Impaired shifting of visuospatial attention in Alzheimer's disease as shown by the covert orienting paradigm: implications for visual construction disability.

OBJECTIVE: To investigate impaired shifting of visuospatial attention in Alzheimer's disease (AD) compared with age-matched controls. METHOD: An attention shifting was examined in 20 AD patients and 10 age-matched normal subjects by choice reaction time (CRT) and covert orienting paradigm. Visuospatial functions tests were also performed. For covert orienting, a peripheral spatial cue method was used, with stimulus-onset (SOA) between the cue and the target time varying from 250 to 2100 ms. RESULTS: The CRT showed no difference between the AD and normal groups. However, the RTs costs plus benefits were greater in the AD than normal group for two SOA conditions independent of dementia severity. Individual profiles in the time course of cue validity revealed two AD subgroups, i.e., a normal pattern for the cue validity of time course, and an abnormal, 'extinction-like' pattern. The latter had a particular difficulty in performing visual construction and spatial attention. CONCLUSIONS: Focusing attention was relatively intact in AD. However, shifting of visuospatial attention was impaired in AD compared with normal controls. There was a subgroup whose deficits were not only in 'disengagement,' but their voluntary shifting of attention was affected. These subgroups may show clinically severe visuospatial symptoms in more advanced stage.

Collage technique may provide new perspectives for Alzheimer patients by exploring messages from their inner world / Técnica de colagem pode dar novas perspectivas para pacientes com doença de Alzheimer através da exploração do seu mundo interior

Abstract: Although the collage art technique has been introduced as a psychotherapeutic method, it has not been fully applied in dementia. Objectives: To analyze characteristics of the collage articles produced by patients with Alzheimer's disease (AD). Methods: Twenty AD patients were asked to select and place several clippings as they wished. The MMSE was used for cognitive assessments. Results: Simplification and poor organization in their articles were found. The themes of one patient were found to change according to behavior. We discussed the images of the articles, especially spiritual images in the early stage and family images in the later stage. Conclusions: We concluded that the collage technique could provide new perspectives for dementia patients by exploring messages from their inner world.

Resumo: Embora a técnica de colagem tenha sido introduzida como um método psicoterapêutico, ela não foi totalmente aplicada em demência. Objetivos: Analisar as características de trabalhos de colagens feitos por pacientes com doença de Alzheimer (DA). Métodos: A 20 pacientes foi solicitado que selecionassem e colocassem peças que apreciassem. O MEEM foi utilizado para avaliação cognitiva. Resultados: Simplificação e organização pobres foram encontradas. Nós demonstramos um paciente cujos temas foram mudando em relação ao comportamento. Nós discutimos as imagens dos artigos, especialmente imagens espirituais no estágio precoce e imagens familiares no estágio tardio. Conclusões: Nós consideramos que a técnica de colagem poderia dar novas perspectivas na demência, explorando a mensagem do mundo interior.

Normative data on Benton Visual Form Discrimination Test for older adults and impaired scores in Clinical Dementia Rating 0.5 participants: community-based study. The Osaki-Tajiri Project.

AIMS: The Benton Visual Form Discrimination test (VFD) is one of the non-verbal tests to assess the capacity for complex visual form discrimination. The purposes of the present study were to investigate the effects of age and education level of the VFD in healthy elderly subjects, rigorously excluding participants with Clinical Dementia Rating (CDR) 0.5, and the characteristics of VFD patterns in CDR 0.5 participants. METHODS: The 597 participants included CDR 0 (healthy elderly, n = 405), CDR 0.5 (mild cognitive impairment, n = 161), and CDR 1 and 2 (dementia, n = 31). The VFD, Digit Forwards, Digit Backwards and Rey-Osterrieth Complex Figure Test (RCFT) copying were used for neuropsychological assessment. RESULTS: There were significant effects of age and education level on the VFD in healthy participants, and the CDR 0.5 group had a lower score on the VFD than the healthy group. Low performance on the VFD was associated with Digit Backward and RCFT copying in both healthy and CDR 0.5 participants. CONCLUSIONS: CDR 0.5 participants exhibit deficits of visual form discrimination related to attention, visual construction and organization.

Collage technique may provide new perspectives for Alzheimer patients by exploring messages from their inner world.

Although the collage art technique has been introduced as a psychotherapeutic method, it has not been fully applied in dementia. OBJECTIVES: To analyze characteristics of the collage articles produced by patients with Alzheimer's disease (AD). METHODS: Twenty AD patients were asked to select and place several clippings as they wished. The MMSE was used for cognitive assessments. RESULTS: Simplification and poor organization in their articles were found. The themes of one patient were found to change according to behavior. We discussed the images of the articles, especially spiritual images in the early stage and family images in the later stage. CONCLUSIONS: We concluded that the collage technique could provide new perspectives for dementia patients by exploring messages from their inner world.

Embora a técnica de colagem tenha sido introduzida como um método psicoterapêutico, ela não foi totalmente aplicada em demência. OBJETIVOS: Analisar as características de trabalhos de colagens feitos por pacientes com doença de Alzheimer (DA). MÉTODOS: A 20 pacientes foi solicitado que selecionassem e colocassem peças que apreciassem. O MEEM foi utilizado para avaliação cognitiva. RESULTADOS: Simplificação e organização pobres foram encontradas. Nós demonstramos um paciente cujos temas foram mudando em relação ao comportamento. Nós discutimos as imagens dos artigos, especialmente imagens espirituais no estágio precoce e imagens familiares no estágio tardio. CONCLUSÕES: Nós consideramos que a técnica de colagem poderia dar novas perspectivas na demência, explorando a mensagem do mundo interior.

Alzheimer's patients do not show left unilateral spatial neglect but exhibit peripheral inattention and simplification.

The Rey-Osterrieth Complex Figure Test (RCFT) is widely used to measure visuoperceptual and visuoconstructional skills, while the Line Bisection (LB) test is commonly employed to assess unilateral spatial neglect (USN). Previous studies have suggested that Alzheimer's disease (AD) patients may suffer from left USN. OBJECTIVES: The purpose of this study was to clarify whether left USN occurs in AD. METHODS: Forty controls, 40 very mild AD patients and 31 mild/moderate AD patients performed both the RCFT copying and the LB test. RESULTS: The very mild AD and mild/moderate AD groups had lower total RCFT copying scores and also scored lower in the "left" and "detail" categories compared to controls. However, there were no correlations between the left-category score for RCFT and the LB score. Instead, peripheral inattention and simplification patterns were noted. CONCLUSIONS: We found that the RCFT copying test is effective for detecting early AD and suggest that AD patients manifest peripheral inattention and simplification but not left USN.

O teste da figura complexa de Rey-Osterrieth (TFCR) é muito utilizado para avaliar habilidades vísuo-espaciais e vísuo-construtivas, enquanto o teste de Bisecção de Linhas (TBL) é usualmente empregado para avaliar a presença de negligência espacial unilateral. Estudos anteriores têm sugerido que pacientes com doença de Alzheimer (DA) podem apresentar negligência espacial unilateral esquerda. OBJETIVOS: O propósito deste estudo foi o de verificar se negligência espacial unilateral esquerda ocorre na DA. MÉTODOS: Quarenta controles, 40 pacientes com DA muito leve e 31 com DA leve/moderada foram avaliados mediante o TFCR e o TBL. RESULTADOS: Os pacientes com DA muito leve e com DA leve/moderado tiveram escores mais baixos na cópia do TFCR e também nas categorias "esquerda" e "detalhe" comparados com controles. Entretanto, não houve correlação entre os escores na categoria-esquerda do TFCR e os escores no TBL. Por outro lado, foram notados padrões de inatenção periférica e simplificação. CONCLUSÕES: Nós observamos que a cópia do TFCR é eficaz para detector DA inicial e sugerimos que pacientes com DA manifestam inatenção periférica e simplificação, mas não negligência espacial unilateral esquerda.

Non-verbal learning is impaired in very mild Alzheimer's disease (CDR 0.5): normative data from the learning version of the Rey-Osterrieth Complex Figure Test.

Mild cognitive impairment (MCI) is a transitional state between normal aging and dementia. Although there have been some studies on the role of verbal memory in learning ability, there have been no reports on the part played by visual memory. In the present study, the Rey-Osterrieth Complex Figure Test (RCFT) was given to healthy subjects and to those with MCI to determine if visual memory was maintained in these two groups. Additionally, normative data from the learning version of the RCFT for Japanese subjects were examined, for purpose of reference. The participants consisted of 381 clinical dementia rating (CDR) 0 subjects and 137 CDR 0.5 subjects who could perform the full set of RCFT tasks. The CDR 0 group had significantly higher scores than the CDR 0.5 group in all trials. The CDR 0 participants also showed a significant step-by-step learning effect, while the CDR 0.5 participants did not show a significant learning effect. These results suggest that the CDR 0 participants maintained intact learning abilities of encoding and retrieval, while the CDR 0.5 participants did not do so; but further studies will be needed to clarify these findings.

Trialkyltin compounds bind retinoid X receptor to alter human placental endocrine functions.

Retinoid X receptor (RXR) is a nuclear receptor that plays important and multiple roles in mammalian development and homeostasis. We previously reported that, in human choriocarcinoma cells, tributyltin chloride and triphenyltin hydroxide, which are typical environmental contaminants and cause masculinization in female mollusks, are potent stimulators of human chorionic gonadotropin production and aromatase activity, which play key endocrine functions in maintaining pregnancy and fetal development. However, the molecular mechanism through which these compounds stimulate these endocrine functions remains unclear. Our current study shows that trialkyltin compounds, including tributyltin chloride and triphenyltin hydroxide, function as RXR agonists. Trialkyltins directly bind to the ligand-binding domain of RXR with high affinity and function as transcriptional activators. Unlike the natural RXR ligand, 9-cis-retinoic acid, the activity of trialkyltins is RXR specific and does not activate the retinoic acid receptor pathway. In addition, trialkyltins activate RXR to stimulate the expression of a luciferase reporter gene containing the human placental promoter I.1 sequence of aromatase, suggesting that trialkyltins stimulate human placental endocrine functions through RXR-dependent signaling pathways. Therefore, our results suggest that activation of RXR may be a novel mechanism by which trialkyltins alter human endocrine functions.

Prevalence and cognitive performances of clinical dementia rating 0.5 and mild cognitive impairment in Japan. The Tajiri project.

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

Executive dysfunction can explain word-list learning disability in very mild Alzheimer's disease: the Tajiri project.

Elderly people with questionable dementia (i.e. a Clinical Dementia Rating (CDR) of 0.5) have been focused on as representing the borderline zone condition between healthy people and dementia patients. Many of them are known to have pathologic traits of very mild Alzheimer's disease (AD). Although they present mild memory disorder, the underlying mechanism has not been fully investigated. Herein is reported the mechanism of learning disability in very mild AD. Eighty-six CDR 0.5 participants and 101 age- and education-matched healthy controls (CDR 0) were randomly selected from a community in the town of Tajiri, Miyagi Prefecture. The word-recall task of the Alzheimer Disease Assessment Scale-Japanese (i.e. learning and recall of 10 words) was administered. The numbers of words recalled in each trial and those never recalled throughout the trials were compared for the two CDR groups. The serial-position function was depicted for three parts (i.e. primary, middle, and recency). The CDR 0.5 group recalled significantly fewer words than the CDR 0 group. The number of never-recalled words was greater in the CDR 0.5 group. A remarkable difference was found in the middle part of the word list. The number of never-recalled words of the CDR 0.5 group was greater in the middle part. The large number of never-recalled words accounted for the poor learning performance of very mild AD participants. The results suggested that very mild AD participants have difficulty in learning and retaining words in the middle part of the word-list because of a functional decline of the central executive system.

Corpus callosum atrophy, white matter lesions, and frontal executive dysfunction in normal aging and Alzheimer's disease. A community-based study: the Tajiri Project.

BACKGROUND AND OBJECTIVES: Cerebral MRIs of normal aging and Alzheimer's disease (AD) frequently reveal corpus callosum (CC) atrophy, white matter hyperintensity (WMH), and hippocampal atrophy. However, their relationship or the relationship between these findings and cognitive function has not been fully studied. We investigated the relationship between CC atrophy, WMH, and hippocampal atrophy, together with frontal executive dysfunction in both normal aging and AD. METHOD: We examined 170 randomly selected residents from a designated community: 99 Clinical Dementia Rating (CDR) 0 (healthy, control group, HC) participants, 54 CDR 0.5 (very mild AD) patients, and 17 CDR 1 & 2 (probable AD) patients. By means of MRI, WMH and CC atrophy were visually rated. Four portions of the CC and the hippocampal width were measured. A Mini-Mental State Examination and Cognitive Abilities Screening Instrument (CASI) were performed to assess global function. For the frontal function, the CASI subitems of attention and word fluency, letter-based fluency, the Digit Symbol test of the WAIS-R, and Trail Making Tests were performed. RESULTS: Those patients with CDR 1 & 2 had both hippocampal and CC atrophy, whereas the CDR 0.5 patients had only hippocampal atrophy. Frontal executive dysfunction was associated with CC atrophy in both the HC and AD groups. Significant Spearman correlations were noted between CC atrophy and WMH in both groups. The combined effect of CC atrophy and WMH was noted only in the verbal fluency test in the HC group. CONCLUSION: In both groups, CC atrophy was associated with frontal executive dysfunction. The combined effect of CC atrophy and WMH in normal aging was probably due to subclinical ischemic conditions.

Therapeutic psychosocial intervention for elderly subjects with very mild Alzheimer disease in a community: the tajiri project.

Elderly subjects with mild memory impairment but not apparent dementia are the focus of early intervention trials. To examine the effects of structural psychosocial intervention for elderly subjects with very mild Alzheimer disease, i.e., Clinical Dementia Rating 0.5. The design is a prospective study. The experimental group (14 Clinical Dementia Rating 0.5 subjects) and the control group (11 Clinical Dementia Rating 0.5 subjects) were studied. Subjects with cerebrovascular disease as shown by magnetic resonance imaging were excluded. The experimental group participated in activities in a day-care-like setting once a week over a period of 6 months, whereas the control group did not. Each group was reevaluated after approximately 9 months. The effects of intervention were evaluated by cognitive tests, affective scales, a global clinical measure, an observation scale in the sessions, and a projective test. The experimental group showed a significant improvement on the word fluency test, whereas the control group showed a significant decline on the Mini-Mental State Examination, the digit span, and the Trail Making-A test. The experimental group revealed significantly higher levels on the Mini-Mental State Examination and the digit span compared with the control group after the 6-month intervention. A significant improvement was found for the global clinical measure, the observation scale, and the projective test in the experimental group after the intervention. After controlling the potential confounders (age, educational level, baseline cognitive, and affective status) in a multiple regression analysis, the same results were found. We considered that psychosocial intervention had beneficial effects for subjects with very mild Alzheimer disease.

Prevalence of dementia and dementing diseases in Japan: the Tajiri project.

BACKGROUND: Vascular dementia (VaD) has been considered to be more prevalent than Alzheimer disease in Japan. However, this might be the result of overdiagnosis stemming from some problematic diagnosis of VaD or of the frequent use of magnetic resonance imaging to detect cerebrovascular disease in older adults. OBJECTIVES: We investigated the prevalence of dementia and the ratios of dementing diseases. The effects of different criteria for VaD (DSM-IV, Alzheimer's Disease Diagnostic and Treatment Centers [ADDTC], and National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences [NINDS-AIREN]) were considered. Hippocampal atrophy and vascular contribution to dementia were evaluated using magnetic resonance imaging findings. METHODS: We targeted all residents 65 years and older (n = 3207) in Tajiri, Japan, and examined 1654 (participant group 1). Of these, 564 (participant group 2) were randomly selected, and 497 underwent magnetic resonance imaging and diagnosis of dementing diseases. RESULTS: We found the overall prevalence of dementia to be 8.5% (141/1654) in participant group 1. Of these, 21 (14.9%) had a history of stroke. Of the 113 participants who had a history of stroke independent of dementia, 18.6% (21/113) were demented. For participant group 2 (n = 497), 32 were demented. The ratio among the dementia for probable VaD based on the NINDS-AIREN criteria was 18.8% (6/32), whereas that for ischemic vascular dementia was 31.3% (10/32) according to the ADDTC criteria. CONCLUSION: We confirmed the overall prevalence of dementia in adults 65 years and older to be 8.5%. We found that VaD was not a common disorder according to the NINDS-AIREN criteria. Rather, the condition of possible Alzheimer disease with cerebrovascular disease was more common.

Trialkyltin compounds enhance human CG secretion and aromatase activity in human placental choriocarcinoma cells.

Human choriocarcinoma cell lines have been used as placental models for the study of endocrine function, including aromatase (CYP19) activity and the secretion of human CG (hCG). In the present study, we investigated the effects of trialkyltin compounds, which are suspected endocrine disrupters, on aromatase activity and hCG secretion in human choriocarcinoma JAR, JEG-3, and BeWo cells. Protein synthesis as measured by (35)S-methionine incorporation in all cell lines was markedly decreased by treatment with both tributyltin (TBT) and triphenyltin (TPT) at concentrations above 3 x 10(-7) M, due to cytotoxicity. In JAR cells, (35)S-methionine uptake was decreased by 50% at 3 x 10(-7) M of TBT. At a TPT concentration of 1 x 10(-7) M, protein synthesis in JAR cells was not affected, whereas JEG-3 and BeWo cells demonstrated slightly decreases. In all cell lines, both TBT and TPT increased levels of hCG secretion and aromatase activity in a dose- and time-dependent fashion following exposure to nontoxic concentration ranges. In addition, these trialkyltin compounds enhanced 8-bromo-cAMP-induced hCG secretion and aromatase activity in JAR cells. TBT caused dose-related increases in steady-state mRNA levels of both hCGbeta and CYP19 in JAR cells following 24- or 48-h exposure to nontoxic concentrations of TBT. However, these mRNA changes in JAR cells were not comparable to the changes in both hCG secretion and aromatase activity. These results indicate that the observed trialkyltin-induced alterations in human choriocarcinoma cells are due to other mechanism in addition to a regulation of hCG and CYP19 mRNA levels. Our studies suggest that trialkyltin compounds are potent stimulators of human placental hCG production and aromatase activity in vitro; and the placenta represents a potential target organ for trialkyltin compounds, whose endocrine-disrupting effects might be the result of local changes in hCG and estrogen concentrations in pregnant women.

Discrepancy between mental rotation and perspective-taking abilities in normal aging assessed by Piaget's Three-mountain task.

In a cross-sectional study, we examined age-related differences in visuo-spatial ability associated with image rotation, using two variants of Piaget's 'Three-Mountain Task.' The object-mental rotation (OMR) task detects the ability to mentally rotate an image, whereas the subject-mental rotation (SMR) task reveals the ability to mentally change one's perspective. A group of 33 young adults, 26 middle-aged adults, and 31 elderly normal adults were studied. Both tasks revealed age-related differences in performance but a larger difference between middle-aged and elderly group was observed for SMR than OMR performance. Age-related increases in the 'egocentric' type of error were found only on the SMR task. The results suggest that the ability to mentally change one's perspective declines with age, perhaps more than the ability to mentally rotate objects.

MRE-binding transcription factor-1 is activated during endotoxemia: a central role for metallothionein.

Endotoxin (LPS) has been established to induce hepatic metallothionein (MT), but the specific role of MT remains unknown. In this study, we examined whether MT can modulate MTF-1 activity during endotoxemia. Treatment with IL-6, the main mediator of MT induction during endotoxemia, enhanced the expression of the MRE(d)-driven reporter gene. MTF-1 DNA-binding activity was increased 16-24 h after LPS administration in wild-type mice, while no such activation was observed in MT-null mice during the same period. The expression of alpha(1)-acid glycoprotein (AGP) mRNA, an RNA regulated by MTF-1, was lower in MT-null than in wild-type mice. Our results suggested that MTF-1 was activated during endotoxemia. MT can act as an activator of MTF-1, and MT can induce MTF-1 targeted gene expression during endotoxemia.