Safety and Effectiveness of Perospirone in Comparison to Risperidone for Treatment of Delirium in Patients with Advanced Cancer: A Multicenter Prospective Observational Study in Real-World Psycho-Oncology Settings

The clinical benefit of perospirone for treatment of delirium in patients with advanced cancer is not sufficiently clear. The objective of this study was to compare the safety and effectiveness of perospirone to those of risperidone for the treatment of delirium in patients with advanced cancer. This is a secondary analysis of a multicenter prospective observational study in nine psycho-oncology consultation services in Japan. The study used the Delirium Rating Scale (DRS) Revised-98 to measure effectiveness and the CTCAE (Common Terminology Criteria for Adverse Events) version 4 to assess safety. Data from 16 patients who received perospirone and 53 patients who received risperidone were analyzed. The mean age was 70 years in the perospirone group and 73 years in the risperidone group. Both groups showed a significant decrease in the total score of DRS-R-98 after three days of treatment (perospirone: 11.7 (7.9-15.4) to 7.0 (3.3-10.7), difference −4.7, effect size=0.72, p=0.003; risperidone: 15.5 (13.6-17.4) to 12.2 (10.1-14.2), difference −3.3, effect size=0.55, p=0.00). The risperidone group showed significant improvements in sleep-wake cycle disturbance, orientation, attention, and visuospatial ability. In the perospirone group, there was a significant improvement of sleep-wake cycle disturbance. The median daily dose of perospirone was 4 mg/day. There were fewer episodes of somnolence as an adverse event in the perospirone group. Low-dose perospirone was thus found to be effective for the treatment of delirium in patients with advanced cancer and may be associated with fewer episodes of over-sedation as an adverse event

Prevalence of dementia in people with intellectual disabilities: Cross‐sectional study

Background There are only a few studies of the prevalence of dementia in people with intellectual disability (ID) without Down syndrome (DS), and there is a large difference in the prevalences between reported studies. Moreover, the prevalence of mild cognitive impairment (MCI) in ID has not been reported. We aimed to evaluate the prevalence of dementia in adults of all ages and the prevalence of MCI in people with ID. Furthermore, we tried to clarify the differences depending on the various diagnostic criteria. Methods The survey included 493 adults with ID at 28 facilities in Japan. The caregivers answered a questionnaire, and physicians directly examined the participants who were suspected of cognitive decline. Dementia and MCI were diagnosed according to ICD‐10, DC‐LD, and DSM‐5 criteria. Results The prevalence of dementia was 0.8% for the 45 to 54 years old group, 3.5% for the 55 to 64 years old group, and 13.9% for the 65 to 74 years old group in people with ID without DS. The prevalence of MCI was 3.1% for patients 45 to 54, 3.5% for patients 55 to 64, and 2.8% for patients 65 to 74 with ID without DS. DSM‐5 was the most inclusive in diagnosing dementia and MCI in people with ID. Conclusions People with ID without DS may develop dementia and MCI at an earlier age and higher rate than the general population. Among the diagnostic criteria, DSM‐5 was the most useful for diagnosing their cognitive impairment

Prevalence of dementia in people with intellectual disabilities: Cross‐sectional study

Background There are only a few studies of the prevalence of dementia in people with intellectual disability (ID) without Down syndrome (DS), and there is a large difference in the prevalences between reported studies. Moreover, the prevalence of mild cognitive impairment (MCI) in ID has not been reported. We aimed to evaluate the prevalence of dementia in adults of all ages and the prevalence of MCI in people with ID. Furthermore, we tried to clarify the differences depending on the various diagnostic criteria. Methods The survey included 493 adults with ID at 28 facilities in Japan. The caregivers answered a questionnaire, and physicians directly examined the participants who were suspected of cognitive decline. Dementia and MCI were diagnosed according to ICD‐10, DC‐LD, and DSM‐5 criteria. Results The prevalence of dementia was 0.8% for the 45 to 54 years old group, 3.5% for the 55 to 64 years old group, and 13.9% for the 65 to 74 years old group in people with ID without DS. The prevalence of MCI was 3.1% for patients 45 to 54, 3.5% for patients 55 to 64, and 2.8% for patients 65 to 74 with ID without DS. DSM‐5 was the most inclusive in diagnosing dementia and MCI in people with ID. Conclusions People with ID without DS may develop dementia and MCI at an earlier age and higher rate than the general population. Among the diagnostic criteria, DSM‐5 was the most useful for diagnosing their cognitive impairment

Secondary autoimmune hypothalamitis with severe memory impairment 7 years after the onset of diabetes insipidus due to lymphocytic hypophysitis: a case report

Background Autoimmune hypothalamitis is a very rare neuroendocrine disorder that causes central diabetes insipidus, headache, visual impairment, and sometimes cognitive impairment. Autoimmune hypothalamitis may occur in association with autoimmune hypophysitis, including lymphocytic hypophysitis, or in isolation. It is not known whether autoimmune hypothalamitis and autoimmune hypophysitis are consecutive diseases. Case presentation A 52-year-old woman developed autoimmune hypothalamitis 7 years after developing central diabetes insipidus due to lymphocytic hypophysitis, resulting in severe memory impairment. High-dose intravenous methylprednisolone therapy improved her cognitive function and decreased the size of the lesion. Conclusion This case presented a unique clinical course, with a long period of time between the onset of autoimmune hypopituitaritis and the development of autoimmune hypothalamitis

Patient affect and caregiver burden in dementia

BACKGROUND: Numerous studies focusing on the burden of caregivers of dementia patients have been published. However, there have been few studies focusing on positive affect as an important factor affecting the caregiver burden, and only a few studies comparing the caregiver burden between different dementia diseases have been reported. METHODS: Three hundred and thirty-seven consecutive caregivers of people with dementia participated in this study. The caregiver burden was evaluated by the short version of the Japanese version of the Zarit Burden Interview. RESULTS: Positive affect scores had a significant relationship with the scores of the short version of the Zarit Burden Interview. Caregivers for patients with dementia with Lewy bodies or frontotemporal dementia suffered from a greater burden than those for patients with Alzheimer's disease dementia. CONCLUSIONS: The caregiver burden differed between people caring for patients with different dementia diseases. Positive affect of dementia patients has a significant relationship with caregiver burden, independently from neuropsychiatric symptoms of patients

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

Factors associated with development and distribution of granular/fuzzy astrocytes in neurodegenerative diseases

Granular/fuzzy astrocytes (GFAs), a subtype of “aging‐related tau astrogliopathy,” are noted in cases bearing various neurodegenerative diseases. However, the pathogenic significance of GFAs remains unclear. We immunohistochemically examined the frontal cortex, caudate nucleus, putamen and amygdala in 105 cases composed of argyrophilic grain disease cases (AGD, N = 26), and progressive supranuclear palsy (PSP, N = 10), Alzheimer’s disease (AD, N = 20) and primary age‐related tauopathy cases (PART, N = 18) lacking AGD, as well as 31 cases bearing other various neurodegenerative diseases to clarify (i) the distribution patterns of GFAs in AGD, and PSP, AD and PART lacking AGD, (ii) the impacts of major pathological factors and age on GFA formation and (iii) immunohistochemical features useful to understand the formation process of GFAs. In AGD cases, GFAs consistently occurred in the amygdala (100%), followed by the putamen (69.2%) and caudate nucleus and frontal cortex (57.7%, respectively). In PSP cases without AGD, GFAs were almost consistently noted in all regions examined (90–100%). In AD cases without AGD, GFAs were less frequent, developing preferably in the putamen (35.0%) and caudate nucleus (30.0%). PART cases without AGD had GFAs most frequently in the amygdala (35.3%), being more similar to AGD than to AD cases. Ordered logistic regression analyses using all cases demonstrated that the strongest independent factor of GFA formation in the frontal cortex and striatum was the diagnosis of PSP, while that in the amygdala was AGD. The age was not significantly associated with GFA formation in any region. In GFAs in AGD cases, phosphorylation and conformational change of tau, Gallyas‐positive glial threads indistinguishable from those in tufted astrocytes, and the activation of autophagy occurred sequentially. Given these findings, AGD, PSP, AD and PART cases may show distinct distributions of GFAs, which may provide clues to predict the underlying processes of primary tauopathies

Wandering and fecal smearing in people with dementia

ABSTRACT Background: Wandering and fecal smearing (scatolia) are among the problematic behaviors in dementia, and many caregivers are troubled by these behaviors. The purpose of this study was to clarify the clinical characteristics of patients with these symptoms

Astrocytic Tau Pathologies in Argyrophilic Grain Disease and Related Four-repeat Tauopathies

Neurodegenerative diseases in which tau accumulation plays a cardinal role in the pathogenic process are called tauopathies, and when tau isoforms having four repeats of the microtubule binding sites, four-repeat tau, are selectively accumulated as pathological hallmarks, the term four-repeat tauopathy is used. The major four-repeat tauopathies are progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and argyrophilic grain disease (AGD). Historically, neuronal cytopathologies, e.g., neurofibrillary tangles and ballooned neurons, were emphasized as characteristic lesions in PSP and CBD. Now, however, astrocytic tau pathologies, i.e., tufted astrocytes (TAs) and astrocytic plaques (APs), are considered to be highly disease-specific lesions. Although granular/fuzzy astrocytes (GFAs) frequently develop in the limbic system in AGD cases, the specificity is not conclusive yet. Some AGD cases have a few TAs, and to a lesser frequency, a few APs in the frontal cortex and subcortical nuclei. The number of astrocytic tau pathologies including TAs and GFAs increases with the progression of AGD. In this paper, histopathological features of astrocytic tau pathologies in PSP, CBD, and AGD are first reviewed. Then, recent findings regarding the coexistence of these tauopathies are summarized from a viewpoint of astrocytic tau pathologies. Further biochemical and pathological studies focusing tau-positive astrocytic lesions may be useful to increase understanding of the pathological process in four-repeat tauopathies and to develop novel therapeutic strategies for patients with these diseases