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.

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.

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.

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.

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.

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.

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.

Burden of caregivers for patients with mild cognitive impairment in Japan.

BACKGROUND: Caregivers of patients with mild cognitive impairment (MCI) already experience a need for increased services comparable to that of individuals caring for Alzheimer's disease patients. However, there have been only a few studies on the MCI caregiver burden. In this study, we examined MCI caregiver burden in a larger number of consecutive outpatients in Japan. METHODS: One hundred and four consecutive caregivers of people with MCI participated in this study. The caregiver burden was evaluated by the short version of the Japanese version of the Zarit Burden Interview (sZBI). RESULTS: About 20% of the caregivers reported a clinically significant burden. The multiple linear regression analysis showed that the caregiver burden was significantly associated with neurobehavioral symptoms (p < 0.001) and memory problems (p = 0.022) of the patient. CONCLUSIONS: The caregiver burden of MCI patients should be given more attention. The management of neurobehavioral symptoms may be important to reduce the burden on caregivers of MCI patients.

Validation of the revised Addenbrooke's Cognitive Examination (ACE-R) for detecting mild cognitive impairment and dementia in a Japanese population.

BACKGROUND: Early detection of dementia will be important for implementation of disease-modifying treatments in the near future. We aimed to investigate the diagnostic validity and reliability of the Japanese version of the revised Addenbrooke's Cognitive Examination (ACE-R J) for identifying mild cognitive impairment (MCI) and dementia. METHODS: We translated and adapted the original ACE-R for use with a Japanese population. Standard tests for evaluating cognitive decline and dementing disorders were applied. A total of 242 subjects (controls = 73, MCI = 39, dementia = 130) participated in this study. RESULTS: The optimal cut-off scores of ACE-R J for detecting MCI and dementia were 88/89 (sensitivity 0.87, specificity 0.92) and 82/83 (sensitivity 0.99, specificity 0.99) respectively. ACE-R J was superior to the Mini-Mental State Examination in the detection of MCI (area under the curve (AUC): 0.952 vs. 0.868), while the accuracy of the two instruments did not differ significantly in identifying dementia (AUC: 0.999 vs. 0.993). The inter-rater reliability (ICC = 0.999), test-retest reliability (ICC = 0.883), and internal consistency (Cronbach's α = 0.903) of ACE-R J were excellent. CONCLUSION: ACE-R J proved to be an accurate cognitive instrument for detecting MCI and mild dementia. Further neuropsychological evaluation is required for the differential diagnosis of dementia subtypes.

Frontal assessment battery and brain perfusion imaging in Alzheimer's disease.

BACKGROUND: The frontal assessment battery (FAB) is reported to be a useful tool for assessing frontal dysfunction. However, the neural substrates involved in patients with Alzheimer's disease (AD) remain to be elucidated. The aim of the present study was to identify the regional perfusion patterns of the brain associated with performance scores on the FAB of patients with AD using brain perfusion assessed by single photon emission computed tomography (SPECT). METHODS: Twenty-four AD patients with high scores and 24 age- and sex-matched AD patients with low scores on the FAB were selected from 470 consecutive Japanese patients of the Memory Clinic of Okayama University Hospital. All 48 participants underwent brain SPECT with 99mTc-ethylcysteinate dimer, and the SPECT images were analyzed by statistical parametric mapping. RESULTS: No significant differences were found between high and low FAB scoring groups with respect to Addenbrooke's Cognitive Examination scores, Mini-Mental State Examination scores, or the depression score of the Neuropsychiatric Inventory subscale. Compared with patients with high scores on the FAB, AD patients with low scores showed significant hypoperfusion in the left middle frontal gyrus (MFG) and the right superior frontal gyrus (SFG) extending to the left SFG. CONCLUSION: Our results suggest that functional activity of the SFG and MFG is closely related to the FAB score. The FAB might be a promising strategy to detect early stages of AD with low SFG and MFG function.

Latent structure analysis of the process variables and pharmaceutical responses of an orally disintegrating tablet.

A multivariate statistical technique was applied to the design of an orally disintegrating tablet and to clarify the causal correlation among variables of the manufacturing process and pharmaceutical responses. Orally disintegrating tablets (ODTs) composed mainly of mannitol were prepared via the wet-granulation method using crystal transition from the δ to the ß form of mannitol. Process parameters (water amounts (X(1)), kneading time (X(2)), compression force (X(3)), and amounts of magnesium stearate (X(4))) were optimized using a nonlinear response surface method (RSM) incorporating a thin plate spline interpolation (RSM-S). The results of a verification study revealed that the experimental responses, such as tensile strength and disintegration time, coincided well with the predictions. A latent structure analysis of the pharmaceutical formulations of the tablet performed using a Bayesian network led to the clear visualization of a causal connection among variables of the manufacturing process and tablet characteristics. The quantity of ß-mannitol in the granules (Q(ß)) was affected by X(2) and influenced all granule properties. The specific surface area of the granules was affected by X(1) and Q(ß) and had an effect on all tablet characteristics. Moreover, the causal relationships among the variables were clarified by inferring conditional probability distributions. These techniques provide a better understanding of the complicated latent structure among variables of the manufacturing process and tablet characteristics.

Validation of Addenbrooke's cognitive examination for detecting early dementia in a Japanese population.

There is a clear need for brief, but sensitive and specific, cognitive screening instruments for dementia. We assessed the diagnostic accuracy of the Japanese version of Addenbrooke's Cognitive Examination (ACE) in identifying early dementia in comparison with the conventional Mini-Mental State Examination (MMSE). Standard tests for evaluating dementia screening tests were applied. A total of 201 subjects (Alzheimer's disease (AD)=65, frontotemporal dementia (FTD)=24, vascular dementia=26, dementia with Lewy bodies=11, mild cognitive impairment (MCI)=13, and controls=62) participated in this study. The reliability of the ACE was very good (alpha coefficient=0.82). In our patient series, the sensitivity for diagnosing dementia with an ACE score of ≤74 was 0.889 with a specificity of 0.987, and the sensitivity of an ACE score of ≤80 was 0.984 with a specificity of 0.867. The Japanese version of the ACE is a very accurate instrument for the detection of early dementia, and should be widely used in clinical practice.

Perseverative errors on the Wisconsin Card Sorting Test and brain perfusion imaging in mild Alzheimer's disease.

BACKGROUND: The Wisconsin Card Sorting Test (WCST) has long been used to investigate deficits in executive function in humans. The majority of studies investigating deficient WCST performance focused on the number of categories achieved (CA) and the number of perseverative errors of the Nelson type (PEN). However, there is insufficient evidence that these two measures reflect the same neural deficits. METHODS: Twenty AD patients with high PEN scores, and 20 age- and sex-matched AD patients with low PEN scores were selected. All 40 subjects underwent brain SPECT, and the SPECT images were analyzed by Statistical Parametric Mapping. RESULTS: No significant differences were found between high and low PEN score groups with respect to years of education, Addenbrooke's Cognitive Examination scores, and Mini-Mental State Examination scores. However, higher z scores for hypoperfusion in the bilateral rectal and orbital gyri were observed in the high PEN score group compared with the low PEN score group. CONCLUSIONS: Our results suggest that functional activity of the bilateral rectal and orbital gyri is closely related to PEN scores on a modified WCST (mWCST). The PEN score on a mWCST might be a promising index of dysfunction of the orbitofrontal area among patients with mild AD.

Wisconsin card sorting test and brain perfusion imaging in early dementia.

BACKGROUND/AIMS: The presence of frontal or executive deficits in patients even at early stages of dementia is now widely recognized. We investigated the relationship between the scores of the Wisconsin card sorting test (WCST) and brain perfusion in patients with early dementia. METHODS: A total of 77 subjects participated in this study. They underwent the WCST and brain single photon emission computed tomography with 99mTc-ethylcisteinate dimer. We analyzed the data using a regional cerebral blood flow (rCBF) quantification software program, 3DSRT. RESULTS: The number of categories achieved (CA) scores of the WCST had a weakly positive correlation with regional cerebral blood flow in the bilateral precentral, bilateral callosomarginal, bilateral pericallosal, right thalamus, left central and left parietal segments. The number of perseverative errors of the Nelson type (PEN) scores had a weakly negative correlation with rCBF in the right thalamus. CONCLUSION: The results in this study suggest that CA scores mainly reflect the function of the precentral segments, especially the left side, and that PEN scores correlate with rCBF in the right thalamus. The results suggest that CA scores and PEN scores should be differentially estimated in the WCST.

Repetitive questioning behavior in Alzheimer's disease: relationship to regional cerebral blood flow.

Repetitive questioning is among the most common and burdensome of the behavioral and psychological symptoms of Alzheimer's disease (AD). Regardless of the clinical significance of the repetitive questioning, the neural substrates involved remain unclear. Fifty-eight consecutive patients with AD participated in this study. The score of repetitive questioning behavior was evaluated by multiplying the severity by the frequency of the behavior. They underwent brain SPECT with (99m)Tc-ethylcysteinate dimer. Scores of repetitive questioning behavior had a significant positive correlation with regional cerebral blood flow (rCBF) in the bilateral pericallosal regions. After removing the effect of memory test scores, we found a significant positive correlation of scores of repetitive questioning behavior to rCBF in the left pericallosal region. The pericallosal region includes the upper precuneus, cingulate, and posterior cingulate cortices on 3DSRT. Repetitive questioning behavior among AD patients might be a manifestation of mental state associated with a relative increase or preservation of rCBF in the left pericallosal region.

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.

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.