[Effectiveness in reducing BPSD of care intervention using the Himotoki Sheet from the perspective of individuals with dementia].

AIM: This study aimed to examine the effect of intervention using the Himotoki Sheet versus conventional care on behavioral and psychological symptoms of dementia (BPSD) in residents of care facilities. METHODS: This non-randomized controlled trial included 37 institutionalized individuals with dementia. During the four-week intervention period, the care workers in the intervention group, which consisted of 17 participants, were asked to 1) select one BPSD item for intervention from the items of the Behavioral and Psychological Symptoms of Dementia Plus Questionnaire (BPSD+Q), 2) complete the Himotoki Sheet and share information about the BPSD focused on by the team led by the Himotoki Sheet manager, and 3) provide care according to the contents of the Himotoki Sheet. The 18 patients in the control group received conventional care for four weeks. A two-way analysis of variance was used to compare changes in scores between groups and the BPSD+Q. RESULTS: A total of 32 participants (intervention group, n=16; control group, n=16) were analyzed. There were no significant differences in basic attributes between the groups. There was a significant interaction between the group and the BPSD+Q distress score (F=4.704, p=0.038) and Hyperactive domain distress score (F=4.946, p=0.034). The BPSD+Q (p=0.002) and Hyperactive domain (p=0.001) distress scores were significantly reduced in the intervention group but not the control group. CONCLUSIONS: In comparison to conventional care, care using the Himotoki Sheet was associated with a significant reduction in the BPSD+Q and Hyperactive domain distress scores.

γ-Secretase Activity Is Associated with Braak Senile Plaque Stages.

Amyloid ß-proteins (Aßs) Aß1-42 and Aß1-43 are converted via two product lines of γ-secretase to Aß1-38 and Aß1-40. This parallel stepwise processing model of γ-secretase predicts that Aß1-42 and Aß1-43, and Aß1-38 and Aß1-40 are proportional to each other, respectively. To obtain further insight into the mechanisms of parenchymal Aß deposition, these four Aß 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 Aß1-43 in the brain increased proportionally to those of Aß1-42. Similarly, the amounts of deposited Aß1-38 correlated with those of Aß1-40. Surprisingly, the ratios of deposited Aß1-38/Aß1-42 and Aß1-40/Aß1-43 were proportional and discriminated the Braak SP stages accurately. This result indicates that the generation of Aß1-38 and Aß1-40 decreased and the generation of Aß1-42 and Aß1-43 increased with advancing SP stages. Thus, Aßs 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 Aß1-42 and Aß1-43 compared with cognitively normal brains. This refractory γ-secretase localized in detergent-solubilized fractions from brain cortices. But activity modulated γ-secretase, which decreases Aß1-42 and Aß1-43 in the cerebrospinal fluid, localized in detergent-insoluble fractions. These drastic alterations reflect Aß situation in Alzheimer disease brains.

Development of the Dementia Caregiver Positive Feeling Scale 21-item version (DCPFS-21) in Japan to recognise positive feelings about caregiving for people with dementia.

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 < 0.01). The DCPFS-21 also showed good intra-rater reliability (1.1: ρ = 0.62). CONCLUSION: We developed and validated the DCPFS-21, which measures the positive feelings of family caregivers of people with dementia, in Japan.

Effects of a group-based physical and cognitive intervention on social activity and quality of life for elderly people with dementia in a geriatric health service facility: a quasi-randomised controlled trial.

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.

Gullibility may be a warning sign of Alzheimer's disease dementia.

ABSTRACTBackground: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.

Comparison between group and personal rehabilitation for dementia in a geriatric health service facility: single-blinded randomized controlled study.

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.

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.

[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.

Relations of morale and physical function to advanced activities of daily living in health promotion class participants.

[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.

Effect of a simple and adherent home exercise program on the physical function of community dwelling adults sixty years of age and older with pre-sarcopenia or sarcopenia.

[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.

Biochemical stages of amyloid-ß peptide aggregation and accumulation in the human brain and their association with symptomatic and pathologically preclinical Alzheimer's disease.

Alzheimer's disease is characterized by the deposition of amyloid-ß peptide in the brain. N-terminal truncation resulting in the formation of AßN3pE and phosphorylation at serine 8 have been reported to modify aggregation properties of amyloid-ß. Biochemically, soluble, dispersible, membrane-associated, and insoluble, plaque-associated amyloid-ß aggregates have been distinguished. Soluble and dispersible amyloid-ß aggregates are both in mixture with the extracellular or intracellular fluid but dispersible aggregates can be cleared from proteins in solution by ultracentrifugation. To clarify the role of phosphorylated amyloid-ß and AßN3pE in soluble, dispersible, membrane-associated, and plaque-associated amyloid-ß aggregates in the pathogenesis of Alzheimer's disease we studied brains from 21 cases with symptomatic Alzheimer's disease, 33 pathologically preclinical Alzheimer's disease cases, and 20 control cases. Western blot analysis showed that soluble, dispersible, membrane-associated and plaque-associated amyloid-ß aggregates in the earliest preclinical stage of Alzheimer's disease did not exhibit detectable amounts of AßN3pE and phosphorylated amyloid-ß. This stage was referred to as biochemical stage 1 of amyloid-ß aggregation and accumulation. In biochemical amyloid-ß stage 2, AßN3pE was additionally found whereas phosphorylated amyloid-ß was restricted to biochemical amyloid-ß stage 3, the last stage of amyloid-ß aggregation. Phosphorylated amyloid-ß was seen in the dispersible, membrane-associated, and plaque-associated fraction. All cases with symptomatic Alzheimer's disease in our sample fulfilled biochemical amyloid-ß stage 3 criteria, i.e. detection of phosphorylated amyloid-ß. Most, but not all, cases with pathologically preclinical Alzheimer's disease had biochemical amyloid-ß stages 1 or 2. Immunohistochemistry confirmed the hierarchical occurrence of amyloid-ß, AßN3pE, and phosphorylated amyloid-ß in amyloid plaques. Phosphorylated amyloid-ß containing plaques were, thereby, seen in all symptomatic cases with Alzheimer's disease but only in a few non-demented control subjects. The biochemical amyloid-ß stages correlated with the expansion of amyloid-ß plaque deposition and with that of neurofibrillary tangle pathology. Taken together, we demonstrate that AßN3pE and phosphorylated amyloid-ß are not only detectable in plaques, but also in soluble and dispersible amyloid-ß aggregates outside of plaques. They occur in a hierarchical sequence that allows the distinction of three stages. In light of our findings, it is tempting to speculate that this hierarchical, biochemical sequence of amyloid-ß aggregation and accumulation is related to disease progression and may be relevant for an increasing toxicity of amyloid-ß aggregates.

Twelve-week physical and leisure activity programme improved cognitive function in community-dwelling elderly subjects: a randomized controlled trial.

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 (F(1,38) = 4.242, P = 0.046) and improved quality of life (F(1,38) = 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.

The impact of subjective memory complaints on quality of life in community-dwelling older adults.

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.

[Impairment of Attention in Dementia].

Impairment of attention, especially complex attention, appears in the early stage of dementia. Complex attention is one of the six neurocognitive domains, which are disturbed in dementia. Impairment of complex attention promotes symptoms of dementia, difficulties in activities of daily living (ADLs), and disturbed communication in dementia due to Alzheimer disease, Lewy body disease, and cerebrovascular diseases. Despite its importance, research on "impairment of attention in dementia" is scarce. We look forward to future studies addressing this topic. In this article, we emphasized on providing care for ADL and communication for people with dementia, who have attention deficits.

Transgenic expression of intraneuronal Aß42 but not Aß40 leads to cellular Aß lesions, degeneration, and functional impairment without typical Alzheimer's disease pathology.

An early role of amyloid-ß peptide (Aß) aggregation in Alzheimer's disease pathogenesis is well established. However, the contribution of intracellular or extracellular forms of Aß to the neurodegenerative process is a subject of considerable debate. We here describe transgenic mice expressing Aß1-40 (APP47) and Aß1-42 (APP48) with a cleaved signal sequence to insert both peptides during synthesis into the endoplasmic reticulum. Although lower in transgene mRNA, APP48 mice reach a higher brain Aß concentration. The reduced solubility and increased aggregation of Aß1-42 may impair its degradation. APP48 mice develop intracellular Aß lesions in dendrites and lysosomes. The hippocampal neuron number is reduced already at young age. The brain weight decreases during aging in conjunction with severe white matter atrophy. The mice show a motor impairment. Only very few Aß1-40 lesions are found in APP47 mice. Neither APP47 nor APP48 nor the bigenic mice develop extracellular amyloid plaques. While intracellular membrane expression of Aß1-42 in APP48 mice does not lead to the AD-typical lesions, Aß aggregates develop within cells accompanied by considerable neurodegeneration.

Tannic acid is a natural ß-secretase inhibitor that prevents cognitive impairment and mitigates Alzheimer-like pathology in transgenic mice.

Amyloid precursor protein (APP) proteolysis is essential for production of amyloid-ß (Aß) peptides that form ß-amyloid plaques in brains of Alzheimer disease (AD) patients. Recent focus has been directed toward a group of naturally occurring anti-amyloidogenic polyphenols known as flavonoids. We orally administered the flavonoid tannic acid (TA) to the transgenic PSAPP mouse model of cerebral amyloidosis (bearing mutant human APP and presenilin-1 transgenes) and evaluated cognitive function and AD-like pathology. Consumption of TA for 6 months prevented transgene-associated behavioral impairment including hyperactivity, decreased object recognition, and defective spatial reference memory, but did not alter nontransgenic mouse behavior. Accordingly, brain parenchymal and cerebral vascular ß-amyloid deposits and abundance of various Aß species including oligomers were mitigated in TA-treated PSAPP mice. These effects occurred with decreased cleavage of the ß-carboxyl-terminal APP fragment, lowered soluble APP-ß production, reduced ß-site APP cleaving enzyme 1 protein stability and activity, and attenuated neuroinflammation. As in vitro validation, we treated well characterized mutant human APP-overexpressing murine neuron-like cells with TA and found significantly reduced Aß production associated with less amyloidogenic APP proteolysis. Taken together, these results raise the possibility that dietary supplementation with TA may be prophylactic for AD by inhibiting ß-secretase activity and neuroinflammation and thereby mitigating AD pathology.

Pathology of clinical and preclinical Alzheimer's disease.

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 ß-protein (Aß) 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 Aß aggregates from pre-AD compared to that in AD cases suggests that, in addition to more widespread AD-related pathologies, soluble/dispersible Aß aggregates in the neuropil play a role in the conversion of pre-AD to clinical AD.

Relative preservation of the recognition of positive facial expression "happiness" in Alzheimer disease.

BACKGROUND: Positivity recognition bias has been reported for facial expression as well as memory and visual stimuli in aged individuals, whereas emotional facial recognition in Alzheimer disease (AD) patients is controversial, with possible involvement of confounding factors such as deficits in spatial processing of non-emotional facial features and in verbal processing to express emotions. Thus, we examined whether recognition of positive facial expressions was preserved in AD patients, by adapting a new method that eliminated the influences of these confounding factors. METHODS: Sensitivity of six basic facial expressions (happiness, sadness, surprise, anger, disgust, and fear) was evaluated in 12 outpatients with mild AD, 17 aged normal controls (ANC), and 25 young normal controls (YNC). To eliminate the factors related to non-emotional facial features, averaged faces were prepared as stimuli. To eliminate the factors related to verbal processing, the participants were required to match the images of stimulus and answer, avoiding the use of verbal labels. RESULTS: In recognition of happiness, there was no difference in sensitivity between YNC and ANC, and between ANC and AD patients. AD patients were less sensitive than ANC in recognition of sadness, surprise, and anger. ANC were less sensitive than YNC in recognition of surprise, anger, and disgust. Within the AD patient group, sensitivity of happiness was significantly higher than those of the other five expressions. CONCLUSIONS: In AD patient, recognition of happiness was relatively preserved; recognition of happiness was most sensitive and was preserved against the influences of age and disease.

High-molecular weight Aß oligomers and protofibrils are the predominant Aß species in the native soluble protein fraction of the AD brain.

Alzheimer's disease (AD) is characterized by the aggregation and deposition of amyloid ß protein (Aß) in the brain. Soluble Aß oligomers are thought to be toxic. To investigate the predominant species of Aß 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 Aß(42) -positive material in the AD brain, whereas low-molecular weight and monomeric Aß species were not detected. SDS-PAGE analysis, on the other hand, allowed the detection of prominent Aß monomer and dimer bands in AD cases but not in controls. Immunoelectron microscopy of immunoprecipitated oligomers and protofibrils/fibrils showed spherical and protofibrillar Aß-positive material, thereby confirming the presence of high-molecular weight Aß (hiMWAß) aggregates in the AD brain. In vitro analysis of synthetic Aß(40) - and Aß(42) preparations revealed Aß fibrils, protofibrils, and hiMWAß 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 Aß (loMWAß) oligomers. In contrast, SDS-PAGE showed large amounts of loMWAß but no hiMWAß(40) and strikingly reduced levels of hiMWAß(42) . These results indicate that hiMWAß aggregates, particularly Aß(42) species, are most prevalent in the soluble fraction of the AD brain. Thus, soluble hiMWAß aggregates may play an important role in the pathogenesis of AD either independently or as a reservoir for release of loMWAß oligomers.

Pitfall Intention Explanation Task with Clue Questions (Pitfall task): assessment of comprehending other people's behavioral intentions in Alzheimer's disease.

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.

Benefits of off-campus education for students in the health sciences: a text-mining analysis.

BACKGROUND: In Japan, few community-based approaches have been adopted in health-care professional education, and the appropriate content for such approaches has not been clarified. In establishing community-based education for health-care professionals, clarification of its learning effects is required. A community-based educational program was started in 2009 in the health sciences course at Gunma University, and one of the main elements in this program is conducting classes outside school. The purpose of this study was to investigate using text-analysis methods how the off-campus program affects students. METHODS: In all, 116 self-assessment worksheets submitted by students after participating in the off-campus classes were decomposed into words. The extracted words were carefully selected from the perspective of contained meaning or content. With the selected terms, the relations to each word were analyzed by means of cluster analysis. RESULTS: Cluster analysis was used to select and divide 32 extracted words into four clusters: cluster 1-"actually/direct," "learn/watch/hear," "how," "experience/participation," "local residents," "atmosphere in community-based clinical care settings," "favorable," "communication/conversation," and "study"; cluster 2-"work of staff member" and "role"; cluster 3-"interaction/communication," "understanding," "feel," "significant/important/necessity," and "think"; and cluster 4-"community," "confusing," "enjoyable," "proactive," "knowledge," "academic knowledge," and "class." CONCLUSIONS: The students who participated in the program achieved different types of learning through the off-campus classes. They also had a positive impression of the community-based experience and interaction with the local residents, which is considered a favorable outcome. Off-campus programs could be a useful educational approach for students in health sciences.