Neuropsychiatric Behaviors Research Articles

SOCIAL RELATIONS AND HEALTH OF KOREAN ELDERLY WOMEN: AN ANALYSIS OF THE DIFFERENCES ACROSS AGE GROUPS

relationship score was 15.83(6 4.49) and care burden score was 29.58(6 7.42). Social support score was 60.53(6 21.31) and depression score was 22.73 (6 12.87). In addition, seriousness of behavior of dementia elderly was 14.20(6 8.92) and the score of suffering from the neuropsychiatric behavior was 17.14(6 12.74). In multiple regression analysis, the significant factors influencing QoL of the caregiver were depression, ADL function, social support, subjective health, and daily mean caring time. These five variables explained about 67 percent of variance of QoL among primary caregivers.Conclusions: Subjective health and social support were consistent influencing factors like the results of previous studies, but care burden was not significant factor in this study. To improve caregivers’ QoL, these significant variables need to be intervened in personal, social and health policy aspects.

The spectrum of neurobehavioral sequelae after repetitive mild traumatic brain injury: a novel mouse model of chronic traumatic encephalopathy.

There has been an increased focus on the neurological sequelae of repetitive mild traumatic brain injury (TBI), particularly neurodegenerative syndromes, such as chronic traumatic encephalopathy (CTE); however, no animal model exists that captures the behavioral spectrum of this phenomenon. We sought to develop an animal model of CTE. Our novel model is a modification and fusion of two of the most popular models of TBI and allows for controlled closed-head impacts to unanesthetized mice. Two-hundred and eighty 12-week-old mice were divided into control, single mild TBI (mTBI), and repetitive mTBI groups. Repetitive mTBI mice received six concussive impacts daily for 7 days. Behavior was assessed at various time points. Neurological Severity Score (NSS) was computed and vestibulomotor function tested with the wire grip test (WGT). Cognitive function was assessed with the Morris water maze (MWM), anxiety/risk-taking behavior with the elevated plus maze, and depression-like behavior with the forced swim/tail suspension tests. Sleep electroencephalogram/electromyography studies were performed at 1 month. NSS was elevated, compared to controls, in both TBI groups and improved over time. Repetitive mTBI mice demonstrated transient vestibulomotor deficits on WGT. Repetitive mTBI mice also demonstrated deficits in MWM testing. Both mTBI groups demonstrated increased anxiety at 2 weeks, but repetitive mTBI mice developed increased risk-taking behaviors at 1 month that persist at 6 months. Repetitive mTBI mice exhibit depression-like behavior at 1 month. Both groups demonstrate sleep disturbances. We describe the neurological sequelae of repetitive mTBI in a novel mouse model, which resemble several of the neuropsychiatric behaviors observed clinically in patients sustaining repetitive mild head injury.

Deterioration of basic activities of daily living and their impact on quality of life across different cognitive stages of dementia: a European study.

Performing basic activities of daily living (ADLs) is one of the major difficulties encountered in dementia, which can have considerable negative impacts on the quality of life (QoL) of people with dementia (PwD). However, the extent to which basic ADL performance deteriorates across mild, moderate, and severe dementia is little examined and its impact, together with depression and neuropsychiatric behavior, upon QoL, is of considerable relevance across European countries. Data were drawn from people living in the community who were participants in a large-scale European study on transition from community living to care homes of PwD. PwD completed measures on cognitive functioning and QoL, and informal carers reported upon QoL, depressive symptomatology, psychopathology, and functional ability of the PwD. ADL performance deteriorated differently for each activity. In particular, toileting, transfer, and feeding remained relatively intact throughout, whereas performance on bathing and dressing deteriorated to a greater extent from mild to severe dementia. It appears that continence was not affected by the stage of dementia with similar levels of impairment. Basic ADL performance impacted to different degrees on QoL across dementia stages and countries. Interventions aimed at maintaining independence or QoL need to target different ADLs across different dementia stages and perhaps also tailor interventions to the context of different countries. Findings contribute to the development of non-pharmaceutical interventions and governmental pledges to promote independence in dementia.

Use of the Tailored Activities Program to reduce neuropsychiatric behaviors in dementia: an Australian protocol for a randomized trial to evaluate its effectiveness

Behavioral and psychological symptoms of dementia (BPSD) are often considered to be the greatest challenge in dementia care, leading to increased healthcare costs, caregiver burden, and placement into care facilities. With potential for pharmacological intervention to exacerbate behaviors or even lead to mortality, the development and rigorous testing of non-pharmacological interventions is vital. A pilot of the Tailored Activities Program (TAP) for reducing problem behaviors in people with dementia was conducted in the United States with promising results. This randomized trial will investigate the effectiveness of TAP for reducing the burden of BPSD on persons with dementia and family caregivers within an Australian population. This trial will also examine the cost-effectiveness and willingness to pay for TAP compared with a control group. This randomized trial aims to recruit 180 participant dyads of a person with dementia and their caregivers. Participants will have a diagnosis of dementia, exhibit behaviors as scored by the Neuropsychiatric Inventory, and the caregiver must have at least 7 h per week contact. Participants will be randomly allocated to intervention (TAP) or control (phone-based education sessions) groups, both provided by a trained occupational therapist. Primary outcome measure will be the revised Neuropsychiatric Inventory - Clinician rating scale (NPI-C) to measure BPSD exhibited by the person with dementia. This trial investigates the effectiveness and cost-effectiveness of TAP within an Australian population. Results will address a significant gap in the current Australian community-support base for people living with dementia and their caregivers.

Altered Monoamine Metabolism in High Fat Diet Induced Neuropsychiatric Changes in Rats

Objective: To investigate the role of central and peripheral monoamine metabolism on neuropsychological status in high fat diet induced obese rats. Method: Animals were fed on high fat diet for 12 weeks. Periodically blood was collected to estimate serum Metanephrine (MN) levels. After 11 weeks, behavioural paradigms of depression, locomotor activity and cognition were performed. Central (brain) and peripheral i.e. Visceral White Adipose Tissue (vWAT) and Brown Adipose Tissue (BAT) MN levels, Monoamine Oxidase A and B (MAO-A, MAO-B) enzyme activity and Acetylcholinesterase (AChE) activity was estimated. Results: High fat diet significantly increased the body weight which was negatively correlated with the serum metanephrine concentration. However, metanephrine concentration in brain was significantly decreased whereas it significantly increased in vWAT with no change in BAT. In obese animals, immobility time in forced swim test and transfer latency in elevated plus maze was significantly increased while locomotor activity was significantly decreased. Central MAO-A and MAO-B activities were increased while enzyme activities showed a significant reduction in vWAT with no change in BAT. Brain AChE activity was also increased significantly in obese rats. Conclusion: Metabolism of biogenic monoamines plays a critical role in altered neuropsychiatric behaviours associated with diet induced obesity.

Correlates of quality of life for individuals with dementia living at home: the role of home environment, caregiver, and patient-related characteristics.

To examine prevalence of modifiable risk factors and their contribution to patient quality of life (QoL) as rated by dementia patients and family caregivers. Cross-sectional. Home environment. 88 patients and their caregivers. Modifiable characteristics of home environments, patients, and caregivers were observed or obtained through interview. Demographics and ratings of patients' QoL were obtained from patients and caregivers. Patients had mean Mini-mental Status Examination (MMSE) score = 17.7 ± 4.6, (range: 10-28) on an average 7.7 ± 2.4 neuropsychiatric behaviors, 6.0 ± 3.1 health conditions and moderate functional challenges; 70.7% (N = 58) had fall risk; 60.5% (N = 52) had sleep problems at least once weekly; and 42.5% (N = 37) had pain. An average of 8.1 ± 5.2 home hazards and 5.4 ± 4.1 adaptations were observed; 51.7% had unmet device/navigation needs. Patients' and caregivers' QoL ratings were unrelated to MMSE; and patients' self-rated QoL was higher than rated by caregivers. Number of health conditions and unmet device/navigation needs were inversely associated with patient self-rated QoL, and number of health conditions, frequency of behaviors, and level of negative communications were inversely associated with caregiver's assessment of patient QoL. Positive endorsement of caregiving was positively associated with caregiver's appraisal of patient QoL. Other factors were unrelated. Most patients lived at home with high fall risk, unmanaged behavioral symptoms, pain, sleep disturbances, environmental challenges, and multiple hazards. Except for health, factors associated with lower QoL differed for patients and caregivers. Results suggest need to improve QoL by addressing modifiable risk factors and tailoring interventions to patient and caregiver perspectives.

Enhancing genotyping of MAOA‐LPR and 5‐HTT‐LPR in rhesus macaques (Macaca mulatta)

Genetic variation in monoamine oxidase A (MAOA) and serotonin transporter (5-HTT)-linked polymorphic regions (LPR) is associated with neuropsychiatric behavior. We genotyped 37 macaques using conventional PCR product gel fractionation and by capillary electrophoresis of multiplexed amplicons and compared the data. Genotype concordance was 97% and 95% for MAOA-LPR and 5-HTT-LPR, respectively. Capillary electrophoresis was more sensitive and cost-effective. Multiplexing MAOA-LPR and 5-HTT-LPR will enhance the genotyping of large sample sets.

Comparative Analysis of Two Musical Genres Within a Multisensory Environmental Intervention

The purpose of this study was to determine if there were any differences in the behavioral responses of persons with dementia while listening to nonreligious and religious music within a multisensory environment. A within-subjects, repeated measures design was used. Participants were exposed to both musical genres during multiple sessions over a 4-week period. Neuropsychiatric symptoms were recorded before and after the musical intervention. Behavioral responses to the music were recorded while listening to the music. No significant difference was found between the numbers of neuropsychiatric behaviors observed before and after the participants listened to the nonreligious and religious music. A significant difference was found between the musical interventions as a whole and the number of agitated behaviors before and after intervention. No significant difference was found in the observed behavioral responses with the nonreligious and religious music. Music can be a useful intervention to reduce neuropsychiatric symptoms in persons with dementia.

Streptococcus and rheumatic fever

To give an overview of the current hypotheses of the pathogenesis of rheumatic fever and group A streptococcal autoimmune sequelae of the heart valve and brain. Human monoclonal antibodies (mAbs) derived from rheumatic heart disease have provided evidence for crossreactive autoantibodies that target the dominant group A streptococcal epitope of the group A carbohydrate, N-acetyl-beta-D-glucosamine (GlcNAc), and heart valve endothelium, laminin and laminar basement membrane. T cells in peripheral blood and in rheumatic heart valves revealed the presence of T cells crossreactive with streptococcal M protein and cardiac myosin. For initiation of disease, evidence suggests a two-hit hypothesis for antibody attack on the valve endothelium with subsequent extravasation of T cells through activated endothelium into the valve to form granulomatous lesions and Aschoff bodies. Autoantibodies against the group A streptococcal carbohydrate epitope GlcNAc and cardiac myosin and its peptides appear during progression of rheumatic heart disease. However, autoantibodies against collagen that are not crossreactive may form because of the release of collagen from damaged valve or to responses to collagen bound in vitro by certain serotypes of streptococci. In Sydenham chorea, human mAbs derived from disease target the group A carbohydrate epitope GlcNAc and gangliosides and dopamine receptors found on the surface of neuronal cells in the brain. Human mAbs and autoantibodies in Sydenham chorea were found to signal neuronal cells and activate calcium calmodulin-dependent protein kinase II (CaMKII) in neuronal cells and recognize the intracellular protein biomarker tubulin. To summarize, pathogenic mechanisms of crossreactive autoantibodies which target the valve in rheumatic heart disease and the neuronal cell in Sydenham chorea share a common streptococcal epitope GlcNAc and target intracellular biomarkers of disease including cardiac myosin in the myocardium and tubulin, a protein abundant in the brain. However, intracellular antigens are not believed to be the basis for disease. The theme of molecular mimicry in streptococcal autoimmune sequelae is the recognition of targeted intracellular biomarker antigens such as cardiac myosin and brain tubulin, while targeting extracellular membrane antigens such as laminin on the valve surface endothelium or lysoganglioside and dopamine receptors in the brain. Antibody binding to these cell surface antigens may lead to valve damage in rheumatic heart disease or neuropsychiatric behaviors and involuntary movements in Sydenham chorea.

P1‐084: Comparison of the prevalence of neuropsychiatric behaviors between amnestic and nonamnestic MCI subjects

P1‐084: Comparison of the prevalence of neuropsychiatric behaviors between amnestic and nonamnestic MCI subjects

Neurodevelopmental and neuropsychiatric behaviour defects arise from 14-3-3ζ deficiency

Complex neuropsychiatric disorders are believed to arise from multiple synergistic deficiencies within connected biological networks controlling neuronal migration, axonal pathfinding and synapse formation. Here, we show that deletion of 14-3-3ζ causes neurodevelopmental anomalies similar to those seen in neuropsychiatric disorders such as schizophrenia, autism spectrum disorder and bipolar disorder. 14-3-3ζ-deficient mice displayed striking behavioural and cognitive deficiencies including a reduced capacity to learn and remember, hyperactivity and disrupted sensorimotor gating. These deficits are accompanied by subtle developmental abnormalities of the hippocampus that are underpinned by aberrant neuronal migration. Significantly, 14-3-3ζ-deficient mice exhibited abnormal mossy fibre navigation and glutamatergic synapse formation. The molecular basis of these defects involves the schizophrenia risk factor, DISC1, which interacts isoform specifically with 14-3-3ζ. Our data provide the first evidence of a direct role for 14-3-3ζ deficiency in the aetiology of neurodevelopmental disorders and identifies 14-3-3ζ as a central risk factor in the schizophrenia protein interaction network.

Dopamine D2 receptor gene polymorphisms in newborn infants of drug-using women

ObjectivesTo determine the characteristics of dopamine D2 receptor gene (DRD2) polymorphisms in drug-exposed and unexposed neonates and the relationship to neonatal abstinence syndrome (NAS).DesignRetrospective case-control analysis between drug-exposed and unexposed...

The effects of oxytocin on social cognition and behaviour in frontotemporal dementia

Patients with behavioural variant frontotemporal dementia demonstrate abnormalities in behaviour and social cognition, including deficits in emotion recognition. Recent studies suggest that the neuropeptide oxytocin is an important mediator of social behaviour, enhancing prosocial behaviours and some aspects of emotion recognition across species. The objective of this study was to assess the effects of a single dose of intranasal oxytocin on neuropsychiatric behaviours and emotion processing in patients with behavioural variant frontotemporal dementia. In a double-blind, placebo-controlled, randomized cross-over design, 20 patients with behavioural variant frontotemporal dementia received one dose of 24 IU of intranasal oxytocin or placebo and then completed emotion recognition tasks known to be affected by frontotemporal dementia and by oxytocin. Caregivers completed validated behavioural ratings at 8 h and 1 week following drug administrations. A significant improvement in scores on the Neuropsychiatric Inventory was observed on the evening of oxytocin administration compared with placebo and compared with baseline ratings. Oxytocin was also associated with reduced recognition of angry facial expressions by patients with behavioural variant frontotemporal dementia. Together these findings suggest that oxytocin is a potentially promising, novel symptomatic treatment candidate for patients with behavioural variant frontotemporal dementia and that further study of this neuropeptide in frontotemporal dementia is warranted.

The effect of vignette activity on the neuropsychiatric behaviours expressed by individuals with dementia, living in long-term Care

The effect of vignette activity on the neuropsychiatric behaviours expressed by individuals with dementia, living in long-term Care

Undiagnosed illness and neuropsychiatric behaviors in community residing older adults with dementia.

The aim of this retrospective analysis was to examine prevalence of undiagnosed acute illness and characteristics including neuropsychiatric symptoms associated with illness in community residing older adults with Alzheimer disease or related disorders. Subjects included 265 community residing older adults with dementia who participated in 1 of 2 interventions being tested in randomized clinical trials. Measures included a brief nursing assessment and laboratory evaluations including complete blood count, blood chemistry (Chem 7), and thyroid function tests of serum samples and culture and sensitivity tests of urine samples. Undiagnosed illness was identified according to currently published criteria. Neuropsychiatric behaviors were assessed using 21 behaviors derived from standard measures. Thirty-six percent (N=96) of patients had clinical findings indicative of undetected illness. Conditions most prevalent were bacteriuria (15%), followed by hyperglycemia (6%) and anemia (5%). The behavior most often demonstrated among those with detected illness was resisting or refusing care (66% vs. 47% for those without detected illness). Individuals with detected illness had significantly lower functional status scores [3.8 vs. 4.4, t(275)=7.01, P=0.01], lower cognitive status scores [10.5 vs. 14.4, t(275)=12.1, P<0.01], and were more likely to be prescribed psychotropic medications for behavior (41% vs. 26%, χ=3.67, P<0.05) than those without illness. Findings suggest that challenges of diagnosing acute illness with atypical presentation must be addressed to promote quality of care and the specialized needs for this vulnerable population.

Hippocampal neurofibrillary tangle changes and aggressive behaviour in dementia

Neuropsychiatric behaviours occur frequently in Alzheimer's disease and other dementias and are thought to arise from the neurodegenerative process. However, it is unclear whether neurodegenerative changes in the hippocampus are associated with neuropsychiatric behaviours such as aggression. In this study, semiquantitative measurements of cell loss, atrophy, neuritic plaque and neurofibrillary tangle load in the postmortem hippocampus were taken for dementia patients, prospectively assessed for neuropsychiatric behaviours. It was found that increased tangle load, but not other hippocampal neuropathological variables, was associated with increased severity of aggressive behaviours and presence of chronic aggression. This study suggests a pathogenic link between neurofibrillary tangle load and aggressive behaviours in the hippocampus of dementia patients.

Neuropsychiatric symptoms and syndromes in institutionalized elderly people without dementia

Neuropsychiatric disorders are mainly studied in people with dementia but estimates are still not available for institutionalized elderly people without dementia. The aim of this work was to investigate neuropsychiatric syndromes in non-demented elderly people living in residential facilities (RFs). Data from the PROGRES-Older people project, including 95 RFs in Italy, were analyzed. From a total of 1215 people, 252 without dementia were recruited. Behavioral syndromes were identified using both factor and cluster analysis of results from the 12-item Neuropsychiatric Inventory. Logistic regression was used to assess factors associated with behavioral syndromes. Global cognitive functioning was assessed with the Mini-mental State Examination (MMSE). Current pharmacological treatments were taken from the residents' records. Five neuropsychiatric syndromes were identified: (1) Affective (depression, anxiety, night-time behaviors); (2) Hyperactive (agitation, irritability, appetite abnormalities); (3) Psychotic (delusions and hallucinations); (4) Manic (euphoria and disinhibition); (5) Apathetic (apathy and aberrant motor behavior). The risk of having a neuropsychiatric syndrome was higher in people with younger age (OR: 5.1, 1.3-20.0), higher education (OR: 7.3, 2.4-22.1), and low MMSE score (OR: 6.5, 1.9-22.2). Almost half of people with behavioral syndromes were not undergoing psychotropic treatment. Hypnotic and anxiolytic agents were the most frequently used drugs for most of the syndromes. Older people without dementia living in RFs exhibit a syndrome pattern of neuropsychiatric behaviors different from those observed in patients with dementia, which are associated with cognitive and sociodemographic characteristics. A large proportion of non-demented older people with neuropsychiatric syndromes are not having adequate treatment for their psychiatric disturbances.

Differential involvement of hippocampal serotonin1A receptors and re-uptake sites in non-cognitive behaviors of Alzheimer’s disease

Previous studies have shown extensive serotonergic deficits in the hippocampus of Alzheimer's disease (AD) patients. However, it is unclear whether such deficits play a role in non-cognitive, neuropsychiatric behaviors that occur frequently in AD and cause significant caregiver distress. In this study, we aimed to correlate serotonergic markers in the AD hippocampus with neuropsychiatric behaviors. Using postmortem hippocampal homogenates from aged controls as well as a cohort of longitudinally assessed AD patients, measurements of 5-HT(1A) receptors, 5-HT(2A) receptors, and serotonin re-uptake (5-HTT) sites were performed by binding with (3)H-labeled 8-OH-DPAT, ketanserin, and citalopram, respectively. Alterations of 5-HT(1A) receptors and 5-HTT were found to be differentially involved in neuropsychiatric behaviors, with loss of 5-HT(1A) receptors specifically correlated with depressive symptoms, while 5-HTT sites were preserved or up-regulated in patients with aggressive behaviors. Our data suggest that neuropsychiatric behaviors in AD share certain neurochemical features with psychiatric disorders like major depression and that serotonergic drugs used in psychiatric disorders may also be efficacious against behavioral symptoms in AD.

Impact of Underlying Depression on Treatment of Neuropsychiatric Symptoms in Older Adults with Dementia

This article examines the moderating effect of depression on interdisciplinary treatment approaches for behaviors in dementia. A secondary analysis of data collected on tailored treatment of 105 long-term care residents with dementia found a significant relationship between treatment and passivity (p < 0.001), treatment and agitation (p = 0.001), and the mediating effect of change in passivity on change in agitation (p < 0.001). The moderating effect of depression was found as a significant factor. For participants with depression and agitation, a significant change in passive behavior was related to significant change in agitated behavior. Thus, by focusing treatment on passivity, both types of neuropsychiatric behaviors improved. The implications of thoroughly assessing not only a behavior problem such as agitation but also other neuropsychiatric symptoms that complicate the delivery of the intervention are discussed.

Rat model of influenza-associated encephalopathy (IAE): studies of electroencephalogram (EEG) in vivo

Influenza-associated encephalopathy (IAE) is characterized by severe neurological complications during high-grade fever with high morbidity and mortality in children. The major neurological complications during high-grade fever include convulsive seizures, loss of consciousness, neuropsychiatric behavior (hallucination, meaningless speech, disorientation, laughing alone); high voltage amplitude slow waves and the occurrence of theta oscillation are depicted on the electroencephalogram (EEG) in the IAE patients. At the early phase of the disease, the cytokines levels increase in severe cases. To understand the neuronal properties in the CNS leading to these neurological complications in IAE patients, we recorded EEG signals from the hippocampus and cortex of rats infected with influenza A/WSN/33 H1N1 virus (IAV) strain. Abnormal EEG activities were observed in all infected rats under anesthesia, including high voltage EEG burst amplitude and increased EEG spikes in the early phase (8 h–day 2) of infection, and these increases at the early phase were in parallel with a significant increase level of interleukin-6 (IL-6) in the serum. When the infected rats were heat-stressed by elevating the rat body core temperature to 39–41 °C, these abnormal EEG activities were enhanced, and the oscillation pattern shifted in most of rats from slow bursting waves (<1 Hz) to theta oscillation (3–6 Hz). These results indicate that the abnormal EEG activities in IAE patients could be well reproduced in anesthetized IAV infected rats under hyperthermia, hence this animal model will be useful for further understandings the mechanism of neuronal complications in IAE patient during high-grade fever.