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Wilson’s disease is a rare autosomal recessive disease due to the pathogenic mutations in the ATP7B gene that causes impaired copper excretion in the liver and its accumulation in tissues and organs. Clinically, the disorder of copper metabolism is manifested by various symptoms, usually changes in the liver function, neuropsychiatric symptoms, and Kayser-Fleischer rings in the cornea. Wilson’s disease can be manifested by various neuropsychiatric disorders: cognitive and executive function, sleep and mood disorders, personality changes, or psychosis. Diagnosis of the disease is often delayed, especially when psychiatric symptoms appear. The mechanism of these symptoms is not clear, and the data of the conducted studies are controversial. Copper chelators and zinc are prescribed for the treatment. In order to treat mental disorders, psychotropic drugs and psychotherapy can be used. It is important for healthcare professionals to understand the link of the symptoms of Wilson’s disease and neuropsychiatric disorders in order to achieve timely disease diagnosis and effective treatment. In this article, we review the latest literature on neuropsychiatric disorders in people with Wilson’s disease, their causes, diagnosis, and treatment recommendations.

Abstract INTRODUCTION We compared three operational case definitions of mild behavioral impairment (MBI) in the context of MBI prevalence estimates and dementia risk modeling. METHODS Participants were dementia‐free older adults (n = 13701) from the National Alzheimer's Coordinating Center. Operational case definitions of MBI were generated based on neuropsychiatric symptoms at one (OV), two‐consecutive (TCV), or more than two‐thirds (TTV) of dementia‐free study visits. Definitions were compared in prevalence and in Cox regressions using MBI to predict incident dementia. RESULTS OV MBI was the most prevalent (54.4%), followed by TCV (32.3%) and TTV (26.7%) MBI. However, OV MBI had the lowest rate of incident dementia (hazard ratio [HR] = 2.54, 95% confidence interval [CI]: 2.33–2.78) and generated poorer model metrics than TCV MBI (HR = 4.06, 95% CI: 3.74–4.40) and TTV MBI (HR = 5.77, 95% CI: 5.32–6.26). DISCUSSION Case ascertainment with longer timeframe MBI operational case definitions may more accurately define groups at risk of dementia in datasets lacking tools designed to detect MBI. Highlights Mild behavioral impairment (MBI) can identify older adults at risk of dementia. Neuropsychiatric symptom (NPS) assessment tools can be proxy measures for MBI. Hazard for dementia was highest for MBI defined by NPS presence at more than two‐thirds of visits.

BackgroundNeuropsychiatric symptoms (NPS) are often overlooked and under-identified symptoms associated with dementia, despite their significant impact on the prognosis of individuals living with the disease. The specific role of certain NPS in functional prognosis remains unclear.AimsTo determine the association of different NPS with functional decline in people living with Alzheimer’s disease (AD) or Lewy body dementia (LBD).MethodsThis is an analysis of data from the Dementia Study of Western Norway (DemVest) with 196 patients included of which 111 had AD and 85 LBD. The Neuropsychiatric Inventory (NPI) and the Rapid Disability Rating Scale (RDRS-2) for activities of daily living were administered annually for 5 years. NPI total score and individual items with RDRS-2 trajectories were analyzed with linear mixed models.ResultsThe LBD group exhibited higher levels of functional impairment and a greater burden of NPS at baseline. Over the 5-year follow-up, hallucinations, aggression, depression, anxiety, apathy, disinhibition, aberrant motor behavior, nighttime behavior disturbances, and abnormal eating patterns were significantly associated with the decline in functional abilities in individuals with AD, as well as irritability and aberrant motor behavior in those with LBD.DiscussionThese results highlight the relevance of early detection and intervention of these particularly relevant NPS, due to its potential of also impacting physical function. Better detection and management of these NPS could improve functional prognosis in people living with dementia.ConclusionSpecific NPS demonstrate relevant distinct associations with Longitudinal trajectories of functional decline in AD and LBD.

Neuropsychiatric symptoms (NPS) in Alzheimer’s disease (AD) affect up to 97% of AD patients, with an estimated 80% of current AD patients experiencing these symptoms. Common AD-associated NPS include depression, anxiety, agitation, aggression, and apathy. The severity of NPS in AD is typically linked to the disease’s progression and the extent of cognitive decline. Additionally, these symptoms are responsible for a significant increase in morbidity, mortality, caregiver burden, earlier nursing home placement, and greater healthcare expenditure. Despite their high prevalence and significant impact, there is a notable lack of clinical research on NPS in AD. In this article, we explore and analyze the prevalence, symptom manifestations, challenges in diagnosis, and treatment options of NPS associated with AD. Our literature review reveals that distinguishing and accurately diagnosing the NPS associated with AD remains a challenging task in clinical settings. It is often difficult to discern whether NPS are secondary to pathophysiological changes from AD or are comorbid psychiatric conditions. Furthermore, the availability of effective pharmaceutical interventions, as well as non-pharmacotherapies for NPS in AD, remains limited. By highlighting the advance and challenges in diagnosis and treatment of AD-associated NPS, we aspire to offer new insights into the complexity of identifying and treating these symptoms within the context of AD, and contribute to a deeper understanding of the multifaceted nature of NPS in AD.

Background: Caregiver burden is related to personal factors and patient characteristics and is greater when neuropsychiatric symptoms (NPSs) are present. Objective: Estimate the prevalence of burden among caregivers of dementia patients and its association with NPSs and identify NPSs causing greater caregiver distress according to dementia stage. Methods: A cross-sectional observational study in caregivers of noninstitutionalized dementia patients was conducted. Caregiver variables were sociodemographic, time of care, NPS-associated distress based on the Neuropsychiatric Inventory Caregiver Distress Scale (NPI-D) and burden based on the Zarit Burden Interview (ZBI). Patient variables were time since disease onset, Global Deterioration Scale (GDS) disease stage, functional assessment and NPS presence and intensity according to the Neuropsychiatric Inventory (NPI). The mean ZBI score, prevalence of burden and NPI-D score with 95% CIs at each dementia stage were estimated. Factors associated with burden were identified by multivariate analysis. Results: Of the 125 caregivers included, 77.6% were women, with a mean age of 60.7 (± 14.3) years; 78.4% (95%CI: 71.0; 86.0) experienced burden. The mean ZBI score was 12.3 (95%CI: 11.6; 12.9) and increased according to NPS number (p = 0.042). The NPSs causing the most burden were disinhibition (93.5%), irritability (87.3%) and agitation (86.1%). Agitation, apathy, and sleep disorders were the NPSs generating the greatest overall caregiver distress; depression (max NPI-D 1.9), hyperactivity (max NPI-D 2.1), and psychosis symptoms (max NPI-D 1.6) generated the greatest distress at stage GDS 3, stages GDS 4–5, and stages GDS 6–7, respectively. The NPI score (OR = 1.0, 95%CI 1.0; 1.1), intensity of irritability (OR = 1.2, 95%CI 1.0; 1.6), disinhibition (OR = 2.6, 95%CI 1.1; 5.8) and hyperactivity subsyndrome (OR = 1.1, 95%CI 1.0; 1.2) were associated with caregiver burden. Other associated factors were female gender (OR = 6.0, 95%CI 1.6; 22.8), ≥ 8 h daily care (OR = 5.6, 95%CI 1.4; 22.8), working outside the home (OR = 7.6, 95%CI 1.8; 31.8), living with the patient (OR = 4.5, 95%CI 1.1; 19.6), kinship (OR = 5.4, 95%CI 1.0; 28.2) and lower patient education (OR = 8.3, 95%CI 2.3; 30.3). Conclusions: The burden on caregivers of dementia patients is high and associated with NPS presence and intensity. Disinhibition and irritability caused the highest burden. Depression, hyperactivity and psychosis produce more distress in mild, mild-moderate and severe dementia, respectively. [ABSTRACT FROM AUTHOR]

Aspartame is the methyl-ester of the aspartate-phenylalanine dipeptide. Over time, it has become a very popular artificial sweetener. However, since its approval by the main food safety agencies, several concerns have been raised related to neuropsychiatric effects and neurotoxicity due to its ability to activate glutamate receptors, as well as carcinogenic risks due to the increased production of reactive oxygen species. Within this review, we critically evaluate reports concerning the safety of aspartame. Some studies evidenced subtle mood and behavioral changes upon daily high-dose intake below the admitted limit. Epidemiology studies also evidenced associations between daily aspartame intake and a higher predisposition for malignant diseases, like non-Hodgkin lymphomas and multiple myelomas, particularly in males, but an association by chance still could not be excluded. While the debate over the carcinogenic risk of aspartame is ongoing, it is clear that its use may pose some dangers in peculiar cases, such as patients with seizures or other neurological diseases; it should be totally forbidden for patients with phenylketonuria, and reduced doses or complete avoidance are advisable during pregnancy. It would be also highly desirable for every product containing aspartame to clearly indicate on the label the exact amount of the substance and some risk warnings. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to (1) validate the Thai version of the Neuropsychiatric Inventory Questionnaire (NPI-Q) as a screening tool for behavioral and psychological symptoms of dementia (BPSD), and (2) examine the relationship between cognitive performance and BPSD in an elderly population with amnestic mild cognitive impairment (aMCI) and dementia of Alzheimer’s type (DAT). Methods: One hundred and twenty participants, comprising 80 aMCI and 40 DAT patients, and their respective caregivers were included in the study. Participants completed the NPI-Q and the Neuropsychiatric Inventory (NPI) within 2 weeks of each other and cognitive performance was primarily assessed using the Montreal Cognitive Assessment (MoCA). Results: The Thai NPI-Q had good validity and reliability. Pure exploratory bifactor analysis revealed that a general factor and a single-group factor (with high loadings on delusions, hallucinations, apathy, and appetite) underpinned the NPI-Q domains. Significant negative correlations between the MoCA total score and the general and single-group NPI-Q scores were found in all subjects (aMCI + DAT combined) and DAT alone, but not in aMCI. Cluster analysis allocated subjects with BPSD (10% of aMCI and 50% of DAT participants) into a distinct “DAT + BPSD” class. Conclusion: The NPI-Q is an appropriate instrument for assessing BPSD and the total score is largely predicted by cognitive deficits. It is plausible that aMCI subjects with severe NPI-Q symptoms (10% of our sample) may have a poorer prognosis and constitute a subgroup of aMCI patients who will likely convert into probable dementia. [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric symptoms (NPS) are associated with faster decline in mild cognitive impairment (MCI). This study aimed to investigate the association between NPS severity and Alzheimer's disease (AD) biomarkers, i.e., amyloid-β (Aβ), phosphorylated tau protein (p-tau) and hippocampal volume ratio (HR), to characterise in more detail MCI patients with a poor prognosis. Methods: A total of 506 individuals with MCI and 99 cognitively unimpaired older adults were selected from the ADNI dataset. The patients were divided into three different groups based on their NPI-Q total scores: no NPS (n = 198), mild NPS (n = 160) and severe NPS (n = 148). Regression models were used to assess the association between the severity of NPS and each biomarker level and positivity status. Results: Cerebrospinal fluid Aβ levels were positively associated with older age and lower MMSE scores, while higher p-tau levels were associated with female sex and lower MMSE scores. Only patients with severe NPS had a lower HR (β = −0.18, p = 0.050), i.e., more pronounced medio-temporal atrophy, than those without NPS. Discussion: Only HR was associated with the presence of NPS, partially in line with previous evidence showing that severe NPS may be explained primarily by greater grey matter loss. Future longitudinal studies will be needed to ascertain the relevance of this finding. [ABSTRACT FROM AUTHOR]

Objectives: Neuropsychiatric symptoms (NPS) are highly prevalent in individuals with subjective cognitive decline (SCD) and mild cognitive impairment (MCI), and are strongly linked to accelerated cognitive decline and dementia onset. While mindfulness‐based interventions have shown promise in improving psychological well‐being in clinical and community settings, their efficacy for individuals in these pre‐dementia stages remains unclear. This meta‐analysis examined the effects of mindfulness‐based interventions on NPS and psychological outcomes in these preclinical cohorts. Methods: Eligible studies were retrieved from PubMed, EMBASE, JBI EPB, Web of Science, and Cochrane library. Two independent researchers conducted the literature search and data extraction. Cochrane Risk‐of‐Bias Assessment Tool was used to assess the methodological quality of included studies. Quality of evidence was evaluated using the GRADE approach. Intervention effects were estimated by Hedge's g and 95% confidence interval (CI). Results: A total of 18 randomized controlled trials (including 974 participants from 21 studies) were included in the meta‐analysis. The results demonstrated statistically significant immediate post‐intervention effects of mindfulness‐based interventions on anxiety (g = −0.30, 95% CI −0.49 to −0.11), stress (g = −0.58, 95% CI −0.91 to −0.24), and quality of life (g = 0.50, 95% CI 0.12–0.87). However, no significant effects were found for depression, apathy, mindfulness, and stress‐related biomarkers. Follow‐up data analysis also did not reveal significant effects for depression and anxiety. Conclusions: The findings of this meta‐analysis suggest that mindfulness‐based interventions may improve anxiety, stress, and quality of life in individuals with SCD and MCI. However, more rigorous randomized controlled trials with larger sample sizes and evaluation using physiological parameters are needed to establish more definitive conclusions. Future interventions could consider incorporating cognitive training and health education to address the specific needs of the pre‐dementia population. Registration Number: PROSPERO: CRD42022359906. Key points: Neuropsychiatric symptoms are highly prevalent in individuals with subjective cognitive decline and mild cognitive impairment, and strongly associated with an increased risk of developing dementia.The effectiveness of mindfulness‐based interventions for individuals in the pre‐dementia stages is still uncertain, despite their widespread use in improving psychological well‐being among clinical and community populations.Mindfulness‐based interventions showed immediate beneficial effects on anxiety, stress, and quality of life compared to control treatments.More rigorous and large‐scale randomized controlled trials, evaluated using physiological parameters, are needed to ensure the robustness of study findings and draw definitive conclusions. [ABSTRACT FROM AUTHOR]

The aims of this study were twofold. First, we examined the relationship between patient and caregiver ratings of neuropsychiatric symptoms in Parkinson's disease (PD). Second, we examined if the severity of depressive symptoms affects patient and caregiver perceptions of other neuropsychiatric symptoms and contributes to discrepancies between their perceptions. We examined data from a retrospective clinical cohort of 209 patients with PD and their caregivers. We used intra-class correlation coefficients and the Bland Altman method to assess intra-respondent (retrospective versus current) and inter-respondent (patient versus caregiver) agreement between Frontal Systems Behavior Scales (FrSBe) subscale scores. We then used generalized estimating equation models to examine FrSBe subscale scores and the magnitude of the intra- and inter-respondent discrepancies in FrSBe subscale scores, as a function of Beck Depression Inventory-2nd Edition scores, with patient demographic variable adjustments. There was low agreement between patient and caregiver ratings on all three subscales, at both time points, and high response variability within and between raters. Patients generally reported more severe neuropsychiatric symptoms than caregivers. Depression severity predicted patients' perceptions at both time points, but was more strongly associated with current perceptions. Depression severity predicted caregivers' current perceptions only. The inter-respondent discrepancy in perceived apathy and disinhibition, but not executive dysfunction, increased as a function of depression severity. There are differences in how patients with PD and caregivers perceive neuropsychiatric behaviors and the extent to which depressive symptoms influence their perceptions. Shared neuropathology and negative response biases likely contribute to these relationships. [ABSTRACT FROM AUTHOR]

Background and Objective: The purpose of our study was to explore the immediate and long-term effects of socially assistive robots (SARs) on neuropsychiatric symptoms (NPSs), behavioral and psychological symptoms of dementia (BPSD), positive emotional experiences, and social interaction in older people living with dementia. Methods: We set keywords and used Boolean operators to search the CINAHL, Cochrane Library, EMBASE, IEEE Digital Library, MEDLINE, PsycINFO, PubMed, Web of Science, Scopus, and Chinese Electronic Periodical Service from inception to February 2022 for randomized controlled trials. The Cochrane Collaboration bias assessment tool was used to assess article quality, and RevMan 5.4.1 software was used to conduct the meta-analysis. Results: A total of 14 studies were included in the meta-analysis. SARs can help people living with dementia reduce their NPS of depression and anxiety, provide happiness from positive emotional experiences, and improve their social interaction through conversation. However, there was no significant improvement in agitation behavior, overall BPSD, or quality of life in people living with dementia. In follow-up, it was found that the effect of SRT was limited. Conclusion: SARs can reduce depression and increase positive emotions in people living with dementia. They may also reduce the burden on healthcare workers during the COVID-19 pandemic. This research was registered on PROSPERO CRD42020169340. [ABSTRACT FROM AUTHOR]

The neuropsychiatric symptoms associated with dementia, often referred to as unwanted behaviors, are one of the most difficult aspects of this disorder for caregivers to navigate. This article presents strategies to manage dementia-related neuropsychiatric symptoms. [ABSTRACT FROM AUTHOR]

Aims: In this study, we aimed to investigate the effect of neuropsychiatric symptoms (NPS) on the rate of cognitive decline for both global cognition and specific cognitive domains in a cohort of patients from the Parkinson's Progression Markers Initiative (PPMI). Method: Prospectively longitudinal data were obtained from the PPMI cohort. NPS, including depression, anxiety, apathy, psychosis, impulse control disorders (ICDs), and cognition ability, were evaluated by a series of questionnaires. Linear mixed‐effects models were used to investigate the relationship between NPS and the rate of cognitive decline. Generalized estimating equations (GEEs) were used to investigate the relationship between NPS and the occurrence of mild cognitive impairment (MCI). Results: In total, 423 patients with Parkinson's disease (PD) were recruited at baseline and 395, 378, 366, 346, and 315 participants were followed up at 1, 2, 3, 4, and 5 years, respectively. Depression, anxiety, apathy, and psychosis were associated with global cognitive decline. Except for those with ICDs, patients with psychosis, depression, anxiety, and apathy were more likely to meet the criteria for MCI. Patients with depression and anxiety showed a progressive decline in four major cognitive domains. Apathy and ICDs were separately associated with a progressive decline in processing speed‐attention and memory, respectively. Conclusions: Neuropsychiatric symptoms, including psychosis, depression, anxiety, and apathy, could be used to predict future cognitive decline in patients with PD. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? Do patients with neurocognitive disorders commit crimes after they have received a dementia diagnosis? • What is the main finding of this study? In our large nationwide Finnish register study, the crime rates were lower in the patient groups of Alzheimer´s disease (AD), frontotemporal dementia (FTD) and Lewy body dementias (LBD) than in the same-aged general population, except in the group of FTD women. In comparison between the different neurocognitive groups, we found the highest crime rates in the LBD and FTD groups and in males. • What is the meaning of the finding? The diagnosis of a neurocognitive disorder does not increase criminal behavior and the observed crime incidence was lower than expected. To explore criminal behavior of individuals with Alzheimer's disease (AD), frontotemporal dementia (FTD), or Lewy body dementias (LBD) after the diagnosis. Nationwide register study. Information on diagnoses and criminality was received from Finnish registers. Crime types and incidences were compared between disorders and the general population. All Finnish individuals diagnosed with AD, LBD, or FTD (n = 92 189) during 1998–2015. Types of crimes and incidences, the standardized criminality ratio (SCR, number of actual crimes per number of expected crimes), numbers of observed cases, and person-years at risk counted in 5-year age groups and for both sexes and yearly. Among men, at least one crime was committed by 2.8% of AD, 7.2% of FTD, and 4.8% of LBD patients. Among women, the corresponding figures were 0.4%, 2.0%, and 2.1%. The most frequent type of crime was traffic offence, followed by property crime. After age adjustment, the relative number of crimes between groups did not differ, except that men with FTD and LBD committed more crimes than those with AD. The SCR (95% CI) among men were 0.40 (0.38–0.42) in AD, 0.45 (0.33–0.60) in FTD, and 0.52 (0.48–0.56) in LBD. Among women, these were 0.34 (0.30–0.38), 0.68 (0.39–1.09), and 0.59 (0.51–0.68). The diagnosis of a neurocognitive disorder does not increase criminal behavior, but rather reduces it by up to 50%. Differences in crime activity are present between different neurocognitive disorders and between the sexes. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Neuropsychiatric symptoms (NPS) are a risk factor for dementia; however, their prevalence and severity among ethnoracial groups are poorly understood. METHODS: We used data from the National Alzheimer's Coordinating Center (NACC) (n = 6958; ≥50 years old). Cognitively normal participants at baseline, without any NPS or dementia diagnosis, had at least one follow‐up. Survival analyses assessed the hazard ratio for 12 NPS models and progression to cognitive impairment. Propensity score weighting (PSW) matched participants on age, sex, education, and race/ethnicity. RESULTS: All 12 NPS were significantly associated with progression to cognitive impairment. In the PSW models, compared to whites, Black/African Americans were more likely to progress to cognitive impairment across all 12 NPS models, followed by Hispanic, and then Asian participants. DISCUSSION: PSW minimized selection bias to provide robust risk estimates. There is a higher risk of progressing to cognitive impairment for ethnoracial groups with NPS. Tailored screening of NPS and cognitive impairment should incorporate patient and caregiver reports. [ABSTRACT FROM AUTHOR]

Background: Disease-modifying drug use necessitates better Alzheimer disease (AD) detection. Mild cognitive impairment (MCI) leverages cognitive decline to identify the risk group; similarly, mild behavioral impairment (MBI) leverages behavioral change. Adding MBI to MCI improves dementia prognostication over conventional approaches of incorporating neuropsychiatric symptoms (NPS). Here, to determine if adding MBI would better identify AD, we interrogated associations between MBI in MCI, and cerebrospinal fluid biomarkers [β-amyloid (Aβ), phosphorylated-tau (p-tau), and total-tau (tau)-ATN], cross-sectionally and longitudinally. Methods: Data were from two independent referral-based cohorts, ADNI (mean[SD] follow-up 3.14[1.07] years) and MEMENTO (4.25[1.40] years), collected 2003–2021. Exposure was based on three-group stratification: 1) NPS meeting MBI criteria; 2) conventionally measured NPS (NPSnotMBI); and 3) noNPS. Cohorts were analyzed separately for: 1) cross-sectional associations between NPS status and ATN biomarkers (linear regressions); 2) 4-year longitudinal repeated-measures associations of MBI and NPSnotMBI with ATN biomarkers (hierarchical linear mixed-effects models-LMEs); and 3) rates of incident dementia (Cox proportional hazards regressions). Results: Of 510 MCI participants, 352 were from ADNI (43.5% females; mean [SD] age, 71.68 [7.40] years), and 158 from MEMENTO (46.2% females; 68.98 [8.18] years). In ADNI, MBI was associated with lower Aβ42 (standardized β [95%CI], -5.52% [-10.48-(-0.29)%]; p = 0.039), and Aβ42/40 (p = 0.01); higher p-tau (9.67% [3.96–15.70%]; p = 0.001), t-tau (7.71% [2.70–12.97%]; p = 0.002), p-tau/Aβ42 (p < 0.001), and t-tau/Aβ42 (p = 0.001). NPSnotMBI was associated only with lower Aβ42/40 (p = 0.045). LMEs revealed a similar 4-year AD-specific biomarker profile for MBI, with NPSnotMBI associated only with higher t-tau. MBI had a greater rate of incident dementia (HR [95%CI], 3.50 [1.99–6.17; p < 0.001). NPSnotMBI did not differ from noNPS (HR 0.96 [0.49–1.89]; p = 0.916). In MEMENTO, MBI demonstrated a similar magnitude and direction of effect for all biomarkers, but with a greater reduction in Aβ40. HR for incident dementia was 3.93 (p = 0.004) in MBI, and 1.83 (p = 0.266) in NPSnotMBI. Of MBI progressors to dementia, 81% developed AD dementia. Conclusions: These findings support a biological basis for NPS that meet MBI criteria, the continued inclusion of MBI in NIA-AA ATN clinical staging, and the utility of MBI criteria to improve identification of patients for enrollment in disease-modifying drug trials or for clinical care. [ABSTRACT FROM AUTHOR]

Background: The term sundowning is used to describe the emergence or worsening of neuropsychiatric symptoms in late afternoon or early evening in people with dementia. Objective: Our aim was to evaluate sundowning's prevalence and clinical manifestations among patients attending a tertiary memory clinic and to investigate its clinical and neuropsychological correlates. Methods: Patients with dementia attending our memory clinic were enrolled in the study. Sundowning was identified through a specifically designed questionnaire. Sociodemographic and clinical features of sundowners and non-sundowners were compared, and a logistic regression was performed to identify the variables associated with the phenomenon. A subgroup of patients underwent a complete neuropsychological assessment. Results: Among 184 recruited patients, 39 (21.2%) exhibited sundowning, mostly expressed as agitation (56.4%), irritability (53.8%), and anxiety (46.2%). Sundowners were significantly older, had a later dementia onset, exhibited more severe cognitive and functional impairment, more frequent nocturnal awakenings, and hearing loss relative to non-sundowners. They were also more likely to use anticholinergic medications and antipsychotics, and less likely to use memantine. In a multi-adjusted model, the factors significantly associated with sundowning were the Clinical Dementia Rating score (OR 3.88; 95% CI 1.39–10.90) and the use of memantine (OR 0.20; 95% CI 0.05–0.74). Participants with and without sundowning obtained similar results in single domain neuropsychological tests. Conclusion: Sundowning is commonly experienced by patients with dementia and appears as a multiply determined condition. Its presence should always be evaluated in clinical practice and a multidimensional approach should be adopted to identify its predictors. [ABSTRACT FROM AUTHOR]

Korsakoff's syndrome (KS) is a chronic neuropsychiatric disorder. The large majority of people with KS experience multiple comorbid health problems, including cardiovascular disease, malignancy, and diabetes mellitus. To our knowledge pain has not been investigated in this population. The aim of this study was to investigate self-reported pain as well as pain behavior observations reported by nursing staff. In total, 38 people diagnosed with KS residing in a long-term care facility for KS participated in this research. The Visual Analogue Scale (VAS), Pain Assessment in Impaired Cognition (PAIC-15), Rotterdam Elderly Pain Observation Scale (REPOS), and the McGill Pain Questionnaire–Dutch Language Version (MPQ-DLV) were used to index self-rated and observational pain in KS. People with KS reported significantly lower pain levels than their healthcare professionals reported for them. The highest pain scores were found on the PAIC-15, specifically on the emotional expression scale. Of importance, the patient pain reports did not correlate with the healthcare pain reports. Moreover, there was a high correlation between neuropsychiatric symptoms and observational pain reports. Specifically, agitation and observational pain reports strongly correlated. In conclusion, people with KS report less pain than their healthcare professionals indicate for them. Moreover, there is a close relationship between neuropsychiatric symptoms and observation-reported pain in people with KS. Our results suggest that pain is possibly underreported by people with KS and should be taken into consideration in treating neuropsychiatric symptoms of KS as a possible underlying cause. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the rate of occurrence of neuropsychiatric symptoms (NPS) and their relationship with age, sex and cognitive performance in subjects with Alzheimer's disease and related dementias (Alzheimer's disease and related dementias [ADRD]). Methods: This is a retrospective matched case‐control study. Data from memory clinic patients included demographic information presence of NPS, and cognitive testing of Orientation, Immediate and Delayed Memory, Visuospatial Function, Working Memory, Attention, Executive Control and Language. Participants were Individuals with subjective cognitive impairment (n = 352), mild cognitive impairment (MCI) (n = 369), vascular MCI (n = 80), Alzheimer's disease (n = 147), vascular dementia (n = 41), mixed dementia (n = 33), and healthy controls (n = 305). Logistic regression was used to investigate the relationship between the presence of NPS, age and sex. A generalised additive model was used to investigate the relationship between presence of NPS, age and cognitive impairment. Analysis of variance was used to investigate differences in cognition between younger and older groups with and without NPS. Results: We found an increased likelihood of occurrence of NPS in younger individuals and females across cohorts. Anxiety, depression, agitation, and apathy were associated with higher overall rate of NPS. We also found that individuals under 65 years of age with NPS had worse cognitive scores than their counterpart without NPS. Conclusion: The younger group with ADRD and NPS had lower cognitive scores, probably reflecting more aggressive neurodegenerative disease. Further work will be needed to elicit the degree to which imaging or mechanistic abnormalities distinguish this group. Key points: Younger individuals with Alzheimer's disease and related dementias (ADRD) were more likely to present with neuropsychiatric symptoms (NPS) than older individuals.Younger individuals with ADRD and NPS showed lower cognitive scores than individuals in the same age group without NPS, which was not observed in the older group. [ABSTRACT FROM AUTHOR]

Neuropsychiatric symptoms are common manifestations of dementia. The presence and severity of these symptoms differ depending on different personal and contextual factors. This study aimed to investigate the presence and predictors of neuropsychiatric symptoms and the association between the severity of these symptoms and the quality of life in a sample of patients with dementia in Jordan. In this cross-sectional study, 112 patients with dementia residing in Jordanian nursing homes were recruited using the consecutive sampling method. The mean severity of neuropsychiatric symptoms was 9.58. The most prevalent neuropsychiatric symptoms among patients were depression (61.6%), followed by irritability (55.4%), and a feeling of euphoria (54.5%). The regression analysis results indicated that gender, marital status, and dementia severity significantly predicted the neuropsychiatric symptoms severity score and explained 17.70% of the variance. A significant negative correlation between the severity of neuropsychiatric symptoms and quality of life was found. The study's results indicate that our sample reported mild neuropsychiatric symptoms. These symptoms' high prevalence and persistence negatively impact patients' quality of life. The study's results can help mental health nurses determine the factors impacting effective treatment strategies to combat these symptoms. Future longitudinal studies are warranted to help explain the importance of early diagnosis and management of these symptoms in preventing dementia progression. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Methylphenidate has been shown to improve apathy in patients with Alzheimer's disease (AD). The authors evaluated the impact of methylphenidate on neuropsychiatric symptoms (NPS) of AD, excluding apathy, using data from the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) study. METHODS: A secondary analysis was conducted on data from the ADMET 2 study to determine the effect of methylphenidate on Neuropsychiatric Inventory (NPI) scores outside of apathy. Caregiver scores were compared from baseline to month 6 in 199 participants receiving methylphenidate (20 mg/day) or placebo regarding the presence or absence of individual neuropsychiatric symptoms, emergence of new symptoms, and individual domain scores. RESULTS: No clinically meaningful improvement was observed in any NPI domain, excluding apathy, in participants treated with methylphenidate compared to placebo after 6 months. A statistical difference between groups was appreciated in the domains of elation/euphoria (P = 0.044) and appetite/eating disorders (P = 0.014); however, these findings were not considered significant. DISCUSSION: Methylphenidate is a selective agent for symptoms of apathy in patients with AD with no meaningful impact on other NPS. Findings from this secondary analysis are considered exploratory and multiple limitations should be considered when interpreting these results, including small sample size and use of a single questionnaire. HIGHLIGHTS: Methylphenidate was not associated with significant improvement on the Neuropsychiatric Inventory in domains outside of apathy.Methylphenidate did not show a statistically significant emergence of new neuropsychiatric symptoms (NPS) throughout the 6‐month treatment period compared to placebo.Methylphenidate appears to be a highly selective agent for apathy in Alzheimer's disease, potentially supporting catecholaminergic dysfunction as the driving force behind this presentation of symptoms. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We examined associations between plasma‐derived biomarkers of Alzheimer's disease (AD) and neuropsychiatric symptoms (NPS) in community‐dwelling older adults. METHODS: Cross‐sectional study involving 1005 persons ≥50 years of age (mean 74 years, 564 male, 118 cognitively impaired), who completed plasma‐derived biomarker (amyloid beta 42 [Aβ42]/Aβ40, phosphorylated tau 181 [p‐tau181], p‐tau217, total tau [t‐tau], neurofilament light [NfL]), and NPS assessment. RESULTS: P‐tau181 (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.41–3.00, p < 0.001), p‐tau217 (OR 1.70, 95% CI 1.10–2.61, p = 0.016), and t‐tau (OR 1.44, 95% CI 1.08–1.92, p = 0.012) were associated with appetite change. We also found that p‐tau181 and p‐tau217 were associated with increased symptoms of agitation (OR 1.93, 95% CI 1.20–3.11, p = 0.007 and OR 2.04, 95% CI 1.21–3.42, p = 0.007, respectively), and disinhibition (OR 2.39, 95% CI 1.45–3.93, p = 0.001 and OR 2.30, 95% CI 1.33–3.98, p = 0.003, respectively). Aβ42/Aβ40 and NfL were not associated with NPS. CONCLUSION: Higher plasma‐derived p‐tau181 and p‐tau217 levels are associated with increased symptoms of appetite change, agitation, and disinhibition. These findings may support the validity of plasma tau biomarkers for predicting behavioral symptoms that often accompany cognitive impairment. HIGHLIGHTS: We studied 1005 community‐dwelling persons aged ≥ 50 yearsHigher plasma tau levels are associated with increased neuropsychiatric symptomsAβ42/Aβ40 and NfL are not associated with neuropsychiatric symptomsClinicians should treat neuropsychiatric symptoms in persons with high plasma‐derived tau [ABSTRACT FROM AUTHOR]

Porencephalic cysts in combination with cerebral hemiatrophy have been described rarely. Herewith, we describe an 18-year-old female who presented with seizures, neuropsychiatric symptoms, and mild intellectual disability without facial asymmetry or neurological signs of weakness or rigidity. Magnetic resonance imaging head and brain, neuropsychological tests, and video electroencephalography findings are presented. The combination of porencephaly with cerebral hemiatrophy and intellectual disability with neuropsychiatric symptoms is extremely rare and probably the only case. A review of available studies is presented. [ABSTRACT FROM AUTHOR]

Frontotemporal lobar degeneration (FTLD) with tau pathology (FTLD-tau) commonly causes dementia syndromes that include primary progressive aphasia (PPA) and behavioral variant frontotemporal dementia (bvFTD). Cognitive decline in PPA and bvFTD is often accompanied by debilitating neuropsychiatric symptoms. In 44 participants with PPA or bvFTD due to autopsy-confirmed FTLD-tau, we characterized neuropsychiatric symptoms at early and late disease stages and determined whether the presence of certain symptoms predicted a specific underlying FTLD-tauopathy. Participants completed annual research visits at the Northwestern University Alzheimer's Disease Research Center. All participants had an initial Global Clinical Dementia Rating (CDR) Scale score ≤ 2, and neuropsychiatric symptoms were evaluated via the Neuropsychiatric Inventory-Questionnaire (NPI-Q). We assessed the frequency of neuropsychiatric symptoms across all participants at their initial and final visits and performed logistic regression to determine whether symptoms predicted a specific FTLDtau pathologic diagnosis. Across the FTLD-tau cohort, irritability and apathy were most frequently endorsed at initial and final visits, respectively, whereas psychosis was highly uncommon at both timepoints. Irritability at initial visit predicted greater odds of a 4-repeat compared to a 3-repeat tauopathy (OR = 3.95, 95% CI = 1.10-15.83, p < 0.05). Initial sleep disturbance predicted greater odds of progressive supranuclear palsy (PSP) compared to other FTLD-tau subtypes (OR = 10.68, 95% CI = 2.05-72.40, p < 0.01). Appetite disturbance at final evaluation predicted lower odds of PSP (OR = 0.15, 95% CI = 0.02-0.74, p < 0.05). Our findings suggest that characterization of neuropsychiatric symptoms can aid in the prediction of underlying FTLD-tauopathies. Given considerable pathologic heterogeneity underlying dementias, neuropsychiatric symptoms may be useful for differential diagnosis and treatment planning. [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric symptoms (NPS) are a core feature of most neurodegenerative and cerebrovascular diseases. White matter hyperintensities and brain atrophy have been implicated in NPS. We aimed to investigate the relative contribution of white matter hyperintensities and cortical thickness to NPS in participants across neurodegenerative and cerebrovascular diseases. Methods: Five hundred thirteen participants with one of these conditions, i.e. Alzheimer's Disease/Mild Cognitive Impairment, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Parkinson's Disease, or Cerebrovascular Disease, were included in the study. NPS were assessed using the Neuropsychiatric Inventory – Questionnaire and grouped into hyperactivity, psychotic, affective, and apathy subsyndromes. White matter hyperintensities were quantified using a semi-automatic segmentation technique and FreeSurfer cortical thickness was used to measure regional grey matter loss. Results: Although NPS were frequent across the five disease groups, participants with frontotemporal dementia had the highest frequency of hyperactivity, apathy, and affective subsyndromes compared to other groups, whilst psychotic subsyndrome was high in both frontotemporal dementia and Parkinson's disease. Results from univariate and multivariate results showed that various predictors were associated with neuropsychiatric subsyndromes, especially cortical thickness in the inferior frontal, cingulate, and insula regions, sex(female), global cognition, and basal ganglia-thalamus white matter hyperintensities. Conclusions: In participants with neurodegenerative and cerebrovascular diseases, our results suggest that smaller cortical thickness and white matter hyperintensity burden in several cortical-subcortical structures may contribute to the development of NPS. Further studies investigating the mechanisms that determine the progression of NPS in various neurodegenerative and cerebrovascular diseases are needed. [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric symptoms (NPS) are highly prevalent in Alzheimer's disease (AD) and are associated with negative outcomes. However, NPS are currently underrecognized at the memory clinic and non-pharmacological interventions are scarcely implemented. Objective: To evaluate the effectiveness of the Describe, Investigate, Create, Evaluate (DICE) method™ to improve the care for NPS in AD at the memory clinic. Methods: We enrolled sixty community-dwelling people with mild cognitive impairment or AD dementia and NPS across six Dutch memory clinics with their caregivers. The first wave underwent care as usual (n = 36) and the second wave underwent the DICE method (n = 24). Outcomes were quality of life (QoL), caregiver burden, NPS severity, NPS-related distress, competence managing NPS, and psychotropic drug use. Reliable change index was calculated to identify responders to the intervention. A cost-effectiveness analysis was performed and semi-structured interviews with a subsample of the intervention group (n = 12). Results: The DICE method did not improve any outcomes over time compared to care as usual. Half of the participants of the intervention group (52%) were identified as responders and showed more NPS and NPS-related distress at baseline compared to non-responders. Interviews revealed substantial heterogeneity among participants regarding NPS-related distress, caregiver burden, and availability of social support. The intervention did not lead to significant gains in quality-adjusted life years and well-being years nor clear savings in health care and societal costs. Conclusion: The DICE method showed no benefits at group-level, but individuals with high levels of NPS and NPS-related distress may benefit from this intervention. [ABSTRACT FROM AUTHOR]

Background: Associations between epigenetic aging with cognitive aging and neuropsychiatric measures are not well-understood. Objective: 1) To assess cross-sectional correlations between second-generation DNA methylation (DNAm)-based clocks of healthspan and lifespan (i.e., GrimAge, PhenoAge, and DNAm-based estimator of telomere length [DNAmTL]) and cognitive and neuropsychiatric measures; 2) To examine longitudinal associations between change in DNAm markers and change in cognition over 2 years. Methods: Participants were members of VITAL-DEP (VITamin D and OmegA-3 TriaL- Depression Endpoint Prevention) study. From previously ascertained cognitive groups (i.e., cognitively normal and mild cognitive impairment), we randomly selected 45 participants, aged≥60 years, who completed in-person neuropsychiatric assessments at baseline and 2 years. The primary outcome was global cognitive score (averaging z-scores of 9 tests). Neuropsychiatric Inventory severity scores were mapped from neuropsychiatric symptoms (NPS) from psychological scales and structured diagnostic interviews. DNAm was assayed using Illumina MethylationEPIC 850K BeadChip at baseline and 2 years. We calculated baseline partial Spearman correlations between DNAm markers and cognitive and NPS measures. We constructed multivariable linear regression models to examine longitudinal relations between DNAm markers and cognition. Results: At baseline, we observed a suggestive negative correlation between GrimAge clock markers and global cognition but no signal between DNAm markers and NPS measures. Over 2 years: each 1-year increase in DNAmGrimAge was significantly associated with faster declines in global cognition; each 100-base pair increase in DNAmTL was significantly associated with better global cognition. Conclusion: We found preliminary evidence of cross-sectional and longitudinal associations between DNAm markers and global cognition. [ABSTRACT FROM AUTHOR]

Objective: Neuropsychiatric symptoms (NPS) are common in mild cognitive impairment (MCI) and even more in Alzheimer's disease (AD). The symptom‐based cluster including nighttime disturbances, depression, appetite changes, anxiety, and apathy (affective and vegetative symptoms) was associated with an increased risk of dementia in MCI and has common neuroanatomical associations. Our objective was to investigate the differences in brain morphology associations with affective and vegetative symptoms between three groups: cognitively normal older adults (CN), MCI and AD. Material and Methods: Alzheimer's Disease Neuroimaging Initiative data of 223 CN, 367 MCI and 175 AD, including cortical volumes, surface areas and thicknesses and severity scores of the five NPS were analyzed. A whole‐brain vertex‐wise general linear model was performed to test for intergroup differences (CN‐MCI, CN‐AD, AD‐MCI) in brain morphology associations with five NPS. Multiple regressions were conducted to investigate cortical change as a function of NPS severity in the AD‐MCI contrast. Results: We found (1) signature differences in nighttime disturbances associations with prefrontal regions in AD‐MCI, (2) signature differences in NPS associations with temporal regions in AD‐MCI for depression and in CN‐AD for anxiety, (3) decreased temporal metrics in MCI as nighttime disturbances and depression severity increased, (4) decreased pars triangularis metrics in AD as nighttime disturbances and apathy severity increased. Conclusion: Each NPS seems to have a signature on brain morphology. Affective and vegetative NPS were primarily associated with prefrontal and temporal regions. These signatures open the possibility of potential future assessments of links between brain morphology and NPS on an individual level. Key points: Signature differences in nighttime disturbances associations with prefrontal regions in Alzheimer's disease mild cognitive impairment (AD‐MCI).Signature differences in Neuropsychiatric symptoms associations with temporal regions in AD‐MCI for de‐pression and in cognitively normal‐AD for anxiety.Dreased temporal metrics in MCI as nighttime dis‐turbances and depression severity increased.Decreased pars triangularis metrics in AD as nighttime disturbances and apathy severity increased. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic was associated with high mortality and negative consequences for patients with Alzheimer's disease or dementia and their caregivers. Memory clinics play an important role in enabling early dementia diagnosis and providing support for patients and their caregivers. Objective: This study investigates the impact of the COVID-19 pandemic and its restrictions on patients of a memory clinic and their caregivers between March 2020 and March 2021. Methods: We conducted a prospective, single-center, questionnaire-based, observational study to assess consequences and perception of the COVID-19 pandemic on emotion, cognitive function, social living, areas of care, and information retrieval. Results: Results of 255 participants' (mean age 76.78, SD 8.9; 12% cognitively intact, 33% mild cognitive impairment, 55% dementia) and 203 caregivers' COVID-19 questionnaires (valid response rate 71%) could be included in the study. Participants reported a prevalence of psychological symptoms associated with the pandemic between 3-20%. Caregivers living outside compared to those living with the participant reported higher rates of new onset or worsening of neuropsychiatric symptoms in participants since pandemic onset. Patients with dementia showed the lowest use of digital communication before (15.7%) and after (17.1%) pandemic onset in the diagnostic groups. Conclusion: The COVID-19 pandemic frequently led to social isolation and reduced cognitive stimulation due to restrictions in elderly persons with cognitive deficits resulting in negative effects on emotional and social levels. We hypothesize that the implementation and sensitization with digital communication in clinical routine could provide a useful tool to counteract these negative effects. [ABSTRACT FROM AUTHOR]

Objectives: Neuropsychiatric symptoms are related to disease progression and cognitive decline over time in cerebral small vessel disease (SVD) but their significance is poorly understood in covert SVD. We investigated neuropsychiatric symptoms and their relationships between cognitive and functional abilities in subjects with varying degrees of white matter hyperintensities (WMH), but without clinical diagnosis of stroke, dementia or significant disability. Methods: The Helsinki Small Vessel Disease Study consisted of 152 subjects, who underwent brain magnetic resonance imaging (MRI) and comprehensive neuropsychological evaluation of global cognition, processing speed, executive functions, and memory. Neuropsychiatric symptoms were evaluated with the Neuropsychiatric Inventory Questionnaire (NPI-Q, n = 134) and functional abilities with the Amsterdam Instrumental Activities of Daily Living questionnaire (A-IADL, n = 132), both filled in by a close informant. Results: NPI-Q total score correlated significantly with WMH volume (r s = 0.20, p = 0.019) and inversely with A-IADL score (r s = −0.41, p < 0.001). In total, 38% of the subjects had one or more informant-evaluated neuropsychiatric symptom. Linear regressions adjusted for age, sex, and education revealed no direct associations between neuropsychiatric symptoms and cognitive performance. However, there were significant synergistic interactions between neuropsychiatric symptoms and WMH volume on cognitive outcomes. Neuropsychiatric symptoms were also associated with A-IADL score irrespective of WMH volume. Conclusions: Neuropsychiatric symptoms are associated with an accelerated relationship between WMH and cognitive impairment. Furthermore, the presence of neuropsychiatric symptoms is related to worse functional abilities. Neuropsychiatric symptoms should be routinely assessed in covert SVD as they are related to worse cognitive and functional outcomes. [ABSTRACT FROM AUTHOR]

Objective: To review studies reporting on the effectiveness of psychiatry service delivery for older people and people with dementia in hospital and residential aged care. Methods: A systematic search of four databases was conducted to obtain peer-reviewed literature reporting original research published since June 2004 evaluating a psychiatry service for older people (aged 60 years and over) or people with dementia in inpatient or residential aged care settings. Results: From the 38 included studies, there was consistent low-to-moderate quality evidence supporting the effectiveness of inpatient older persons’ mental health wards (n = 14) on neuropsychiatric symptoms, mood, anxiety and quality of life. Inpatient consultation/liaison old age psychiatry services (n = 9) were not associated with improved depression, quality of life or mortality in high-quality randomised studies. However, low-quality evidence demonstrated improved patient satisfaction with care and reduced carer stress. The highest quality studies demonstrated no effect of psychiatric in-reach services to residential aged care (n = 9) on neuropsychiatric symptoms but a significant reduction in depressive symptoms among people with dementia. There was low-quality evidence that long-stay intermediate care wards (n = 6) were associated with reduced risk for dangerous behavioural incidents and reduced costs compared to residential aged care facilities. There was no effect of these units on neuropsychiatric symptoms or carer stress. Conclusions and implications: The scarcity of high-quality studies examining the effectiveness of old age psychiatry services leaves providers and policy-makers to rely on low-quality evidence when designing services. Future research should consider carefully which outcomes to include, given that staff skill and confidence, length of stay, recommendation uptake, patient- and family-reported experiences, and negative outcomes (i.e. injuries, property damage) are as important as clinical outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Apathy is a common symptom in dementia, though can be difficult to distinguish from depression due to shared features and frequent co-occurrence. As such, a significant limitation of much previous research on apathy is the failure to control for depression. The current study sought to address this by examining the trajectory and clinical correlates of apathy after controlling for depression. Methods: Seven hundred and seventy-nine patients with dementia were recruited from nine memory clinics around Australia. Measures of dementia severity, cognition, functional ability, neuropsychiatric symptoms, caregiver burden and medication use were completed at baseline and at regular intervals over a 3-year period. Driving and institutionalisation data were obtained throughout the study. Mortality data were obtained from state registries 8 years after baseline. Results: Of the 662 patients with completed measures of neuropsychiatric symptoms, 342 (51.7%) had apathy and 332 (50.2%) had depression at baseline, while 212 (32.0%) had both. Whereas apathy increased over time, depression remained relatively stable. Apathy, but not depression, was associated with greater dementia severity, poorer cognition and function, driving cessation and mortality. Both apathy and depression were associated with greater neuropsychiatric symptoms, psychosis, caregiver burden and institutionalisation. Conclusions: Apathy increases over the course of dementia and is associated with worse clinical outcomes independent of depression. Distinguishing apathy and depression appears important given their different implications for prognosis and management. [ABSTRACT FROM AUTHOR]

Introduction: It is aimed to report the effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on motor symptoms, neuropsychiatric symptoms, and quality of life in Parkinson's Disease (PD) patients. Methods: The results of 22 patients with PD, who had undergone bilateral STN-DBS, were analyzed. The Unified Parkinson's Disease Rating Scale (UPDRS) was applied to assess the patients' clinical characteristics before surgery and 6-, and 12-month follow-up after surgery. The quality of life of the patients was evaluated with the Parkinson's Disease Questionnaire (PDQ-39). Neuropsychological tests including Minnesota Impulse Control Disorders Interview (MIDI), Beck Depression Inventory-II (BDI), Hospital Anxiety and Depression Scale (HADS), Lille Apathy Rating Scale (LARS), and Mini-Mental State Examination (MMSE) were also routinely performed at baseline and 6 months and 12 months after surgery. Results: The mean age of patients was 57.3±8.8 years. Fourteen patients (63.6%) were male. Significant improvements were seen in UPDRS-part- II, UPDRS-part-III UPDRS-part-IV, and PDQ-39 in the follow-ups after the surgery. No significant change was observed in 6- and 12-month followup visits for BDI, HADS, MMSE, and LARS, compared to baseline. A depressive episode, requiring antidepressant treatment was recorded in four (18.1%) patients. Before DBS surgery, eight patients had at least one current impulse control behaviors (ICBs). Among these eight patients; ICBs disappeared in one patient, did not change in two patients, and worsened in five patients after STN-DBS treatment. Conclusion: In patients with a history of psychiatric disease, bilateral STN-DBS treatment may aggravate psychiatric symptoms such as depression, and ICBs. [ABSTRACT FROM AUTHOR]

Neuroimaging is widely utilized in studying traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD). The risk for PTSD is greater after TBI than after non-TBI trauma, and PTSD is associated with worse outcomes after TBI. Studying the neuroimaging correlates of TBI-related PTSD may provide insights into the etiology of both conditions and help identify those TBI patients most at risk of developing persistent symptoms. The objectives of this systematic review were to examine the current literature on neuroimaging in TBI-related PTSD, summarize key findings, and highlight strengths and limitations to guide future research. A Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) compliant literature search was conducted in PubMed (MEDLINE®), PsycINFO, Embase, and Scopus databases prior to January 2022. The database query yielded 4486 articles, which were narrowed based on specified inclusion criteria to a final cohort of 16 studies, composed of 854 participants with TBI. There was no consensus regarding neuroimaging correlates of TBI-related PTSD among the included articles. A small number of studies suggest that TBI-related PTSD is associated with white matter tract changes, particularly in frontotemporal regions, as well as changes in whole-brain networks of resting-state connectivity. Future studies hoping to identify reliable neuroimaging correlates of TBI-related PTSD would benefit from ensuring consistent case definition, preferably with clinician-diagnosed TBI and PTSD, selection of comparable control groups, and attention to imaging timing post-injury. Prospective studies are needed and should aim to further differentiate predisposing factors from sequelae of TBI-related PTSD. [ABSTRACT FROM AUTHOR]

Background Pharmacological treatments are very common to be used for alleviating neuropsychiatric symptoms (NPS) in dementia. However, decision on drug selection is still a matter of controversy. Aims To summarise the comparative efficacy and acceptability of currently available monotherapy drug regimens for reducing NPS in dementia. Method We searched PubMed, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials between inception and 26 December 2022 without language restrictions; and reference lists scanned from selected studies and systematic reviews. Double-blind randomised controlled trials were identified from electronic databases for reporting NPS outcomes in people with dementia. Primary outcomes were efficacy and acceptability. Confidence in the evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). Results We included 59 trials (15,781 participants; mean age, 76.6 years) and 15 different drugs in quantitative syntheses. Risperidone (standardised mean difference [SMD] −0.20, 95% credible interval [CrI] −0.40 to −0.10) and galantamine (−0.20, −0.39 to −0.02) were more effective than placebo in short-term treatment (median duration: 12 weeks). Galantamine (odds ratio [OR] 1.95, 95% CrI 1.38–2.94) and rivastigmine (1.87, 1.24–2.99) were associated with more dropouts than placebo, and some active drugs. Most of the results were rated as low or very low according to CINeMA. Conclusions Despite the scarcity of high-quality evidence, risperidone is probably the best pharmacological option to consider for alleviating NPS in people with dementia in short-term treatment when considering the risk–benefit profile of drugs. [ABSTRACT FROM AUTHOR]

Second-generation integrase strand transfer inhibitors such as bictegravir (BIC) and dolutegravir (DTG) are the standard of care for starting therapy in people living with HIV (PLHIV). However, their use has been associated with neuropsychiatric symptoms (NPSs) that may lead to treatment discontinuation. We aim to describe and synthesize information on safety and discontinuation rates and to summarize potential risk factors associated with the development of NPSs in PLHIV treated with these regimens. A systematic review of the literature was carried out in the international databases PubMed/Medline, Web of Science (WoS), Scopus, Embase, and Cochrane Library from 2013 to June 2022. Ninety observational studies reporting data on treatment discontinuation due to drug-related adverse events and NPSs were identified. Discontinuation rates due to NPSs increase with treatment time and, in light of the reviewed studies, are higher in PLHIV treated with DTG-based regimens compared with those treated with BIC/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF). This information could be useful for clinicians during treatment decision-making, reducing discontinuation rates and thereby promoting treatment success and durability. Additionally, the identification of potential risk factors in PLHIV prior to starting therapy could also help make the best therapy choices based on the characteristics of each individual. [ABSTRACT FROM AUTHOR]

Post-COVID-19 syndrome is an ongoing challenge for healthcare systems as well as for society. The clinical picture of post-COVID-19 syndrome is heterogeneous, including fatigue, sleep disturbances, pain, hair loss, and gastrointestinal symptoms such as chronic diarrhea. Neurological complaints such as fatigue, cognitive impairment, and sleep disturbances are common. Due to the short timeframe of experience and small amount of evidence in this field, the treatment of post-COVID-19 syndrome remains a challenge. Currently, therapeutic options for post-COVID-19 syndrome are limited to non-pharmaceutical interventions and the symptomatic therapy of respective symptoms. In this article, we summarize the current knowledge about therapeutic options for the treatment of neurological symptoms of post-COVID-19 syndrome. [ABSTRACT FROM AUTHOR]

Antipsychotic drugs are still widely prescribed to control various severe neuropsychiatric symptoms in the elderly and dementia patients although they are off-label use in the United States. However, clinical practice shows greater side effects and lower efficacy of antipsychotics for this vulnerable population and the mechanisms surrounding this aged-related sensitivity are not well understood. Our previous studies have shown that aginginduced epigenetic alterations may be involved in the increasing severity of typical antipsychotic haloperidol induced side effects in aged mice. Still, it is unknown if similar epigenetic mechanisms extend to atypical antipsychotics, which are most often prescribed to dementia patients combined with severe neuropsychiatric symptoms. In this study, we report that atypical antipsychotic risperidone also causes increased motor side effect behaviors in aged mice and 5xFAD mice. Histone deacetylase (HDAC) inhibitor Valproic Acid and Entinostat can mitigate the risperidone induced motor side effects. We further showed besides D2R, reduced expression of 5-HT2A, one of the primary atypical antipsychotic targets in the striatum of aged mice that are also mitigated by HDAC inhibitors. Finally, we demonstrate that specific histone acetylation mark H3K27 is hypoacetylated at the 5htr2a and Drd2 promoters in aged mice and can be reversed with HDAC inhibitors. Our work here establishes evidence for a mechanism where aging reduces expression of 5-HT2A and D2R, the key atypical antipsychotic drug targets through epigenetic alteration. HDAC inhibitors can restore 5-HT2A and D2R expression in aged mice and decrease the motor side effects in aged and 5xFAD mice. [ABSTRACT FROM AUTHOR]

BackgroundAffective neuropsychiatric symptoms (aNPS: depression, anxiety, apathy, irritability) have been linked to increased dementia risk. However, less is known whether this association is independent of Alzheimer's disease (AD) pathophysiology.ObjectiveTo investigate the contribution of early aNPS to dementia risk in cognitively normal (CN) older adults and mild cognitive impairment (MCI) patients, with and without AD biomarker abnormality.MethodsParticipants included 763 community-dwelling, stroke-free older adults identified as CN and 617 with MCI at baseline, drawn from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Baseline assessments included a neuropsychological battery, the Neuropsychiatric Inventory (NPI), and apolipoprotein E ɛ4 (ApoE4) genotyping. A participant subset completed cerebrospinal fluid (CSF) AD biomarker assessment. Time to progression to dementia was measured based on months at follow-up when an individual was diagnosed with dementia, over the follow-up period of 48 months.ResultsLatent class analysis identified 3 subgroups of older adults in CN and MCI, indicated by the baseline profiles of neuropsychiatric symptoms (NPS). Subgroups with higher aNPS were at increased risk of progression to dementia in both CN (HR = 3.65, 95% CI [1.80, 7.40]) and MCI (HR = 1.52, 95% CI [1.16, 2.00]; HR = 1.86 [1.05, 3.30]) groups, adjusting for age, sex, global cognition, and ApoE4, compared with their counterparts with minimal NPS. There was no difference between higher aNPS and minimal NPS subgroups in their CSF AD biomarker profiles.ConclusionFindings suggest that aNPS may represent a neurobiological vulnerability that uniquely contribute to the dementia risk, independent of AD biomarker profiles.

Clinically mild encephalitis/encephalopathy with reversible splenial lesions (MERS) is a mild form of encephalitis/encephalopathy that appears in association with various conditions, including infection. COVID-19 is also known to cause MERS. MERS more commonly occurs in children, and adult cases are relatively rare. Typical head MRI findings include a round lesion in the mid-layer of the corpus callosum with a high signal intensity on diffusion-weighted images. Most improve within a week. Although the exact mechanism by which the cerebral corpus callosum is affected is still unknown, several hypotheses have been proposed, including the involvement of electrolyte abnormalities (e.g., hyponatremia) and inflammatory cytokines (e.g., IL-6). In this report, we describe the first case of COVID-associated MERS with a typical imaging course and hyponatremia, with a review of the relevant literature. When psychiatric symptoms and the disturbance of consciousness appear in COVID patients, MERS should be considered in addition to delirium due to fever and hypoxia.

Porencephalic cysts in combination with cerebral hemiatrophy have been described rarely. Herewith, we describe an 18-year-old female who presented with seizures, neuropsychiatric symptoms, and mild intellectual disability without facial asymmetry or neurological signs of weakness or rigidity. Magnetic resonance imaging head and brain, neuropsychological tests, and video electroencephalography findings are presented. The combination of porencephaly with cerebral hemiatrophy and intellectual disability with neuropsychiatric symptoms is extremely rare and probably the only case. A review of available studies is presented.

Abstract Background Aggression, agitation, psychosis, and sleep disturbances are common behavioral symptoms of people with dementia and they can be distressing for both individuals and their carers. Due to their potential side effects, antipsychotic medications are recommended only for severe behavioral and psychological symptoms of dementia (BPSD). This study explores the prevalence, patterns, and associated factors with antipsychotic drug use among patients with dementia attending geriatric psychiatry services at Sultan Qaboos University Hospital (SQUH). Using a retrospective cross-sectional design, this study examines antipsychotic use among elderly patients aged 60 years or older with dementia who attended geriatric psychiatry services from January 2020 to December 2021. The following information was solicited: socio-demographic factors, type and severity of dementia, presence of co-morbid medical or mental illness, the psychotropic medications prescribed, the anti-psychotic medication use, duration of use, and the indication of use were solicited as well. A multivariate logistic regression analysis was conducted. Results The total prevalence of anti-psychotic use among elderly patients with dementia was 56.6%, and among them, 59% were prescribed anti-psychotics for more than 2 years. Being female, having non-Alzheimer’s dementia, experiencing severe stages of dementia, and having other medical or mental co-morbid conditions were independent predictors of antipsychotic drug use (odds ratio [OR] =1.85, confidence interval [CI] =1.04–3.30; OR=2.77, C.I. 1.52–5.04; OR=4.47, C.I. 2.18–9.18; and OR=2.54, C.I. 1.11–5.78, respectively). Conclusions Antipsychotic medication use is prevalent among elderly patients with dementia in Oman. The results from this study will help the policymakers and psychiatrists in Oman to plan for the use of non-pharmacological strategies as the first line of management for BPSD.

Abstract Introduction Neuropsychiatric symptoms are important treatment targets in the management of dementia and can be present at very early clinical stages of neurodegenerative diseases. Increased cortisol has been reported in Alzheimer’s disease (AD) and has been associated with faster cognitive decline. Elevated cortisol output has been observed in relation to perceived stress, depression, and anxiety. Dehydroepiandrosterone sulfate (DHEAS) has known anti-glucocorticoid effects and may counter the effects of cortisol. Objectives We aimed to examine whether CSF cortisol and DHEAS levels were associated with (1) neuropsychiatric symptoms at baseline, (2) changes in neuropsychiatric symptoms over 3 years, and (3) whether these associations were related to or independent of AD pathology. Methods One hundred and eighteen participants on a prospective study in a memory clinic setting, including patients with cognitive impairment (n = 78), i.e., mild cognitive impairment or mild dementia, and volunteers with normal cognition (n = 40), were included. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). CSF cortisol and DHEAS, as well as CSF AD biomarkers, were obtained at baseline. Neuropsychiatric symptoms were re-assessed at follow-up visits 18 and 36 months from baseline. We constructed linear regression models to examine the links between baseline neuropsychiatric symptoms, the presence of AD pathology as indicated by CSF biomarkers, and CSF cortisol and DHEAS. We used repeated-measures mixed ANCOVA models to examine the associations between the neuropsychiatric symptoms’ changes over time, baseline CSF cortisol and DHEAS, and AD pathology. Results Higher CSF cortisol was associated with higher NPI-Q severity scores at baseline after controlling for covariates including AD pathology status (B = 0.085 [0.027; 0.144], p = 0.027; r = 0.277). In particular, higher CSF cortisol was associated with higher baseline scores of depression/dysphoria, anxiety, and apathy/indifference. Elevated CSF cortisol was also associated with more marked increase in NPI-Q scores over time regardless of AD status (p = 0.036, η 2 = 0.207), but this association was no longer significant after controlling for BMI and the use of psychotropic medications. CSF DHEAS was associated neither with NPI-Q scores at baseline nor with their change over time. Cortisol did not mediate the association between baseline NPI-Q and changes in clinical dementia rating sum of boxes over 36 months. Conclusion Higher CSF cortisol may reflect or contribute to more severe neuropsychiatric symptoms at baseline, as well as more pronounced worsening over 3 years, independently of the presence of AD pathology. Our findings also suggest that interventions targeting the HPA axis may be helpful to treat neuropsychiatric symptoms in patients with dementia.