Decreased perfusion of the posterior cingulate gyri shown by a cingulate island score is a possible marker of vulnerability to behavioural and psychological symptoms of Alzheimer's disease: a pilot study.

BACKGROUND: The cingulate island score (CIScore), which indicates the Z-score ratio of the posterior cingulate gyri to the medial occipital area, has been shown to be useful for differentiating dementia with Lewy bodies from Alzheimer's disease (AD). Our aim was to investigate associations between the clinical symptoms of AD and the CIScore as an index of the relative decrease in perfusion of the posterior cingulate gyri that occurs in the early stages of AD. METHODS: Seventeen patients with early-stage AD and 13 patients with amnesic mild cognitive impairment were examined. Z-score maps of technetium-99m ethyl cysteinate dimer single-photon emission computed tomography images acquired from the patients were converted, and the CIScore was determined by using the easy Z-score imaging system. The relationships between the CIScore and clinical symptom scores were tested. RESULTS: A significant correlation was identified between the CIScore and the Neuropsychiatric Inventory Questionnaire score. No significant correlations were identified between the CIScore and other measures of cognitive function. Based on a CIScore of 0.39, we correctly differentiated patients with and without behavioural and psychological symptoms of dementia (BPSD), with a sensitivity of 72.2% and specificity of 75.0%. DISCUSSION: Using technetium-99m ethyl cysteinate dimer single-photon emission computed tomography, we observed that decreased posterior cingulate gyri perfusion, relative to the medial occipital area, in prodromal and early AD was closely associated with behavioural and psychological symptoms of dementia. Therefore, our findings suggest that CIScore is not only useful for discriminating dementia with Lewy bodies from AD, but it can also be clinically used as a specific indicator of the vulnerability to behavioural and psychological symptoms of dementia in the early stages of AD.

Haloperidol prophylaxis for preventing aggravation of postoperative delirium in elderly patients: a randomized, open-label prospective trial.

PURPOSES: The aim of this study was to evaluate the safety and efficacy of the early administration haloperidol in preventing the aggravation of postoperative delirium in elderly patients. METHODS: A total of 201 patients (age ≥75 years) who underwent elective surgery were enrolled. The patients were divided into two groups: the intervention group (n = 101) received prophylactic haloperidol (5 mg); the control group (n = 100) did not. Haloperidol was administered daily during postoperative days 0-5 to the patients who presented with NEECHAM scores of 20-24 when measured at 18:00. The primary endpoint was the incidence of severe postoperative delirium. RESULTS: The incidence of severe postoperative delirium in all patients was 25.1%. The incidence of severe postoperative delirium in the intervention group (18.2%) was significantly lower than that in the control group (32.0%) (p = 0.02). The difference between the two groups was larger when the analysis was limited to the 70 patients who had NEECHAM scores of 20-24 for at least one day during postoperative days 0-5. No adverse effects of the haloperidol were observed. CONCLUSION: The prophylactic administration of haloperidol at the early stage of delirium significantly reduced the incidence of severe postoperative delirium in elderly patients. Clinical Trial Registration UMIN000007204.

Haloperidol prophylaxis does not prevent postoperative delirium in elderly patients: a randomized, open-label prospective trial.

PURPOSE: Postoperative delirium is the most common postoperative complication in the elderly. The purpose of this study was to evaluate the safety and effectiveness of the preventive administration of low-dose haloperidol on the development of postoperative delirium after abdominal or orthopedic surgery in elderly patients. SUBJECTS: A total of 119 patients aged 75 years or older who underwent elective surgery for digestive or orthopedic disease were included in this study. METHODS: Patients were divided into those who did (intervention group, n = 59) and did not (control group, n = 60) receive 2.5 mg of haloperidol at 18:00 daily for 3 days after surgery; a randomized, open-label prospective study was performed on these groups. The primary endpoint was the incidence of postoperative delirium during the first 7 days after the operation. RESULTS: The incidence of postoperative delirium in all patients was 37.8%. No side effects involving haloperidol were noted; however, the incidences of postoperative delirium were 42.4 and 33.3% in the intervention and control groups, respectively, which were not significantly different (p = 0.309). No significant effect of the treatment was observed on the severity or persistence of postoperative delirium. CONCLUSIONS: The preventive administration of low-dose haloperidol did not induce any adverse events, but also did not significantly decrease the incidence or severity of postoperative delirium or shorten its persistence.

[Palliative care in patients without cancer: Impact of the end-of-life care team].

Palliative care improves the quality of life of patients and their families facing problems associated with life-threatening illnesses by promoting the prevention and relief of suffering. Palliative care in Japan has been developed mainly for cancer patients. At the National Center for Geriatrics and Gerontology, an end-of-life care team (EOLCT) has been developed to promote palliative care for patients without cancer. In the first 6 months of its operation, 109 requests were received by the team, 40% of which were for patients without cancer or related disease, including dementia, frailty due to advanced age, chronic respiratory failure, chronic heart failure, and intractable neurologic diseases. The main purpose of the EOLCT is to alleviate suffering. The relevant activities of the team include the use of opioids, providing family care, and giving support in decision-making (advance care planning) regarding withholding; enforcement; and withdrawal of mechanical ventilators, gastric feeding tubes, and artificial alimentation. The EOLCT is also involved in ongoing discussions of ethical problems. The team is actively engaged in the activities of the Japanese Geriatric Society and contributes to the development of decision-making guidelines for end-of-life by the Ministry of Health, Labour and Welfare. The EOLCT can be helpful in promoting palliative care for patients with diseases other than cancer. The team offers support during times of difficulty and decision-making.

[Depression in older adults: the National Mental Care Project for People with Physical Illness].

Political attention is being increasingly directed to mental health in Japan. Mental disorders are now the fifth priority disease after cancer, stroke, acute myocardial infarction and diabetes for national medical services since April 2013. Each prefecture has to implement strategic mental healthcare plans at the regional level. With the increase in co-morbid mental and physical illnesses, patient information should be shared between psychiatric and non-psychiatric healthcare providers, and coordination is required in the healthcare systems. A better understanding of mental health between patients and medical staffs could contribute to improved access to psychiatric services in the integrated mental health care system. Collaborative care programs focusing on depression screening and management in the Mental Health Care Project for Patients with Physical Illness have been launched among six national specialized care and research centers (cancer, cardiovascular disease, diabetes, child care, geriatric care and neurology and psychiatry) since 2012. These efforts to integrate mental health care into the general health care system would help to improve psychiatric care for elderly patients with physical illnesses.

[Usefulness of support from end-of-life care teams in difficult decision-making].

It is unclear how hospitals should support a patient's decision to return home to die. Thus, we retrospectively examined the usefulness of support from an End-Of-Life Care Team in such difficult decision making. The subjects included non-cancer patients and the elderly. Our results suggest that the burden of making difficult decisions decreases with support from End- Of-Life Care Teams.

Assessment of the risk of postoperative delirium in elderly patients using E-PASS and the NEECHAM Confusion Scale.

BACKGROUND: The incidences of surgery-field disorders such as femur neck fracture and colorectal cancer in elderly persons have increased with the rapid aging of society. In such patients, postoperative delirium is also frequent. Patients should be generally assessed from the aspect of both physical and mental conditions in order to predict a high-delirium risk group. If so, delirium may be prevented more efficiently. In this study, we investigated whether the early detection of postoperative delirium in elderly patients is possible using a simple, useful behavior-assessing scale, the NEECHAM Confusion Scale, and a method for comprehensively evaluating elderly persons' stress related to surgery, E-PASS. METHODS: The subjects were 160 patients aged more than 75 years who underwent surgery. Among them, three patients had vascular surgery-field disorders, 67 had orthopedic-field disorders, and 90 had digestive surgery-field disorders. To comprehensively evaluate surgery-related stress, E-PASS was employed. In addition, we assessed recognition, activities of daily living (ADL), and the quality of life (QOL). For delirium diagnosis and severity assessment, we used the NEECHAM Confusion Scale. The cut-off value of the NEECHAM score was established as 20 points, and patients showing values less than this after surgery were regarded as having postoperative delirium. Evaluation was performed until 10 days after surgery. RESULTS: Postoperative delirium was noted in 54.7% of the subjects. There was a decrease in the NEECHAM score between the first and fourth postoperative days, but it gradually increased thereafter. Both uni- and multivariate analyses showed that postoperative delirium was associated with an advanced age (more than 80 years), low preoperative NEECHAM and MMSE scores, the preoperative QOL, and E-PASS. In groups showing an MMSE score of less than 25 or a preoperative NEECHAM score of less than 27, the incidence of postoperative delirium was 76%. CONCLUSION: The results suggest that E-PASS and the NEECHAM score facilitate assessment of the risk of postoperative delirium in elderly patients, contributing to early prevention/treatment.

Validation of the Telephone Interview for Cognitive Status (TICS) in Japanese.

BACKGROUND: In recent years, the population of elderly people in Japan with dementia has increased. Detection of cognitive impairment in the early stages is important for adequate treatment, care, and prevention. AIM: To investigate whether the reliability and validity of the instrument would carry over to a different population and language before using it for population-based epidemiological studies. METHODS: We studied 135 subjects, 49 patients with Alzheimer's disease (AD) and 86 healthy controls (CTL) using the Telephone Interview for Cognitive Status (TICS) and developed the Japanese version of the TICS (TICS-J). We also evaluated combination of another telephone battery, the Category Fluency Test (CF). RESULTS: The sensitivity and specificity of the TICS-J to differentiate AD patients from CTL was 98.0% and 90.7%, respectively. Pearson's correlation coefficient for the TICS-J and Mini-Mental State Examination (MMSE) was 0.858 (p < 0.001). On the Receiver Operating Characteristic (ROC), the area under the curve for the TICS-J was 98.7%. The combination of the TICS-J with the CF did not change the validity of the discrimination. CONCLUSION: These results indicated that TICS-J was a sensitive and specific instrument for differentiating AD patients from healthy controls.

The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between beta-amyloid production and tau phosphorylation in Alzheimer disease.

We scanned throughout chromosome 21 to assess genetic associations with late-onset Alzheimer disease (AD) using 374 Japanese patients and 375 population-based controls, because trisomy 21 is known to be associated with early deposition of beta-amyloid (Abeta) in the brain. Among 417 markers spanning 33 Mb, 22 markers showed associations with either the allele or the genotype frequency (P < 0.05). Logistic regression analysis with age, sex and apolipoprotein E (APOE)-epsilon4 dose supported genetic risk of 17 markers, of which eight markers were linked to the SAMSN1, PRSS7, NCAM2, RUNX1, DYRK1A and KCNJ6 genes. In logistic regression, the DYRK1A (dual-specificity tyrosine-regulated kinase 1A) gene, located in the Down syndrome critical region, showed the highest significance [OR = 2.99 (95% CI: 1.72-5.19), P = 0.001], whereas the RUNX1 gene showed a high odds ratio [OR = 23.3 (95% CI: 2.76-196.5), P = 0.038]. DYRK1A mRNA level in the hippocampus was significantly elevated in patients with AD when compared with pathological controls (P < 0.01). DYRK1A mRNA level was upregulated along with an increase in the Abeta-level in the brain of transgenic mice, overproducing Abeta at 9 months of age. In neuroblastoma cells, Abeta induced an increase in the DYRK1A transcript, which also led to tau phosphorylation at Thr212 under the overexpression of tau. Therefore, the upregulation of DYRK1A transcription results from Abeta loading, further leading to tau phosphorylation. Our result indicates that DYRK1A could be a key molecule bridging between beta-amyloid production and tau phosphorylation in AD.