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BACKGROUND AND OBJECTIVES: Behavioral and neuropsychiatric symptoms are frequent in patients with genetic frontotemporal dementia (FTD). We aimed to describe behavioral and neuropsychiatric phenotypes in genetic FTD, quantify their temporal association, and investigate their regional association with brain atrophy. METHODS: We analyzed data of pathogenic variant carriers in the chromosome 9 open reading frame 72 (c9orf72), progranulin (GRN), or microtubule-associated protein tau (MAPT) gene from the Genetic Frontotemporal dementia Initiative cohort study that enrolls both symptomatic pathogenic variant carriers and first-degree relatives of known carriers. Principal component analysis was performed to identify behavioral and neuropsychiatric clusters that were compared with respect to frequency and severity between groups. Associations between neuropsychiatric clusters and MRI-assessed atrophy were determined using voxel-based morphometry. We applied linear mixed effects and generalized linear mixed effects models to assess the longitudinal course of symptoms. RESULTS: A total of 522 participants were included: 221 c9orf72 (138 presymptomatic), 213 GRN (157 presymptomatic), and 88 MAPT (62 presymptomatic) pathogenic variant carriers. Principal component analysis revealed 5 phenotypic clusters (67.6% of variance), labeled diverse behavioral, affective, psychotic, euphoric/hypersexual, and tactile hallucinations phenotype. In participants presenting behavioral or neuropsychiatric symptoms, affective symptoms were most frequent across groups (83.6%-88.1%), followed by diverse behavioral symptoms (68.4%-77.9%). In c9orf72 and GRN pathogenic variant carriers, psychotic symptoms (32.0% and 19.4%, respectively) were more frequent than euphoric/hypersexual symptoms (28.7% and 14.2%, respectively), which was the other way around in MAPT pathogenic variant carriers (28.6% and 23.8%). Although diverse behavioral symptoms were associated with gray and white matter frontotemporal atrophy, only a small atrophy cluster in the right thalamus was associated with psychotic symptoms. Euphoric/hypersexual symptoms were associated with atrophy in mesial temporal lobes, basal forebrain structures, and the striatum (p < 0.05). Estimated time to symptom onset, genetic group, education, and sex influenced behavioral and neuropsychiatric symptoms (p < 0.05). Particularly, in c9orf72 pathogenic variant carriers, psychotic symptoms may be starting decades before recognition of onset of illness. DISCUSSION: We identified multiple clusters of behavioral and neuropsychiatric symptoms in participants with genetic FTD that relate to distinct cerebral atrophy patterns. Their severity depends on time, affected gene, sex, and education. These clinical-genetic associations can guide diagnostic evaluations and the design of clinical trials for new disease-modifying and preventive treatments.
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Proteína C9orf72 , Demencia Frontotemporal , Progranulinas , Proteínas tau , Humanos , Demencia Frontotemporal/genética , Demencia Frontotemporal/diagnóstico por imagen , Demencia Frontotemporal/patología , Demencia Frontotemporal/psicología , Masculino , Femenino , Proteína C9orf72/genética , Persona de Mediana Edad , Progranulinas/genética , Proteínas tau/genética , Anciano , Estudios Longitudinales , Atrofia/patología , Síntomas Conductuales/etiología , Síntomas Conductuales/genética , Imagen por Resonancia Magnética , Trastornos Mentales/genética , Estudios de Cohortes , Fenotipo , Encéfalo/diagnóstico por imagen , Encéfalo/patologíaRESUMEN
BACKGROUND: Latinos are more likely than non-Latino Whites to develop dementia and be prescribed antipsychotics for dementia-related behavioral symptoms. Antipsychotics have significant risks yet are often overprescribed. Our understanding of how Latino caregivers of Latino older adults living with dementia perceive and address behavioral issues is limited, impeding our ability to address the root causes of antipsychotic overprescribing. METHODS: We interviewed Latino older adults' caregivers and community-based organization workers serving older adults with cognitive impairment (key informants), focusing on the management of behavioral symptoms and experiences with health services. RESULTS: We interviewed 8 caregivers and 2 key informants. Caregivers were the spouses, children, or grandchildren of the older adult living with cognitive impairment; their ages ranged from 30 to 95. We identified three categories of how caregivers learned about, managed, and coped with behavioral symptoms: caregivers often faced shortcomings with dementia care in the medical system, receiving limited guidance and support; caregivers found community organizations and senior day centers to be lifelines, as they received relevant, timely advice and support, caregivers often devised their own creative strategies to manage behavioral symptoms. CONCLUSION: In-depth interviews suggest that the healthcare system is failing to provide support for behavioral symptoms from dementia; caregivers of Latino older adults rely on community organizations instead.
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Cuidadores , Demencia , Hispánicos o Latinos , Trastornos de la Memoria , Investigación Cualitativa , Humanos , Cuidadores/psicología , Demencia/etnología , Demencia/psicología , Demencia/terapia , Hispánicos o Latinos/psicología , Femenino , Masculino , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Adulto , Trastornos de la Memoria/etnología , Trastornos de la Memoria/psicología , Trastornos de la Memoria/terapia , Síntomas Conductuales/terapia , Síntomas Conductuales/etnologíaRESUMEN
Guided by developmental models examining the legacy of childhood caregiving environments, we examined the longitudinal pattern of associations between harsh parenting and children's internalizing and externalizing symptoms across late childhood to late adolescence. Participants included 199 youth (48.7% female, 65.3% White, 32.2% Black, 2.5% biracial) and their mothers and fathers from a diverse range of socioeconomic backgrounds. The study utilized a multi-informant, longitudinal design including five waves of data (youths' mean ages were 9, 10, 11, 17, and 18 across waves). Harsh parenting at Age 9 predicted higher levels of (a) externalizing symptoms at Ages 11, 17, and 18 and (b) internalizing symptoms at Ages 17 and 18. Developmental sensitivity analyses revealed that the magnitude of the more distal association between early harsh parenting and later internalizing and externalizing symptoms was statistically stronger as compared to more proximal associations. Bidirectional analyses revealed that externalizing symptoms at Age 9 predicted harsh parenting at Ages 9, 10, 11, 17, and 18. Whereas links between harsh parenting and internalizing symptoms were consistent with a sleeper effects model, links between harsh parenting and externalizing symptoms provided some support for both enduring and sleeper effects models. Findings inform an understanding of youth developmental sensitivity to harsh parenting and the downstream consequences of harsh parenting. Results have important translational implications, including testing the long-term efficacy of therapeutic programs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Responsabilidad Parental , Humanos , Responsabilidad Parental/psicología , Femenino , Masculino , Adolescente , Niño , Estudios Longitudinales , Relaciones Padres-Hijo , Conducta Infantil/fisiología , Conducta Infantil/psicología , Síntomas ConductualesRESUMEN
INTRODUCTION: Youth with a family history of bipolar disorder (At-Risk) have a higher risk of developing psychiatric disorders and experiencing environmental stressors than youth without such family history (Control). We studied the differential associations of familial and environmental factors on developing psychiatric diagnoses and symptoms, in At-Risk and Control youth. METHODS: At-Risk and Control youth (N = 466, ages 9-22) were systematically assessed for severity of symptoms, psychiatric diagnoses, and self-reported measures of stress and social support. We tested the association of family history and measures of stress or support with symptom severity and diagnoses. RESULTS: At-Risk youth had higher symptom severity scores and were more frequently diagnosed with psychiatric disorders (all p values < 0.001). When predicting mood symptom severity, family history had an interaction effect with stressful life events (p < 0.001) and number of distinct traumatic events (p = 0.001). In multivariate models, At-Risk status predicted anxiety disorders (OR = 2.7, CI 1.3-5.4, p = 0.005) and anxiety severity (Coefficient = 0.4, CI 0.2-0.7, p < 0.001) but not mood or behavioral disorder diagnoses or severity. LIMITATIONS: Measures of stress and social support were based on self-report. Not all participants had passed through the period of risk for developing the outcomes under study and the follow up period was variable. We could not fully study the differential impact of physical or sexual abuse due to low frequency of occurrence in controls. CONCLUSION: At-Risk youth exhibit more severe mood symptoms compared to Controls when exposed to similar levels of stress or trauma. At-Risk youth are also more prone to develop anxiety which may be a precursor for bipolar disorder.
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Trastornos de Ansiedad , Trastorno Bipolar , Apoyo Social , Estrés Psicológico , Humanos , Trastorno Bipolar/psicología , Trastorno Bipolar/epidemiología , Masculino , Femenino , Adolescente , Estrés Psicológico/psicología , Niño , Trastornos de Ansiedad/epidemiología , Trastornos de Ansiedad/psicología , Trastornos de Ansiedad/diagnóstico , Adulto Joven , Factores de Riesgo , Síntomas Conductuales/epidemiología , Afecto , Ansiedad/psicología , Ansiedad/epidemiología , Índice de Severidad de la Enfermedad , Acontecimientos que Cambian la Vida , AdultoRESUMEN
OBJECTIVES: Olanzapine and risperidone have emerged as the most widely used drugs as short-term prescription in the treatment of behavioral disturbances in dementia. The present systematic review and meta-analysis was hence performed to investigate the effectiveness and safety profile of olanzapine and risperidone in the treatment of behavioral and psychological symptoms of dementia (BPSD), aiming to provide updated suggestion for clinical physicians and caregivers. DESIGN: Prospective controlled clinical studies were included, of which available data was extracted. Outcomes of BEHAVE-AD scores with the variation of grades, specific behaviors variables, as well as safety signals were pooled for the analysis by odds rates and weighted mean differences, respectively. DATA SOURCES: Medline, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WanFang. ELIGIBILITY CRITERIA: Prospective, controlled clinical studies, conducted to compare the effectiveness and safety profile of olanzapine and risperidone in the treatment of BPSD. DATA EXTRACTION AND SYNTHESIS: Interested data including baseline characteristics and necessary outcomes from the included studies were extracted independently by 2 investigators. BEHAVE-AD scale was adopted to assess the efficacy in the present study. All behaviors were evaluated at the time of the initiation of the treatment, as well as the completion of drugs courses. Adverse events were assessed with the criteria of Treatment Emergent Symptom Scale, or Coding Symbols for a Thesaurus of Adverse Reaction Terms dictionary. Weighted mean difference was used for the pooled analysis. RESULTS: A total of 2427 participants were included in the present meta-analysis. Comparative OR on response rate, and remarkable response rate between olanzapine and risperidone was 0.65 (95% CI: 0.51-0.84; Pâ =â .0008), and 0.62 (95% CI: 0.50-0.78; Pâ <â .0001), respectively. There were statistical differences observed by olanzapine on the improvement of variables including delusions (WMD, -1.83, 95% CI, -3.20, -0.47), and nighttime behavior disturbances (WMD, -1.99, 95% CI, -3.60, -0.38) when compared to risperidone. CONCLUSION: Our results suggested that olanzapine might be statistically superior to risperidone on the reduction of BPSD of Alzheimer's disease, especially in the relief of delusions and nighttime behavior disturbances. In addition, olanzapine was shown statistically lower risks of agitation, sleep disturbance, and extrapyramidal signs.
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Enfermedad de Alzheimer , Antipsicóticos , Olanzapina , Risperidona , Risperidona/uso terapéutico , Risperidona/efectos adversos , Humanos , Olanzapina/uso terapéutico , Olanzapina/efectos adversos , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/psicología , Antipsicóticos/uso terapéutico , Antipsicóticos/efectos adversos , Benzodiazepinas/uso terapéutico , Benzodiazepinas/efectos adversos , Resultado del Tratamiento , Síntomas Conductuales/tratamiento farmacológicoRESUMEN
PURPOSE OF REVIEW: Alongside motor and cognitive symptoms, amyotrophic lateral sclerosis (ALS) and ALS with frontotemporal dementia (ALSFTD) present with behavioural symptoms, which can be challenging for all affected by the disease. A scoping review of studies published between 2011 and 2024 was conducted to present the breadth of behavioural symptoms in ALS and ALSFTD, explore how they are described and assessed, and identify patterns in the literature. FINDINGS: This scoping review identified 3939 articles, with 111/3939 meeting eligibility criteria. Most studies were from Australia (23.22%), Italy (16.94%) and the UK (14.29%); 75.67% were cross-sectional. Sample size ranged from 1 to 1013, as case studies were included. Overall mean age (100/111 studies) was 61.32 (SDâ=â4.15). Proportion of male patients (reported 102/111 studies) was 61.49%; mean disease duration (reported in 86/111 records) was 32.63âmonths (SDâ=â24.72). Papers described a broad range of behavioural symptoms (465 examples), which were thematically collated into seven categories: disinhibition (27.74%), apathy (25.16%), perseverative/compulsive behaviours (17.42%), hyperorality (10.53%), loss of sympathy or empathy (8.6%), psychotic symptoms (7.74%), and loss of insight about disease and changes (2.8%). Most studies (78.37%) used validated behavioural assessments that elicited carer's perspectives. SUMMARY: Despite extensive evidence of behavioural symptoms in ALS, implementation of assessments and management of behavioural symptoms in clinical care remain limited. Clinicians must assess behavioural symptoms, as these can negatively affect disease prognosis, patient treatment engagement and increase family distress. Measures capturing carers' perspectives through interviews are ideal as they can reveal anosognosia, lack of sympathy and lack of empathy.
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Esclerosis Amiotrófica Lateral , Demencia Frontotemporal , Humanos , Demencia Frontotemporal/psicología , Demencia Frontotemporal/fisiopatología , Demencia Frontotemporal/diagnóstico , Esclerosis Amiotrófica Lateral/psicología , Esclerosis Amiotrófica Lateral/complicaciones , Esclerosis Amiotrófica Lateral/diagnóstico , Síntomas Conductuales/etiología , Síntomas Conductuales/diagnósticoRESUMEN
BACKGROUND: To explore carers' experiences of behavioural symptoms in Motor Neurone Disease (MND), before and after using the MiNDToolkit, a novel internet-based psychoeducational intervention to support management of behavioural symptoms (BehSymp) in MND. The study also investigated carers' views and acceptability of MiNDToolkit. METHODS: A qualitative process evaluation of carers engagement with, and acceptability of, the MiNDToolkit conducted using semi-structured interviews with carers (n = 11). All interviews were audio-recorded, professionally transcribed verbatim and analysed thematically. RESULTS: Five themes were identified: (1) In the dark: carers' experiences and reactions to BehSymp; (2) Others can see: the role of HCPs in identifying symptoms - and perceived opportunities for carers to receive support; (3) Shedding light: carers implementation and perceived impact of the MiNDToolkit content; (4) Acceptability and carers' engagement with MiNDToolkit; (5) Future implementation. Carers' experience of BehSymp was particularly distressing when symptoms were apparently out of context. MiNDToolkit appeared to support learning that BehSymp were part of MND. Content resonated with carers, who reported learning about the full picture of MND, which led to acceptance and use of newly learned strategies. Engagement with the platform was good, with varied input from HCPs. Greater and nuanced involvement from HCPs seem important to support management of BehSymp. Recommendations for a full-scale trial emerged, including adding a paper booklet to accompany the intervention and creation of new modules on emotional lability, changes in relationships, and transitioning to a care home. CONCLUSIONS: MiNDToolkit was acceptable to carers overall. Recommended improvements should be actioned in a full-scale trial.
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Síntomas Conductuales , Cuidadores , Enfermedad de la Neurona Motora , Humanos , Cuidadores/psicología , Masculino , Enfermedad de la Neurona Motora/psicología , Enfermedad de la Neurona Motora/terapia , Femenino , Persona de Mediana Edad , Síntomas Conductuales/terapia , Síntomas Conductuales/etiología , Anciano , Adulto , Investigación CualitativaRESUMEN
BACKGROUND: Behavioural and psychological symptoms of dementia (BPSD) are highly prevalent in people living with dementia. Second-generation antipsychotics (SGAs) are commonly used to treat BPSD, but their comparative efficacy and acceptability are unknown. METHODS: The standard mean difference (SMD) was used to pool the fixed effects of continuous outcomes. We calculated ORs with corresponding 95% credible intervals (CI) for the categorical variable. Efficacy was defined as the scores improved on the standardised scales. Acceptability was defined as the all-cause dropout rate. Tolerability was defined as the discontinuation rate due to adverse effects (AEs). The relative treatment rankings were reported with the surface under the cumulative curve. The AE outcomes included mortality, cerebrovascular adverse events (CVAEs), falls, sedation, extrapyramidal symptoms and urinary symptoms. RESULTS: Twenty randomised controlled trials with a total of 6374 individuals containing 5 types of SGAs (quetiapine, olanzapine, risperidone, brexpiprazole and aripiprazole) with intervention lengths ranging from 6 weeks to 36 weeks were included in this network meta-analysis. For the efficacy outcome, compared with the placebo, brexpiprazole (SMD=-1.77, 95% CI -2.80 to -0.74) was more efficacious, and brexpiprazole was better than quetiapine, olanzapine and aripiprazole. Regarding acceptability, only aripiprazole (OR=0.72, 95% CI 0.54 to 0.96) was better than the placebo, and aripiprazole was also better than brexpiprazole (OR=0.61, 95% CI 0.37 to 0.99). In terms of tolerability, olanzapine was worse than placebo (OR=6.02, 95% CI 2.87 to 12.66), risperidone (OR=3.67, 95% CI 1.66 to 8.11) and quetiapine (OR=3.71, 95% CI 1.46 to 9.42), while aripiprazole was better than olanzapine (OR=0.25, 95% CI 0.08 to 0.78). Quetiapine presented good safety in CVAE. Brexpiprazole has better safety in terms of falls and showed related safety in sedation among included SGAs. CONCLUSION: Brexpiprazole showing great efficacy in the treatment of BPSD, with aripiprazole showing the highest acceptability and olanzapine showing the worst tolerability. The results of this study may be used to guide decision-making.
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Antipsicóticos , Demencia , Metaanálisis en Red , Humanos , Antipsicóticos/uso terapéutico , Antipsicóticos/efectos adversos , Demencia/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Olanzapina/uso terapéutico , Olanzapina/efectos adversos , Aripiprazol/uso terapéutico , Aripiprazol/efectos adversos , Síntomas Conductuales/tratamiento farmacológicoRESUMEN
OBJECTIVES: Behavioral and psychological symptoms of dementia (BPSD) are common and impart a significant burden to patients, caregivers, and the health system. However, there are few pharmacological options for treating BPSD. We conducted a systematic review of clinical trials examining the efficacy of anticonvulsants in BPSD. METHODS: We searched five electronic databases through January 2023, for randomized controlled trials and systematic reviews evaluating the efficacy of non-benzodiazepine anticonvulsants for the treatment of BPSD. We used the Cochrane risk of bias tool to ascertain the risk of bias in included trials. Because statistical pooling of results using meta-analysis was not feasible, we synthesized findings using the Cochrane Synthesis Without Meta-analysis reporting guidelines. RESULTS: We identified 12 studies, including randomized controlled trials (RCTs) and 1 systematic review. Five RCTs evaluating valproic acid were synthesized by a recent Cochrane review which concluded that this drug is likely ineffective for BPSD. We extracted data from 6 trials involving 248 individuals comparing non-benzodiazepine anticonvulsants to either placebo or risperidone. Four trials (n = 97 participants) evaluated carbamazepine, only one of which demonstrated an improvement in the Brief Psychiatric Rating Scale measuring agitation, hostility, psychosis, and withdrawal/depression (effect size: 1.13; 95% confidence interval [CI]: 0.54-1.73) relative to placebo. Adverse effects were more common in patients receiving carbamazepine (20/27; 74%) relative to placebo (5/24; 21%). There is low quality evidence that oxcarbazepine is likely ineffective and that topiramate may be comparable to risperidone. CONCLUSION: Anticonvulsants are unlikely to be effective in BPSD, although the quality of existing evidence is low.
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Anticonvulsivantes , Demencia , Humanos , Demencia/tratamiento farmacológico , Anticonvulsivantes/uso terapéutico , Síntomas Conductuales/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: This study aims to describe maternal depressive symptoms (MDS) trajectories in a longitudinal study extending from pregnancy to 27 years after the birth of the firstborn child. We also explored the associations of both MDS trajectories and child internalizing and externalizing problem trajectories with maternal adjustment (adaptive functioning, emotional and behavioral problems). METHODS: The population-based study was conducted in Tampere, Finland, and the sample comprised 356 first-time mothers. MDS were screened with the Edinburgh Postnatal Depression Scale during pregnancy, first week after delivery, 2 and 6 months postnatally, and when the child was 4-5, 8-9, 16-17, and 26-27 years of age. The internalizing and externalizing problems of the children were assessed with the Child Behavior Checklist when the child was 4-5, 8-9, and 16-17 years of age. Maternal adaptive functioning and internalizing and externalizing problems were assessed with the Adult Self Report at 26-27 years after the birth of the first child. Complete follow-up data were available for 168 mothers. RESULTS: We describe a three-group trajectory model of MDS (High Stable, Low Stable, Very Low). Elevated depressive symptom patterns were associated with less optimal maternal outcomes regarding both adaptive and problem dimensions. The child's internalizing and externalizing problem trajectories were associated with maternal internalizing and externalizing problems but not with maternal adaptive functioning. LIMITATIONS: Maternal and child measures were based on maternal reports only. CONCLUSIONS: The interconnectedness of the well-being of the mother and child should be noted in health and mental health services for adults and children.
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Adaptación Psicológica , Madres , Humanos , Femenino , Adulto , Madres/psicología , Adolescente , Niño , Finlandia , Estudios Longitudinales , Preescolar , Embarazo , Relaciones Madre-Hijo , Depresión/psicología , Masculino , Síntomas Conductuales/psicología , Depresión Posparto/psicología , Depresión Posparto/diagnóstico , Trastornos de la Conducta Infantil/psicología , Trastornos de la Conducta Infantil/diagnósticoRESUMEN
BACKGROUND: Little is known about how clinical features prospectively influence peer relationships in autistic populations. AIMS: This study investigated the clinical symptoms mediating the link between autism spectrum disorder (ASD) diagnosis and peer relationships at follow-up, i.e. the second time evaluation of this study. METHODS: The sample consisted of 366 autistic youths and 134 non-autistic comparisons. The autistic traits and emotional/behavioral problems were measured at baseline by Social Responsiveness Scale (SRS) and Child Behavior Checklist (CBCL). The interactions and problems with peers were assessed by the Social Adjustment Inventory for Children and Adolescents (SAICA) at follow-up. RESULTS: Each subscore of SRS and CBCL showed significant mediation effects. Multiple mediation analyses showed atypical social communication, social awareness problems, and delinquent behaviors mediated the link from ASD to less active peer interactions after controlling for sex, age, and IQ. Moreover, atypical social communication, social-emotional problems, and attention difficulties predicted problems with peers. After considering these mediation effects, the diagnosis of ASD still demonstrated a significantly direct effect on peer relationships at follow-up. CONCLUSIONS AND IMPLICATIONS: Our findings support that social-related autistic features, attention problems, and delinquent behaviors mediated a link between ASD and peer relationships. These mediators are potential measures for improving interactions and decreasing difficulties with peers in the autistic population.
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Trastorno del Espectro Autista , Grupo Paritario , Humanos , Masculino , Femenino , Niño , Trastorno del Espectro Autista/psicología , Adolescente , Estudios de Seguimiento , Conducta Social , Relaciones Interpersonales , Estudios de Casos y Controles , Emociones , Problema de Conducta/psicología , Interacción Social , Comunicación , Delincuencia Juvenil/psicología , Ajuste Social , Síntomas Conductuales/psicologíaRESUMEN
BACKGROUND: The seven tiered behavioural and psychological symptoms of dementia (BPSD) model of service delivery has been used by inpatient units. The classification of each tier is broadly defined and not always agreed upon by clinicians. The case study uses novel approach by combining the BPSD classification criteria with clinical presentation to identify the clinical characteristics of the case and match these characteristics against the BPSD classification. This process was enhanced by using case specific measures such as the Neuropsychiatric Inventory (NPI) and Cohen Mansfield Agitation Inventory (CMAI) scales and key clinical data. CASE PRESENTATION: A case study of 76 year old male diagnosed with mixed Alzheimer's and Vascular dementia. The clinical presentation of the symptomatology was deemed to be extreme, thus fitting into the seventh tier (Extreme) of the BPSD model of service delivery. The case is considered to fit into the Extreme BPSD category given the high levels of aggression, which were consistently reflected in high scores on NPI and CMAI, as well as long length of inpatient stay (over 3 years). The average number of Pro re nata (PRN) psychotropics medications per month was 56 and seclusion episodes of 6 times per month, with each episode lasting on average 132 min shows severity of behaviours. His level of aggression had resulted in environmental damage and staff injuries. CONCLUSION: We recommend patient clinical characteristics, relevant hospital data and specific measures should be used to develop consensus around defining and classifying cases into Extreme BPSD.
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Agresión , Demencia Vascular , Humanos , Masculino , Anciano , Agresión/psicología , Demencia Vascular/psicología , Enfermedad de Alzheimer/psicología , Demencia/psicología , Síntomas Conductuales/diagnóstico , Síntomas Conductuales/psicología , Síntomas Conductuales/etiología , Escalas de Valoración PsiquiátricaRESUMEN
OBJECTIVE: MiNDToolkit is a novel psychoeducational intervention for carers to support management of behavioral symptoms in people living with motor neuron disease (PlwMND). Implementation of MiNDToolkit involves delivery of an online intervention to carers, which is reinforced by trained healthcare professionals (HCPs). METHODS: A mixed-methods process evaluation of the MiNDToolkit feasibility trial was conducted, focusing on reinforcement of the intervention by HCPs. Quantitative data, descriptively analyzed, were included from platform analytics, questionnaire, and 10 semi-structured interviews with HCPs. Interviews were transcribed verbatim; data were inductively analyzed using Reflective Thematic Analysis. RESULTS: The MiNDToolkit training and platform is a beneficial and acceptable resource for HCPs with potential to increase knowledge and confidence in identifying and managing behavioral symptoms in MND. Implementation barriers included HCPs' perceptions that highlighting behavior changes would be burdensome to carers and assumptions that carers would take the initiative to ask for support from clinicians. Degree of intervention reinforcement varied, with most HCPs delegating intervention delivery solely to the online platform. CONCLUSIONS: Implementation of the MiNDToolkit was viewed to be feasible and the platform thought to increase accessibility of support to carers. The flexible approach to delivery (online platform and optional HCP reinforcement) is acceptable as an intervention for supporting carers of PlwMND with behavioral symptoms. However, MiNDToolkit should not negate HCP involvement in providing medical and practical information to PlwMND and families. Future research should explore ways to incorporate support for carers in the management of PlwMND alongside standard care, alongside tools such as the MiNDToolkit.
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Cuidadores , Personal de Salud , Enfermedad de la Neurona Motora , Humanos , Personal de Salud/psicología , Personal de Salud/educación , Masculino , Femenino , Enfermedad de la Neurona Motora/psicología , Enfermedad de la Neurona Motora/terapia , Cuidadores/psicología , Síntomas Conductuales/terapia , Síntomas Conductuales/etiología , Persona de Mediana Edad , Adulto , Encuestas y Cuestionarios , Estudios de FactibilidadRESUMEN
BACKGROUND: Evidence on management of behavioral symptoms in motor neuron disease (MND) is lacking. The MiNDToolkit, an online psychoeducational platform, supports carers dealing with behavioral symptoms (BehSymp). The study objectives were to ascertain recruitment and retention rates, carer and healthcare professional (HCP) use of the platform, and completion of online assessments, to inform a full-scale trial. Design: Randomized, parallel, multi-center, feasibility trial. SETTING: England and Wales, across diverse MND services; recruitment from July/21 to November/22; last participant follow-up in March/23. PARTICIPANTS: Carers of people with motor neuron disease (PwMND) with BehSymp, recruited through MND services. After confirming eligibility, participants completed screening and baseline assessments online via the MiNDToolkit platform and were randomized centrally in a 1:1 ratio to MiNDToolkit or control. INTERVENTION: MiNDToolkit offered tailored modules to carers for the 3-month study period. Carers in the intervention group could receive additional support from MiNDToolkit trained HCPs. The control group was offered access to the intervention at the end of the study. Data were collected on platform usage and psychosocial variables. MAIN OUTCOMES: One hundred and fifty-one carers from 11 sites were invited to join the study (letter, face-to-face); 30 were screened; 29 were randomized. Fifteen people were allocated to the control arm; 14 to intervention. Carers were mostly female; median age for was 62.5 (IQR: 58, 68; intervention) and 57 (IQR: 56, 70; controls). Study retention was high (24/29 = 82.76%); carers engaged with the platform on average 14 times (median (IQR):14.0 (10.0, 18.5)) during the study period. CONCLUSION: The MiNDToolkit study was feasible and well accepted by carers and trained HCPs. A definitive trial is warranted.
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Cuidadores , Estudios de Factibilidad , Enfermedad de la Neurona Motora , Humanos , Enfermedad de la Neurona Motora/psicología , Enfermedad de la Neurona Motora/terapia , Masculino , Femenino , Cuidadores/psicología , Persona de Mediana Edad , Anciano , Síntomas Conductuales/etiología , Síntomas Conductuales/terapia , AdultoRESUMEN
OBJECTIVE: Alcohol withdrawal syndrome (AWS) is a complex condition associated with alcohol use disorder (AUD), characterized by significant variations in symptom severity among patients. The psychological and emotional symptoms accompanying AWS significantly contribute to withdrawal distress and relapse risk. Despite the importance of neural adaptation processes in AWS, limited genetic investigations have been conducted. This study primarily focuses on exploring the single and interaction effects of single-nucleotide polymorphisms in the ANK3 and ZNF804A genes on anxiety and aggression severity manifested in AWS. By examining genetic associations with withdrawal-related psychopathology, we ultimately aim to advance understanding the genetic underpinnings that modulate AWS severity. METHODS: The study involved 449 male patients diagnosed with alcohol use disorder. The Self-Rating Anxiety Scale (SAS) and Buss-Perry Aggression Questionnaire (BPAQ) were used to assess emotional and behavioral symptoms related to AWS. Genomic DNA was extracted from peripheral blood, and genotyping was performed using PCR. RESULTS: Single-gene analysis revealed that naturally occurring allelic variants in ANK3 rs10994336 (CC homozygous vs. T allele carriers) were associated with mood and behavioral symptoms related to AWS. Furthermore, the interaction between ANK3 and ZNF804A was significantly associated with the severity of psychiatric symptoms related to AWS, as indicated by MANOVA. Two-way ANOVA further demonstrated a significant interaction effect between ANK3 rs10994336 and ZNF804A rs7597593 on anxiety, physical aggression, verbal aggression, anger, and hostility. Hierarchical regression analyses confirmed these findings. Additionally, simple effects analysis and multiple comparisons revealed that carriers of the ANK3 rs10994336 T allele experienced more severe AWS, while the ZNF804A rs7597593 T allele appeared to provide protection against the risk associated with the ANK3 rs10994336 mutation. CONCLUSION: This study highlights the gene-gene interaction between ANK3 and ZNF804A, which plays a crucial role in modulating emotional and behavioral symptoms related to AWS. The ANK3 rs10994336 T allele is identified as a risk allele, while the ZNF804A rs7597593 T allele offers protection against the risk associated with the ANK3 rs10994336 mutation. These findings provide initial support for gene-gene interactions as an explanation for psychiatric risk, offering valuable insights into the pathophysiological mechanisms involved in AWS.
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Ancirinas , Factores de Transcripción de Tipo Kruppel , Polimorfismo de Nucleótido Simple , Humanos , Masculino , Polimorfismo de Nucleótido Simple/genética , Ancirinas/genética , Adulto , Factores de Transcripción de Tipo Kruppel/genética , Persona de Mediana Edad , Síndrome de Abstinencia a Sustancias/genética , Síndrome de Abstinencia a Sustancias/psicología , Alcoholismo/genética , Alcoholismo/psicología , Agresión/psicología , Agresión/fisiología , Ansiedad/genética , Ansiedad/psicología , Epistasis Genética , Síntomas Conductuales/genética , Predisposición Genética a la Enfermedad/genética , AlelosRESUMEN
Background: Behavioral and psychological symptoms of dementia (BPSD) and prescribed central nervous system (CNS) active drugs to treat them are prevalent among persons living with Alzheimer's disease and related dementias (PLWD) and lead to negative outcomes for PLWD and their caregivers. Yet, little is known about racial/ethnic disparities in diagnosis and use of drugs to treat BPSD. Objective: Quantify racial/ethnic disparities in BPSD diagnoses and CNS-active drug use among community-dwelling PLWD. Methods: We used a retrospective cohort of community-dwelling Medicare Fee-for-Service beneficiaries with dementia, continuously enrolled in Parts A, B and D, 2017-2019. Multivariate logistic models estimated rates of BPSD diagnosis and, conditional on diagnosis, CNS-active drug use. Results: Among PLWD, 67.1% had diagnoses of an affective, psychosis or hyperactivity symptom. White (68.3%) and Hispanic (63.9%) PLWD were most likely, Blacks (56.6%) and Asians (52.7%) least likely, to have diagnoses. Among PLWD with BPSD diagnoses, 78.6% took a CNS-active drug. Use was highest among whites (79.3%) and Hispanics (76.2%) and lowest among Blacks (70.8%) and Asians (69.3%). Racial/ethnic differences in affective disorders were pronounced, 56.8% of white PLWD diagnosed; Asians had the lowest rates (37.8%). Similar differences were found in use of antidepressants. Conclusions: BPSD diagnoses and CNS-active drug use were common in our study. Lower rates of BPSD diagnoses in non-white compared to white populations may indicate underdiagnosis in clinical settings of treatable conditions. Clinicians' review of prescriptions in this population to reduce poor outcomes is important as is informing care partners on the risks/benefits of using CNS-active drugs.
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Demencia , Medicare , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Síntomas Conductuales/diagnóstico , Fármacos del Sistema Nervioso Central/uso terapéutico , Demencia/psicología , Demencia/etnología , Demencia/diagnóstico , Etnicidad/psicología , Disparidades en Atención de Salud/etnología , Vida Independiente , Estudios Retrospectivos , Estados Unidos/epidemiología , Blanco , Negro o Afroamericano , Asiático , Hispánicos o LatinosRESUMEN
Background: The term Behavioral and Psychological Symptoms of Dementia (BPSD) covers a group of phenomenologically and medically distinct symptoms that rarely occur in isolation. Their therapy represents a major unmet medical need across dementias of different types, including Alzheimer's disease. Understanding of the symptom occurrence and their clusterization can inform clinical drug development and use of existing and future BPSD treatments. Objective: The primary aim of the present study was to investigate the ability of a commonly used principal component analysis to identify BPSD patterns as assessed by Neuropsychiatric Inventory (NPI). Methods: NPI scores from the Aging, Demographics, and Memory Study (ADAMS) were used to characterize reported occurrence of individual symptoms and their combinations. Based on this information, we have designed and conducted a simulation experiment to compare Principal Component analysis (PCA) and zero-inflated PCA (ZI PCA) by their ability to reveal true symptom associations. Results: Exploratory analysis of the ADAMS database revealed overlapping multivariate distributions of NPI symptom scores. Simulation experiments have indicated that PCA and ZI PCA cannot handle data with multiple overlapping patterns. Although the principal component analysis approach is commonly applied to NPI scores, it is at risk to reveal BPSD clusters that are a statistical phenomenon rather than symptom associations occurring in clinical practice. Conclusions: We recommend the thorough characterization of multivariate distributions before subjecting any dataset to Principal Component Analysis.
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Enfermedad de Alzheimer , Humanos , Análisis de Componente Principal , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/psicología , Síntomas Conductuales/diagnóstico , Síntomas Conductuales/etiología , Envejecimiento , Pruebas NeuropsicológicasRESUMEN
Behavioural and psychological symptoms of dementia (BPSD) are a clinical challenge for the lack of a sound taxonomy, frequent presentation with comorbid BPSD, lack of specific pharmacologic interventions, poor base of methodologically sound evidence with randomized clinical trials, contamination from the treatment of behavioural disturbances of young and adult psychiatric conditions, and small efficacy window of psychotropic drugs. We present here a treatment workflow based on a concept-driven literature review based on the notions that (i) the aetiology of BPSD can be mainly neurobiological (so-called 'primary' symptoms) or mainly environmental and functional ('secondary' symptoms) and that this drives treatment; (ii) the clinical efficacy of psychotropic drugs is driven by their specific profile of receptor affinity; (iii) drug treatment should follow the rules of 'start low-go slow, prescribe and revise'. This article argues in support of the distinction between primary and secondary BPSD, as well as their characteristics, which until now have been just sketchily described in the literature. It also offers comprehensive and pragmatic clinician-oriented recommendations for the treatment of BPSD.
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Demencia , Psicotrópicos , Humanos , Demencia/tratamiento farmacológico , Demencia/psicología , Psicotrópicos/uso terapéutico , Anciano , Síntomas Conductuales/tratamiento farmacológico , Síntomas Conductuales/diagnóstico , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/terapiaRESUMEN
OBJECTIVE: To synthesize recommendations on assessing and managing behavioral and psychological symptoms of dementia (BPSDs) in existing clinical practice guidelines on dementia care to learn from and adapt recommendations to a Canadian context and language for describing BPSDs. DESIGN: Systematic review. SETTING AND PARTICIPANTS: Moderate to high-quality clinical practice guidelines on dementia care that made 1 or more recommendations on BPSD assessment or management. METHODS: We searched MEDLINE, Embase, JBI EBM, PsycINFO, AgeLine, and gray literature for clinical practice guidelines on dementia care making recommendations on BPSD, published between January 1, 2011, and October 13, 2022. Two independent reviewers conducted study screening and data abstraction. Four independent reviewers completed quality appraisal using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool; included guidelines had a mean overall AGREE II score ≥4. RESULTS: Our systematic review identified 23 moderate to high-quality clinical practice guidelines (264 recommendations). The mean overall quality score on the AGREE II tool ranged from 4 to 6.5. Recommendations were clearly presented (mean clarity of presentation score 73.5%), but guideline applicability was not consistently addressed (mean applicability score 39.3%). BPSD was the most prevalent term describing neuropsychiatric symptoms (number of guidelines [n] = 14). People with lived experience contributed to 6 guidelines (26.1%). Ten guidelines (43.5%) described 1 or more health equity considerations. Guidelines made recommendations for assessing and managing agitation (n = 12), aggression (n = 10), psychosis (n = 11), depression (n = 9), anxiety (n = 5), apathy (n = 6), inappropriate sexual behavior (n = 3), nighttime behavior (n = 5), and eating disturbances (n = 3). There was substantial variability in recommendation statements, evidence quality assigned to each statement, and strength of recommendations. CONCLUSIONS AND IMPLICATIONS: There are several moderate to high-quality clinical practice guidelines making recommendations on BPSD assessment and management, but variability in recommendation statements across guidelines and insufficient consideration of guideline applicability may hamper guideline dissemination and implementation in clinical practice.
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Demencia , Guías de Práctica Clínica como Asunto , Humanos , Demencia/terapia , Canadá , Síntomas Conductuales/terapia , Síntomas Conductuales/diagnóstico , Anciano , Femenino , MasculinoRESUMEN
Despite the significant burden, cost, and worse prognosis of Alzheimer's disease (AD) with behavioral and psychological symptoms of dementia (BPSD), little is known about the molecular causes of these symptoms. Using antemortem assessments of BPSD in AD, we demonstrate that individual BPSD can be grouped into 4 domain factors in our cohort: affective, apathy, agitation, and psychosis. Then, we performed a transcriptome-wide analysis for each domain utilizing bulk RNA-seq of post-mortem anterior cingulate cortex (ACC) tissues. Though all 4 domains are associated with a predominantly downregulated pattern of hundreds of differentially expressed genes (DEGs), most DEGs are unique to each domain, with only 22 DEGs being common to all BPSD domains, including TIMP1. Weighted gene co-expression network analysis (WGCNA) yielded multiple transcriptional modules that were shared between BPSD domains or unique to each domain, and NetDecoder was used to analyze context-dependent information flow through the biological network. For the agitation domain, we found that all DEGs and a highly associated transcriptional module were functionally enriched for ECM-related genes including TIMP1, TAGLN, and FLNA. Another unique transcriptional module also associated with the agitation domain was enriched with genes involved in post-synaptic signaling, including DRD1, PDE1B, CAMK4, and GABRA4. By comparing context-dependent changes in DEGs between cases and control networks, ESR1 and PARK2 were implicated as two high-impact genes associated with agitation that mediated significant information flow through the biological network. Overall, our work establishes unique targets for future study of the biological mechanisms of BPSD and resultant drug development.