Yurinosuke Kitabayashi

Anosognosia in Alzheimer's disease : Association with patient characteristics, psychiatric symptoms and cognitive deficits

Abstract  Anosognosia is one of the major problems in the treatment and care of Alzheimers disease (AD) patients. The aim of the study was to determine the patient characteristics, psychiatric symptoms, and cognitive deficits associated with anosognosia, because these are currently poorly understood. Eighty‐four patients who met the National Institute of Neurological and Communicative Disease and Stroke‐Alzheimers Disease and Related Disorders Association criteria for probable AD were examined for anosognosia based on the difference between questionnaire scores of the patient and their caregiver. The relationship of anosognosia with patient characteristics (age, age at onset, duration of illness, education, Mini‐Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Hyogo Activities of Daily Living Scale (HADLS)), psychiatric symptoms (Neuropsychiatric Inventory (NPI), Geriatric Depression Scale (GDS)), and cognitive function (Digit Span, Word Fluency Test, Trail Making Test, Stroop Test, Ravens Coloured Progressive Matrices Test) were studied. Anosognosia showed positive correlations with age, age at onset, duration of illness, CDR, HADLS, and NPI disinhibition, and negative correlations with MMSE and GDS. Regarding cognitive function, only Part III of the Stroop Test was a predictor of anosognosia. The severity of anosognosia increased with disease progression and with a later age at onset. Subjective complaints of depression requiring self‐monitoring of mood tended to decrease and, in contrast, inhibition of socially unsuitable behavior became more difficult as anosognosia worsened. Regarding cognitive function, anosognosia appeared to be associated with response inhibition impairment. Both disinhibition, as a psychiatric symptom, and response inhibition impairment are known to be correlated with disturbance of orbitofrontal function, which therefore may be associated with anosognosia.

Alteration of fractional anisotropy and apparent diffusion coefficient in obsessive-compulsive disorder: a diffusion tensor imaging study.

BACKGROUND Abnormalities of fractional anisotropy (FA) have been reported in previous diffusion tensor imaging (DTI) studies in patients with obsessive-compulsive disorder (OCD). However, there are some inconsistencies in the results and the apparent diffusion coefficient (ADC) has not been investigated. The goal of this study was to investigate white matter abnormalities and water diffusivity, as reflected by FA and ADC, using DTI in patients with OCD. METHODS Fifteen patients with OCD and 15 healthy volunteers underwent DTI. Voxelwise analysis was used to compare FA in white matter and ADC in gray matter/white matter of the two groups. RESULTS Compared with healthy volunteers, the patients had higher FA in the bilateral semioval center extending to the subinsular white matter; and a higher ADC in the left medial frontal cortex. There were no areas with a significantly lower FA or ADC in patients compared with healthy volunteers. CONCLUSIONS A significantly higher FA was found in regions associated with the emotion of disgust and a trend for a higher ADC was found in a region associated with the regulation of emotions. These findings suggest that neurocircuits involved in disgust processing may play an important role in the pathophysiology of OCD.

Regional cerebral blood flow changes associated with interoceptive awareness in the recovery process of anorexia nervosa.

BACKGROUND An abnormality in regional cerebral blood flow (rCBF) in anorexia nervosa (AN) patients has been reported. There are very few studies that have investigated the rCBF changes in the recovery process of AN. METHODS For eight female AN patients, we performed (123)I-IMP single photon emission computed tomography (SPECT) and four psychological assessments (Eating Disorder Inventory (EDI), Eating Attitude Test (EAT), Self-Rating Depression Scale (SDS) and State-Trait Anxiety Inventory (STAI)) both before and after inpatient-behavioral therapy. SPECT images were analyzed using statistical parametric mapping software. We also performed correlational analysis between rCBF and clinical variables. RESULTS Following treatment, the patients showed significant body weight recovery. They showed significant improvement in EAT, SDS, STAI and a subscale of EDI - interoceptive awareness (IA) - but not in total EDI or other EDI subscales. Significant rCBF increases were observed in the precuneus, posterior cingulate cortex (PCC), right dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC) and medial prefrontal cortex (MPFC) by the treatment. Significant correlation was observed between rCBF of right DLPFC and IA score before treatment. CONCLUSIONS Changes of rCBF in right DLPFC, ACC, MPFC, PCC and precuneus were related to the AN recovery process and might be associated with improvement of IA following treatment.

Relationship between clock drawing test performance and regional cerebral blood flow in Alzheimer's disease : A single photon emission computed tomography study

Abstract The clock drawing test (CDT) is a useful tool for screening cognitive impairment. Previous neuropsychological studies have revealed that CDT performance requires several cognitive functions including semantic memory, visuospatial function and executive function. However, the neural substrates involved remain to be elucidated. The aim of the present study was to identify the brain regions responsible for CDT performance in patients with Alzheimers disease (AD). Twenty‐six patients satisfying the National Institute of Neurological and Communicative Disease and Stroke‐Alzheimers Disease and Related Disorders Association criteria for probable AD underwent the CDT and the Mini‐Mental State Examination (MMSE), together with a N‐isopropyl‐p‐[123I] iodoamphetamine (IMP) single photon emission computed tomography measurements of the resting regional cerebral blood flow (rCBF). The CDT score correlated significantly with the MMSE score (r = 0.582; P < 0.05). Stepwise multiple regression analysis revealed that the MMSE score and the left posterior temporal rCBF were major predictors of CDT score. These findings suggest that the CDT score may reflect the severity of dementia, and that it has a close relationship with the left posterior temporal function. Our findings provide the first functional neuroimaging evidence for the neural substrates involved in CDT performance.

Relationships among burnout, coping style and personality: Study of Japanese professional caregivers for elderly

Aim:  To investigate relationships among burnout, coping style and personality.

Qualitative analyses of clock drawings in Alzheimer's disease and vascular dementia

Although quantitative analyses of clock drawings (CD) have achieved widespread clinical use as a cognitive screening, little is known about the qualitative profiles of CD in Alzheimers disease (AD) and vascular dementia (VD). To address this issue, the present study examined the significance of qualitative analyses of CD in AD and VD. Sixty‐seven AD patients, 44 VD patients and eight controls underwent a clock drawing test and took the Mini‐Mental State Examinations (MMSE). In the dementia groups, quantitative scores significantly decreased compared with controls and were significantly correlated with MMSE scores. Qualitative analysis demonstrated that in AD patients qualitative error patterns were stable and independent of severity. In contrast, in VD patients the frequency of graphic difficulties and conceptual deficit increased, while the frequency of spatial and/or planning deficit decreased, as severity worsened. In mild dementia groups the frequency of spatial and/or planning deficit was significantly higher in VD. In moderate dementia groups, the frequency of graphic difficulties was significantly higher in VD and the difference in the frequency of spatial and/or planning deficit seen in mild dementia disappeared. The present study suggests that qualitative analyses of clock drawings could demonstrate the neuropsychological profiles of AD and VD and their differences between these dementias.

Correlation between anosognosia and regional cerebral blood flow in Alzheimer's disease

The purpose of this study was to determine the brain regions associated with anosognosia in Alzheimers disease (AD). Anosognosia for memory disturbance was assessed in 29 probable AD patients, based on the discrepancy between questionnaire scores of the patients and their caregivers. In I-123-IMP single photon emission computed tomography (SPECT), a significant association was found between anosognosia and decreased perfusion in the orbitofrontal cortex, using regression analysis. This result is consistent with the previous studies that have reported an association between frontal dysfunction and anosognosia, and further suggests that the orbitofrontal cortex specifically associates with anosognosia in AD within the frontal cortex.

Relationship between regional cerebral blood flow and verbal fluency in Alzheimer's disease

Abstract Category and letter verbal fluency tests are widely used for dementia detection and severity measure. Performances of these tasks have been regarded to be mainly associated with the left frontal lobe function. However, some recent studies suggest that there are different neuropsychological bases between these two tasks, and the brain region which contributes to these performances still remains unclear in Alzheimers disease (AD). To clarify the neural basis of verbal fluency in AD, we examined the relationship between performances of these tasks and regional cerebral blood flow (rCBF). Twenty‐five AD patients were administered verbal fluency tasks and single photon emission computed tomography (SPECT) scans. Thirteen cortical regions of interest were symmetrically defined in each hemisphere. Letter fluency scores were correlated significantly only with the left prefrontal (Brodmanns area (BA) 10–46) regional cerebral blood flow (rCBF). In contrast, category fluency scores were correlated most strongly with the left temporal rCBF and also with the left prefrontal (BA 10–46) rCBF. In conclusion, the present study suggests that left prefrontal (BA 10‐46) dysfunction contributes to decline in both letter and category fluency scores in AD, while typical posterior dysfunction of AD has a closer relationship with decline in category fluency scores.

Regional cerebral blood flow changes in a patient with delusional parasitosis before and after successful treatment with risperidone: A case report

The pathophysiology and appropriate pharmacological interventions for delusional parasitosis (DP) remain unknown. Here, we present a case of DP following brain infarction of the right temporoparietal region. Pharmacotherapy with risperidone resulted in a dramatic therapeutic response over a short period. In a sequential N-isopropyl-p-[(123)I]-iodoamphetamine single photon emission computed tomography ([(123)I]-IMP SPECT) study, post-treatment SPECT images revealed a marked increase of rCBF in the large areas including the bilateral frontal and left temporoparietal regions, the right parietal operculum and the bilateral basal ganglia, in contrast to pre-treatment SPECT images showing a global decrease of rCBF. Our clinical outcome suggests the efficacy and safety of risperidone for treatment of DP and that both dopaminergic and serotonergic dysfunction may play a role in DP. Our sequential SPECT findings suggest that psychiatric improvement of DP is associated with increased rCBF.

Effect of traditional Japanese herbal medicine toki-shakuyaku-san for mild cognitive impairment: SPECT study.

Traditional Japanese herbal medicines (so-called Kampo) are widely used in clinical settings in Japan. Toki-shakuyaku-san (TSS) was described in the classic Kampo text Kinkiyoryaku approximately 1000 years ago and is mainly used for gynecologic disorders (climacteric disorders, dysmenorrhea, anemia), because it improves peripheral circulation disturbance (so-called ‘Oketsu syndrome’); but TSS may also have neuroprotective and antidementia effects. Amnestic mild cognitive impairment (MCI) is defined as a subtle but measurable memory disorder, in which memory problems are greater than normally expected with aging, but no other symptoms of dementia are observed. Amnestic MCI carries a high risk of progression to Alzheimer’s disease (AD). Cholinesterase inhibitors (ChEI) may prevent progression to AD, but pharmacological therapy for MCI has not been established; therefore, we examined the efficacy of TSS for treatment of amnestic MCI. The subjects were three patients with amnestic MCI diagnosed based on criteria of the international working group on MCI. The patients were treated with TSS for 8 weeks. TSS is registered in the Pharmacopoeia of Japan as Kampo Medicine TJ-23 and was provided by Tsumura (Tokyo, Japan). TSS is prepared from the extract of a mixture of dried plants: 4.0 g peony root, 4.0 g Atractylodes lancea rhizome, 4.0 g Alisma rhizome, 4.0 g Hoelen, 3.0 g Cnidium rhizome, and 3.0 g Japanese angelica root, giving 7.5 g of powder as a daily dose. Magnetic resonance imaging (MRI) was performed before treatment and N-isopropyl-p[I]iodoamphetamine single-photon emission computed tomography (SPECT) and a mini-mental state examination (MMSE) were performed before and after treatment. SPECT images were analyzed using 3-D stereotactic surface projections (3D-SSP). This study was approved by the ethics committee of Kyoto Prefectural University of Medicine (C-97) and written informed consent was obtained from the subjects. Patient 1 was a 74-year-old woman with 11 years of education.MRI showed very mild brain atrophy, including in the hippocampus; MMSE scores before and after treatment were 23 (time, -2; place, -1; recall, -3; 3-step order -1) and 26 (time, -2; serial 7, -2), respectively; and SPECT showed decreased regional cerebral blood flow (rCBF) in the bilateral posterior cingulate before treatment. The decrease diminished following treatment. Patient 2 was a 79-year-old woman with 11 years of education. MRI showed left-dominant very mild brain atrophy, including in the hippocampus; MMSE scores before and after treatment were 26 (place, -1; recall, -3) and 27 (place, -1; recall, -2), respectively; and SPECT showed decreased rCBF in the left temporoparietal lobe and the left superior lateral frontal lobe before treatment. The decrease diminished following treatment. Patient 3 was a 76-year-old woman with 10 years of education. MRI showed left-dominant mild brain atrophy, including the hippocampus; MMSE scores before and after treatment were 22 (time, -1; place, -1; serial 7, -4; recall, -1; 3-step order, -1) and 25 (serial 7, -4; recall, -1), respectively; and SPECT showed decreased rCBF in the bilateral anterior temporal and inferior frontal lobes before treatment. Although the decrease diminished following treatment, a new decrease in rCBF appeared in the bilateral frontal poles. An 8-week prescription of TSS improved cognitive dysfunction in all three cases of amnestic MCI, rCBF decrease markedly in two of the patients, and no marked adverse effects were observed in any of the patients. This suggests that TSS may improve central nervous circulation and enhance cognitive function in amnestic MCI. TSS activates the central nervous acetylcholinergic system, similarly to ChEI, and may also affect the activities of superoxide dismutase, lipid peroxides, glutamate, monoamine, and nerve growth factors in the central nervous system; these properties suggest that TSS exerts neuroprotective effects via pathways that are unaffected by conventional antidementia drugs. Although studies in more subjects are required, TSS may be a pharmacotherapeutic option for MCI to prevent progression to AD because its safety and cost-effectiveness have been established over its long history of use. This study was supported by the research fund of the Institute of Kampo Medicine (Japan).