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Background This study aimed to develop and validate the Dementia Caregiver Positive Feeling Scale 21‐item version (DCPFS‐21) in Japan. Methods We selected and generated 27 items based on the preliminary 25‐item version of the DCPFS. Next, the DCPFS‐21 was developed and validated through two phases. In Phase 1, we obtained data from 147 caregivers of people with dementia by using the 27‐item version, examined the construct validity and internal consistency of the scale and then selected 21 items (DCPFS‐21). In Phase 2, we compared the scores of 30 caregivers of people with dementia on the DCPFS‐21 with the standard scales. Four weeks after the first examination, we re‐examined the intra‐rater reliability. Results In Phase 1, via factor analysis, we reduced the 27 items to 21 items (DCPFS‐21). Moreover, the DCPFS‐21 was grouped into four subscales, namely, meaning in caregiving, caregiving mastery, positive emotion on caregiving and support from others. This classification agreed with the following factors extracted from the pilot study. The DCPFS‐21 showed good internal consistency (Cronbach's α = 0.92). In Phase 2, the DCPFS‐21 correlated with the Caregiving Gratification Scale by 0.54 (P

Background The aim of this study was to assess the effects of group-based motor and cognitive-combined intervention on social activity and quality of life. Methods This quasi-randomised controlled trial included 31 elderly participants with dementia in a geriatric health service facility. Participants were randomly allocated to the intervention group (n = 16) or the control group (n = 15) by stratification of cognitive function. The 8-week intervention program consisted of group exercise and cognitive stimulation twice per week for 45 min per session. Outcome measures were social activity in daily behaviour, cognitive function, apathy, muscle and grip strength, independence of activity of daily living, life-space, and objective quality of life (QOL). Results Twenty-five participants were analysed (10 in the control group, 15 in the intervention group). Analysis of covariance with covariates of age, gender, and baseline data showed a significant difference in social activity (F = 8.67, P = 0.008; significant decline in control group vs. maintenance in intervention group) and QOL (F = 9.74, P = 0.006; maintenance in control group vs. tendency of improvement in intervention group). A Wilcoxon signed-rank test revealed that helping behaviour (P = 0.035) increased in the intervention group, whereas interest to the surrounding (P = 0.026) decreased in the control group. Conclusions Group-based combined intervention for dementia is effective for maintaining social activity and QOL in a geriatric health service facility.

Amyloid β-proteins (Aβs) Aβ1-42 and Aβ1-43 are converted via two product lines of γ-secretase to Aβ1-38 and Aβ1-40. This parallel stepwise processing model of γ-secretase predicts that Aβ1-42 and Aβ1-43, and Aβ1-38 and Aβ1-40 are proportional to each other, respectively. To obtain further insight into the mechanisms of parenchymal Aβ deposition, these four Aβ species were quantified in insoluble fractions of human brains (Brodmann areas 9 to 11) at various Braak senile plaque (SP) stages, using specific enzyme-linked immunosorbent assays. With advancing SP stages, the amounts of deposited Aβ1-43 in the brain increased proportionally to those of Aβ1-42. Similarly, the amounts of deposited Aβ1-38 correlated with those of Aβ1-40. Surprisingly, the ratios of deposited Aβ1-38/Aβ1-42 and Aβ1-40/Aβ1-43 were proportional and discriminated the Braak SP stages accurately. This result indicates that the generation of Aβ1-38 and Aβ1-40 decreased and the generation of Aβ1-42 and Aβ1-43 increased with advancing SP stages. Thus, Aβs deposition might depend on γ-secretase activity, as it does in the cerebrospinal fluid. Here, the extracted γ-secretase from Alzheimer disease brains generates an amount of Aβ1-42 and Aβ1-43 compared with cognitively normal brains. This refractory γ-secretase localized in detergent-solubilized fractions from brain cortices. But activity modulated γ-secretase, which decreases Aβ1-42 and Aβ1-43 in the cerebrospinal fluid, localized in detergent-insoluble fractions. These drastic alterations reflect Aβ situation in Alzheimer disease brains.

Background: End-of-life care quality should ideally be evaluated by patients themselves. However, patients suffer clinical symptoms and conspicuous cognitive and physical decline in end-stage dementia. Therefore, family members and nurses are often good proxies for evaluating patients’ satisfaction with end-of-life care and symptoms in end-stage dementia. The End-of-Life in Dementia scales, originally written in English, were specifically designed to examine the quality of end-of-life care for persons with dementia. This study aimed to develop a Japanese version of the End-of-Life in Dementia scales and evaluate its validity and reliability in Japan.Methods: The Japanese version of the End-of-Life in Dementia scales (EOLD-J) was created by translating the following original scale measurements: Satisfaction with Care (SWC-EOLD-J), Symptom Management (SM-EOLD-J), and Comfort Assessment in Dying with dementia (CAD-EOLD-J). Participants were 113 family members of deceased residents who received end-of-life care and died at 33 participating nursing homes, and 113 nurses who provided care to the residents. Participants were asked to recall the residents’ last months and respond using the designated scales. The reliability of the scales was evaluated using a Cronbach’s alpha. The construct validity of the relationships between the SWC-EOLD-J scores and the Japanese Decision Regret Scale (DRS-J), the SM-EOLD-J and the short version of Quality of Life Questionnaire for Dementia (short QOL-D), and the CAD-EOLD-J and the short QOL-D were evaluated using Spearman’s rank correlation coefficient. The short QOL-D is composed of positive and negative dimensions.Results: Responses from 83 deceased residents’ family members, and 62 nurses were analyzed. The Cronbach’s alphas of the SWC-EOLD-J was 0.77, the SM-EOLD-J was 0.60, and the CAD-EOLD-J was 0.88. The SWC-EOLD-J score was significantly correlated with DRS-J (γ＝0.504, p < 0.001). The SM-EOLD-J score was significantly correlated with subscale of the short QOL-D: negative dimension ( γ＝0.587, p < 0.001), the CAD-EOLD-J score was significantly correlated with subscale of the short QOL-D: negative dimension (γ＝0.509, p < 0.001). Conclusions: This study developed the EOLD-J and confirmed the reliability and validity of this scale.

Background: Music therapy (MT) may exert beneficial preventive effects in frail elderly individuals in psychophysiological health. Objectives: One hundred and fifteen frail elderly individuals (65–89 years old) participated. Methods: Subjects were randomly divided into 2 groups for a controlled crossover trial. The MT-first group participated in group sessions of 45–50 min conducted by a certified music therapist for 12 weeks, followed by a 12-week waiting period. The waiting-first group participated in the reverse order. Cognitive function was assessed by the Verbal Fluency Test (VFT) and Yamaguchi Kanji Symbol Substitution Test (YKSST). Physical function was assessed by the Timed Up and Go test (TUG). Psychophysical health was assessed by the Geriatric Depression Scale 15-item version (GDS-15), General Health Questionnaire 12-item version (GHQ-12), Instrumental Activity of Daily Living (IADL) scale, and Life Space Assessment (LSA) scale. We also evaluated the outcome of MT using the Clinical Global Impressions of Improvement (CGI-I) scale. Results: After 12 weeks of MT, significant improvements were observed in TUG, GDS-15, and GHQ-12 scores. However, no improvements were noted in other scores. CGI-I scores revealed the significant benefits of MT. Conclusions: MT may improve physical function, depressive mood, and quality of life in frail elderly individuals.

Lobar cerebral microbleeds (CMBs) in Alzheimer's disease (AD) are associated with cerebral amyloid angiopathy (CAA) due to vascular amyloid beta (Aβ) deposits. However, the relationship between lobar CMBs and clinical subtypes of AD remains unknown. Here, we enrolled patients with early- and late-onset amnestic dominant AD, logopenic variant of primary progressive aphasia (lvPPA) and posterior cortical atrophy (PCA) who were compatible with the AD criteria. We then examined the levels of cerebrospinal fluid (CSF) biomarkers [Aβ1-42, Aβ1-40, Aβ1-38, phosphorylated tau 181 (P-Tau), total tau (T-Tau), neurofilament light chain (NFL), and chitinase 3-like 1 protein (YKL-40)], analyzed the number and localization of CMBs, and measured the cerebral blood flow (CBF) volume by 99mTc-ethyl cysteinate dimer single photon emission computerized tomography (99mTc ECD-SPECT), as well as the mean cortical standard uptake value ratio by 11C-labeled Pittsburgh Compound B-positron emission tomography (11C PiB-PET). Lobar CMBs in lvPPA were distributed in the temporal, frontal, and parietal lobes with the left side predominance, while the CBF volume in lvPPA significantly decreased in the left temporal area, where the number of lobar CMBs and the CBF volumes showed a significant inversely correlation. The CSF levels of NFL in lvPPA were significantly higher compared to the other AD subtypes and non-demented subjects. The numbers of lobar CMBs significantly increased the CSF levels of NFL in the total AD patients, additionally, among AD subtypes, the CSF levels of NFL in lvPPA predominantly were higher by increasing number of lobar CMBs. On the other hand, the CSF levels of Aβ1-38, Aβ1-40, Aβ1-42, P-Tau, and T-Tau were lower by increasing number of lobar CMBs in the total AD patients. These findings may suggest that aberrant brain hypoperfusion in lvPPA was derived from the brain atrophy due to neurodegeneration, and possibly may involve the aberrant microcirculation causing by lobar CMBs and cerebrovascular injuries, with the left side dominance, consequently leading to a clinical phenotype of logopenic variant.

The goal of dementia treatment is to improve the quality of life for both people with dementia and their families. Rehabilitation as a non-pharmacological approach, coordinated with pharmacological treatment, aims to allow patients to live better by slowing the progression, and relieving the behavioral and psychological symptoms of dementia. In dementia, the manifestation of symptoms caused by neurological impairment is modified by various factors; thus, multidimensional assessment and approaches are effective based on the concept of the International Classification of Functioning, which emphasizes the healthy components of every person's functioning. Regarding the process of rehabilitation, every person with dementia should take initiative throughout the course of rehabilitation, and shared decision-making is a fundamental requirement at every phase of intervention. The needs of rehabilitation differ depending on the stage of dementia. In the early stages, cognitive rehabilitation is needed, and interventions are carried out using preserved functions and compensatory strategies. As the disease progresses, capacities of instrumental and then basic activities of daily living deteriorate, and interventions need to be tailor-made and carried out in the context of actual living situations. In the early-to-moderate stages, prevention and management of behavioral and psychological symptoms of dementia are required. In the interventions to alleviate behavioral and psychological symptoms of dementia, it is critical to consider the individual and the meaning behind his/her behaviors from a holistic perspective. Family carers also need support, and education to learn coping strategies can be beneficial for both people with dementia and their carers. Rehabilitation can empower people with dementia and their families to live better with dementia. Geriatr Gerontol Int 2018; 18: 1529-1536.

Background A rapidly aging society needs effective approaches to support frail older people who have a high risk of requiring long‐term care. We investigated the validity of the Basic Checklist (the “Kihon Checklist”) as a tool to select candidates for a program to prevent long‐term care. Method A survey with questions from the Basic Checklist was conducted with functionally independent older residents aged ≥65 years living in Takasaki City, Japan. Subjects who completed the questionnaire were followed over 3 years for the presence or absence of certification for long‐term care requirement. We used multiple logistic regression analysis to calculate the odds ratio (OR) and 95% confidence interval (95%CI) for long‐term care requirement certification. Results A total of 21 325 subjects were analyzed. The odds ratio was the highest when items number one‐20 had a total of ≥10 checked answers (OR, 2.71; 95%CI, 2.22‐3.32). Physical function (OR, 2.29; 95%CI, 2.05‐2.55), nutritional condition (OR, 1.85; 95%CI, 1.38‐2.48), oral function (OR, 1.40; 95%CI, 1.25‐1.57), whether patients were elected as a care prevention program candidate (OR, 1.90; 95%CI, 1.73‐2.08), Homebound state (OR, 1.91; 95%CI, 1.55‐2.37), the presence of dementia (OR, 1.97; 95%CI, 1.75‐2.20), and depression (OR, 1.96; 95%CI, 1.73‐2.22) were associated with a higher odds ratio. Conclusion Individuals who were selected as long‐term care prevention program candidates based on the Basic Checklist had a higher risk of requiring long‐term care. Older residents who corresponded to 10 or more of the 20 Basic Checklist items are at the highest risk of becoming certified as needing long‐term care.

Aim The aim of this study was to compare the effects of rehabilitation involving group and personal sessions on demented participants. Methods This single-blinded randomized controlled trial included 60 elderly participants with dementia in a geriatric health service facility, or R oken. Staff members, who did not participate in the intervention, examined cognitive function, mood, communication ability, severity of dementia, objective quality of life, vitality, and daily behaviour. After a baseline assessment, participants were randomly divided into three groups: (i) group intervention; (ii) personal intervention; and (iii) control. The 1-h group intervention (3–5 subjects) and 20-min personal intervention (one staff member per participant) were performed twice a week for 12 weeks (24 total sessions). The cognitive rehabilitation programme consisted of reminiscence, reality orientation, and physical exercise, and it was based on five principles of brain-activating rehabilitation; (i) pleasant atmosphere; (ii) communication; (iii) social roles; (iv) praising; and (v) errorless support. Data were analyzed after the second assessment. Results Outcome measures were analyzed in 43 participants—14 in the control group, 13 in group intervention, and 16 in personal intervention. Repeated measure ancova showed a significant interaction for cognitive function score (Mini-Mental State Examination) between group intervention and controls ( F = 5.535, P = 0.029). In the post-hoc analysis, group intervention showed significant improvement (P = 0.016). Global severity of dementia tended to improve (P = 0.094) in group intervention compared to control (Mann–Whitney U -test). There were no significant interactions or improvements for other measurements. Conclusions Group rehabilitation for dementia is more effective for improving cognitive function and global severity of dementia than personal rehabilitation in Roken.

[Purpose] The aim of this study was to clarify the relations of morale and physical function to the presence/absence of advanced activities of daily living. [Subjects] The subjects were 86 elderly community residents participating in health promotion classes. [Methods] A questionnaire survey on age, gender, presence/absence of advanced activities of daily living, and Philadelphia Geriatric Center Morale Scale score was conducted, in addition to assessment of fitness, consisting of measurement of height, body weight, grip and knee extensor muscle strength, functional reach, one-leg standing time, and Timed Up and Go test. Furthermore, multiple logistic regression analysis was performed with the presence/absence of advanced activities of daily living as a dependent variable. [Results] Grip strength and Timed Up and Go time were identified as variables influencing the presence/absence of advanced activities of daily living. [Conclusion] Physical function represented by grip strength and Timed Up and Go time was higher among subjects performing advanced activities of daily living.

[Purpose] This study examined whether low-frequency group exercise improved the motor functions of community-dwelling elderly people in a rural area when combined with home exercise with self-monitoring. [Subjects] The subjects were community-dwelling elderly people in a rural area of Japan. [Methods] One group (n = 50) performed group exercise combined with home exercise with self-monitoring. Another group (n = 37) performed group exercise only. Low-frequency group exercise (warm-up, exercises for motor functions, and cool-down) was performed in seven 40 to 70-minute sessions over 9 weeks by both groups. Five items of motor functions were assessed before and after the intervention. [Results] Significant interactions were observed between groups and assessment times for all motor functions. Improvements in motor functions were significantly greater in the group that performed group exercise combined with home exercise with self-monitoring than in the group that performed group exercise only. Post-hoc comparisons revealed significant differences in 3 items of motor functions. No significant improvements were observed in motor functions in the group that performed group exercise only. [Conclusions] Group exercise combined with home exercise with self-monitoring improved motor functions in the setting of low-frequency group exercise for community-dwelling elderly people in a rural area.

Objective: In Japan, the Integrated Community Care System aims to support residents to live as independently as possible at home. Koreisya-Kyoshitsu and Fureaiikiiki salons are two types of group activities for community-dwelling elderly. We investigated effective ways of conducting such activities. Methods: We analyzed 96 subjects from 8 salons and 354 subjects from 10 Koreisya-Kyoshitsu. Self-completed questionnaires included the following: attributes, the Motor Fitness Scale (MFS), revised Philadelphia Geriatric Center Morale Scale (PGCMS), Measurement of Psychological Independence (MPI), instrumental activities of daily living (IADL), and self-rated health status (SRH). Follow-up assessment was conducted 6 months later. Representatives from 8 salons and staff members from 10 Koreisya-Kyoshitsu answered an additional questionnaire on management. Results: In Koreisya-Kyoshitsu, physical performance (MFS) (p = 0.007) and subjective well-being (PGCMS) (p = 0.001) improved significantly, whereas psychological independence (MPI) deteriorated significantly (p = 0.015). The MFS scores significantly improved in the sub-group with a high number of sessions (7 or more) (p = 0.043), as well as in the non-volunteer sub-group (p = 0.004). The PGCMS scores significantly improved in the sub-group with a high number of sessions (p < 0.001). The MPI scores significantly deteriorated in the sub-group with a low frequency of sessions (6 or less) and in the non-volunteer sub-group (p = 0.013 and p = 0.010, respectively). In salons, the frequency of going out decreased significantly (p = 0.049). Functional status (IADL) significantly improved in the “twice or more a month” sub-group (p = 0.046), whereas it significantly deteriorated in the “once a month” sub-group (p = 0.004). The proportion of volunteers/organizers in Koreisya-Kyoshitsu (23.4%) was significantly lower than that in salons (39.6%). Conclusion: The frequency (number) of sessions, but not the volunteer/non-volunteer attribute, was a key factor in obtaining the health promotion effects of group activities in both Koreisya-Kyoshitsu and salons.

[Purpose] To evaluate the effect of a home exercise program on physical function in community dwelling elderly with pre-sarcopenia or sarcopenia. [Subjects and Methods] Fifty-two community-dwelling individuals, over 60 years and meeting the diagnostic criteria for pre-sarcopenia or sarcopenia, were randomly assigned to intervention group (n=34) and control group (n=18). The intervention group completed 6-months home exercise programs, combining walking with lower limb resistance exercises. Body mass index, skeletal mass index, body fat percentage, handgrip strength, single-leg standing, walking speed (comfortable and maximal), and knee extension strength were evaluated at baseline and post-intervention. Activity was assessed using the 25-question Geriatric Locomotive Functional Scale (GLFS-25) and quality of life using the Euro QOL questionnaire. [Results] Pre- and post-training assessments were completed by 76.5% and 77.8% of participants in the intervention and control groups, respectively. The intervention improved single-leg standing (60.5 s to 77.2 s) and knee extension strength (1.38 Nm/kg to 1.69 Nm/kg). In the control group, maximum walking speed (2.02 m/s to 1.86 m/s) and GLFS-25 score (2.9 to 5.1) worsened. Change of pre-sarcopenia/sarcopenia status was comparable for the intervention (15.4%) and control (14.3%) groups. [Conclusion] A 6-month home exercise program improved physical function in community-dwelling individuals with pre-sarcopenia or sarcopenia.

Background:Theory of Mind reasoning, which plays a pivotal role in social interaction, is required to detect deception. Empirically, those with cognitive decline are vulnerable to deception.Methods:Participants were 45 healthy elderly adults with clinical dementia rating (CDR) 0, and 76 outpatients: 25 with amnestic mild cognitive impairment (aMCI, CDR 0.5), 34 with mild Alzheimer's disease dementia (ADD, CDR 1), and 17 with moderate ADD (CDR 2). The task consisted of two single-frame cartoons that depicted a character with an intention to deceive another character using social signs of gaze and pointing, and participants are provided clue questions to detect the character's intentions.Results:The percentage of participants who detected the character's intention decreased with ADD progression (CDR 0, 82.2%; CDR 0.5, 48.0%; CDR 1, 29.4%; and CDR 2, 0%). Total score (0–6) also decreased with ADD progression (CDR 0, 4.4 +/−1.1; CDR 0.5, 3.0 +/−1.3; CDR 1, 2.9 +/−1.5; and CDR 2, 1.6 +/−0.9).Discussion and Conclusions:The present study demonstrated that those with aMCI have difficulty in detecting other's deceiving intentions, when the intention was shown implicitly using social signs. In a previous study, we have reported that mild ADD showed difficulties in detecting intention, while aMCI succeeded in detection when the intention was depicted explicitly. These results together suggested that those with aMCI is vulnerable to deception when the intention was shown implicitly using non-verbal cues, while ADD may fail to detect the intention even when the intention was shown explicitly.

The goal of dementia treatment is to improve the quality of life for both people with dementia and their families. Rehabilitation as a non-pharmacological approach, coordinated with pharmacological treatment, aims to allow patients to live better by slowing the progression, and relieving the behavioral and psychological symptoms of dementia. In dementia, the manifestation of symptoms caused by neurological impairment is modified by various factors; thus, multidimensional assessment and approaches are effective based on the concept of the International Classification of Functioning, which emphasizes the healthy components of every person's functioning. Regarding the process of rehabilitation, every person with dementia should take initiative throughout the course of rehabilitation, and shared decision-making is a fundamental requirement at every phase of intervention. The needs of rehabilitation differ depending on the stage of dementia. In the early stages, cognitive rehabilitation is needed, and interventions are carried out using preserved functions and compensatory strategies. As the disease progresses, capacities of instrumental and then basic activities of daily living deteriorate, and interventions need to be tailor-made and carried out in the context of actual living situations. In the early-to-moderate stages, prevention and management of behavioral and psychological symptoms of dementia are required. In the interventions to alleviate behavioral and psychological symptoms of dementia, it is critical to consider the individual and the meaning behind his/her behaviors from a holistic perspective. Family carers also need support, and education to learn coping strategies can be beneficial for both people with dementia and their carers. Rehabilitation can empower people with dementia and their families to live better with dementia. Geriatr Gerontol Int 2018; 18: 1529-1536.

Aim Evaluating effects of an enjoyable walking-habituation program. Methods We carried out a 12-week intervention, consisting of an enjoyable walking-habituation program based on five principles of brain-activating rehabilitation: pleasant atmosphere, interactive communication, social roles, praising each other and errorless support. The program, once a week for 90 min, was carried out in small groups. Participants were 71 community-dwelling people (72.2 ± 4.3) without dementia. Cognitive function was evaluated in five cognitive domains: memory, executive function, word fluency, visuospatial abilities and sustained attention. Additionally, quality of life, depressive state, functional capacity, range of activities, social network and subjective memory complaints were assessed using questionnaires. Motor function was also evaluated. Measurement was carried out before the observation period, after observation and after intervention. Results A total of 63 participants were included in the analysis. Daily steps, executive function, subjective memory complaints, functional capacity and 5-m maximum walking time significantly improved during the intervention period (after observation to after intervention) compared with the observation period (before the observation period to after observation). No significant differences were seen in other evaluations. At 6 months after the intervention, 52 of 63 participants (82.5%) continued to walk once a week or more, and all of them were confident about continuing to walk in the future. Furthermore, all participants were satisfied with our walking-habituation program and all replied that they felt delighted. Conclusion The intervention program, based on the five principles of brain-activating rehabilitation, resulted in improvement of some cognitive and physical functions, as well as a high walking-habituation rate at 6 months' follow up. Geriatr Gerontol Int 2015; ●●: ●●-●●. Language: en

OBJECTIVE: Rehabilitation for dementia is important in Roken Geriatric Health Service Facilities in Japan. This study evaluated the effects of a cooking program as rehabilitation for elderly residents with dementia. METHODS: We carried out a 12-week cooking program based on the five principles of brain-activating rehabilitation (BAR): fostering a pleasant atmosphere, interactive communication, establishing social roles, giving and receiving praise, and errorless learning. The program was carried out in small groups and consisted of 90-min classes once a week. Participants were 36 elderly residents with dementia (mean 85.4 ± 6.5 years) who were randomly divided into intervention (n = 18) and control (n = 18) groups. The control group participated in recreation and both groups received individual conventional rehabilitation twice a week for 30 min. The effects of intervention were evaluated using nine outcome measures. RESULTS: A total of 29 participants were included in the analysis (two-way analysis of variance). The attendance rate was 86.6% in the intervention group (n = 13). The Yamaguchi Kanji Symbol Substitution Test (executive function) showed significant interaction (F(1, 27) = 4.305, P = 0.048) between the two groups: the control group (n = 16) showed significant deterioration (pre 4.9 ± 5.6 to post 3.0 ± 4.9; P = 0.032). The dementia behavior disturbance scale also showed significant interaction (F(1, 29) = 13.298, P = 0.001): the intervention group (n = 16) showed significant improvement (pre 21.6 ± 12.2 to post 11.4 ± 11.5; P < 0.001). No significant differences were observed in the other outcome measures. CONCLUSIONS: Our findings suggest that a cooking program based on BAR can reduce the behavioral and psychological symptoms of dementia and maintain executive function.

Purpose The aim of this study was to evaluate the impact of memory complaints on quality of life (QOL) in elderly community dwellers with or without mild cognitive impairment (MCI). Methods Participants included 120 normal controls (NC) and 37 with MCI aged 65 and over. QOL was measured using the Japanese version of Satisfaction in Daily Life, and memory complaints were measured using a questionnaire consisting of four items. The relevance of QOL was evaluated with psychological factors of personality traits, sense of self-efficacy, depressive mood, self-evaluation of daily functioning, range of social activities (Life-Space Assessment), social network size, and cognitive functions including memory. The predictors of QOL were analyzed by multiple linear regression analysis. Results QOL was not significantly different between the NC and MCI groups. In both groups, QOL was positively correlated with self-efficacy, daily functioning, social network size, Life-Space Assessment, and the personality traits of extraversion and agreeableness; QOL was negatively correlated with memory complaints, depressive mood, and the personality trait of neuroticism. In regression analysis, memory complaints were a negative predictor of QOL in the MCI group, but not in the NC group. The partial correlation coefficient between QOL and memory complaints was −0.623 (P < 0.05), after scores of depressive mood and self-efficacy were controlled. Depressive mood was a common negative predictor in both groups. Positive predictors were Life-Space Assessment in the NC group and sense of self-efficacy in the MCI group. Conclusions Memory complaints exerted a negative impact on self-rated QOL in the MCI group, whereas a negative correlation was weak in the NC group. Memory training has been widely practised in individuals with MCI to prevent the development of dementia. However, such approaches inevitably identify their memory deficits and could aggravate their awareness of memory decline. Thus, it is critical to give sufficient consideration not to reduce QOL in the intervention for those with MCI.

Early detection of dementia is recommended in the stages from mild cognitive impairment to early dementia, excluding the asymptomatic stage. The advantages of early detection for patients and their caregivers include early receipt of pharmacological and non-pharmacological therapies, and early access to appropriate agencies and/or support networks. The disadvantages include psychological damage related to anxiety and depression, and risk of stigmatization and/or social exclusion. The possibility of false positive diagnoses is also problematic. For detection of dementia, various screening tests and questionnaires have been developed. However, none of these techniques are sensitive and specific enough to avoid false positives. Thus, these screening tools are recommended for assessment of the severity of functional decline after sufficient information has been gathered to suspect dementia. In terms of social services, early detection might delay institutionalization. However, implementation of early detection would add a heavy burden on social resources, especially human resources. For effective implementation of early diagnosis and management of dementia, measures are required to improve social and human resources, including the following: improvement of the diagnostic abilities of general practitioners, improvement of necessary care and support systems after diagnosis, and organizing volunteers to support local communities. Under a community-based integrated care system, each community will create a "tailored" system that meets the health needs, health status and values of the community. Promoting social participation and community involvement of the residents should be one of the key strategies to address the shortage of human resources.

Background Japan is one of the most rapidly ageing societies in the world. A number of municipalities have started services for the prevention of cognitive decline for community-dwelling elderly individuals, but the effectiveness of these services is currently insufficient. Our study explored the efficacy of a comprehensive intervention programme consisting of physical and leisure activities to prevent cognitive decline in community-dwelling elderly subjects. Method We administered a 12-week intervention programme consisting of physical and leisure activities aimed at enhancing participants' motivation to participate and support one another by providing a pleasant atmosphere, empathetic communication, praise, and errorless support. This programme for the prevention of cognitive decline was conducted as a service by the city of Maebashi. All participants underwent the Five-Cog test, which evaluated the cognitive domains of attention, memory, visuospatial function, language, and reasoning. Executive function was evaluated by the Wechsler Digit Symbol Substitution Test and Yamaguchi Kanji-Symbol Substitution Test. Subjective health status, level of social support, functional capacity, subjective quality of life, and depressive symptoms were assessed with a questionnaire. Grip strength test, timed up-and-go test, 5-m maximum walking times test, and functional reach test were performed to evaluate physical function. Fifty-two participants were randomly allocated to intervention (n = 26) and control (n = 26) groups. Twenty-six participants, aged between 65–87 years, received intervention once a week at a community centre. The programme was conducted by health-care professionals, with the help of senior citizen volunteers. Results The intervention group (n = 19) showed significant improvement on the analogy task of the Five-Cog test (F1,38 = 4.242, P = 0.046) and improved quality of life (F1,38 = 4.773, P = 0.035) as compared to the control group (n = 24). Conclusion A community-based 12-week intervention programme that aimed to enhance motivation to participate in activities resulted in improvements in some aspects of cognitive function and quality of life. Senior citizens who volunteered in the present intervention enabled the smooth implementation of the programme and alleviated the burden on professional staff.

Aims: The objective is to propose a brief method to evaluate anosognosia in Alzheimer's disease (AD) using the Symptoms of Early Dementia-11 Questionnaire (SED-11Q), a short informant-based screening questionnaire for identifying dementia. Methods: The participants were 107 elderly individuals: 13 with a Clinical Dementia Rating (CDR) of 0.5, 73 with mild AD of CDR 1, and 21 with moderate AD of CDR 2. The patients and caregivers answered the SED-11Q independently, and the degree of discrepancy indicated the severity of anosognosia. Results: The scores were as follows: caregiver scores were 2.46 ± 1.85 (mean ± SD) in CDR 0.5, 6.36 ± 3.02 in CDR 1, and 9.00 ± 1.14 in CDR 2; patient scores were 2.00 ± 1.78, 2.55 ± 2.33, and 1.33 ± 2.46, respectively. Discrepancy was 0.46 ± 1.61, 3.81 ± 3.95, and 7.67 ± 2.87, respectively, and the caregiver assessments were significantly higher than the patient assessments in CDR 1 and CDR 2 (p < 0.001 in both groups). The SED-11Q for anosognosia was validated with the standardized Anosognosia Questionnaire for Dementia (AD-Q). The caregiver scores were moderately correlated with behavioral and psychological symptoms of dementia scores (r = 0.524), and the patient scores were moderately correlated with depression scores (r = 0.561). Conclusion: The SED-11Q serves a dual purpose: caregiver assessment is useful for the screening of dementia, and any discrepancy between the patient and the caregiver assessment is considered as an indication of the severity of anosognosia; this can be informative for caregivers and essential for successful care.

Alzheimer's disease (AD) is characterized neuropathologically by the presence of amyloid plaques, neuritic plaques, and neurofibrillary tangles (NFTs). These lesions occur not only in demented individuals with AD but also in non-demented persons. In non-demented individuals, amyloid and neuritic plaques are usually accompanied with NFTs and are considered to represent asymptomatic or preclinical AD (pre-AD) pathology. Here, we defined and characterized neuropathological differences between clinical AD, non-demented pre-AD, and non-AD control cases. Our results show that clinical AD may be defined as cases exhibiting late stages of NFT, amyloid, and neuritic plaque pathology. This is in contrast to the neuropathological changes characteristic of pre-AD, which display early stages of these lesions. Both AD and pre-AD cases often exhibit cerebral amyloid angiopathy (CAA) and granulovacuolar degeneration (GVD), and when they do, these AD-related pathologies were at early stages in pre-AD cases and at late stages in symptomatic AD. Importantly, NFTs, GVD, and CAA were also observed in non-AD cases, i.e., in cases without amyloid plaque pathology. Moreover, soluble and dispersible, high-molecular-weight amyloid β-protein (Aβ) aggregates detected by blue-native polyacrylamide gel electrophoresis were elevated in clinical AD compared to that in pre-AD and non-AD cases. Detection of NFTs, GVD, and CAA in cases without amyloid plaques, presently classified as non-AD, is consistent with the idea that NFTs, GVD, and CAA may precede amyloid plaque pathology and may represent a pre-amyloid plaque stage of pre-AD not yet considered in the current recommendations for the neuropathological diagnosis of AD. Our finding of early stages of AD-related NFT, amyloid, and GVD pathology provides a more clear definition of pre-AD cases that is in contrast to the changes in clinical AD, which is characterized by late stages of these AD-related pathologies. The observed elevation of soluble/dispersible Aβ aggregates from pre-AD compared to that in AD cases suggests that, in addition to more widespread AD-related pathologies, soluble/dispersible Aβ aggregates in the neuropil play a role in the conversion of pre-AD to clinical AD.

Aim To examine the efficacy of rehabilitation for elderly individuals with dementia at intermediate facilities between hospitals and home, based on the policies for elderly individuals to promote community-based care at home and dehospitalization. Methods Participants were older adults with dementia newly admitted to intermediate facilities. A total of 158 in the intervention group who claimed Long-Term Care Insurance for three consecutive months, and 54 in the control group were included in the analysis. The interventions were carried out in a tailor-made manner to meet individual needs. The personal sessions were carried out three times a week for 3 months after admission by physical, occupational or speech therapists. Outcome measures were cognitive tests (Hasegawa Dementia Scale revised [HDS-R] and Mini-Mental State Examination), and observational assessments of dementia severity, activities of daily living (ADL), social activities, behavioral and psychological symptoms of dementia (BPSD) using a short version of the Dementia Disturbance Scale (DBD13), depressive mood, and vitality. Results Significant improvement in the intervention group was shown in cognitive function measured by HDS-R (interaction F[1, 196] = 5.190, P = 0.024), observational evaluation of dementia severity (F[1,198] = 9.550, P = 0.002) and BPSD (DBD13; F[1,197] = 4.506, P = 0.035). Vitality, social activities, depressive mood and ADL were significantly improved only in the intervention group, although interaction was not significant. Conclusions Significant improvement by intervention was shown in multiple domains including cognitive function and BPSD. Cognitive decline and worsening of BPSD are predictors of care burden and hospitalization, thus intensive rehabilitation for dementia was beneficial for both individuals with dementia and their caregivers. Geriatr Gerontol Int 2014; 14: 206–211.

We studied seven cases of Alzheimer's disease (AD). Six of the patients had presenilin 1 (PS1) mutations (PS1AD). Three novel PS1 mutations (T99A, H131R and L219R) and three other missense mutations (M233L, H163R and V272A) were found in the PS1AD group. We measured the levels of phosphorylated tau (ptau-181, ptau-199) and Aβ (Aβ1-42, Aβ1-40 and Aβ1-38) in the cerebrospinal fluid (CSF) of PS1AD patients, early-onset sporadic AD (EOSAD), late-onset sporadic AD (LOSAD) and non-demented subjects (ND). The CSF levels of Aβ1-42 in the three AD groups were significantly lower than those of the ND group (p < 0.0001). CSF levels of Aβ1-42 in the PS1AD group were significantly lower than those in the two sporadic AD groups. The Aβ1-40 and Aβ1-38 levels in the CSF of the PS1AD group were significantly lower than those of the three other groups (p < 0.0001, respectively). The levels of Aβ1-40, Aβ1-38 and Aβ1-42 in the CSF of the PS1AD group remained lower than those of the ND group for 4 years. Not only CSF Aβ1-42, but also Aβ1-40 and Aβ1-38 decreased in the advanced stages of PS1AD.

In a rapidly aging society, like that in Japan, it is imperative to establish strategies to prevent dementia. We investigated the effects of a dementia prevention program, conducted as part of a municipality's long-term care prevention project, on cognitive/motor functions among the community-dwelling elderly. Participants underwent a physical activity program involving muscle training and aerobic exercise, once a week, for 12 weeks. Cognitive and motor tests were performed twice, before and after the intervention. Thirty participants, aged 75.7 ± 6.7 years, were included in the analysis. Scores from the immediate word memory task were significantly increased (23.0 ± 7.8 vs. 25.7 ± 6.5) after the program. Scores from the Yamaguchi Kanji Symbol Substitution Test were also significantly increased (36.2 ± 13.1 vs. 40.1 ± 14.1). Time spent during the 5 m maximum walking speed test was significantly shorter after the program (3.4 ± 0.8 vs. 3.0 ± 0.7 s), whereas the daily walking distance increased significantly (1.9 ± 1.5 vs. 3.1 ± 2.2 km). Participants showed improvement in some aspects of their cognitive/motor function and walking distance per day. Therefore, this program can be regarded as a practical community-based healthcare activity.

Soluble amyloid β-protein (Aβ) aggregates have been identified in the Alzheimer's disease (AD) brain. Dispersed Aβ aggregates in the brain parenchyma are different from soluble, membrane-associated and plaque-associated solid aggregates. They are in mixture with the extra- or intracellular fluid but can be separated from soluble proteins by ultracentrifugation. To clarify the role of dispersible Aβ aggregates for neurodegeneration we analyzed 2 different amyloid precursor protein (APP)-transgenic mouse models. APP23 mice overexpress human mutant APP with the Swedish mutation. APP51/16 mice express high levels of human wild type APP. Both mice develop Aβ-plaques. Dendritic degeneration, neuron loss, and loss of asymmetric synapses were seen in APP23 but not in APP51/16 mice. The soluble and dispersible fractions not separated from one another were received as supernatant after centrifugation of native forebrain homogenates at 14,000 × g. Subsequent ultracentrifugation separated the soluble, i.e., the supernatant, from the dispersible fraction, i.e., the resuspended pellet. The major biochemical difference between APP23 and APP51/16 mice was that APP23 mice exhibited higher levels of dispersible Aβ oligomers, protofibrils and fibrils precipitated with oligomer (A11) and protofibril/fibril (B10AP) specific antibodies than APP51/16 mice. These differences, rather than soluble Aβ and Aβ plaque pathology were associated with dendritic degeneration, neuron, and synapse loss in APP23 mice in comparison with APP51/16 mice. Immunoprecipitation of dispersible Aβ oligomers, protofibrils, and fibrils revealed that they were associated with APP C-terminal fragments (APP-CTFs). These results indicate that dispersible Aβ oligomers, protofibrils, and fibrils represent an important pool of Aβ aggregates in the brain that critically interact with membrane-associated APP C-terminal fragments. The concentration of dispersible Aβ aggregates, thereby, presumably determines its toxicity.

Background/Aims: We aimed to prove the effectiveness of brain-activating rehabilitation for dementia, which consisted of 5 principles: pleasant atmosphere, communication, praising, social role, and supportive care. Methods: The design was a randomized controlled trial that was not blinded. Fifty-four elderly participants with dementia (mean age: 85.2 years) were selected. Intervention based on the 5 principles of brain-activating rehabilitation was conducted for 1 h, twice a week, for 12 weeks (24 sessions). The control group had no treatment. Outcome measures consisted of two observation scales, namely sum of boxes in clinical dementia rating (CDR-SB) and the multidimensional observation scale for elderly subjects (MOSES), and two cognitive tests: the Hasegawa dementia scale revised (HDS-R) and trail making test A. Results: Repeated measure ANCOVA showed a significant interaction for total score of CDR-SB (F = 7.190, p = 0.015) and MOSES (F = 4.525, p = 0.038). There were no significant changes in the two cognitive test scores. Conclusion: Intervention based on the principles of brain-activating rehabilitation was effective in maintaining and improving daily life functions in elderly participants with dementia in residential care homes.

We aimed to study how patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) suffer from awareness of their deficits. Self-awareness was assessed using the Anosognosia Questionnaire for Dementia in 12 pairs of MCI outpatients and caregivers, 23 with mild AD, and 18 with moderate AD. The discrepancy between patient’s and caregiver’s evaluation (anosognosia) became greater as AD progressed. The predictors of patients’ distress, shown by multiple linear regression analyses, were awareness of decline in intellectual or social functioning; self-awareness of deficits in remembering appointments in MCI; in remembering appointments, writing, mental calculation, and understanding the newspaper in mild AD; and in mental calculation and doing clerical work in moderate AD. Caregivers assumed the predictors of patients’ distress differently: awareness of deterioration of memory in MCI and mild AD, and basic activities of daily living in moderate AD. Understanding patients’ disability from patients’ perspective is required for successful care.

Background: In Alzheimer's disease (AD) patients, deficits in contextual understanding and intentions/beliefs of other people (theory of mind; ToM) cause communication problems between patients and caregivers. To evaluate deficits of contextual understanding/ToM, we developed the Pitfall Intention Explanation Task with Clue Questions (Pitfall task).Methods: We recruited 26 healthy older adults in clinical dementia rating (CDR) 0, and 62 outpatients: 12 with amnestic mild cognitive impairment (aMCI) in CDR 0.5; 36 mild AD in CDR 1; and 14 moderate AD in CDR 2. The Pitfall task consists of a single-frame cartoon that shows a character's intention and seven serial questions that provide clues for contextual understanding/ToM.Results: The total score (0–7) was decreased with progression of AD (CDR 0, 5.4 ± 2.6; CDR 0.5, 3.7 ± 2.7; CDR 1, 1.9 ± 3.1; CDR 2, 0.0 ± 0.0; respectively). In CDR 0, two-third of the participants responded correctly without clue questions. In CDR 0.5, one-third of the participants responded correctly without clue questions, and half of them understood with the help of the clue questions. In CDR 1, one-fourth of the participants responded correctly without clue questions, and the clue questions did not increase the correct response. In CDR 2, none responded correctly. Additionally, the Pitfall task provided the chance for patients’ families to observe patients’ responses.Conclusion: Contextual understanding/ToM, a kind of social cognition, was impaired with progression of AD. The Pitfall task evaluates the function quickly with low burden for memory function, and may provide helpful clues for caregivers to achieve good communication with AD patients.

Aim: Japan is one of the most rapidly aging societies in the world. Measures to prevent dementia are urgently required in Japan, although such strategies have not yet been established. This study investigated the effectiveness of a pleasant physical exercise intervention on the prevention of cognitive decline in community-dwelling elderly participants with subjective memory complaints. In this intervention, a pleasant atmosphere was emphasized to enhance the participants' motivation. Method: We administered a 12-week intervention program consisting of pleasant physical exercise. This program for the prevention of cognitive decline was carried out as a service of Maebashi city. The service targeted elderly residents aged 65 years and older who had subjective memory complaints. After a control period of 12 weeks, 42 participants, aged between 65–86 years, received intervention once a week at community centers. Participants carried out group exercise, and were encouraged to perform home exercise and walking during the intervention period. The program was carried out by co-medical professional staff, with the help of senior citizen volunteers. Results: A total of 30 participants were included in the analysis. There was significant improvement on the Wechsler digit symbol substitution test (P = 0.01). Conclusion: Participants with subjective memory complaints who continued the pleasant physical exercise programs for 12 weeks showed improvement in some aspects of cognitive function. Participation of senior citizen volunteers enabled smooth implementation of the program, and alleviated the burden on the professional staff. The pleasant physical exercise intervention described in the present study could be regarded as a community-led intervention to prevent cognitive decline. Geriatr Gerontol Int 2012; ••: ••–••.

To evaluate the efficacy of a municipality-led walking program under the Japanese public Long-Term Care Insurance Act to prevent mental decline.Randomized controlled trial.The city of Takasaki.One hundred fifty community members aged 72.0 ± 4.0 were randomly divided into intervention (n = 75) and control (n = 75) groups.A walking program was conducted once a week for 90 minutes for 3 months. The program encouraged participants to walk on a regular basis and to increase their steps per day gradually. The intervention was conducted in small groups of approximately six, so combined benefits of exercise and social interaction were expected.Cognitive function was evaluated focusing on nine tests in five domains: memory, executive function, word fluency, visuospatial abilities, and sustained attention. Quality of life (QOL), depressive state, functional capacity, range of activities, and social network were assessed using questionnaires, and motor function was evaluated.Significant differences between the intervention and control groups were shown in word fluency related to frontal lobe function (F(1, 128) = 6.833, P = .01), QOL (F(1,128) = 9.751, P = .002), functional capacity including social interaction (F(1,128) = 13.055, P.001), and motor function (Timed Up and Go Test: F(1,127) = 10.117, P = .002). No significant differences were observed in other cognitive tests.Walking programs may provide benefits in some aspects of cognition, QOL, and functional capacity including social interaction in elderly community members. This study could serve as the basis for implementation of a community-based intervention to prevent mental decline.

Alzheimer's disease (AD) is characterized by the aggregation and deposition of amyloid β protein (Aβ) in the brain. Soluble Aβ oligomers are thought to be toxic. To investigate the predominant species of Aβ protein that may play a role in AD pathogenesis, we performed biochemical analysis of AD and control brains. Sucrose buffer-soluble brain lysates were characterized in native form using blue native (BN)-PAGE and also in denatured form using SDS-PAGE followed by Western blot analysis. BN-PAGE analysis revealed a high-molecular weight smear (>1000 kD) of Aβ(42) -positive material in the AD brain, whereas low-molecular weight and monomeric Aβ species were not detected. SDS-PAGE analysis, on the other hand, allowed the detection of prominent Aβ monomer and dimer bands in AD cases but not in controls. Immunoelectron microscopy of immunoprecipitated oligomers and protofibrils/fibrils showed spherical and protofibrillar Aβ-positive material, thereby confirming the presence of high-molecular weight Aβ (hiMWAβ) aggregates in the AD brain. In vitro analysis of synthetic Aβ(40) - and Aβ(42) preparations revealed Aβ fibrils, protofibrils, and hiMWAβ oligomers that were detectable at the electron microscopic level and after BN-PAGE. Further, BN-PAGE analysis exhibited a monomer band and less prominent low-molecular weight Aβ (loMWAβ) oligomers. In contrast, SDS-PAGE showed large amounts of loMWAβ but no hiMWAβ(40) and strikingly reduced levels of hiMWAβ(42) . These results indicate that hiMWAβ aggregates, particularly Aβ(42) species, are most prevalent in the soluble fraction of the AD brain. Thus, soluble hiMWAβ aggregates may play an important role in the pathogenesis of AD either independently or as a reservoir for release of loMWAβ oligomers. ispartof: Journal of Cellular and Molecular Medicine vol:16 issue:2 pages:287-295 ispartof: location:England status: published

We investigated why the cerebrospinal fluid (CSF) concentrations of Aβ42 are lower in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients. Because Aβ38/42 and Aβ40/43 are distinct product/precursor pairs, these four species in the CSF together should faithfully reflect the status of brain γ-secretase activity, and were quantified by specific enzyme-linked immunosorbent assays in the CSF from controls and MCI/AD patients. Decreases in the levels of the precursors, Aβ42 and 43, in MCI/AD CSF tended to accompany increases in the levels of the products, Aβ38 and 40, respectively. The ratios Aβ40/43 versus Aβ38/42 in CSF (each representing cleavage efficiency of Aβ43 or Aβ42) were largely proportional to each other but generally higher in MCI/AD patients compared to control subjects. These data suggest that γ-secretase activity in MCI/AD patients is enhanced at the conversion of Aβ43 and 42 to Aβ40 and 38, respectively. Consequently, we measured the in vitro activity of raft-associated γ-secretase isolated from control as well as MCI/AD brains and found the same, significant alterations in the γ-secretase activity in MCI/AD brains.

Background: In out-patient clinics, having simple procedures to check for signs of dementia is invaluable. In the present study, we evaluated the imitation of hand gestures to detect visuomotor deficits in dementia in clinical practice. Methods: In all, 1219 subjects were enrolled in the present study, including 497 with Alzheimer's disease (AD), 98 with dementia with Lewy bodies (DLB), 71 with other types of dementia diseases, 175 with a Clinical Dementia Rating (CDR) of 0.5, and 378 normal controls. All subjects were aged 65 years or older. Subjects were recruited from 10 clinics and two communities. Visuomotor function was evaluated by the Yamaguchi fox–pigeon imitation test (YFPIT), which consists of a simple one-handed sign for ‘fox’ and a complex two-handed sign for ‘pigeon’, a rapid, game-like test with low psychological burden. Results: The success rate (successful/total) for imitating the ‘pigeon’ hand gesture was reduced as the severity of the dementia increased: 85.7% in normal controls, 60.6% in CDR 0.5 (mild cognitive impairment), 39.2% in CDR 1 (mild dementia), 21.2% in CDR 2 (moderate dementia), and 5.7% in CDR 3 (severe dementia). The success rate for imitating the ‘pigeon’ hand gesture was higher in patients with DLB than AD within the CDR 1 group (51.2% vs 35.4%, respectively), but lower for patients with DLB than AD within the CDR 2 group (12.5% vs 24.4%, respectively). The success of imitating the hand gesture for ‘fox’ was similar for patients with AD and DLB. Of those subjects who failed to imitate the hand gesture for ‘pigeon’, 49.5% of those with AD showed the palm–palm pattern (both palms facing outward), suggesting deficits of perspective conversion from the first-person to the third-person. Conversely, 52.8% of patients with DLB showed a dorsum–dorsum pattern (both dorsa facing outwards), suggesting deterioration of visual attention and recognition. Conclusion: In conclusion, the YFPIT is a useful test to detect visuomotor deficits in dementia that can differentiate between AD and DLB.