Kyoko Akanuma

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.

A Randomized Controlled Trial of the Group Reminiscence Approach in Patients with Vascular Dementia

Aim: To evaluate the beneficial effect of the group reminiscence approach (GRA) in patients with vascular dementia on the aspect of cognitive and observed behavioral parameters. Methods: Sixty patients who were diagnosed to have vascular dementia were randomly assigned to three arms: group reminiscence arm, social contact arm, and control arm. A 1-hour session of GRA and social contact was given once a week for 3 months to the group reminiscence and the social contact arm, respectively. Only supportive care was given in the control arm. Improvement in cognitive function and behavioral activities were defined as the primary outcome. Results: No significant improvements in the main outcome measures were demonstrated. Conclusion: These results do not support the hypothesis that GRA is beneficial to patients with vascular dementia.

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.

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.

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.

Singing therapy can be effective for a patient with severe nonfluent aphasia.

Patients with severe aphasia are rarely treated using speech therapy. We used music therapy to continue to treat a 79-year-old patient with chronic severe aphasia. Interventions 1, 2, and 3 were to practice singing a song that the patient knew, to practice singing a song with a therapist, and to practice saying a greeting using a song with lyrics, respectively. In addition, practice of uttering names of body parts was initiated using touch and rhythm. After intervention 1, the patient could sing spontaneously and repeat lyrics. After intervention 2, she could sing with the therapist, and sing spontaneously and repeat lyrics. After intervention 3, she could memorize words with meaning, say the words in context, and use them. The patient could utter the names of two body parts after therapy with touch and rhythm. These suggest that rehabilitation therapy can still be used in patients with severe cognitive impairment.

Impaired instrumental activities of daily living affect conversion from mild cognitive impairment to dementia: the Osaki-Tajiri Project.

Aim:  To determine whether impaired instrumental activities of daily living affect conversion from mild cognitive impairment to dementia for subjects in a community.

Impaired memory and executive function associated with decreased medial temporal and prefrontal blood flow in Clinical Dementia Rating 0.5 status: the Osaki‐Tajiri project

Aim:  The Clinical Dementia Rating (CDR) is an assessment of dementia severity based on observations of activities of daily living, and a CDR of 0.5 (CDR 0.5) represents questionable dementia. A combination of the Cognitive Abilities Screening Instrument (CASI) and the Trail Making Test (TMT) scores discriminated CDR 0.5 subjects from healthy participants with a high degree of accuracy. We investigated the neurological background of CDR 0.5 subjects by correlating CASI and TMT scores with regional cerebral blood flow (rCBF) as measured by single photon emission computed tomography (SPECT).