Competency of aMCI patients to consent to cholinesterase treatment.

BACKGROUND: In medical practice, a patient's loss of competency is a major obstacle when choosing a treatment and a starting treatment program smoothly. A large number of studies have revealed the lack of medical competency in patients with dementia. However, there have been only a few reports focusing on the capacity of patients with mild cognitive impairment (MCI) to make a medical choice. METHODS: In this study, we evaluated the competency of 40 patients with amnestic MCI (aMCI) and 33 normal subjects to make a medical choice using the MacArthur Competence Assessment Tool-Treatment (MacCAT-T). We compared the judgement of a team conference using the recorded semi-structured interview with the clinical judgement of a chief clinician. RESULTS: A team conference concluded that 12 aMCI patients had no competency, and the clinical judgement, without any special interview, judged that five aMCI patients had no competency. All subjects in the control groups were judged to be competent to consent to treatment by both clinicians and the team conference. CONCLUSIONS: Without supplementary tools such as explanatory documents, not a few patients with aMCI were judged by a team conference to have no competency to consent to therapy even in a relatively simple and easy case. In contrast, clinical physicians tended to evaluate the competency of aMCI patients in a generous manner.

Clinical characteristics of elderly depressive patients with low metaiodobenzylguanidine uptake.

BACKGROUND: Recently, depression with Lewy body pathology before the appearance of parkinsonism and cognitive dysfunction has been drawing attention. Low cardiac metaiodobenzylguanidine (MIBG) uptake is helpful for early differentiation of Lewy body disease (LBD) from late-onset psychiatric disorders even before parkinsonism or dementia appears. In this study, we used MIBG uptake as a tool in suspected LBD, and evaluated the relationship of MIBG results to clinical characteristics and depressive symptoms. METHODS: Fifty-two elderly inpatients with depression were included in this study. The Hamilton Depression Rating Scale (HDRS) was administered at admission, and 123 I-MIBG cardiac scintigraphy was performed. Of 52 patients, 38 had normal and 14 had reduced MIBG uptake. RESULTS: Correlation analyses of the late phase heart-to-mediastinum (H/M) ratio on the MIBG test and each item of the HDRS revealed that the H/M ratio was significantly correlated with scores of 'agitation', 'anxiety-somatic', and 'retardation' on the HDRS. Mean HDRS composite scores of 'somatic and psychic anxiety (Marcos)' and 'somatic anxiety/somatization factor (Pancheri)' were higher in the low uptake group than in the normal uptake group. CONCLUSION: Elderly patients with depression who manifested an obvious somatic anxiety tend to show low MIBG uptake, and are more likely to have Lewy body pathology.

Creutzfeldt-Jakob disease with Alzheimer pathology, presenting with status epilepticus following repeated partial seizures: a case report and literature review.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disease. Common first symptoms are dementia, cerebellar ataxia, visual disturbance, and psychiatric symptoms. Seizure as the first symptom of CJD is a very rare finding. CASE PRESENTATION: We experienced an elderly woman who presented initially with status epilepticus following repeated partial seizures in the course of Alzheimer disease (AD) dementia. Anti-convulsive therapy had no effect. Autopsy revealed definite CJD with AD pathology. COCLUSIONS: This is the first reported CJD case presenting with status epilepticus in the course of AD dementia.

Verbal or Visual Memory Score and Regional Cerebral Blood Flow in Alzheimer Disease.

OBJECTIVE: Among many cognitive function deficits, memory impairment is an initial and cardinal symptom in Alzheimer disease (AD). In most cases, verbal and visual memory scores correlate highly, but in some cases the deficit of verbal or visual memory is very different from that of the other memory. In this study, we examined the neural substrates of verbal and visual memory in patients with AD. METHODS: One hundred eighty-eight consecutive patients with AD were recruited from outpatient units. Verbal and visual memory scores were evaluated using the Wechsler Memory Scale - revised. The patients underwent brain SPECT with 99mTc-ethylcysteinate dimer. RESULTS: After removing the effects of age, sex, education, and Mini-Mental State Examination scores, correlation analysis showed a significant correlation of verbal memory scores to regional cerebral blood flow (rCBF) in the bilateral cingulate gyrus and left precuneus. Similarly, a significant correlation of visual memory scores to rCBF was found in the right precuneus and right cingulate gyrus. CONCLUSION: The posterior medial cortices (PMC) are very important areas in episodic memory among patients with mild AD. Verbal memory is more closely related to the both sides of the PMC, while visual memory is more closely related to the right PMC.

Survival times with and without tube feeding in patients with dementia or psychiatric diseases in Japan.

BACKGROUND: It is widely supposed that there has been no evidence of increased survival in patients with advanced dementia receiving enteral tube feeding. However, more than a few studies have reported no harmful outcome from tube feeding in dementia patients compared to in patients without dementia. METHODS: This was a retrospective study. Nine psychiatric hospitals in Okayama Prefecture participated in this survey. All inpatients fulfilling the entry criteria were evaluated. All subjects suffered from difficulty with oral intake. Attending physicians thought that the patients could not live without long-term artificial nutrition. The physicians decided whether to make use of long-term artificial nutrition between January 2012 and December 2014. RESULTS: We evaluated 185 patients. Their mean age was 76.6 ± 11.4 years. Of all subjects, patients with probable Alzheimer's disease (n = 78) formed the biggest group, schizophrenia patients (n = 44) the second, and those with vascular dementia (n = 30) the third. The median survival times were 711 days for patients with tube feeding and 61 days for patients without tube feeding. In a comparison different types of tube feeding, median survival times were 611 days for patients with a nasogastric tube and more than 1000 days for those with a percutaneous endoscopic gastrostomy tube. CONCLUSION: Patients with tube feeding survived longer than those without tube feeding, even among dementia patients. This study suggests that enteral nutrition for patients with dementia prolongs survival. Additionally, percutaneous endoscopic gastrostomy tube feeding may be safer than nasogastric tube feeding among patients in psychiatric hospitals.

Long-Term Survival of Patients Receiving Artificial Nutrition in Japanese Psychiatric Hospitals.

BACKGROUND/AIMS: Most patients with dementia suffer from dysphagia in the terminal stage of the disease. In Japan, most elderly patients with dysphagia receive either tube feeding or total parenteral nutrition. METHODS: In this study, we investigated the factors determining longer survival with artificial nutrition. Various clinical characteristics of 168 inpatients receiving artificial nutrition without oral intake in psychiatric hospitals in Okayama Prefecture, Japan, were evaluated. RESULTS: Multiple logistic regression analysis showed that the duration of artificial nutrition was associated with a percutaneous endoscopic gastrostomy (PEG) tube, diagnosis of mental disorder, low MMSE score, and absence of decubitus. CONCLUSION: Patients with mental disorders survived longer than those with dementia diseases on artificial nutrition. A PEG tube and good nutrition seem to be important for long-term survival.

Positive affect and regional cerebral blood flow in Alzheimer's disease.

Quality of life (QOL) has been recently recognized as the central purpose of healthcare, and positive affect is one of the core dimension of QOL. However, positive affect among patients with dementia or Alzheimer's disease (AD) has not received much attention in the medical research field. One hundred sixteen consecutive patients with AD were recruited from the outpatient units of the Memory Clinic of Okayama University Hospital. The positive affect score was evaluated using the positive affect domain of the Quality of Life questionnaire for Dementia (QOL-D). Patients underwent brain SPECT with 99mTc-ethylcysteinate dimer. Positive affect scores were inversely related to apathy scores, subjective depressive scores, and delusion scores. After removing the effects of age, sex, duration of education, and cognitive function, positive affect scores showed a significant correlation with regional cerebral blood flow in the left premotor and superior frontal gyri. The left premotor and superior frontal area is significantly involved in the pathogenesis of the decrease of positive affect in AD. Apathy and depression are closely related to the prefrontal area in AD, and they may affect the relationship between positive affect and the left prefrontal area.

Encephalitis With Antibodies to GluN2B During Administration of Clozapine.

Clozapine's immunomodulatory properties may contribute to its effect on schizophrenia as well as various adverse effects. However, a possible relationship between N-methyl-D-aspartate-type glutamate receptor antibodies, refractory schizophrenia, and clozapine has not been reported. We experienced a patient who developed refractory schizophrenia that mimicked an exacerbation of encephalitis with antibodies to N-methyl-D-aspartate-type glutamate receptor (GluN2B) after administration of clozapine for 26 days. We performed plasma exchange 5 times and subsequent steroid pulse therapy. The level of consciousness improved within a few weeks, but involuntary movement as well as psychotic symptoms remained. The production of anti-GluN2B antibodies may have contributed to the patient's resistance to the antipsychotic effects of clozapine in addition to mediating the encephalitis. When we administer clozapine to patients with refractory schizophrenia, we should be careful to differentiate between a diagnosis of refractory schizophrenia and encephalitis with antibodies to GluN2B.

Behavioral variant of frontotemporal dementia: Fundamental clinical issues associated with prediction of pathological bases.

Behavioral variant of frontotemporal dementia (bvFTD) is a clinical syndrome characterized mainly by behavioral symptoms due to frontal dysfunction. Major neurodegenerative bases of bvFTD include Pick's disease, frontotemporal lobar degeneration with trans-activation response DNA protein 43-positive inclusions, corticobasal degeneration, and progressive supranuclear palsy. Early disinhibition characterized by socially inappropriate behaviors, loss of manners, and impulsive, rash and careless actions is the most important clinical feature of bvFTD. On the other hand, it was reported that clinical presentations of some Alzheimer's disease cases and patients with psychiatric disorders (e.g., addictive disorders, gambling disorder and kleptomania) often resemble that of bvFTD. Although clinical differentiation of 'true' bvFTD cases with frontotemporal lobar degeneration (FTLD) pathology from mimicking cases without it is not always easy, evaluation of the following features, which were noted in autopsy-confirmed FTLD cases and/or clinical bvFTD cases with circumscribed lobar atrophy, may often provide clues for the diagnosis. (i) The initial symptoms frequently develop at 65 years or younger, and (ii) 'socially inappropriate behaviors' can be frequently interpreted as contextually inappropriate behaviors prompted by environmental visual and auditory stimuli. Taking a detailed history usually reveals various kinds of such behaviors in various situations in everyday life rather than the repetition of a single kind of behavior (e.g., repeated shoplifting). (iii) A correlation between the distribution of cerebral atrophy and neurological and behavioral symptoms is usually observed, and the proportion of FTLD cases with right side-predominant cerebral atrophy may be higher in a psychiatric setting than a neurological setting. Finally, (iv) whether the previous course and the combination of symptoms observed at the first medical visit can be explained by major evolution patterns of clinical syndromes in pathologically confirmed FTLD cases should be considered. These views may provide clues to differentiate FTLD from Alzheimer's disease and to predict a subsequent clinical course and therapeutic interventions needed in the future.

Comparison of QOL between patients with different degenerative dementias, focusing especially on positive and negative affect.

BACKGROUND: Quality of life (QOL) has become an important outcome measure in the care of dementia patients. However, there have been few studies focusing on the difference in QOL between different dementias. METHODS: Two-hundred seventy-nine consecutive outpatients with Alzheimer's disease (AD), dementia with Lewy bodies (DLB) or frontotemporal dementia (FTD) were recruited. The QOL was evaluated objectively using the QOL Questionnaire for Dementia (QOL-D).The QOL-D comprises six domains: positive affect, negative affect and actions, communication, restlessness, attachment to others, and spontaneity. General cognition, daily activities, and behavioral and psychological symptoms of dementia were also evaluated. RESULTS: The scores of positive affect of QOL-D of AD patients were significantly higher than those of patients with DLB or FTD (AD 3.1 ± 0.8, DLB 2.6 ± 0.9, FTD 2.6 ± 0.7). The scores of negative affect and action of QOL-D of FTD patients were significantly higher than those of patients with AD or DLB (FTD 2.0 ± 0.8, AD 1.4 ± 0.5, DLB 1.5 ± 0.6). The apathy scores of FTD and DLB patients were significantly higher than those of patients with AD. The disinhibition scores of FTD patients were significantly higher than those of patients with AD or DLB. CONCLUSIONS: The apathy of FTD and DLB patients and depression of DLB patients might affect the lower positive affect of FTD and DLB patients compared to AD patients. The disinhibition of FTD patients might affect the abundance of negative affect & actions in FTD patients compared to AD and DLB patients.

Heterogeneity of patients receiving artificial nutrition in Japanese psychiatric hospitals: a cross-sectional study.

AIM: Artificial nutrition, including tube feeding, continues to be given to dementia patients in numerous geriatric facilities in Japan. However, the clinical characteristics of patients receiving artificial nutrition have not been fully investigated. Therefore, we tried to evaluate the clinical features of those patients in this study. METHODS: Various clinical characteristics of all inpatients at 18 of 20 psychiatric hospitals in Okayama Prefecture, Japan, with a percutaneous endoscopic gastrostomy tube, nasogastric tube, or total parenteral nutrition were evaluated. RESULTS: Two hundred twenty-one patients (5.4% of all inpatients) had been receiving artificial nutrition for more than 1 month, and 187 (130 women, 57 men; 84.6% of 221 patients) were fully investigated. The mean age was 78.3 years old, and the mean duration of artificial nutrition was 29.8 months. Eighty-four patients (44.7% of 187 patients) were receiving artificial nutrition for more than 2 years. Patients with Alzheimer's disease (n = 78) formed the biggest group, schizophrenia (n = 37) the second, and vascular dementia (n = 26) the third. CONCLUSION: About one-fifth of the subjects receiving artificial nutrition were in a vegetative state. More than a few patients with mental disorders, including schizophrenia, also received long-term artificial nutrition. We should pay more attention to chronic dysphasia syndrome in mental disorders.

The Relationship Between Development of Neuronal and Astrocytic Tau Pathologies in Subcortical Nuclei and Progression of Argyrophilic Grain Disease.

Progressive supranuclear palsy (PSP) cases frequently have argyrophilic grain disease (AGD). However, the PSP-like tau pathology in AGD cases has not been fully clarified. To address this, we examined tau pathologies in the subcortical nuclei and frontal cortex in 19 AGD cases that did not meet the pathological criteria of PSP or corticobasal degeneration, nine PSP cases and 20 Braak NFT stage-matched controls. Of the 19 AGD cases, five (26.3%) had a few Gallyas-positive tau-positive tufted astrocytes (TAs) and Gallyas-negative tau-positive TA-like astrocytic inclusions (TAIs), and six (31.6%) had only TAIs in the striatum and/or frontal cortex. Subcortical tau pathology was sequentially and significantly greater in AGD cases lacking these tau-positive astrocytic lesions, AGD cases having them, and PSP cases than in controls. There was a significant correlation between three histologic factors, including the AGD stage and the quantities of subcortical neuronal and astrocytic tau pathologies. Tau immunoblotting demonstrated 68- and 64-kDa bands and 33-kDa low-molecular mass tau fragments in PSP cases, and although with lesser intensity, in AGD cases with and without TAs and TAIs also. Given these findings, the progression of AGD may be associated with development of the neuronal and astrocytic tau pathologies characteristic of PSP.

A genome-wide association study of late-onset Alzheimer's disease in a Japanese population.

OBJECTIVE: Although a number of genome-wide association studies (GWASs) of late-onset Alzheimer's disease (LOAD) have been carried out, there have been little GWAS data on East Asian populations. DESIGN: To discover the novel susceptibility loci of LOAD, we carried out a GWAS using 816 LOAD cases and 7992 controls with a replication analysis using an independent panel of 1011 LOAD cases and 7212 controls in a Japanese population. In addition, we carried out a stratified analysis by APOE-ε4 status to eliminate the established effect of APOE region. RESULTS: Our data indicated that 18p11.32 (rs1992269, P = 9.77 × 10(-7)), CNTNAP2 (rs802571, P = 1.26 × 10(-6)), and 12q24.23 (rs11613092, P = 6.85 × 10(-6)) were suggestive loci for susceptibility to LOAD. CONCLUSION: We identified three suggestive loci for susceptibility to LOAD in a Japanese population. Among these, rs802571, located at intron 1 of CNTNAP2, was considered to be a plausible candidate locus from a functional perspective.

Difference in determinants of caregiver burden between amnestic mild cognitive impairment and mild Alzheimer's disease.

Care for the disabled elderly can be stressful and exhausting, especially in cases of dementia. There have been a number of studies on the dementia caregiver burden, but studies focusing on differences by stages of the disease are rare. The caregiver burden of 85 caregivers of patients with amnestic mild cognitive impairment (aMCI) and 106 caregivers of patients with mild Alzheimer׳s disease (AD) was evaluated by the short version of the Japanese version of the Zarit Burden Interview (sZBI). The caregiver burden in mild AD was more severe than that in aMCI. In mild AD, the risk factors of caregiver burden were neurobehavioral symptoms and disturbances instrumental activities of daily living (IADL), whereas the risk factors in aMCI were neurobehavioral symptoms and memory dysfunction. The severity of dementing disease affects the caregiver burden, and somewhat different factors contribute to the burden at different stages. We should pay attention to different factors in evaluating and reducing the caregiver burden in aMCI and mild AD.

Development and evaluation of a short version of the quality of life questionnaire for dementia.

BACKGROUND: There are many quality of life (QOL) instruments for evaluating dementia patients. The QOL questionnaire for Dementia (QOL-D) is one of such instruments and a validated objective measure of QOL for patients with dementia. It comprises 31 items encompassing six domains. However, with 31 items, its length is a disadvantage. The purpose of this study was to develop a short version of QOL-D (short QOL-D). METHODS: We used data from two studies. The participants were 264 inpatients with dementia in the first sample and 395 outpatients at a memory clinic in the second sample. We used maximum likelihood factor analysis with promax rotation to reduce the number of items. RESULTS: We produced a nine-item version of QOL-D (short QOL-D) with positive (six items) and negative (three items) dimensions. The correlation coefficients of short and total versions of QOL-D were 0.892-0.918 for total scores, 0.903-0.936 for positive dimension scores, and 0.788-0.837 for negative dimension scores. Total short QOL-D scores showed a significant correlation to the Geriatric Depression Scale score and the apathy score of the Neuropsychiatric Inventory. CONCLUSIONS: The short QOL-D produced results comparable with that of the full version. Reducing the number of items may make administration of the instrument easier.

Left frontal lobe hypoperfusion and depressive symptoms in Alzheimer's disease patients taking cholinesterase inhibitors.

Depressive symptoms are common in patients with Alzheimer's disease (AD) and increase the caregiver burden. Many studies have reported dorsolateral prefrontal hypometabolism or hypoperfusion in AD patients with depressive symptoms, most of whom did not take acetylcholinesterase inhibitors (AChEI). It is not clear, however, whether a similar condition is present in patients taking AChEI medication. Fifty-seven consecutive AD patients taking AChEI were recruited at a memory clinic. Objective depressive symptoms were evaluated using the depression domain of the Neuropsychiatric Inventory (NPI-dep). All patients underwent brain single photon emission computed tomography (SPECT) with (99m)Tc-ethylcysteinate dimer, and the SPECT images were analyzed using the Statistical Parametric Mapping 8 program. No significant differences between groups with positive and negative NPI-dep scores were found with respect to age, sex, years of education, and cognitive function. Compared with patients with negative NPI-dep scores, patients with NPI-dep scores ≥1 showed significant hypoperfusion in the left middle frontal region. Our results indicate that the dorsolateral prefrontal area is significantly involved in the pathogenesis of depressive symptoms in AD patients being treated with AChEI. The area on the left side especially may be closely related to the depressive symptoms evaluated using the NPI.

Subjective depressive mood and regional cerebral blood flow in mild Alzheimer's disease.

BACKGROUND: Depressive symptoms are common in patients with Alzheimer's disease (AD) and increase the caregiver burden, although the etiology and pathologic mechanism of depressive symptoms in AD patients remain unclear. In this study, we tried to clarify the cerebral blood flow (CBF) correlates of subjective depressive symptoms in AD. METHODS: Seventy-six consecutive patients with AD were recruited from outpatient units of the Memory Clinic of Okayama University Hospital. Subjective depressive symptoms were evaluated using the short version of the Geriatric Depression Scale (GDS). All patients underwent brain SPECT with 99mTc-ethylcysteinate dimer, and the SPECT images were analyzed by the Statistical Parametric Mapping 8 program. RESULTS: No significant differences between groups with high and low GDS scores were found with respect to age, sex, years of education, and revised Addenbrooke's Cognitive Examination scores. Compared to patients with low scores on GDS, patients with high scores showed significant hypoperfusion in the left inferior frontal region. CONCLUSIONS: The left inferior frontal region may be significantly involved in the pathogenesis of subjective depressive symptoms in AD. Subjective and objective depressive symptoms may have somewhat different neural substrates in AD.

Depressive symptoms and regional cerebral blood flow in Alzheimer's disease.

Depressive symptoms are common in patients with Alzheimer's disease (AD) and increase the caregiver burden, although the etiology and pathologic mechanism of depressive symptoms in AD patients remain unclear. In this study, we tried to clarify the cerebral blood flow (CBF) correlates of depressive symptoms in AD, excluding the effect of apathy and anxiety. Seventy-nine consecutive patients with AD were recruited from outpatient units of the Memory Clinic of Okayama University Hospital. The level of depressive symptoms was evaluated using the depression domain of the Neuropsychiatric Inventory (NPI). The patients underwent brain SPECT with 99mTc-ethylcysteinate dimer. After removing the effects of age, anxiety and apathy scores of NPI, and five subscales of Addenbrooke's Cognitive Examination-revised (ACE-R), correlation analysis of NPI depression scores showed a significant cluster of voxels in the left middle frontal gyrus (Brodmann area 9), similar to the areas in the simple correlation analysis. The dorsolateral prefrontal area is significantly involved in the pathogenesis of depressive symptoms in AD, and the area on the left side especially may be closely related to the depressive symptoms revealed by NPI.

Trail making test B and brain perfusion imaging in mild cognitive impairment and mild Alzheimer's disease.

The trail making test (TMT) has long been used to investigate deficits in cognitive processing speed and executive function in humans. However, there are few studies that elucidate the neural substrates of the TMT. The aim of the present study was to identify the brain regional perfusion patterns associated with performance on TMT part B (TMT-B) in patients with amnestic mild cognitive impairment (aMCI) or mild Alzheimer's disease (AD). Twenty-one patients with good TMT-B scores and 21 age- and sex-matched patients with poor TMT-B scores were selected. All 42 subjects underwent brain single photon emission computed tomography (SPECT), and the SPECT images were analyzed by statistical parametric mapping. No significant differences between good- and poor-scoring groups were found with respect to years of education, Addenbrooke's Cognitive Examination scores, and scores on TMT-A. Compared to patients with good scores on TMT-B, patients with poor scores showed significant hypoperfusion in the bilateral anterior cingulate extending to the posterior region on the right side, bilateral caudate nucleus and putamen, and bilateral thalamus. Analysis of 63 AD or aMCI subjects revealed significant correlation a between regional cerebral blood flow in the right cingulate cortex and TMT-B scores. Our results suggest that functional activity of the anterior cingulate, striatum and thalamus is closely related to performance time on TMT-B. The performance time on the TMT-B score might be a promising index of dysfunction of the anterior cingulate, striatum, and thalamus among patients with aMCI or mild AD.