Mitsue Meguro

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.

Risperidone is effective for wandering and disturbed sleep/wake patterns in Alzheimer's disease

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

Improved social interaction and increased anterior cingulate metabolism after group reminiscence with reality orientation approach for vascular dementia

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

Comprehensive approach of donepezil and psychosocial interventions on cognitive function and quality of life for Alzheimer's disease: the Osaki-Tajiri Project

many disease-modifying treatments are in early stages of development [11]. Multimodal therapies, targeting ı́-amyloid, tau, inflammation and cognitive symptoms, may prove to be more efficacious than monotherapy. However, as these are more likely to cause adverse effects, they may not be acceptable to many patients during the earliest stages of the disease. On the other hand, the availability of an early predictor for rapid disease progression may mean those positive would be willing to accept aggressive treatments and concomitant side-effects. This case demonstrates that Alzheimer’s disease can progress extremely rapidly, with seizures and myoclonus as early manifestations. The presence of 14-3-3 proteins in the cerebrospinal fluid may suggest rapid disease progression. However, other neurological diseases associated with extensive neurological damage and 14-3-3 proteins in the cerebrospinal fluid should always be considered, and excluded with a detailed history and physical examination, together with appropriate investigations and imaging.

Language deterioration in four Japanese–Portuguese bilingual patients with Alzheimer's disease: a trans‐cultural study of Japanese elderly immigrants in Brazil

Background:  Bilingualism is an area of linguistics that has been investigated in aphasic patients. However, bilingualism and Alzheimers disease (AD) have not been fully investigated despite the fact that language impairment is a frequent symptom of AD. Brazil has the greatest number of Japanese immigrants and, consequently, there are many bilingual people who are fluent in both Japanese and Portuguese in Brazil.

Combined Memory and Executive Function Tests Can Screen Mild Cognitive Impairment and Converters to Dementia in a Community: The Osaki-Tajiri Project

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

Executive dysfunction can explain word‐list learning disability in very mild Alzheimer's disease: The Tajiri Project

Abstract  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 Alzheimers 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.

Confabulations on episodic and semantic memory questions are associated with different neurologic backgrounds in Alzheimer disease.

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

Confabulations in Episodic Memory Are Associated With Delusions in Alzheimer’s Disease:

Although confabulations and delusions are observed in Alzheimer’s disease, the relationship between the 2 has not been fully investigated. This study involved 50 patients with Alzheimer’s disease and 10 healthy participants. After the patients were divided into delusional and nondelusional groups, confabulations and cognitive function were assessed. No confabulations appeared in the healthy participants, and only patients with Alzheimer’s disease showed confabulations. The delusional group produced more confabulations on episodic subjects than on semantic subjects. There was a correlation between cognitive impairment and confabulations in semantic memory. These findings suggest that different mechanisms are involved in confabulations between semantic and episodic memories.

Behavioral and psychological symptoms assessed with the BEHAVE-AD-FW are differentially associated with cognitive dysfunction in Alzheimer’s disease

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