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BackgroundUnderstanding experiences and challenges faced by persons living with Early-Onset Dementia (EOD) compared to individuals diagnosed with Late-Onset Dementia (LOD) is important for the development of targeted interventions.ObjectiveDescribe differences in sociodemographic, neuropsychiatric behavioral symptoms, caregiver characteristics, and psychotropic use.Design, setting, participantsCross-sectional, retrospective study including 908 UCLA Alzheimer's Dementia Care Program participants (177 with EOD and 731 with LOD).MeasurementsOnset of dementia was determined using age at program enrollment, with EOD defined as age 80 years. Sociodemographic and clinical characteristics were measured once at enrollment. Behavioral symptoms were measured using the Neuropsychiatric Inventory Questionnaire (NPI-Q) severity score and caregiver distress was measured using the NPI-Q distress score. Medications included antipsychotic, antidepressant, benzodiazepines and other hypnotics, antiepileptics, and dementia medications.ResultsEOD compared to LOD participants were more likely men, college graduates, married, live alone, and have fewer comorbidities. EOD caregivers were more often spouses (56% vs 26%, p

ABSTRACT Chronic hepatitis C virus (HCV) infection can be associated with neuropsychiatric symptoms like fatigue and cognitive impairment, independent of the liver status. The present study aims to assess changes in the pattern and extent of neuropsychological symptoms after successful treatment with interferon (IFN)‐based and IFN‐free therapy. HCV‐infected patients who underwent neuropsychological assessment in previous studies were invited to a follow‐up examination. Patients were grouped according to the treatment status: Sustained virological response (SVR) after IFN treatment (IFN SVR, n = 14) or after therapy with direct acting antivirals (DAA SVR, n = 28) or ongoing HCV infection (HCV RNA+, n = 11). A group of 33 healthy controls served as reference. Patients completed self‐report questionnaires addressing health‐related quality of life (HRQoL), mood and sleep quality and a neuropsychological test battery including tests of memory and attention (Luria's list of words, PSE test, cancelling “d” test, Word–Figure–Memory Test and computer‐based test battery for the assessment of attention [TAP]). At baseline, all three patient groups had worse fatigue, depression, anxiety and HRQoL scores compared to healthy controls. Longitudinal analysis revealed that fatigue and mood slightly improved in all patient groups over time, while HRQoL improved in SVR patients but not in HCV RNA+ patients. Memory test results improved significantly in all patient groups, irrespective of their virological status. In contrast, the attention test results showed no clear change from baseline to follow‐up. Our data can be considered as a hint that HCV eradication—independent of therapy regimen—does not substantially ameliorate neuropsychiatric symptoms in HCV‐afflicted patients. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive, degenerative brain disorder that impairs memory and thinking skills, leading to significant economic and humanistic burdens. It is associated with various neuropsychiatric symptoms (NPS) such as anxiety, agitation, depression, aggression, apathy, and psychosis. NPSs are common in patients with AD, affecting up to 97% of individuals diagnosed with AD. The severity of NPS is linked to disease progression and cognitive decline. NPS in Alzheimer's disease leads to increased morbidity, mortality, caregiver burden, earlier nursing home placement, and higher healthcare costs. Despite their significant impact, clinical research on NPS in AD is limited. In clinical settings, accurately distinguishing and diagnosing NPS related to AD remains a challenge. Additionally, conventional treatments for NPS in AD are often ineffective, highlighting the need for new therapies that target these specific symptoms. Understanding these comorbidities can aid in early diagnosis and better management of AD. In this review, we provide a summary of the various neurological and psychiatric symptoms (NPS) associated with AD and new candidates under development for the treatment of NPS based on their therapeutic targets and mechanisms. On top of the conventional NPS studied so far, this review adds recent advancements in the understanding of social functional impairment in AD. This review also provides information that can contribute to the advancement of studies and translational research in this field by emphasizing therapeutic targets and mechanisms of action focused on AD-related NPS rather than conventional mechanisms targeted in AD drug development. Above all, considering the relative lack of research in this new field despite the importance of clinical, medical, and translational research, it may increase interest in NPS in AD, its pathophysiological mechanisms, and potential therapeutic candidates such as molecules with antioxidant potential. [ABSTRACT FROM AUTHOR]

Background: Alpha‐synucleinopathies, such as Parkinson's disease (PD), Parkinson's disease dementia (PDD), and dementia with Lewy bodies (DLB), demonstrate sex differences with regard to prevalence, age of onset, and motor manifestations. Neuropsychiatric symptoms (NPS) are common early and late manifestations of these disorders. Objectives: We aimed to describe sex differences in NPS across alpha‐synucleinopathies. Methods: We searched Web of Science Core collection databases to identify observational studies published between January 1, 2000, and June 1, 2022, reporting the prevalence or severity of NPS among individuals with a diagnosis of PD, PDD, or DLB. Prevalence and severity were pooled for each NPS according to sex using random‐effects models. Results: Two‐hundred‐and‐forty studies, representing 796,026 participants (45% females), were included in the meta‐analysis. Female sex was associated with a higher prevalence of anxiety (OR = 1.60 [95% CI: 1.40, 1.82]), depression (OR = 1.56 [1.45, 1.67]), fatigue (OR = 1.21 [1.02, 1.43]), and psychotic symptoms (OR = 1.26 [1.14, 1.40]) and more severe anxiety (g = 1.35 [95% CI: 0.58, 2.13]), depression (g = 1.57 [1.05, 2.08]), and fatigue (g = 0.86 [0.41, 1.32]), while male sex was associated with a higher prevalence of apathy (OR = 0.77 [0.63, 0.93]), impulse control disorders (OR = 0.67 [0.55, 0.82]), REM sleep behavior disorder (OR = 0.54 [0.42, 0.70]), hypersomnolence (OR = 0.67 [0.56, 0.80]), and suicide (OR = 0.30 [0.20, 0.44]). Conclusions: NPS have different prevalences and severities in alpha‐synucleinopathies according to sex. These findings support consideration of sex in the elaboration of clinical tools. [ABSTRACT FROM AUTHOR]

ObjectivesMethodsResultsConclusionsClinical implicationThis study aimed to assess the knowledge, attitude, and practice of the healthcare professionals and paid caregivers toward non-pharmacological interventions (NPIs) for managing behavioural and psychological symptoms of dementia (BPSD) in Australian residential aged care homes (RACHs).A cross-sectional, online survey was completed by RACH staff and physicians over the period 6 March-31 August 2023. Descriptive statistics were used to present the results.Ninety-six respondents participated (41.7% aged 35–54 years, 80.2% female, 38.5% nurses). While 50–65% of the respondents were extremely familiar with 15 of NPIs, only 22% believed there was a sufficient funding for their implementation, and 6% felt there were sufficient human resources. Although 66% of the respondents viewed NPIs as more useful than medications, only 46% expected consistent positive outcomes from NPIs. The most used NPIs were redirection, behaviour management, and validation therapy.The study highlights that barrier such as inadequate funding, limited human resources, skepticism about NPIs’ effectiveness, unfamiliarity with certain NPIs, and unfavourable attitude toward NPIs are likely to slow NPI adoption for BPSD management.To improve practice, it is essential to address these barriers through targeted education, and training, increased funding, and enhancement of the workforce. [ABSTRACT FROM AUTHOR]

Ziconotide is a non-opioid analgesic that acts on N-type voltage-gated calcium channels. Despite its proven effectiveness in pain treatment, it can induce neuropsychiatric symptoms. The aim of this article is to present a case of psychosis secondary to ziconotide and to explore the variety of neuropsychiatric symptoms it produces, exploring the relationship between these symptoms and the mechanism of action of ziconotide. For this purpose, a clinical case is presented as well as a scoping review of other cases published in the scientific literature. A search on Web of Science, Pubmed and Embase databases was performed on December 11, 2023, following the criteria of the PRISMA-ScR Statement. The clinical case presented shows the variety of neuropsychiatric symptomatology that ziconotide can cause in the same patient. On the other hand, 13 papers were retrieved from the scoping review (9 case reports, 4 case series), which included 21 cases of patients treated with ziconotide who presented adverse effects ranging from psychotic symptoms to delirium. In conclusion, the variety of neuropsychiatric symptoms derived from ziconotide could be related to the blockade of N-type voltage-gated calcium channels in glutamatergic and GABAergic neurons, in turn affecting dopaminergic pathways. [ABSTRACT FROM AUTHOR]

Background: Exercise is considered as a cost-efficient option for individuals with mild cognitive impairment (MCI). Although the potential benefits of exercise for improving cognitive function are recognized, its impact on neuropsychiatric symptoms (NPS) and the quality of life (QoL) in individuals with MCI remains unclear. Objective: This study aims to investigate the effects of exercise interventions on NPS, including depression, anxiety, sleep disorders, and the quality of life in individuals with MCI. Results: There were 17 randomized controlled trials (RCTs) involving 1,575 participants were included. The findings indicate a small but significant positive effect of exercise on depression (standardized mean difference [SMD] = -0.47, 95% confidence interval [CI]: -0.73 to -0.21), but the quality of the evidence is low. Mind-body exercises were relatively more effective in alleviating depression. No significant improvements were observed in sleep disorders (SMD = -1.27, 95% CI: -2.80 to 0.26). Exercise improved anxiety in one study but had no effect in the other. It also improved quality of life in seven studies, with two showing no effect. Conclusion: The findings suggest that exercise, particularly mind-body exercises, can improve depression in individuals with MCI. However, the effect of exercise on anxiety, sleep disorders, and quality of life is still uncertain, necessitating additional research. These findings underscore the significance of integrating customized exercise programs in managing MCI to boost quality of life and mitigate NPS. [ABSTRACT FROM AUTHOR]

Background: The ageing population has increased the demand for healthcare services. In Norway, community-based long-term care are prioritised, leading to fewer nursing home places. As a result, nursing home residents are now older and have more complex needs. Nearly 92% of nursing home residents are affected by cognitive impairments accompanied by neuropsychiatric symptoms (NPS) that affect their daily activity, physical function, cognition, and behaviour. Traditionally, pharmacological therapy has been the prevailing treatment for NPS. However, emerging evidence suggests that physical activity can serve as an alternative treatment approach. Physical activity has the potential to maintain physical independence and enhance the quality of life (QoL) for the residents. Despite these benefits, institutionalisation in a nursing home often restricts activity levels of residents. This study explores facilitators and barriers to physical activity in nursing homes through the experiences of healthcare professionals and family caregivers. The goal is to enhance our understanding of how to promote and support physical activity for nursing home residents by identifying essential factors for successfully implementing daily physical activity initiatives. Methods: Seven focus groups were conducted with a total of 31 participants. Participants included healthcare professionals (physiotherapists, nurses, unit- and department managers, assistant occupational therapists, and assistant nurses) and family caregivers of residents at nursing homes. Data were analysed using Braun and Clarke's reflexive thematic analysis, underpinned by hermeneutic phenomenology. Results: Three main themes related to facilitators and barriers to physical activity in nursing homes were identified: inconsistency in task prioritisation; need for improved interprofessional collaboration; and need for improved utilisation of external resources. The participants experienced task prioritisation and lack of interdisciplinary collaboration as barriers to physical activity. The involvement of external societal resources was considered as both a facilitator and a necessity for obtaining physical activity in nursing homes. Conclusions: This study highlights the need for a consensus in task prioritisation, enhanced competence among healthcare professionals, and better interdisciplinary collaboration to facilitate physical activity in nursing homes. Involving external societal resources could be a strategic approach to address barriers and support physical activity initiatives. Future research should focus on developing effective strategies for interdisciplinary collaboration that prioritises and promotes physical activity in nursing homes. [ABSTRACT FROM AUTHOR]

Dementia is a syndrome characterized by cognitive changes which interfere with daily functioning. Neuropsychiatric symptoms (NPS) are also pervasive and may even occur prior to any noticeable cognitive decline. Still, NPS are less associated with the early stages of the disease course, despite mounting research evidence that NPS present early and often in several dementia syndromes, even in the absence of cognitive decline (i.e., mild behavioral impairment [MBI]). Primary care teams are at the forefront of dementia care, yet they frequently report insufficient training in dementia diagnosis and management. This poses a serious problem considering that timely diagnosis of dementia is critical for optimal outcomes and maximum efficacy of intervention. We provide a concise narrative review of four dementia syndromes (Alzheimer's disease, vascular dementia, dementia with Lewy bodies, and behavioral variant frontotemporal dementia) and their associated neuropsychiatric presentations, as well as at‐a‐glance clinical guides, to help primary care team members recognize possible prodromal neurodegenerative disease and to prompt further workup. We also review next steps in the management of dementia and symptoms of MBI for primary care team members. As evidenced by the NPS profiles of these dementia syndromes, subacute new onset of psychiatric symptoms in an older adult should prompt consideration of an emerging dementia process and possible further workup of such, even in the absence of cognitive decline. [ABSTRACT FROM AUTHOR]

Background: Mild neurocognitive disorder is mild reduction in cognitive abilities than a previous level, requiring compensatory strategies that help maintain independence, and is associated with behavioral and psychiatric symptoms. This cross-sectional comparative study aimed to evaluate prevalence of mild neurocognitive disorder, its risk factors, and associated neuropsychiatric symptoms. It included a sample of 156 elderly people ≥ 60 years old in Suez Canal Area from geriatric homes and primary health care centers. Study tools included a semi-structured clinical interview to assess sociodemographic, clinical, and lifestyle risk factors, DSM-5 criteria for diagnosis of neurocognitive disorders, the Montreal Cognitive Assessment Scale, and the Neuropsychiatric Inventory Questionnaire. Results: Prevalence of mild neurocognitive disorder was 37.2% in total sample with mean total score of 22.7 ± 6.1 by Montreal Cognitive Assessment Scale. The most common subtype was amnestic multiple domain subtype (72.4%). Its predicting factors included advanced age, lower education, physical work, non-adherence to treatment, less physical activity, bone and joint disorders, and family history of cognitive impairment. The neuropsychiatric symptoms with highest scores were sleep/nighttime behavior, depression, irritability, and eating/appetite, respectively. Among the two study groups, geriatric home residents had highly significant lower cognitive scores (p < 0.001) and higher Neuropsychiatric Inventory Questionnaire scores. Conclusion: Mild neurocognitive disorder is common among elderly people and is associated with neuropsychiatric symptoms that need screening and management. Modifiable risk factors should be identified to provide interventions. [ABSTRACT FROM AUTHOR]

Background: Cobalamin C is the most common inborn error of intracellular cobalamin metabolism caused by biallelic pathogenic variants in the MMACHC gene, leading to impaired conversion of dietary vitamin B12 into its two metabolically active forms, methylcobalamin and adenosylcobalamin. Biochemical hallmarks are elevated plasma total homocysteine (HCYs) and low methionine accompanied by methylmalonic aciduria. This study aimed to evaluate the clinical, biochemical, and molecular analysis of Pakistani patients with CblC defect. Methods: Medical charts, urine organic acid (UOA) chromatograms, plasma amino acid levels, plasma tHcy and MMACHC gene results of patients presenting at the Biochemical Genetics Clinic, AKUH from 2013–2021 were reviewed. Details were collected on a pre-structured questionnaire. SPSS 22 was used for data analysis. Results: CblC was found in 33 cases (Male:Female 19:14). The median age of symptoms onset and diagnosis were 300 (IQR:135–1800) and 1380 (IQR: 240–2730) days. The most common clinical features were cognitive impairment (n = 29), seizures (n = 23), motor developmental delay (n = 20), hypotonia (n = 17), and sparse/hypopigmented scalp hair (n = 16). The MMACHC gene sequencing revealed homozygous pathogenic variant c.394C > T, (p.Arg132*) in 32 patients, whereas c.609G > A, (p.TRP203*) in one patient whose ancestors had settled in Pakistan from China decades ago. The median age of treatment initiation was 1530 (IQR: 240–2790). The median pre-treatment HCYs levels were 134 (IQR:87.2–155.5) compared to post-treatment levels of 33.3 (IQR: 27.3–44.95) umol/L. Conclusions: Thirty-three cases of CblC defect from a single center underscores a significant number of the disorder within Pakistan. Late diagnosis emphasizes the need for increased clinical awareness and adequate diagnostic facilities. [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric symptoms (NPS) are prevalent among persons with Alzheimer's disease and related dementias (ADRD). However, there are limited safe and effective nonpharmacological treatments for controlling NPS. Transcranial direct current stimulation (tDCS) is a promising noninvasive and safe treatment. Materials and Methods: This study investigated the effects of remotely supervised tDCS in managing NPS in older adults with mild to moderate ADRD. Forty older adults diagnosed with early-stage ADRD were randomly assigned in a 1:1 ratio to receive home-based active tDCS (n = 20) or sham tDCS (n = 20). Results: Results showed a significantly greater improvement in the following NPS: scratching (P = 0.052, Hedges' g = −0.60 [confidence interval {CI}: −1.24, 0.04], Cliff's δ = −0.41 [CI: −0.67, −0.06]), nighttime behaviors (P = 0.041; Hedges' g = −0.62 [CI: −1.26, 0.03]; Cliff's δ = −0.41 [CI: −0.67, −0.06], and appetite/eating changes (P = 0.010; Hedges' g = −0.78 [CI: −1.43, −0.13]; Cliff's δ = −0.41 [CI: — 0.56, −0.10]). Conclusion: This study shows promising initial results for using home-based, remotely supervised tDCS to manage NPS, such as nighttime behaviors, changes in eating and appetite, and scratching. Larger studies with more participants are needed to explore various tDCS doses and their long-term effects on NPS. [ABSTRACT FROM AUTHOR]

Summary: Steroids are a mainstay in the treatment of acute lymphoblastic leukaemia (ALL) in children and adolescents; however, their use can cause clinically significant steroid‐related neuropsychiatric symptoms (SRNS). As current knowledge on SRNS during ALL treatment is limited, we mapped the phenotypes, occurrence and treatment strategies using a database created by the international Ponte di Legno Neurotoxicity Working Group including data on toxicity in the central nervous system (CNS) in patients treated with frontline ALL protocols between 2000 and 2017. Ninety‐four of 1813 patients in the CNS toxicity database (5.2%) experienced clinically significant SRNS with two peaks: one during induction and one during intensification phase. Dexamethasone was implicated in 86% of SRNS episodes. The most common symptoms were psychosis (52%), agitation (44%) and aggression (31%). Pharmacological treatment, mainly antipsychotics and benzodiazepines, was given to 87% of patients while 38% were hospitalised due to their symptoms. Recurrence of symptoms was reported in 29% of patients and two previously healthy patients required ongoing pharmacological treatment at the last follow up. Awareness of SRNS during ALL treatment and recommendation on treatment strategies merit further studies and consensus. [ABSTRACT FROM AUTHOR]

Aim: This study evaluated the effectiveness of high‐dose vitamin D supplementation in alleviating fatigue and neuropsychiatric symptoms in post‐COVID syndrome. Methods: In an 8‐week, double‐blind, randomized, placebo‐controlled trial, 80 patients with post‐COVID fatigue or neuropsychiatric symptoms were enrolled. Participants were randomly assigned to receive either 60,000 IU of vitamin D weekly (n = 40) or a placebo (n = 40) for 8 weeks. Clinical outcomes were assessed using the 11‐item Chalder Fatigue Scale (CFQ‐11); 21‐item Depression, Anxiety, and Stress Scale (DASS‐21); Pittsburgh Sleep Quality Index (PSQI); Addenbrooke's Cognitive Examination III (ACE); and Trail Making Test A and B (TMT‐A and TMT‐B). Baseline and 8‐week measurements of inflammatory markers, including interleukin 6 (IL‐6) and C‐reactive protein (CRP), were also collected. Results: Significant improvements were found in the vitamin D group for CFQ (coefficient −3.5, P = 0.024), DASS‐anxiety (−2.0, P = 0.011), and ACE (2.1, P = 0.012). No significant differences were observed in PSQI, DASS‐depression, TMT, IL‐6, or CRP levels. The incidence of adverse events was comparable between groups, with no serious adverse events reported. Conclusion: High‐dose vitamin D supplementation may benefit patients with post‐COVID syndrome by reducing fatigue, alleviating anxiety, and improving cognitive symptoms, with minimal side effects. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Behavioral and psychological symptoms in dementia (BPSD) are dynamic phenomena with a high amount of intraindividual variability. We applied a multilevel framework to identify subsyndromes (between‐person factors) that represent clinically relevant profiles of BPSD and identify symptom clusters (within‐person factors) that represent contextually driven daily symptom experiences. METHODS: This study used an intensive longitudinal design in which 68 co‐residing family caregivers to persons living with dementia were recruited to proxy report on their care recipient's daily symptom experiences of 23 different BPSD for eight consecutive days (n = 443 diaries). A multilevel exploratory/confirmatory factor analysis was used to account for nested data and separate within‐person variances from between‐level factor estimates. RESULTS: Exploratory factor analysis identified a 4‐between 3‐within factor structure based on fit statistics and clinical interpretability. DISCUSSION: This study offers major methodological and conceptual advancements for management of BPSD within Alzheimer's disease and related dementias by introducing two related but distinct concepts of subsyndromes and symptom clusters. Highlights: Because behavioral and psychological symptoms of dementia (BPSD) are dynamic temporal phenomenon, this introduces measurement error into aggregate group‐level estimates when trying to create subsyndromes. We propose a multilevel analysis to provide a more valid and reliable estimation by separating out variance due to within‐person daily fluctuations.Using a multilevel exploratory factor analysis with intensive longitudinal data, we identified distinct and meaningful groups of BPSD. The four factors at the between‐person level represented subsyndromes that are based on how BPSD co‐occurred among persons with Alzheimer's disease (AD). These subsyndromes are clinically relevant because they share features of established clinical phenomena and may have similar neurobiological etiologies.We also found three within‐person factors representing distinct symptom clusters. They are based on how BPSD clustered together on a given day for an individual with AD and related dementias. These clusters may have shared environmental triggers. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the beneficial outcomes of giving cannabidiol (CBD) 3% over a six-month period in the BPSD, the management of which is a crucial issue for everyday clinical praxis and to compare the progress in BPSD of patients who receive Cannabidiol 3% with those who follow usual medical treatment (UMT) in everyday clinical praxis. Methods: A total of 20 PwD with severe BPSD were recruited from the database of Alzheimer Hellas with NPI score >30. Ten of them were assigned to UMT, while ten were assigned to a six-month treatment with CBD drops. The follow-up assessment was performed with NPI, both clinically and by structured telephone interview. Results: The follow-up assessment with NPI showed significant improvement of the BPSD in all our patients who received CBD, and no or limited improvement in the second group, regardless of the underlying neuropathology of dementia. Conclusions: We suggest that CBD may be a more effective and safe choice for managing BPSD than the typical intervention. Future large randomized clinical trials are needed to re-assure these findings. Clinical Implications: Healthcare professionals should consider incorporating CBD 3% into their practices to reduce BPSD in PwD. Regular assessments are necessary to ensure long-term effectiveness. [ABSTRACT FROM AUTHOR]

Background and Objectives: Sound is an important environmental factor that influences the expression of behavioral and psychological symptoms of dementia. Recent research on the effect of soundscape has shown promising results in improving environmental impact on people with dementia. However, no controlled studies have aimed to quantify the effects of soundscape intervention on resident outcomes. The aim of this study was to assess the feasibility and impact of a soundscape intervention on people with dementia and behavioral symptoms. Research Design and Methods: Pilot single-blind repeated-measures randomized controlled trial of an augmented soundscape intervention. Participants were people with dementia in a hospital-based specialized dementia unit. Participants were randomized to an augmented soundscape intervention delivered in their room in the morning and evening or treatment as usual, with 2 baseline weeks and 4 weekly post-randomization assessments of the primary and secondary behavioral outcomes. Results: The soundscape intervention was feasible in terms of recruitment, retention, and delivery of the intervention. There were improvements in the neuropsychiatric inventory total scores over time in both groups (−5.89, 95%CI −8.45 to −3.28, p < .001), but no differences between groups. There were no significant group, time, or group × time differences for the Pittsburgh Agitation Scale (PAS) total score. For the PAS-resisting care subscale, there was a significant group × time difference, with a greater reduction in the soundscape group over the study period (−0.81, 95% CI −1.59 to −0.03, p = .042). Discussion and Implications: In this pilot study, soundscape augmentation was a feasible and effective nonpharmacological approach to reducing resistance to care in people with dementia, although it did not improve neuropsychiatric symptoms more globally. Further studies with larger samples and of longer duration are needed to investigate the long-term effects of augmented sonic environments on people with dementia. Clinical Trials Registration Number: NCT04809545 [ABSTRACT FROM AUTHOR]

AbstractThe results of previous research on the relationship between neuropsychiatric symptoms and cognition in multiple sclerosis (MS) have been mixed. The aim of this systematic review was to examine the evidence on the relationship between neuropsychiatric symptoms and different cognitive domains in adult (≥18 years) MS patients. A literature search was conducted in the Ovid Medline, PsycInfo, Scopus, and Web of Science databases. A total of 4,216 nonduplicate records were identified, and after screening, 37 studies met the inclusion criteria and were included in the systematic review. Higher levels of depressive symptoms were related to deficits in processing speed, verbal memory, executive functions, visuospatial functions, and attention in MS patients. Symptoms of anxiety were not consistently related to any of the cognitive functions, but the relationship to deficits in visual memory received a minimal amount of support. Higher levels of apathy were most clearly associated with impairment in executive functions, but the association with deficits in visuospatial functions, visual memory, working memory, and processing speed was also supported. The results indicate that more neuropsychiatric symptoms, especially depressive symptoms and apathy, are associated with cognitive dysfunction in MS patients. These results can be utilized in the clinical examination and treatment planning of MS patients. [ABSTRACT FROM AUTHOR]

Childhood dementias are a group of rare, fatal neurodegenerative disorders, characterised by global cognitive decline, loss of previously acquired developmental skills and behaviours and psychological symptoms of dementia (BPSD). Batten disease, or neuronal ceroid lipofuscinosis, and Sanfilippo syndrome, or mucopolysaccharidosis type III, are two of the more common forms of childhood dementia disorders worldwide. While psychosocial interventions are the best available therapeutic approach for BPSD management in adult-onset dementia, there is very limited literature or clinical experience in the context of childhood dementia. To address this gap, we conducted a descriptive case analysis of BPSD profiles, associated contributing factors and targeted psychosocial interventions in two cases with childhood dementia disorders (Sanfilippo syndrome and CLN3 (juvenile onset) Batten disease) who were referred to Dementia Support Australia, a national dementia behaviour support service in Australia. Primary BPSD identified in these disorders included physical and verbal aggression and irritability/lability. In these cases, contributing factors to the development of BPSD were not monolithic, encompassing pain, caregiver's approach and over or under-stimulation. Improvement in BPSD were observed using the Neuropsychiatric Inventory-Quesionnaire and globally noted as per the qualitative feedback reported by family and caregivers. Person-centred, multimodal psychosocial interventions were recognised as effective therapies in resolving BPSD in these cases. In conclusion, the case studies described the nature and presentation of BPSD in two common forms of childhood dementia and demonstrated the potential benefits of person-centred psychosocial interventions (delivered through national dementia-specific support programs) in alleviating BPSD such as irritability and aggression in these disorders. [ABSTRACT FROM AUTHOR]

Background: To ensure adequate treatment, individuals with delirium superimposed on dementia (DSD) need to be differentiated reliably from those with dementia only (DO). Therefore, we aimed to examine the clinical indicators of DSD by assessing motor subtypes, cognitive performance and neuropsychiatric symptoms in DSD and DO patients. Methods: Cross-sectional design with the Delirium-Motor-Subtyping Scale (DMSS), Mini-Mental-State-Examination (MMSE), Clock-Drawing-Test (CDT), DemTect, and Neuropsychiatric Inventory assessed after admission to an acute hospital. Results: 94 patients were included, 43 with DSD (78 ± 7 years, MMSE = 11 ± 9) and 51 with DO (79 ± 7 years, MMSE = 9 ± 8). DMSS "no subtype" was more common in the DO group (26% vs. 10%, p = .04). The DSD group showed lower CDT scores (DSD: M = 4 ± 3 vs. DO: M = 6 ± 1; p < .001) and higher anxiety (DSD: MED = 3 ± 8 vs. DO: MED = 3 ± 4; p = .01) and sleep/night-time behavior disturbances (DSD: MED = 0 ± 6 vs. DO: MED = 0 ± 0; p = .02). Conclusions: Sleep/night-time behavior disturbances appear to be a clinical indicator of DSD. Motor subtypes can identify cases at increased risk of developing delirium or unrecognized delirium. [ABSTRACT FROM AUTHOR]

Background: While several studies in cerebral amyloid angiopathy (CAA) focus on cognitive function, data on neuropsychiatric symptoms (NPS) and lifelong mental activities in these patients are scarce. Since NPS are associated with functional impairment, faster cognitive decline and faster progression to death, replication studies in more diverse settings and samples are warranted. Methods: We prospectively recruited n = 69 CAA patients and n = 18 cognitively normal controls (NC). The number and severity of NPS were assessed using the Alzheimer's Disease (AD) Assessment Scale's (ADAS) noncognitive subscale. We applied different regression models exploring associations between NPS number or severity and group status (CAA vs. NC), CAA severity assessed with magnetic resonance imaging (MRI) or cognitive function (Mini-Mental State Examination (MMSE), ADAS cognitive subscale), adjusting for age, sex, years of education, arterial hypertension, AD pathology, and apolipoprotein E status. Mediation analyses were performed to test indirect effects of lifelong mental activities on CAA severity and NPS. Results: Patients with CAA had 4.86 times (95% CI 2.20-10.73) more NPS and 3.56 units (95% CI 1.94–5.19) higher expected NPS severity than NC. Higher total CAA severity on MRI predicted 1.14 times (95% CI 1.01.-1.27) more NPS and 0.57 units (95% CI 0.19–0.95) higher expected NPS severity. More severe white matter hyperintensities were associated with 1.21 times more NPS (95% CI 1.05–1.39) and 0.63 units (95% CI 0.19–1.08) more severe NPS. NPS number (MMSE mean difference − 1.15, 95% CI -1.67 to -0.63; ADAS cognitive mean difference 1.91, 95% CI 1.26–2.56) and severity (MMSE − 0.55, 95% CI -0.80 to -0.30; ADAS cognitive mean difference 0.89, 95% CI 0.57–1.21) predicted lower cognitive function. Greater lifelong mental activities partially mediated the relationship between CAA severity and NPS (indirect effect 0.05, 95% CI 0.0007-0.13), and greater lifelong mental activities led to less pronounced CAA severity and thus to less NPS (indirect effect − 0.08, 95% CI -0.22 to -0.002). Discussion: This study suggests that NPS are common in CAA, and that this relationship may be driven by CAA severity. Furthermore, NPS seem to be tied to lower cognitive function. However, lifelong mental activities might mitigate the impact of NPS in CAA. [ABSTRACT FROM AUTHOR]

Background: Anxiety and depression are common non‐motor symptoms in Parkinson's disease (PD) but remain under‐recognized and under‐treated. Objectives: To evaluate functional outcomes associated with baseline anxiety or depression and effects related to the initiation of new psychiatric treatment. Methods: We analyzed 7 years of data from patients with de novo PD enrolled in the Parkinson's Progression Markers Initiative. Longitudinal regression models evaluated the association between baseline anxiety and depression with Schwab and England (SE) and MDS‐UPDRS total scores over time. Cox proportional hazard models assessed effects of baseline anxiety and depression on time to initiation of dopaminergic therapy. Piecewise linear regression models examined the association of treatment initiation for anxiety and depression with SE and MDS‐UPDRS. Results: 490 participants with baseline depression and anxiety data were included. Anxiety and depression were associated with lower SE (anxiety: β = −1.31, P = 0.038, depression: β = −1.96, P = 0.012, co‐morbid: β = −2.70, P = 0.003) and higher MDS‐UPDRS scores (anxiety: β = 5.37, P < 0.001, depression: β = 9.17, P < 0.001, co‐morbid: β = 10.50, P < 0.001) longitudinally. Anxiety was associated with faster time to dopamine replacement therapy initiation (HR 1.30, 95% CI 1.03–1.66, P = 0.03). 16 participants with anxiety initiated treatment for anxiety, which was associated with subsequent lower levodopa daily dose (slope change = −218.49, P = 0.018). 10 participants with depression initiated treatment of depression, which was associated with reduced MDS‐UPDRS total scores (slope change = −8.3, P < 0.001) and higher SE scores (slope change = 5.99, P = 0.004). Conclusions: Anxiety and depression at PD onset are associated with multiple negative longitudinal trajectories. However, preliminary findings suggest that anxiety and depression treatment may be linked with improved motor and non‐motor outcomes. [ABSTRACT FROM AUTHOR]

Neuropsychiatric symptoms (NPS) are risk factors for Alzheimer's disease (AD) but can also manifest secondary to AD pathology. Mild behavioral impairment (MBI) refers to later‐life emergent and persistent NPS that may mark early‐stage AD. To distinguish MBI from NPS that are transient or which represent psychiatric conditions (non‐MBI NPS), we investigated the effect of applying MBI criteria on NPS associations with AD structural imaging biomarkers and incident cognitive decline. Data for participants (n = 1273) with normal cognition (NC) or mild cognitive impairment (MCI) in the National Alzheimer's Coordinating Center Uniform Data Set were analyzed. NPS status (MBI, non‐MBI NPS) was derived from the Neuropsychiatric Inventory Questionnaire and psychiatric history. Normalized measures of bilateral hippocampal (HPC) and entorhinal cortex (EC) volume, and AD meta‐region of interest (ROI) mean cortical thickness were acquired from T1‐weighted magnetic resonance imaging scans. Multivariable linear and Cox regressions examined NPS associations with imaging biomarkers and incident cognitive decline, respectively. MBI was associated with lower volume and cortical thickness in all ROIs in both NC and MCI, except for EC volume in NC. Non‐MBI NPS were only associated with lower HPC volume in NC. Although both of the NPS groups showed higher hazards for MCI/dementia than No NPS, MBI participants showed more rapid decline. Although both types of NPS were linked to HPC atrophy, only NPS that emerged and persisted in later‐life, consistent with MBI criteria, were related to AD neurodegenerative patterns beyond the HPC. Moreover, MBI predicted faster progression to dementia than non‐MBI NPS. [ABSTRACT FROM AUTHOR]

Background and Objective: The Mild Behavioral Impairment-Checklist (MBI-C) was developed to detect and standardize neuropsychiatric symptoms. The objective of this study was to evaluate the Turkish adaptation, validity, and reliability of the MBI-C. Methods: The sample of our study consisted of 80 patients with cognitive impairment and a control group with 113 participants whose cognitive impairment was not detected in standard tests. Participants were evaluated with the Standardized Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Geriatric Depression Scale-15 (GDS-15), MBI-C and Neuropsychiatric Inventory (NPI). Results and Conclusion: In the reliability analysis, the Cronbach-alpha value for MBI-C was found to be.810. In the ROC analysis performed with the total MBI-C score, the area under the curve (AUC) was calculated as.821 and the cut-off score was determined as 8.5; sensitivity was calculated as.77 and specificity as.83. A strong positive correlation was found between test-retest MBI-C scores (r =.886, P <.0019). A strong positive correlation was found between MBI-C and NPI scores (r =.964, P <.001). MBI-C scores were significantly negatively correlated with MMSE and MoCA scores and positively correlated with GDS-15 scores. The results of our study showed that the Turkish version of the MBI-C is a valid and reliable measurement. [ABSTRACT FROM AUTHOR]

• In-depth case studies on assisted home-based music listening and playlist compilation with persons with dementia • HR and movement changes corresponded with changes in the music for participants, sometimes clearly visible, other times more subtle • Participants benefited from repeated listening which allowed them time to disclose genuine favourites rather than those suggested by others in the household • The listening and compilation process may have helped participants reconnect with their music, potentially realising its meaning, value and usefulness to them, particularly autobiographically Neuropsychiatric symptoms (NPS) in dementia can be reduced through music listening. Little has been reported on home-based listening, compilation processes, or individual responses that include biophysiological data. We aim to provide new insights from two home-based case studies focused on specific music selections. Participants were part of a larger study, co-designing an automated radio, diary reminder and personal playlist system for NPS management. Playlists were compiled that would have the best possible chance of achieving this, based on participants' autobiographical, narrative, heart rate (HR) and videoed responses. Participant's responses to their music aligned with the genre they chose – dancing to up-beat music, contrasting with subtle responses to Beethoven. Repeated listens may help to establish consistency of responses and allow time to communicate their genuine preferences, not those others suggested. If all of these data converge, then they could help confirm the suitability of music for NPS management. [ABSTRACT FROM AUTHOR]

Jia Zhou,1,&ast; Wenwen Wang,1,&ast; Qiyu Zhang,1,&ast; Hanlin Zhang,1 Keyun Tang,1 Chenhui Mao,2 Mingli Li,3 Jun Li1 1Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, People’s Republic of China; 2Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Li, Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Disease, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86-010-69151500, Fax +86-010-69151502, Email lijun35@hotmail.comPurpose: Syphilis, caused by Treponema pallidum, presents a diagnostic challenge due to its diverse clinical manifestations. Neurosyphilis has seen a resurgence in recent years, particularly among men who have sex with men and those living with HIV. Diagnosis of neurosyphilis in emergency settings is challenging due to its varied neurological presentations. This study aims to serve as a reference for dermatologists and neurologists in diagnosing and treating neurosyphilis.Patients and Methods: This retrospective study analyzed patients who presented with neuropsychiatric symptoms and were ultimately diagnosed with neurosyphilis. These patients were collected from the emergency department in Peking Union Medical College Hospital between January 2018 and November 2023. The medical history, clinical symptoms, laboratory examinations, cranial MRI characteristics, and treatment regimens of these patients were investigated.Results: Among the included 12 neurosyphilis patients, memory deterioration was observed in 8 out of the 12 neurosyphilis patients. Diagnosis often resulted in delays, with misdiagnoses mainly including Alzheimer’s disease, stroke, and epilepsy. Neuroimaging revealed various abnormalities, predominantly affecting ventricular and temporal regions. Treatment with penicillin-based regimens varied in compliance, with only a minority of patients adhering to guidelines. Treatment outcomes were inconsistent, with some patients experiencing irreversible neurological damage and fluctuating serum rapid plasma reagin (RPR) titers.Conclusion: Diagnosis of neurosyphilis in the emergency department remains challenging, necessitating awareness of its varied neurological presentations. Enhanced diagnostic strategies are imperative to accelerate treatment initiation and improve outcomes for affected individuals.Keywords: neurosyphilis, emergency department, neuropsychiatric symptoms, cerebrospinal fluid, serologic tests

Abstract Background Mild neurocognitive disorder is mild reduction in cognitive abilities than a previous level, requiring compensatory strategies that help maintain independence, and is associated with behavioral and psychiatric symptoms. This cross-sectional comparative study aimed to evaluate prevalence of mild neurocognitive disorder, its risk factors, and associated neuropsychiatric symptoms. It included a sample of 156 elderly people ≥ 60 years old in Suez Canal Area from geriatric homes and primary health care centers. Study tools included a semi-structured clinical interview to assess sociodemographic, clinical, and lifestyle risk factors, DSM-5 criteria for diagnosis of neurocognitive disorders, the Montreal Cognitive Assessment Scale, and the Neuropsychiatric Inventory Questionnaire. Results Prevalence of mild neurocognitive disorder was 37.2% in total sample with mean total score of 22.7 ± 6.1 by Montreal Cognitive Assessment Scale. The most common subtype was amnestic multiple domain subtype (72.4%). Its predicting factors included advanced age, lower education, physical work, non-adherence to treatment, less physical activity, bone and joint disorders, and family history of cognitive impairment. The neuropsychiatric symptoms with highest scores were sleep/nighttime behavior, depression, irritability, and eating/appetite, respectively. Among the two study groups, geriatric home residents had highly significant lower cognitive scores (p

Abstract Background The ageing population has increased the demand for healthcare services. In Norway, community-based long-term care are prioritised, leading to fewer nursing home places. As a result, nursing home residents are now older and have more complex needs. Nearly 92% of nursing home residents are affected by cognitive impairments accompanied by neuropsychiatric symptoms (NPS) that affect their daily activity, physical function, cognition, and behaviour. Traditionally, pharmacological therapy has been the prevailing treatment for NPS. However, emerging evidence suggests that physical activity can serve as an alternative treatment approach. Physical activity has the potential to maintain physical independence and enhance the quality of life (QoL) for the residents. Despite these benefits, institutionalisation in a nursing home often restricts activity levels of residents. This study explores facilitators and barriers to physical activity in nursing homes through the experiences of healthcare professionals and family caregivers. The goal is to enhance our understanding of how to promote and support physical activity for nursing home residents by identifying essential factors for successfully implementing daily physical activity initiatives. Methods Seven focus groups were conducted with a total of 31 participants. Participants included healthcare professionals (physiotherapists, nurses, unit- and department managers, assistant occupational therapists, and assistant nurses) and family caregivers of residents at nursing homes. Data were analysed using Braun and Clarke’s reflexive thematic analysis, underpinned by hermeneutic phenomenology. Results Three main themes related to facilitators and barriers to physical activity in nursing homes were identified: inconsistency in task prioritisation; need for improved interprofessional collaboration; and need for improved utilisation of external resources. The participants experienced task prioritisation and lack of interdisciplinary collaboration as barriers to physical activity. The involvement of external societal resources was considered as both a facilitator and a necessity for obtaining physical activity in nursing homes. Conclusions This study highlights the need for a consensus in task prioritisation, enhanced competence among healthcare professionals, and better interdisciplinary collaboration to facilitate physical activity in nursing homes. Involving external societal resources could be a strategic approach to address barriers and support physical activity initiatives. Future research should focus on developing effective strategies for interdisciplinary collaboration that prioritises and promotes physical activity in nursing homes.

Linda Veith Sanches,1,&ast; Stephan Greten,1,&ast; Johanna Doll-Lee,1 Sophia Marie Rogozinski,1 Johanne Heine,1 Lea Krey,1 Sarana Ulaganathan,1 Ida Jensen,1,2 Matthias Höllerhage,1 Sam Sadeghi Sani,1 Günter U Höglinger,1– 4 Florian Wegner,1 Martin Klietz1 1Department of Neurology, Hannover Medical School, Hannover, Germany; 2Department of Neurology, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany; 3Munich Cluster for Systems Neurology, SyNergy, Munich, Germany; 4German Center for Neurodegenerative Diseases, DZNE, Munich, Germany&ast;These authors contributed equally to this workCorrespondence: Stephan Greten, Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover, 30625, Germany, Tel +49 511 532-6462, Fax +49 511 532-6677, Email Greten.stephan@mh-hannover.deIntroduction: Neuropsychiatric symptoms in particular impair health-related quality of life (QoL) of patients with Parkinson’s disease and atypical Parkinsonian syndromes. For this reason, various scales have been developed for detection of neuropsychiatric symptoms, such as the Scale for evaluation of neuropsychiatric disorders in Parkinson’s disease (SEND-PD).Objective: First, the objective of this study was to explore the interrelation between the SEND-PD and clinical parameters in patients with Parkinson’s disease and thus confirm its validity. In addition, the applicability in a well-defined cohort of patients with atypical Parkinsonian syndromes was investigated for the very first time.Methods: A clinically well-defined cohort of 122 patients with Parkinson’s disease (PD), 55 patients with Progressive Supranuclear Palsy (PSP) and 33 patients with Multiple System Atrophy (MSA) were analyzed. First, the SEND-PD was correlated with established disease-specific scores in patients with PD. Next, the results of the SEND-PD were compared between the different Parkinsonian syndromes.Results: The SEND-PD showed a strong significant correlation with several scores, especially the UPDRS I (Rho = 0.655) and GDS-15 (Rho = 0.645). Depressive burden was significantly higher in MSA patients in comparison to the PD patient cohort (PD, 3.8 ± 3.3; MSA, 5.45 ± 3.87), while PSP patients showed significantly less psychotic (PD 1.6 ± 2.1; PSP 0.6 ± 0.9) and impulse control disorders (PD 0.3 ± 1.0; PSP 0.02 ± 0.1).Conclusion: The SEND-PD is a useful, brief and highly applicable screening tool for neuropsychiatric symptoms in PD, but not in atypical Parkinsonism, as their unique neuropsychiatric symptom composition is not fully captured.Keywords: neuropsychiatric symptoms, SEND-PD, Parkinsonian syndromes

Abstract Background While several studies in cerebral amyloid angiopathy (CAA) focus on cognitive function, data on neuropsychiatric symptoms (NPS) and lifelong mental activities in these patients are scarce. Since NPS are associated with functional impairment, faster cognitive decline and faster progression to death, replication studies in more diverse settings and samples are warranted. Methods We prospectively recruited n = 69 CAA patients and n = 18 cognitively normal controls (NC). The number and severity of NPS were assessed using the Alzheimer’s Disease (AD) Assessment Scale’s (ADAS) noncognitive subscale. We applied different regression models exploring associations between NPS number or severity and group status (CAA vs. NC), CAA severity assessed with magnetic resonance imaging (MRI) or cognitive function (Mini-Mental State Examination (MMSE), ADAS cognitive subscale), adjusting for age, sex, years of education, arterial hypertension, AD pathology, and apolipoprotein E status. Mediation analyses were performed to test indirect effects of lifelong mental activities on CAA severity and NPS. Results Patients with CAA had 4.86 times (95% CI 2.20-10.73) more NPS and 3.56 units (95% CI 1.94–5.19) higher expected NPS severity than NC. Higher total CAA severity on MRI predicted 1.14 times (95% CI 1.01.-1.27) more NPS and 0.57 units (95% CI 0.19–0.95) higher expected NPS severity. More severe white matter hyperintensities were associated with 1.21 times more NPS (95% CI 1.05–1.39) and 0.63 units (95% CI 0.19–1.08) more severe NPS. NPS number (MMSE mean difference − 1.15, 95% CI -1.67 to -0.63; ADAS cognitive mean difference 1.91, 95% CI 1.26–2.56) and severity (MMSE − 0.55, 95% CI -0.80 to -0.30; ADAS cognitive mean difference 0.89, 95% CI 0.57–1.21) predicted lower cognitive function. Greater lifelong mental activities partially mediated the relationship between CAA severity and NPS (indirect effect 0.05, 95% CI 0.0007-0.13), and greater lifelong mental activities led to less pronounced CAA severity and thus to less NPS (indirect effect − 0.08, 95% CI -0.22 to -0.002). Discussion This study suggests that NPS are common in CAA, and that this relationship may be driven by CAA severity. Furthermore, NPS seem to be tied to lower cognitive function. However, lifelong mental activities might mitigate the impact of NPS in CAA.

• What is the primary question addressed by this study? What are the courses of individual neuropsychiatric symptoms (NPS) and their effects on functional decline in patients with Alzheimer's disease? • What is the main finding of this study? Independent of cognition and other neuropsychiatric symptoms, worse apathy profile was most strongly associated with faster rate of functional decline. Worse agitation, delusions, and hallucinations also were associated with faster functional decline, but the magnitudes of the effects were smaller. • What is the meaning of the finding? The magnitude of the estimates and high proportion of individuals who always had apathy or had apathy persistently suggest that treating apathy may have clinically meaningful impact on patient's function and that intervention for apathy could have meaningful impact from a public health perspective. Understanding the course of individual neuropsychiatric symptoms (NPS) and their relationship with function is important for planning targeted interventions for preventing and delaying functional decline. This study aims to disentangle relative contributions of individual NPS on functional decline. Longitudinal study of 9,358 well-characterized participants with baseline diagnoses of Mild Cognitive Impairment or AD in the National Alzheimer's Coordinating Center Uniform Data Set. Function was measured using the Functional Assessment Questionnaire (FAQ). Clinician judgment of seven common behavioral symptoms were examined simultaneously: apathy-withdrawal, depressed mood, visual or auditory hallucinations, delusions, disinhibition, irritability, and agitation. Apathy was the most common NPS at baseline (33.7%) and throughout follow-up, endorsed by clinicians in 63.7% of visits. Apathy was the most persistent with 36.7% of participants having clinician-endorsed apathy in ≥50% of their visits. Apathy strongly correlated with faster rate of functional decline. Compared to those who never had apathy, baseline FAQ was worse in those with intermittent or persistent/always apathy (intermittent: estimated coefficient ±SE=1.228±0.210, 95% CI=[0.817, 1.639]; persistent/always: 2.354±0.244 (95% CI=[1.876, 2.832], both p <0.001). Over time, rate of functional decline was faster in those with intermittent and persistent/always apathy (intermittent: 0.454±0.091, 95% CI=[0.276, 0.632]; persistent/always: 0.635±0.102, 95% CI=[0.436, 0.835], both p <0.001). Worse agitation, delusions, and hallucinations also correlated with functional decline, but magnitudes of the estimates were smaller. Individual NPS may be sensitive targets for tracking longitudinal change in function. The study raises awareness of the need for more comprehensive assessment of functional decline in AD patients with noncognitive symptoms. [ABSTRACT FROM AUTHOR]

Abstract Background Housing has been associated with dementia risk and disability, but associations of housing with differential patterns of neuropsychiatric symptoms (NPS) among dementia-free older adults remain to be explored. The present study sought to explore the contribution of housing status on NPS and subsyndromes associated with cognitive dysfunction in community-dwelling dementia-free elderly in Singapore. Methods A total of 839 dementia-free elderly from the Epidemiology of Dementia in Singapore (EDIS) study aged ≥ 60 were enrolled in the current study. All participants underwent clinical, cognitive, and neuropsychiatric inventory (NPI) assessments. The housing status was divided into three categories according to housing type. Cognitive function was measured by a comprehensive neuropsychological battery. The NPS were assessed using 12-term NPI and were grouped into four clinical subsyndromes: psychosis, hyperactivity, affective, and apathy. Associations of housing with composite and domain-specific Z-scores, as well as NPI scores, were assessed using generalized linear models (GLM). Binary logistic regression models analysed the association of housing with the presence of NPS and significant NPS (NPI total scores ≥ 4). Results Better housing status (5-room executive apartments, condominium, or private housing) was associated with better NPS (OR = 0.49, 95%CI = 0.24 to 0.98, P

Abstract Background Neuropsychiatric symptoms (NPS) are common in older people, may occur early in the development of dementia disorders, and have been associated with faster cognitive decline. Here, our objectives were to investigate whether plasma levels of neurofilament light chain (NfL), glial fibrillary acid protein (GFAP), and tau phosphorylated at threonine 181 (pTau181) are associated with current NPS and predict future NPS in non-demented older people. Furthermore, we tested whether the presence of NPS combined with plasma biomarkers are useful to predict Alzheimer’s disease (AD) pathology and cognitive decline. Methods One hundred and fifty-one participants with normal cognition (n = 76) or mild cognitive impairment (n = 75) were examined in a longitudinal brain aging study at the Memory Centers, University Hospital of Lausanne, Switzerland. Plasma levels of NfL, GFAP, and pTau181 along with CSF biomarkers of AD pathology were measured at baseline. NPS were assessed through the Neuropsychiatric Inventory Questionnaire (NPI-Q), along with the cognitive and functional performance at baseline and follow-up (mean: 20 months). Different regression and ROC analyses were used to address the associations of interest. Results None of the three plasma biomarker was associated with NPS at baseline. Higher GFAP levels were associated with the presence of NPS at follow-up (OR = 2.8, p = .002) and both, higher NfL and higher GFAP with an increase in the NPI-Q severity score over time (β = 0.25, p = .034 and β = 0.30, p = .013, respectively). Adding NPS and the plasma biomarkers to a reference model improved the prediction of future NPS (AUC 0.72 to 0.88, p = .002) and AD pathology (AUC 0.78 to 0.87, p = .010), but not of cognitive decline (AUC 0.79 to 0.85, p = .081). Conclusion Plasma NfL and GFAP are both associated with future NPS and NPS severity change. Considering the presence of NPS along with blood-based AD-biomarkers may improve the prediction of clinical progression of NPS over time and inform clinical decision-making in non-demented older people.

Objective: The World Health Organization declared monkeypox (MPX), a global health crisis, in July 2022. Its symptoms include fever, rash, lymphadenopathy, myalgias, and fatigue; there have also been the reports of neurological manifestations and no data on psychiatric manifestations. In our study, we aimed to study neurologic and psychiatric manifestations in MPX patients. Methodology: Our study used the TriNetX database to identify MPX patients along with their age, gender, race, ethnicity, and geographic location data. Using International Classification of Diseases, tenth revision codes for neurological, psychiatric symptoms, and diagnoses, we identified 331 individuals on November 22, 2022, who had neuropsychiatric signs within a month of diagnosis with MPX (n = 1,006). Results: The most common neurological symptom was pain (17.3%) followed by headache (10.3%), while the most frequent psychiatric symptoms were mood disorders (11.9%), emotional issues (10.5%), and anxiety (9.4%). Conclusion: In this study, neuropsychiatric symptoms were present in about one-third of MPX patients. Physicians, neurologists, and psychiatrists should be aware of the potential for neuropsychiatric side effects associated with MPX infection in patients.

Background and purpose Methods Results Conclusions Behavioral variant frontotemporal dementia (bvFTD) and primary psychiatric disorders (PPD), such as mood, psychotic, and autism spectrum disorders, share similar clinical characteristics of behavior and social cognition. Better understanding of clinical progression in bvFTD and PPD is essential for adequate disease monitoring and trial design.In this longitudinal study (N = 89), patients with bvFTD and PPD with at least one follow‐up assessment were included from the Social Brain Project of the Alzheimer Center Amsterdam. Behavioral change and social cognitive decline were assessed via informant‐rated questionnaires (Cambridge Behavioral Inventory–Revised, Frontal Behavioral Inventory [FBI], Stereotypy Rating Inventory, Frontotemporal Dementia Rating Scale, Revised Self‐Monitoring Scale [RSMS]‐caregiver) and patient assessment (Ekman 60‐Faces Test, RSMS‐patient, Emotional Contagion Scale). Clinical trajectories (median = 1.4 years, interquartile range = 1.0–2.2) were examined using linear mixed models. In a subsample, associations with baseline serum neurofilament light (sNfL) were examined.At baseline, behavioral and social cognitive symptoms were similar between diagnosis groups, except for poorer emotion recognition in bvFTD. Over time, behavioral symptoms worsened in bvFTD, whereas most measures remained stable and the FBI improved in PPD. Regarding social cognition, emotion recognition and caregiver‐reported socioemotional sensitivity worsened in bvFTD and remained stable in PPD. Patient‐reported social cognitive measures did not change over time. Higher sNfL was associated with faster behavioral change.Trajectories of behavior and social cognition differentiate bvFTD from PPD, provided that social cognition is not patient‐reported. Therefore, we stress the need to optimize longitudinal social cognitive assessment in bvFTD. sNfL may be a useful prognostic marker of behavioral progression in neuropsychiatric populations. [ABSTRACT FROM AUTHOR]

Background: Studies that assess cognition prospectively and study in detail anxiety history in the participants' medical records within the context of brain aging and Alzheimer's disease are limited. Objective: To examine the associations of anxiety and unspecified emotional distress (UED) acquired throughout a person's life with prospectively collected cognitive outcomes. Methods: Mayo Clinic Study of Aging participants who were cognitively unimpaired at baseline were included. Anxiety and UED data were abstracted from the medical record using the Rochester Epidemiology Project (REP) resources and were run separately as predictors in our models. The data were analyzed using Cox proportional hazards models for the outcomes of incident mild cognitive impairment (MCI) and dementia and using linear mixed effects models for the outcomes of global and domain specific cognitive z-scores and included key covariates. Results: The study sample (n = 1,808) had a mean (standard deviation) age of 74.5 (7.3) years and 51.4% were male. Anxiety was associated with increased risk of MCI and dementia and was associated with lower baseline cognitive z-scores and accelerated decline over time in the global, memory, and attention domains. UED was associated with faster decline in all domains except visuospatial but did not show evidence of association with incident cognitive outcomes. These results varied by medication use and timing of anxiety. Conclusions: Anxiety and UED both showed inverse associations with cognition. Utilization of anxiety and UED data from across the life course, as available, from the REP system adds robustness to our results. [ABSTRACT FROM AUTHOR]

AbstractObjectivesMethodResultsConclusionThis study aimed to evaluate the effects of a multicomponent psychotherapy programme for people with mild Alzheimer’s dementia (AD) and their caregivers on depression and related neuropsychiatric symptoms.The cognitive behavioural therapy (CBT)-based treatment consisted of 25 weekly sessions, including behavioural activation, behaviour management, interventions for the caregiver, reminiscence, couples counselling, and cognitive restructuring. 41 participants and their caregivers were randomised to either the CBT or the control group, which received treatment-as-usual (TAU). Follow-ups took place at 6 and 12 months posttreatment. The primary outcome was depression in the patient with AD. The secondary outcomes were apathy, other neuropsychiatric symptoms, functional abilities, quality of life, and quality of the relationship with the caregiver.Linear mixed models revealed a statistically significant superiority of CBT regarding clinician-rated depression at the 12-month follow-up with large effect sizes (within-subject d = 1.22, between-subject d = 1.00). Effect sizes were only moderate for self-rated depression and small for informant-rated depression. There was also a significant advantage for CBT regarding clinician-rated apathy, relationship quality, and informant-rated quality of life (QoL) but not for the other neuropsychiatric symptoms or self-rated QoL.The results are very encouraging and support an adequately powered multicentre study.Trial registration: ClinicalTrials.gov NCT01273272. Date of registration: 3 Jan 2011. [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric symptoms (NPS) can be an early manifestation of Alzheimer's disease (AD). However, the associations among NPS, cognition, and AD biomarkers across the disease spectrum are unclear. Objective: We analyzed cross-sectional mediation pathways between cerebrospinal fluid (CSF) biomarkers of AD (Aβ1-42, p-tau181), cognitive function, and NPS. Methods: Primary models included 781 participants from the National Alzheimer's Coordinating Center (NACC) data set who had CSF analyzed for AD biomarkers using Lumipulse. NPS were assessed with the Neuropsychiatric Inventory Questionnaire (NPI-Q). We assessed cognition with the harmonized MMSE/MoCA, as well as neuropsychological tests sensitive to AD pathology: story recall, naming, animal fluency, and Trails B. The Clinical Dementia Rating (CDR®) scale assessed dementia severity. Mediation models were estimated with Kemeny metric covariance in a structural equation model framework, controlling for age, education, sex, and APOEɛ4. Results: The sample was older adults (M = 73.85, SD = 6.68; 49.9% male, 390; 27.9% dementia, 218) who were predominantly white (n = 688, 88.1%). Higher p-tau181/Aβ1-42 ratio predicted higher NPI-Q, which was partially mediated by the MMSE/MoCA and, in a second model, story recall. No other pathway was statistically significant. Both the MMSE/MoCA and NPI-Q independently mediated the association between p-tau181/Aβ1-42 ratio and CDR global impairment. With dementia excluded, p-tau181/Aβ1-42 ratio was no longer associated with the NPI-Q. Conclusions: NPS may be secondary to cognitive impairment and AD pathology through direct and indirect pathways. NPS independently predict dementia severity in AD. However, AD pathology likely plays less of a role in NPS in samples without dementia. [ABSTRACT FROM AUTHOR]

Neuropsychiatric symptoms (NPSs) in Alzheimer's disease (AD) are as prevalent as cognitive decline. The majority of the NPSs appear during the preclinical or mild cognitive impairment (MCI) phase. Genetics, neuropathology, and neurochemical dysregulation likely contribute to the NPSs in AD. Genetic predisposition to AD increases the chance of developing depression in cognitively normal persons >50 years of age. The shared biological processes between serious mental illness (SMI) and AD include the autophagy system, neurotransmitter secretion, vesicle-mediated transport in synapses, synaptic vesicle recycling, SNAP receptor activity, myeloid leukocyte activation, and mitochondrial processes. There are causal proteins and protein interactions shared between AD and SMI. Neuroimaging can help elucidate disruptive pathology in specific circuits. Neuropsychiatric symptoms (NPSs) in Alzheimer's disease (AD) constitute multifaceted behavioral manifestations that reflect processes of emotional regulation, thinking, and social behavior. They are as prevalent in AD as cognitive impairment and develop independently during the progression of neurodegeneration. As studying NPSs in AD is clinically challenging, most AD research to date has focused on cognitive decline. In this opinion article we summarize emerging literature on the prevalence, time course, and the underlying genetic, molecular, and pathological mechanisms related to NPSs in AD. Overall, we propose that NPSs constitute a cluster of core symptoms in AD, and understanding their neurobiology can lead to a more holistic approach to AD research, paving the way for more accurate diagnostic tests and personalized treatments embracing the goals of precision medicine. Neuropsychiatric symptoms (NPSs) in Alzheimer's disease (AD) constitute multifaceted behavioral manifestations that reflect processes of emotional regulation, thinking, and social behavior. They are as prevalent in AD as cognitive impairment and develop independently during the progression of neurodegeneration. Albeit clinically challenging, AD clinical research to date has been focused mostly on cognitive decline. In this opinion article we summarize emerging literature on the prevalence, time course, and the underlying genetic, molecular, and pathological mechanisms related to NPSs in AD. Overall, we propose that NPSs constitute a cluster of core symptoms in AD, and understanding their neurobiology can lead to a more holistic approach to AD research, paving the way for more accurate diagnostic tests and personalized treatments embracing the goals of precision medicine. [ABSTRACT FROM AUTHOR]

Background: Recent studies propose 40 Hz neural activity induction as a promising approach for managing Alzheimer's dementia (AD). However, traditional flickering light is suboptimal in addressing cognitive and neuropsychiatric symptoms (NPS) of AD. This study aims to investigate the clinical efficacy of a novel multi-luminaire lighting technology, with reduced perceptible flickering, for treating AD NPS. Methods: This study is a prospective, convenient sampling, non-randomized case–control investigation involving seventy-eight clinically diagnosed AD patients from 7 daycare centers. Thirty-five were exposed to 40 Hz light through Delta M + BrainCare Light (M +), 4 h daily, 5 days/week, for 12 weeks. The other 43 patients served as controls. Sum of boxes of the Clinical Dementia Rating (CDR-SB) scale, Neuropsychiatric Inventory (NPI), and Zarit Burden Interview (ZBI) were assessed at baseline and the 13th week. Results: At baseline, the cases had worse cognitive function, lower cognitive score (Mini-Mental State Examination, p = 0.04; Cognitive Abilities Screening Instrument, p = 0.04), and advanced caregiver burden with higher ZBI scores (p < 0.01) than the controls. After the intervention, the cases had significant improvements in NPS as assessed using the NPI (p = 0.02), especially depression and euphoria symptoms (p = 0.04 and < 0.01, respectively) and less caregiver burden (ZBI score, p < 0.01). In global function, the control group showed a significant decline in CDR-SB score (p < 0.01), while the cases did not. Conclusions: Results suggest M + may slow global function decline, preserve cognitive function, improve NPS, and reduce caregiver burden in AD patients. Larger studies with biomarkers are needed to explore underlying mechanisms. [ABSTRACT FROM AUTHOR]

Long COVID, a condition characterized by persistent symptoms after COVID-19 infection, is increasingly being recognized worldwide. Neurologic symptoms are frequently reported in survivors of COVID-19, making it crucial to better understand this phenomenon both on a societal scale and for the quality of life of these patients. Between January 1, 2020, and July 31, 2022, Illinois (IL) had a standardized cumulative death rate that ranked it 24th out of the 51 states in the United States (US). However, the US had one of the highest per capita COVID-19 death rates among large, high-income countries. [Bollyky T. et al. 2023] As a result of the increased number of COVID-19 infections, there was a rise in the number of patients experiencing Long COVID. At our neuro-infectious disease clinic in Chicago (IL), we observed an increasing number of patients presenting with cognitive and other neurologic symptoms after contracting COVID-19. Initially, we needed to provide these individuals with a better understanding of their condition and expected outcomes. We were thus motivated to further evaluate this group of patients for any patterns in presentation, neurologic findings, and diagnostic testing that would help us better understand this phenomenon. We aim to contribute to the growing body of research on Long COVID, including its presentation, diagnostic testing results, and outcomes to enlighten the long COVID syndrome. We hypothesize that the neurological symptoms resulting from long COVID persist for over 12 months. We conducted a retrospective analysis of clinical data from 44 patients with long-COVID. Cognitive symptoms were the most common presenting concern. Abnormalities in Montreal Cognitive Assessment, electroencephalogram, serum autoantibody testing, and cerebrospinal fluid were found in minority subsets of our cohort. At 12 months, most patients continue to experience neurologic symptoms, though more than half reported moderate or marked improvement compared to initial presentation. Although most of the patients in this study did not show a consistent occurrence of symptoms suggesting a cohesive underlying etiology, our clinical data demonstrated some features of Long COVID patients in Chicago (IL) that could lead to new research avenues, helping us better understand this syndrome that affects patients worldwide. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We examined the burden of neuropsychiatric symptoms (NPSs) in early‐onset (EO) and late‐onset (LO) Alzheimer's disease (AD) and adjusted for age effects via the inclusion of cognitively unimpaired (CU) individuals. METHODS: Cross‐sectional data from 2940 EOAD, 8665 LOAD, and 8775 age‐stratified CU individuals (early‐CU, n = 2433; late‐CU, n = 6342) from the National Alzheimer's Coordinating Center database were included. Fisher's exact tests compared EOAD and LOAD on the presence and severity of NPSs. Multiple logistic regression models included an age*diagnosis interaction to examine age effects. RESULTS: Presence (ps < 0.0001) and severity (ps < 0.05) of NPS were greater in EOAD than in LOAD. However, after adjusting for base rates in NPS in CU individuals (age effects), only elation and eating behaviors were more frequent in EOAD (ps < 0.05) and nighttime behaviors more frequent and severe in LOAD (ps < 0.05). DISCUSSION: Few NPSs were specific to the EOAD versus LOAD. Previous findings of greater NPS burden in EOAD may partially reflect age effects. Highlights: Adjusting for age effect, elation and eating problems are more frequent in EOAD.Adjusting for age effect, sleep disturbances are more frequent and severe in LOAD.Age effects underlie higher neuropsychiatric symptom presentation in EOAD than in LOAD. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? How do persons with early onset dementia (EOD) differ compared to persons with late onset dementia (LOD)? • What is the main finding of this study? Compared to their LOD counterparts, persons with EOD are more likely to be men, college graduates, married, live alone, and have spouse caregivers. They are also likely to have fewer comorbidities and lower severity of neuropsychiatric symptoms and caregiver distress. • What is the meaning of the finding? Understanding the differences in patient and caregiver characteristics for persons with EOD can guide clinicians in shaping care plans and targeted interventions to better meet their needs. Understanding experiences and challenges faced by persons living with Early-Onset Dementia (EOD) compared to individuals diagnosed with Late-Onset Dementia (LOD) is important for the development of targeted interventions. Describe differences in sociodemographic, neuropsychiatric behavioral symptoms, caregiver characteristics, and psychotropic use. Cross-sectional, retrospective study including 908 UCLA Alzheimer's Dementia Care Program participants (177 with EOD and 731 with LOD). Onset of dementia was determined using age at program enrollment, with EOD defined as age <65 years and LOD defined as age >80 years. Sociodemographic and clinical characteristics were measured once at enrollment. Behavioral symptoms were measured using the Neuropsychiatric Inventory Questionnaire (NPI-Q) severity score and caregiver distress was measured using the NPI-Q distress score. Medications included antipsychotic, antidepressant, benzodiazepines and other hypnotics, antiepileptics, and dementia medications. EOD compared to LOD participants were more likely men, college graduates, married, live alone, and have fewer comorbidities. EOD caregivers were more often spouses (56% vs 26%, p <0.01), whereas LOD caregivers were more often children (57% vs 10%, p <0.01). EOD was associated with lower odds of being above the median (worse) NPI-Q severity (adjusted odds ratio [aOR], 0.58; 95% CI 0.35–0.96) and NPI-Q distress scores (aOR, 0.53; 95% CI 0.31–0.88). Psychotropic use did not differ between groups though symptoms were greater for LOD compared to EOD. Persons with EOD compared to LOD had sociodemographic differences, less health conditions, and fewer neuropsychiatric symptoms. Future policies could prioritize counseling for EOD patients and families, along with programs to support spousal caregivers of persons with EOD. [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric symptoms (NPS) are common in older people, may occur early in the development of dementia disorders, and have been associated with faster cognitive decline. Here, our objectives were to investigate whether plasma levels of neurofilament light chain (NfL), glial fibrillary acid protein (GFAP), and tau phosphorylated at threonine 181 (pTau181) are associated with current NPS and predict future NPS in non-demented older people. Furthermore, we tested whether the presence of NPS combined with plasma biomarkers are useful to predict Alzheimer's disease (AD) pathology and cognitive decline. Methods: One hundred and fifty-one participants with normal cognition (n = 76) or mild cognitive impairment (n = 75) were examined in a longitudinal brain aging study at the Memory Centers, University Hospital of Lausanne, Switzerland. Plasma levels of NfL, GFAP, and pTau181 along with CSF biomarkers of AD pathology were measured at baseline. NPS were assessed through the Neuropsychiatric Inventory Questionnaire (NPI-Q), along with the cognitive and functional performance at baseline and follow-up (mean: 20 months). Different regression and ROC analyses were used to address the associations of interest. Results: None of the three plasma biomarker was associated with NPS at baseline. Higher GFAP levels were associated with the presence of NPS at follow-up (OR = 2.8, p =.002) and both, higher NfL and higher GFAP with an increase in the NPI-Q severity score over time (β = 0.25, p =.034 and β = 0.30, p =.013, respectively). Adding NPS and the plasma biomarkers to a reference model improved the prediction of future NPS (AUC 0.72 to 0.88, p =.002) and AD pathology (AUC 0.78 to 0.87, p =.010), but not of cognitive decline (AUC 0.79 to 0.85, p =.081). Conclusion: Plasma NfL and GFAP are both associated with future NPS and NPS severity change. Considering the presence of NPS along with blood-based AD-biomarkers may improve the prediction of clinical progression of NPS over time and inform clinical decision-making in non-demented older people. [ABSTRACT FROM AUTHOR]

Dipeptidyl peptidase-like protein 6 (DPPX) antibody encephalitis is a rare autoimmune encephalitis. Diagnosis and treatment of DPPX remain challenging, particularly in patients with refractory disease. Herein, we report the first case of anti-DPPX encephalitis treated with ofatumumab. The patient had a chronic insidious onset and predominantly presented with severe neuropsychiatric symptoms and the typical triad of symptoms (weight loss, central nervous system hyperexcitability, and cognitive dysfunction). Positive anti-DPPX antibodies in the serum (1:1,000) and cerebrospinal fluid (CSF) (1:100) were detected at the disease peak. The patient was unresponsive to four types of standard immunotherapies (intravenous globulin, plasma exchange, steroids, and tacrolimus), resulting in a treatment switch to ofatumumab. After five doses of injection and 12 months of follow-up, the patient improved well, with only a mild cognitive deficit. [ABSTRACT FROM AUTHOR]

Background: The NIA-AA Research Framework on Alzheimer's disease (AD) proposes a transitional stage (stage 2) characterized by subtle cognitive decline, subjective cognitive decline (SCD) and mild neurobehavioral symptoms (NPS). Objective: To identify participant clusters based on stage 2 features and assess their association with amyloid positivity in cognitively unimpaired individuals. Methods: We included baseline data of N = 338 cognitively unimpaired participants from the DELCODE cohort with data on cerebrospinal fluid biomarkers for AD. Classification into the AD continuum (i.e., amyloid positivity, A+) was based on Aβ42/40 status. Neuropsychological test data were used to assess subtle objective cognitive dysfunction (OBJ), the subjective cognitive decline interview (SCD-I) was used to detect SCD, and the Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to assess NPS. A two-step cluster analysis was carried out and differences in AD biomarkers between clusters were analyzed. Results: We identified three distinct participant clusters based on presented symptoms. The highest rate of A+ participants (47.6%) was found in a cluster characterized by both OBJ and SCD. A cluster of participants that presented with SCD and NPS (A+:26.6%) and a cluster of participants with overall few symptoms (A+:19.7%) showed amyloid positivity in a range that was not higher than the expected A+ rate for the age group. Across the full sample, participants with a combination of SCD and OBJ in the memory domain showed a lower Aβ42/ptau181 ratio compared to those with neither SCD nor OBJ. Conclusions: The cluster characterized by participants with OBJ and concomitant SCD was enriched for amyloid pathology. [ABSTRACT FROM AUTHOR]

Objective: Identifying neuropsychiatric symptoms (NPS) can aid in the early detection of Alzheimer's disease (AD); however, there is still a need for a greater consensus. This review aims to delineate the predominant NPS, compile a comprehensive list of the most commonly employed NPS assessment tools, and corroborate the principal findings regarding the link between NPS and neuropsychological assessment and neurobiological substrates. Methods: To conduct this scoping review, we followed the Preferred Reporting Items for Systematic Reviews guidelines and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). We searched for relevant articles published between 2017 and 2023 in MEDLINE, PsycINFO, PubMed, Web of Science, and Cochrane Library. Results: Of the 61 eligible articles, depression, anxiety, and apathy were the main NPSs. The Neuropsychiatric Inventory Questionnaire and Neuropsychiatric Inventory were the primary assessment tools used to evaluate NPS. Correlations between NPS severity and neurobiological markers were considered clinically significant. Furthermore, clinical procedures prioritized the use of global cognitive screening tools, assessments of executive functions, and functionality evaluations. Conclusion: Standardization of procedures is necessary because of the diversity of methods. The data show that NPS can predict the etiology, severity, form, and type of disease progression, serving as a precursor sign of AD. The results of the most common cognitive screening tools and NPS instruments provided an interesting overview of future clinical approaches. [ABSTRACT FROM AUTHOR]

Introduction: People with Parkinson's disease (PD) often present with disabling neuropsychiatric symptoms. Compassionate mind training (CMT) is a psychological approach effective in reducing stress and promoting psychological well‐being. Heart rate variability (HRV), a measure reflecting sympathovagal balance, has been associated with psychological well‐being and a compassionate attitude. Aim: To assess the feasibility and effectiveness of CMT in enhancing the quality of life and psychological well‐being in PD patients. Additionally, we evaluated HRV as a physiomarker for assessing the CMT outcomes. Methods: Twenty‐four PD patients participated in the study. A 6‐week online CMT intervention was delivered on a weekly basis. At baseline and post‐intervention patients completed questionnaires assessing depression, anxiety and quality of life. In a subsample of 11 patients, HRV was measured at baseline and post‐intervention in three conditions: at rest, during stress and after 3 min of deep breathing. Results: The attendance rate was 94.3%. Quality of life and perceived stigma improved post‐intervention as compared with baseline (p = 0.02 and p = 0.03 for PD Questionnaire‐39 total score and Stigma subscore, respectively). After CMT, patients presented better physiological regulation to stress, as measured by higher HRV as compared with baseline (p = 0.005). Notably, patients who were more resilient to stress at baseline (less decrease in HRV during stress) experienced a more substantial reduction in anxiety and depression following CMT. Conclusions: CMT is feasible and can improve quality of life and stigma in PD patients. HRV emerges as a promising physiomarker for predicting and measuring the outcomes of psychological interventions in PD. [ABSTRACT FROM AUTHOR]

The emergence of sustained neuropsychiatric symptoms (NPS) among non-demented individuals in later life, defined as mild behavioral impairment (MBI), is linked to a higher risk of cognitive decline. However, the underlying pathophysiological mechanisms remain largely unexplored. A growing body of evidence has shown that MBI is associated with alterations in structural and functional neuroimaging studies, higher genetic predisposition to clinical diagnosis of Alzheimer's disease (AD), as well as amyloid and tau pathology assessed in the blood, cerebrospinal fluid, positron-emission tomography (PET) imaging and neuropathological examination. These findings shed more light on the MBI-related potential neurobiological mechanisms, paving the way for the development of targeted pharmacological approaches. In this review, we aim to discuss the available clinical evidence on the role of amyloid and tau pathology in MBI and the potential underlying pathophysiological mechanisms. Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, disruption of neurotrophic factors, such as the brain-derived neurotrophic factor (BDNF), abnormal neuroinflammatory responses including the kynurenine pathway, dysregulation of transforming growth factor beta (TGF-β1), epigenetic alterations including micro-RNA (miR)-451a and miR-455-3p, synaptic dysfunction, imbalance in neurotransmitters including acetylcholine, dopamine, serotonin, gamma-aminobutyric acid (GABA) and norepinephrine, as well as altered locus coeruleus (LC) integrity are some of the potential mechanisms connecting MBI with amyloid and tau pathology. The elucidation of the underlying neurobiology of MBI would facilitate the design and efficacy of relative clinical trials, especially towards amyloid- or tau-related pathways. In addition, we provide insights for future research into our deeper understanding of its underlying pathophysiology of MBI, and discuss relative therapeutic implications. [ABSTRACT FROM AUTHOR]

BACKGROUND: The mechanisms linking mild behavioral impairment (MBI) and Alzheimer's disease (AD) have been insufficiently explored, with conflicting results regarding tau protein and few data on other metabolic markers. We aimed to evaluate the longitudinal association of the MBI domains and a spectrum of plasma biomarkers. METHODS: Our study is a secondary analysis of data from NOLAN. The longitudinal association of the MBI domains with plasma biomarkers, including pTau181, was tested using adjusted linear mixed‐effects models. RESULTS: The sample comprised 359 participants (60% female, mean age: 78.3, standard deviation: 0.3 years). After 1 year, the MBI domain of abnormal perception was associated with steeper increases in plasma pTau181. Abnormal perception, decreased motivation, and impulse dyscontrol were associated with homocysteine or insulin dysregulation. DISCUSSION: Apart from the association with plasma pTau181, our results suggest that MBI might also represent metabolic dysregulation, probably contributing to dementia transition among older adults with subjective cognitive decline or mild cognitive impairment. Highlights: Mild behavioral impairment (MBI) psychosis was associated with steeper increases in plasma p.pTau could be a pharmacological target to treat agitation and psychosis symptoms.MBI domains were linked to metabolic dysregulation involving insulin and homocysteine. [ABSTRACT FROM AUTHOR]