaluated. RESULTS: More severe delusion of 'residence is not home' was significantly correlated with a lower total MMSE score and poorer orientation as assessed with the CASI. This type of delusion also correlated to activity disturbances and was weakly associated with affective disturbances. CONCLUSION: Our findings suggest that the 'residence is not home' delusion is a particular symptom that has a cognitive background, particularly disorientation, and should be discriminated from other delusional phenomena. We should cope with delusions specifying what types of delusions are present since the content of delusions may critically mark the symptomatology of AD. For this purpose, the BEHAVE-AD-FW may be suitable.

Donepezil can improve daily activities and promote rehabilitation for severe Alzheimer's patients in long-term care health facilities.

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 < 6) in N1 and N2 (16 vs. 16) were compared for the effect of donepezil (10 mg/d for 3 months) with or without psychosocial intervention (n = 8 vs. 8 for each facility). The Vitality Index was used to assess daily activities and the introduction of rehabilitation. RESULTS: The response ratio (MMSE 3+) of donepezil was 37.5% in N2. The combination of donepezil with the psychosocial intervention improved the Vitality Index total score, and Communication, Eating, and Rehabilitation subscores (Wilcoxon, p = 0.016, 0.038, 0.023, and 0.011, respectively). Most of them were smoothly introduced to rehabilitation, and the proportion of accidental falls decreased. Psychosocial intervention in N1 without the drug only improved the total score (Wilcoxon, p = 0.046). CONCLUSIONS: A combined therapeutic approach of donepezil and psychosocial intervention can have a positive effect, even for severe patients through the introduction of rehabilitation and decreasing accidental falls. However, these findings require replication in a larger cohort.