Masaru Mimura

Decision making in Parkinson's disease: Analysis of behavioral and physiological patterns in the Iowa gambling task

Recent studies suggest that social recognition processes are affected by Parkinsons disease (PD). However, whether PD patients exhibit behavioral changes is still controversial. The purpose of the present study was to examine the decision making of PD patients performing the Iowa Gambling Task (IGT). We recruited a large number of early, nondemented PD patients for the IGT. We also recorded the skin conductance responses (SCRs) during the task as a measure of emotional arousal. Compared with the normal control (NC) subjects, PD patients selected more disadvantageous decks in the IGT, and their SCRs were lower than those of NC subjects before making decisions and after receiving reward or punishment. The tendency toward risky choices was not correlated with age, education, global cognitive function, or the severity of the disease. These results confirmed that the decision making of PD patients was affected by the disease, rather than by other cognitive functions; moreover, such behavior was related to lower emotional responses. Behavioral and SCR patterns of PD patients were similar to those of amygdala‐damaged patients. The response bias toward risky choices in PD may be explained by the dysfunction of the amygdala, which is known to be involved in risk evaluation.

Executive dysfunction in medicated, remitted state of major depression

BACKGROUNDnPast neuropsychological studies on depression have documented executive dysfunction and it has been reported that some dysfunction persists even after depressive symptoms disappear. Studies have shown a correlation between cerebrovascular lesions and executive dysfunction in depression among the elderly. The aim of the present study was to focus on executive functions in remitted major depressive disorder (MDD) patients, and to investigate whether remitted young and elderly patients show different patterns of executive dysfunction, and to ascertain the relationships with vascular lesions.nnnMETHODSnSubjects were 79 inpatients with MDD and 85 healthy controls. Each subject received Wisconsin Card Sorting Test (WCST), Stroop test, and Verbal Fluency Test (VFT) in a remitted state. Both the MDD and control groups were divided into young and elderly groups, and the performances between 4 groups were compared.nnnRESULTSnFor Stroop test, the scores of the MDD group were significantly lower than controls. In addition, as for VFT, the scores for the elderly MDD group were significantly lower than the other groups. Multiple regression analysis showed that VFT scores were affected by the presence of vascular lesions.nnnCONCLUSIONSnThe results of the present study demonstrated that executive dysfunction remained even in a remitted state in MDD patients, but the patterns of impairment were different between young and elderly patients. The results also suggested that vascular lesions affect executive dysfunction, particularly in elderly depressive patients.

Changes in regional cerebral blood flow following antidepressant treatment in late-life depression

Reversible/irreversible abnormalities of regional cerebral blood flow (rCBF) are seen in patients with depression. However, in late‐life depression there is little evidence of a longitudinal change in rCBF through remission. We examined whether the decreased rCBF in individuals with late‐life depression resolves following treatment.

Detection of hypofrontality in drivers with Alzheimer's disease by near-infrared spectroscopy

It is important to appropriately evaluate the driving performance of elderly persons. In the present study, near-infrared spectroscopy (NIRS) was employed to investigate differences of brain function between individuals with Alzheimers disease (n=12) and healthy elderly controls (n=14) while they were being tested using a driving simulator. Changes of the oxyhemoglobin level in the prefrontal areas of each subject were measured by NIRS during a driving task (collision avoidance). Compared with healthy controls, the Alzheimers disease group showed a less prominent increase of oxyhemoglobin in the prefrontal cortex during the collision avoidance task. The correlation between delay in braking and changes of oxyhemoglobin was positive in the healthy controls and negative in the Alzheimers disease group, suggesting that a task-related prefrontal increase of oxyhemoglobin has different implications under normal and pathological conditions. NIRS is a potentially useful tool for real-time monitoring of prefrontal activity during simulated or actual driving.

Gender differences in lateralization of mismatch negativity in dichotic listening tasks

OBJECTIVEnWith the aim of investigating gender differences in the functional lateralization subserving preattentive processing of language stimuli, we compared auditory mismatch negativities (MMNs) using dichotic listening tasks.nnnMETHODSnForty-four healthy volunteers, including 23 males and 21 females, participated in the study. MMNs generated by pure-tone and phonetic stimuli were compared, to check for the existence of language-specific gender differences in lateralization. Both EEG amplitude and scalp current density (SCD) data were analyzed.nnnRESULTSnWith phonetic MMNs, EEG findings revealed significantly larger amplitude in females than males, especially in the right hemisphere, while SCD findings revealed left hemisphere dominance and contralateral dominance in males alone. With pure-tone MMNs, no significant gender differences in hemispheric lateralization appeared in either EEG or SCD findings.nnnCONCLUSIONnWhile males exhibited left-lateralized activation with phonetic MMNs, females exhibited more bilateral activity. Further, the contralateral dominance of the SCD distribution associated with the ear receiving deviant stimuli in males indicated that ipsilateral input as well as interhemispheric transfer across the corpus callosum to the ipsilateral side was more suppressed in males than in females.nnnSIGNIFICANCEnThe findings of the present study suggest that functional lateralization subserving preattentive detection of phonetic change differs between the genders. These results underscore the significance of considering the gender differences in the study of MMN, especially when phonetic stimulus is adopted. Moreover, they support the view of Voyer and Flight [Voyer, D., Flight, J., 2001. Gender differences in laterality on a dichotic task: the influence of report strategies. Cortex 37, 345-362.] in that the gender difference in hemispheric lateralization of language function is observed in a well-managed-attention condition, which fits the condition adopted in the MMN measurement; subjects are required to focus attention to a distraction task and thereby ignore the phonetic stimuli that elicit MMN.

Cognitive rehabilitation and cognitive training for mild dementia

Cognitive deficits caused by dementing illnesses are chronic and progressive problems, which should be tackled both by biological and non‐biological approaches. Among the various techniques of non‐biological approaches (cognitive rehabilitation), centered is cognitive training intervention for individuals with dementia. Cognitive training is further divided into two different types of setting: group and individualized. Among group training techniques, the reality orientation training and day care/day services are known to have evidence‐based efficacy. Individually tailored cognitive training aims to directly and explicitly improve cognitive functioning of people with dementia specifically in the early stages. Increasing evidence demonstrates the efficacy of various individualized training programs for dementia, including Alzheimers disease (AD). Specifically, three techniques, known as spaced retrieval, dual cognitive support and procedural memory training, have shown promise in their ability to enhance learning in people with dementia. In addition, recent studies have suggested that a combination of pharmacotherapy and cognitive training may benefit individuals with AD. Cognitive training appears to be particularly effective for people with mild memory impairment who are on cholinergic treatment. It is now widely accepted that the theoretical framework of ‘errorless learning’ is also a guiding principle in the realm of cognitive training for people with dementia. Although the effect of factors, namely effort (effortful vs effortless) and stimulus features (perceptual vs conceptual), has not been fully determined, error elimination during learning sessions is essential for favorable outcomes.

Dysthymia and apathy: diagnosis and treatment.

Dysthymia is a depressive mood disorder characterized by chronic and persistent but mild depression. It is often difficult to be distinguished from major depression, specifically in its partially remitted state because “loss of interest” or “apathy” tends to prevail both in dysthymia, and remitted depression. Apathy may also occur in various psychiatric and neurological disorders, including schizophrenia, stroke, Parkinsons disease, progressive supranuclear palsy, Huntingtons disease, and dementias such as Alzheimers disease, vascular dementia, and frontotemporal dementia. It is symptomatologically important that apathy is related to, but different from, major depression from the viewpoint of its causes and treatment. Antidepressants, especially noradrenergic agents, are useful for depression-related apathy. However, selective serotonin reuptake inhibitors (SSRIs) may be less effective for apathy in depressed elderly patients and have even been reported to worsen apathy. Dopaminergic agonists seem to be effective for apathy. Acetylcholine esterase inhibitors, methylphenidate, atypical antipsychotics, nicergoline, and cilostazol are another choice. Medication choice should be determined according to the background and underlying etiology of the targeting disease.

Validation of the 7-Minute Screen for the Detection of Early-Stage Alzheimer’s Disease

Background/Aims: The 7-Minute Screen (7MS) is a screening battery to identify individuals with a high probability of Alzheimer’s disease (AD). The 7MS consists of four subtests (Temporal Orientation, Enhanced Cued Recall, Clock Drawing, and Verbal Fluency), each measuring a different aspect of cognition. The present study is designed to examine the predictive validity of the 7MS to distinguish between patients with early-stage AD and healthy control subjects. Methods: Sixty-three patients who were diagnosed as having probable or possible AD and 91 community-dwelling elderly individuals of comparable age, sex distribution, and education were administered the 7MS (paper-and-pencil version) and other screening batteries. All patients were rated Clinical Dementia Rating (CDR) 0.5–1, categorized as early-stage AD, and all participants obtained a score of less than 6 for the Geriatric Depression Scale (15-item version). Results: Mean scores for patients and controls on all the four subtests were significantly different. When using the total score of the 7MS, which was calculated by the original logistic regression formula based on all of the four subtests, the sensitivity for early-stage AD was 90.5% with a specificity of 92.3%. Correlation analysis indicated high concurrent validity between the 7MS and existing standard cognitive screening batteries (e.g., MMSE, HDS-R). In correlation analysis and multiple regression analysis, demographic effects (age, sex, and education) were not significantly associated with the total score of the 7MS in controls. Conclusions: The results showed that the 7MS had a high level of sensitivity and specificity. We also found that the 7MS was not affected by demographic characteristics. These findings demonstrated that the 7MS is a useful screening tool for discriminating patients with early-stage AD from intact individuals.

SPECT-Identified Neuroanatomical Predictor of the Cognitive Effects of Donepezil Treatment in Patients with Alzheimer’s Disease

Background/Objective: We attempted to determine whether the pretreatment regional cerebral blood flow (rCBF) might predict cognitive changes in response to donepezil treatment, as assessed in terms of the Alzheimer Disease Assessment Scale cognitive subscale (ADAS-cog), and in relation to the severity of subcortical hyperintensities (SH). Method: Forty-one patients with Alzheimer’s disease (AD) were treated with donepezil at baseline. All the patients underwent a single photon emission computed tomography examination before donepezil therapy. They also completed the ADAS-cog at baseline and after 24 weeks of donepezil therapy. SH were assessed semiquantitatively using a recently developed visual rating scale. We analyzed the correlation between the baseline rCBF and changes in the ADAS-cog score using statistical parametric mapping, including the severity of the SH as a covariate. Results: Lower pretreatment rCBF levels in the right orbitofrontal cortex (OFC) predicted a better improvement in the ADAS-cog score in response to donepezil therapy. The severity of SH did not appear to influence this correlation. Conclusions: This effect may reflect the choline acetyltransferase activity associated with the OFC. The presence of SH did not appear to influence the effect of donepezil therapy on the cognitive function as assessed by ADAS-cog.

Neuro-Behcet's disease presenting with amnesia and frontal dysfunction

We report a 48-year-old patient with neuro-Behcets disease who presented with the combination of severe memory impairment and frontal/executive dysfunction. The clinical feature mimicked that of diencephalic amnesic syndrome. The MRI and SPECT findings supported the notion that the thalamus and related subcortical-frontal connection was responsible for this patients problem.