Neuropsychiatric Inventory Total Score Research Articles

Housing status is protective of neuropsychiatric symptoms among dementia-free multi-ethnic Asian elderly

BackgroundHousing 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.MethodsA 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).ResultsBetter 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 < 0.05) and significant NPS profile (OR = 0.20, 95%CI = 0.08 to 0.46, P < 0.01), after controlling for demographics, risk factors, and cognitive performance. Compared with those living in 1–2 room apartments, older adults in better housing had lower total NPI scores (β=-0.50, 95%CI=-0.95 to -0.04, P = 0.032) and lower psychosis scores (β=-0.36, 95%CI=-0.66 to -0.05, P = 0.025), after controlling for socioeconomic status (SES) indexes. Subgroup analysis indicated a significant correlation between housing type and NPS in females, those of Malay ethnicity, the more educated, those with lower income, and those diagnosed with cognitive impairment, no dementia (CIND).ConclusionsOur study showed a protective effect of better housing arrangements on NPS, especially psychosis in a multi-ethnic Asian geriatric population without dementia. The protective effect of housing on NPS was independent of SES and might have other pathogenic mechanisms. Improving housing could be an effective way to prevent neuropsychiatric disturbance among the elderly.

Effect of Soundscape Augmentation on Behavioral Symptoms in People With Dementia: A Pilot Randomized Controlled Trial.

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. 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. 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). 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. NCT04809545.

Prodromal or mild Alzheimer's disease: Influence of neuropsychiatric symptoms and premordid personality on caregivers' burden

AbstractObjectiveIn Alzheimer's disease (AD), the burden on caregivers is influenced by various factors, including the stage of disease progression and neuropsychiatric symptoms (NPS). To date, there has been limited research examining how patient's premorbid personality could affect this burden. The objective of this study was to investigate the impact of both premorbid personality and NPS in individuals with prodromal to mild AD on their caregivers' burden.MethodOne hundred eighty participants with prodromal or mild AD drown from the PACO (in French: Personnalité Alzheimer COmportement) cohort were included. Personality was assessed by the Revised NEO Personality Inventory (NEO‐PI‐R). Neuropsychiatric symptoms were measured with the short version of the Neuropsychiatric Inventory (NPI‐Q), and caregiver burden was evaluated with the Zarit burden scale. Relationships between personality, Neuro‐Psychiatric Inventory (NPI) scores, and caregiver burden were determined using multivariate linear regressions controlled for age, sex, educational level, and Mini Mental State Examination.ResultsThe total NPI score was related to increased burden (beta = 0.45; p &lt; 0.001). High level of neuroticism (beta = 0.254; p = 0.003) et low level of conscientiousness (beta = ‐ 0.233; p = 0.005) were associated higher burden. Extraversion (beta = −0.185; p = 0.027) and conscientiousness (beta = −0.35; p = 0.006) were negatively associated with burden. In contrast, neuroticism, openness and agreeableness were not correlated with burden. When adjusted on total NPI score, the relationship between extraversion and conscientiousness didn't persist.ConclusionOur results suggest that premorbid personality of patients with prodromal to mild Alzheimer influence caregivers's burden, with a protective effect of a high level of extraversion and conscientiousness.

Influence of Behavioral and Psychological Symptoms on Caregiver Burden for Different Types of Dementia: Clinical Experience in Lima, Peru

Introduction: People caring for patients with dementia are prone to suffering from burden. Behavioral and psychological symptoms of dementia (BPSD) may have an impact on caregiver burden. In Latin American countries, there is a lack of research on caregiver burden. We aimed to determine which BPSD have the greatest impact on caregiver burden among Peruvian patients with dementia and to compare the effects of BPSD on caregiver burden across different types of dementia. Methods: A cross-sectional study was conducted on 231 patients living with Alzheimer’s dementia (AD), behavioral variant frontotemporal dementia (bvFTD), dementia with Lewy bodies (DLB), and vascular dementia (VD) and their caregivers who attended a Peruvian memory clinic. BPSD were assessed with the Neuropsychiatric Inventory (NPI). Caregiver burden was assessed with the Zarit Burden Inventory. We used analysis of variance to compare the AD, bvFTD, DLB, and VD groups. Correlations between Zarit Burden Inventory and NPI subscale scores were assessed with Spearman’s correlation. Results: DLB caregivers had significantly higher levels of burden than the other patient groups (p < 0.05) and higher total NPI scores than caregivers for other patient groups (p < 0.05). bvFTD caregivers had significantly higher total NPI scores than AD and VD caregivers (p < 0.05). Hallucinations, aberrant motor behavior, and apathy were the symptoms most significantly correlated with caregiver burden in those caring for DLB, bvFTD, and AD patients, respectively. Conclusion: Neuropsychiatric symptoms are higher in DLB caregivers. Hallucinations, aberrant motor behavior, and apathy are the main symptoms correlated with burden.

Quetiapine Oral Solution in Alzheimer's Disease: Efficacy and Dosage Insights from a Real-World Retrospective Study.

Neuropsychiatric symptoms (NPS) are distressing for patients with dementia, often accelerating functional decline and nursing home placement. Medications such as quetiapine are used to alleviate NPS, but their side effects require cautious use. Liquid formulations such as quetiapine oral suspension suit specific populations; however, real-world data on their use in patients with dementia are limited. The purpose of this retrospective, naturalistic study was to provide preliminary data on the effects of treatment with quetiapine oral suspension on behavioral and psychiatric disturbances in Alzheimer's disease (AD) outpatients in Taiwan. Between January 2022 and June 2023, data were collected from outpatients with a diagnosis of probable AD who received treatment with Qting® (quetiapine oral solution 25 mg/ml). Primary outcome measures were changes in Neuropsychiatric Inventory (NPI) total score and its sub-items from baseline to the endpoint. We recruited 66 AD patients with a mean age of 72.1±7.6 years, most of whom were female (69.7%). Twenty-three patients had data on neuropsychological test and NPI scores before and after quetiapine treatment. There was no significant change in global cognitive function from baseline to the endpoint. A significant reduction in NPI total score after quetiapine treatment was noted, while the effect on NPI sub-items was limited. The average maintenance dose was 1.5±0.6 ml. We demonstrated our clinical experience of the use of quetiapine oral solution in AD patients with NPS. Our results showed that quetiapine oral solution treatment significantly improved these symptoms at a relatively low dose.

Common neurobiological mechanisms underlying anosognosia and neuropsychiatric symptoms across the Alzheimer’s disease spectrum

AbstractBackgroundBoth loss of awareness for cognitive decline (a.k.a. anosognosia) and neuropsychiatric symptoms (NPS) are common symptoms in Alzheimer’s disease (AD) and have been associated with AD pathology. Recent studies have shown a co‐occurrence between these symptoms across the AD spectrum, suggesting shared underlying neurophysiological processes, especially within the default mode network (DMN). Here, we investigated the relationship between NPS and altered awareness and the structural integrity (as assessed with diffusion tensor imaging, DTI) of brain regions supporting the DMN in participants with and without amyloid pathology.MethodsThree‐hundred participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) underwent an amyloid positron emission tomography (PET), using 18F‐AV45 (florbetapir), and were classified into two groups: amyloid‐positive (A+) and negative (A‐). Individual mean fractional anisotropy (FA) was calculated from tracts overlapping the DMN regions. An awareness index was computed using the discrepancy between Everyday Cognition questionnaire scores from participants and informants. The Neuropsychiatric Inventory Total Score was used to assess the informant‐reported NPS. We compared amyloid groups on demographics and our different measures of interest. Pearson correlations were used to determine associations between measures of interest in each amyloid group. A multivariate multiple regression (MMR) model was performed to determine whether structural brain integrity predicts altered awareness and NPS jointly.ResultsA+ participants were significantly older (74 ± 7 vs. 72 ± 7 for A‐), more impaired (CDR global), and showed lower awareness and diffusion, and greater NPS (all p&lt;0.001, see Table 1). Significant correlations were found between the FA, NPS, and awareness measures in A+ participants, with decreased FA associated with decreased awareness and more NPS. The MMR confirmed these associations between FA, awareness and NPS (p&lt;0.02, see Table 2). The Pillai test revealed that the DTI effect jointly contributed to both models. No significant relationships were observed in the A‐ group.ConclusionOur results show that, in amyloid‐positive individuals across the AD spectrum, decreased awareness and increased NPS were related to decreased structural integrity of the DMN. This supports the hypothesis of common neurobiological mechanisms underlying anosognosia and NPS in AD.

Associations between neuropsychiatric symptoms and ADRD serum biomarkers in Mexican American and non‐Hispanic white adults with mild cognitive impairment

AbstractBackgroundMild cognitive impairment (MCI) is a heterogenous diagnostic category with trajectories ranging from reversion to unimpaired cognition to progression to dementia. Neuropsychiatric symptoms such as depression and irritability are common and influence quality of life of patients and caregivers. The role of neuropsychiatric symptoms on disease biology, presentation, and course remains poorly understood. The goal of this study was to evaluate the associations between neuropsychiatric symptoms and serum ADRD biomarkers in Mexican American and non‐Hispanic white participants diagnosed with MCI.MethodParticipants from the Texas Alzheimer’s Research and Care Consortium underwent a blood draw and clinical evaluation, including psychopathological and cognitive assessments. Diagnoses of MCI were adjudicated in consensus reviews. The presence and severity of neuropsychiatric symptoms were assessed by informant report using the Neuropsychiatric Inventory (NPI). Serum levels of total tau, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) were assessed using Simoa HD‐X Analyzer. Associations between NPI total score and individual items with serum biomarker levels were assessed using linear regression adjusted for age and sex.ResultA total of 425 participants (mean age: 71 ± 9 years, 62% female, 74% Mexican American) had a diagnosis of MCI and serum ADRD biomarkers (Table 1). Total NPI score was not associated with total tau (ß = 0.002, p = 0.609), NfL (ß = 0.001, p = 0.658), or GFAP (ß = 0.001, p = 0.777). However, endorsement of appetite changes was associated with higher NfL (ß = 0.077, p = 0.006) and GFAP (ß = 0.088, p = 0.002) levels. Stratified analyses indicated associations of appetite changes with serum NfL (ß = 0.108, p = 0.002) and GFAP (ß = 0.095, p = 0.003) in Mexican Americans, but not in non‐Hispanic whites (NfL: ß = 0.022, p = 0.633, GFAP: ß = 0.102, p = 0.066).There were no other significant associations between individual items on the NPI with serum biomarkers (p&gt;0.05, Bonferroni adjustment p±0.003).ConclusionWithin Mexican American adults with MCI, changes in appetite were associated with higher serum NFL and GFAP levels. As elevations in circulating NfL and GFAP levels are associated with ADRD pathology and accelerated disease progression, appetite changes, a non‐invasive and easily discernible behavioral phenotype, may predict higher likelihood of worsening cognitive course. Future longitudinal studies will be necessary to confirm predictive utility of appetite changes for disease progression.

Prazosin for Agitation in Alzheimer’s Disease: PEACE‐AD

AbstractBackgroundDisruptive agitation is a major source of distress to patients/caregivers and is a common precipitant of long‐term care placement. High CNS noradrenergic signaling at the alpha‐1 adrenoreceptor (AR) in AD appears contributes to disruptive agitation. Prazosin, a CNS active alpha‐1 AR antagonist, was effective for reducing disruptive agitation and was well tolerated in our previous pilot study. The objective of this study was to evaluate efficacy and safety of prazosin for disruptive agitation in AD participants residing at home or in long‐term care in a multicenter RCT conducted by the NIA‐funded Alzheimer’s Disease Cooperative Study.MethodIn this multi‐site RCT recruitment was substantially handicapped by COVID‐19. Participants were randomized to prazosin or placebo 2:1 for 12 weeks. Prazosin was titrated over 4 weeks to a maximum possible dose of 4 mg mid‐morning and 6 mg at bedtime based on tolerability and persistent agitation. Adverse events and orthostatic blood pressure and heart rate were monitored. Primary outcome: ADCS‐Clinical Global Impression of Change‐Agitation (CGIC‐A) targeting disruptive agitation. Secondary outcomes: 17‐item Neuropsychiatric Inventory (NPI), Cohen Mansfield Agitation Inventory (CMAI), and total # study days completed. An exploratory outcome was the NPI 5‐item subscale reflecting agitation. Methods were adapted to allow for remote consent, participant screening, and outcome and safety assessments.Result35 participants were randomized. MMRM analysis revealed: no significant differences in CGIC‐A or total NPI scores; 7 of 18 prazosin participants were moderately‐markedly improved on the CGIC‐A compared to 1 of 4 placebo participants (NS); change from BL in the CMAI significantly favored prazosin (p = 0.04) and the 5‐item NPI Agitation subscale numerically favored prazosin (NS); 63% of prazosin participants completing compared to 38% of placebo participants (NS). Adverse events were as anticipated for prazosin. Remote consent and assessments allowed continuation of the study without the necessity of in‐person clinic visits.ConclusionAssessments were limited by the small # of participants. There was some benefit with prazosin with the expected safety profile. Feasibility of performing an RCT for disruptive agitation in AD using remote technology was demonstrated. A larger study of prazosin for moderate‐severe disruptive agitation in AD is necessary.

Tau pathology is associated with neuropsychiatric symptoms in a cohort of individuals of predominantly Mexican descent at risk for autosomal‐dominant Alzheimer’s disease

AbstractBackgroundNeuropsychiatric symptoms are common in Alzheimer’s disease (AD), causing significant suffering and diminished quality of life for both individuals and caregivers. The goal of this study was to investigate the relationship between tau pathology in vivo and neuropsychiatric symptoms within a cohort of individuals of predominantly Mexican ancestry at risk for fully penetrant autosomal dominant AD (ADAD) caused by mutations in PSEN1 and APP genes (Figure 1).MethodParticipants from the Estudio de la Enfermedad de Alzheimer en Jalisciences (EEAJ) cohort were selected based on availability of demographic variables, mutation carrier status, tau PET scans (flortaucipir), and completion of the neuropsychiatric inventory (NPI). Linear regression models were used to investigate whether regional tau PET standard uptake value ratio (SUVR) predicted total score on the NPI. Models were adjusted for age, sex, and mutation carrier status. Participants were characterized as carriers if they possessed one of the following ADAD mutations: PSEN1 A431E, PSEN1 I180F, or APP V717I. Analyses were done with and without outliers. The 12‐item total NPI score was used for all analyses. The primary brain regions of interest (i.e., medial orbitofrontal, caudal anterior cingulate, rostral anterior cingulate, parahippocampal, precuneus, and lateral occipital) were selected based on previous findings. Additional analyses were conducted only on individuals who were carriers of 1 of the ADAD mutations.ResultThe sample consisted of 31 participants (45% women, mean age±SD = 37.1±11.7 years, 71% ADAD mutation carriers [81% PSEN1 A431E, 16% PSEN1 I180F, and 3% APP V717I carriers]). A significant relationship was found between regional tau pathology and neuropsychiatric symptoms for all six brain regions (Table 1), all p’s &lt; 0.01. Within all regression models, regional tau pathology explained between 24% to 49% of the variance in neuropsychiatric symptoms. Sub‐set analyses completed on the ADAD mutation carriers sample exhibited similar results (Table 2). No significant results were found for non‐carriers.ConclusionRegional tau pathology within six distinct brain regions is strongly associated with neuropsychiatric symptoms in a cohort of individuals of predominantly Mexican ancestry at risk for fully penetrant ADAD caused by mutations in PSEN1 and APP genes.

Tau pathology is associated with neuropsychiatric symptoms in a cohort of individuals of predominantly Mexican descent at risk for autosomal‐dominant Alzheimer’s disease

AbstractBackgroundNeuropsychiatric symptoms are common in Alzheimer’s disease (AD), causing significant suffering and diminished quality of life for both individuals and caregivers. The goal of this study was to investigate the relationship between tau pathology in vivo and neuropsychiatric symptoms within a cohort of individuals of predominantly Mexican ancestry at risk for fully penetrant autosomal dominant AD (ADAD) caused by mutations in PSEN1 and APP genes (Figure 1).MethodParticipants from the Estudio de la Enfermedad de Alzheimer en Jalisciences (EEAJ) cohort were selected based on availability of demographic variables, mutation carrier status, tau PET scans (flortaucipir), and completion of the neuropsychiatric inventory (NPI). Linear regression models were used to investigate whether regional tau PET standard uptake value ratio (SUVR) predicted total score on the NPI. Models were adjusted for age, sex, and mutation carrier status. Participants were characterized as carriers if they possessed one of the following ADAD mutations: PSEN1 A431E, PSEN1 I180F, or APP V717I. Analyses were done with and without outliers. The 12‐item total NPI score was used for all analyses. The primary brain regions of interest (i.e., medial orbitofrontal, caudal anterior cingulate, rostral anterior cingulate, parahippocampal, precuneus, and lateral occipital) were selected based on previous findings. Additional analyses were conducted only on individuals who were carriers of 1 of the ADAD mutations.ResultThe sample consisted of 31 participants (45% women, mean age±SD = 37.1±11.7 years, 71% ADAD mutation carriers [81% PSEN1 A431E, 16% PSEN1 I180F, and 3% APP V717I carriers]). A significant relationship was found between regional tau pathology and neuropsychiatric symptoms for all six brain regions (Table 1), all p’s &lt; 0.01. Within all regression models, regional tau pathology explained between 24% to 49% of the variance in neuropsychiatric symptoms. Sub‐set analyses completed on the ADAD mutation carriers sample exhibited similar results (Table 2). No significant results were found for non‐carriers.ConclusionRegional tau pathology within six distinct brain regions is strongly associated with neuropsychiatric symptoms in a cohort of individuals of predominantly Mexican ancestry at risk for fully penetrant ADAD caused by mutations in PSEN1 and APP genes.

Specific neuropsychiatric symptoms are associated with functional decline trajectories in Alzheimer's disease and Lewy body dementia: a five-year follow-up study.

Neuropsychiatric 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. To determine the association of different NPS with functional decline in people living with Alzheimer's disease (AD) or Lewy body dementia (LBD). This 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. The 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. These 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. Specific NPS demonstrate relevant distinct associations with Longitudinal trajectories of functional decline in AD and LBD.

Striatal and thalamic automatic segmentation, morphology, and clinical correlates in Parkinsonism: Parkinson's disease, multiple system atrophy and progressive supranuclear palsy

Parkinson's disease (PD), multisystem atrophy (MSA), and progressive supranuclear palsy (PSP) present similarly with bradykinesia, tremor, rigidity, and cognitive impairments. Neuroimaging studies have found differential changes in the nigrostriatal pathway in these disorders, however whether the volume and shape of specific regions within this pathway can distinguish between atypical Parkinsonian disorders remains to be determined. This paper investigates striatal and thalamic volume and morphology as distinguishing biomarkers, and their relationship to neuropsychiatric symptoms. Automatic segmentation to calculate volume and shape analysis of the caudate nucleus, putamen, and thalamus were performed in 18 PD patients, 12 MSA, 15 PSP, and 20 healthy controls, then correlated with clinical measures. PSP bilateral thalami and right putamen were significantly smaller than controls, but not MSA or PD. The left caudate and putamen significantly correlated with the Neuropsychiatric Inventory total score. Bilateral thalamus, caudate, and left putamen had significantly different morphology between groups, driven by differences between PSP and healthy controls. This study demonstrated that PSP patient striatal and thalamic volume and shape are significantly different when compared with controls. Parkinsonian disorders could not be differentiated on volumetry or morphology, however there are trends for volumetric and morphological changes associated with PD, MSA, and PSP.

Immunotherapy responsiveness and risk of relapse in Down syndrome regression disorder

Down syndrome regression disorder (DSRD) is a clinical symptom cluster consisting of neuropsychiatric regression without an identifiable cause. This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation. A prospective, multi-center, non-randomized, observational study was performed. Patients met criteria for DSRD and were treated with IVIg. All patients underwent a standardized wean-off therapy after 9–12 months of treatment. Baseline, on-therapy, and relapse scores of the Neuropsychiatric Inventory Total Score (NPITS), Clinical Global Impression-Severity (CGI-S), and the Bush–Francis Catatonia Rating Scale (BFCRS) were used to track clinical symptoms. Eighty-two individuals were enrolled in this study. Patients had lower BFCRS (MD: −6.68; 95% CI: −8.23, −5.14), CGI-S (MD: −1.27; 95% CI: −1.73, −0.81), and NPITS scores (MD: −6.50; 95% CI: −7.53, −5.47) while they were on therapy compared to baseline. Approximately 46% of the patients (n = 38) experienced neurologic relapse with wean of IVIg. Patients with neurologic relapse were more likely to have any abnormal neurodiagnostic study (χ2 = 11.82, P = 0.001), abnormal MRI (χ2 = 7.78, P = 0.005), and abnormal LP (χ2 = 5.45, P = 0.02), and a personal history of autoimmunity (OR: 6.11, P < 0.001) compared to patients without relapse. IVIg was highly effective in the treatment of DSRD. Individuals with a history of personal autoimmunity or neurodiagnostic abnormalities were more likely to relapse following weaning of immunotherapy, indicating the potential for, a chronic autoimmune etiology in some cases of DSRD.

Predictors of Burden in Carers of Patients with Impulse Control Behaviors in Parkinson's Disease.

Impulse control behaviors (ICBs) are problematic, reward-based behaviors, affecting 15% to 35% of patients with Parkinson's disease. Evidence exists of increased carer burden as a result of these behaviors; however, little is known about the variables mediating this effect and their management. To identify factors predictive of carer burden in a cohort of patients with Parkinson's disease with ICBs to enable the development of targeted therapeutic interventions for carers. Data were collected from 45 patients with clinically significant ICBs and their carers, including levodopa equivalent daily dosage, motor and neuropsychiatric symptoms, cognitive function, and ICB severity. Carer burden was quantified by Zarit Burden Interview (ZBI). Univariate analyses were performed using the Spearman rank correlation. Linear regression was used to create a multivariate model for predicting ZBI. Univariate analysis identified significant correlations between ZBI and patient total Neuropsychiatric Inventory (NPI) (r s = 0.50), 4 NPI subscores (agitation/aggression, r s = 0.41; depression/dysphoria, r s = 0.47; apathy/indifference, r s = 0.49; and irritability/lability, r s = 0.38; all P < 0.02), and the carer 28-item General Health Questionnaire (GHQ-28) (r s = 0.52, P < 0.0005). Multivariate linear regression retained total NPI and GHQ-28 scores and were collectively predictive of 36.6% of the variance in the ZBI. Our study suggests that depressive symptoms and aspects of executive dysfunction (apathy and disinhibition) in the patient are potential drivers of carer burden in patients with ICBs. Such findings suggest the presence of executive difficulties and/or mood disturbance should point the clinician to inquire about burden in the caring role and encourage the carer to seek help for any of their own general health problems, which may compound carer burden.

Diminishment of High PD‐1 Expressing Peripheral Cytotoxic T Lymphocytes in Behavioral and Psychological Symptoms of Alzheimer’s Disease

AbstractBackgroundBehavioral and psychological symptoms of dementia (BPSD) are troublesome in managing Alzheimer’s disease (AD). Growing research strongly suggests the relationship between AD and immunity of peripheral blood. Immunotherapy with blockade of PD‐L1/PD‐1 axis restored cognitive performance in the murine tauopathy model. We analyzed cytotoxic T lymphocyte (CTL) activity or possibility to be regulated, expression of PD‐1 of peripheral blood, and tried to find the correlation between PD‐1 expression and BPSD severity of AD patients.Method16 AD patients meeting NIA‐AA criteria for probable AD dementia (mean age = 80.1, 5 males,11 females) were enrolled in our study. Cognitive function was assessed by clinical dementia rating scale (CDR) and clinical dementia rating scale sum of box (CDR‐SOB). BPSD was evaluated by total neuropsychiatric inventory (NPI) scores. Higher total NPI scores suggested more serious BPSD.Histograms of CTL PD‐1 median fluorescence intensity (MFI) of 16 AD patients were compared head‐to‐head to determine a cutoff MFI value. CTL with high and low PD‐1 expressing populations were seperated. Correlation between total NPI score and CTL PD‐1 expressing population was further analyzed.ResultThe CTL subset located at the peak with the lowest MFI was defined as PD‐1dim CTL, and this subset was positively correlated to total NPI score. The other CTL subset was defined as PD‐1bright CTL, which was negatively correlated to total NPI score. No correlation was found between PD‐1 expression and CDR‐SOB (data not shown)ConclusionOur results revealed that the PD‐1 expression level of CTL decreased with enlarged total NPI scores. Interestingly, CDR‐SOB positively correlated with AD disease progression, yet BPSD could happen in even mild cognitive impairment (MCI) and very early AD stage. Although our study had limitations in sex distribution and small sample size, the results raised concern that CTL might participate in clinical manifestations of BPSD. PD‐1 expressing CTL might not correlate to global dementia progression.Further studies are expected to evaluate how peripheral CTL interplays with inflammatory molecules, excitatory and inhibitory neurons, cerebral blood perfusion, and gating of choroid plexus in the demented brain.

Predicting cognitive decline using neuropsychiatric symptoms in prodromal Lewy body disease

AbstractBackgroundNeuropsychiatric symptoms (NPS) in Lewy body diseases, including dementia with Lewy bodies (DLB) and Parkinson’s disease (PD) dementia, occur frequently and at an early stage in disease progression. Such symptoms are significantly associated with quality of life, caregiver burden and functional limitations. Limited evidence exists, however, outlining the relationship between NPS and cognitive decline.MethodsData from 217 participants were derived from three cohort studies. Patients diagnosed with either MCI with Lewy bodies (MCI‐LB, n = 67), PD‐MCI (n = 56) or Alzheimer’s disease (MCI‐AD, n = 39) and a group of healthy older adults (n = 55) completed comprehensive neuropsychological and neuropsychiatric assessment and were followed up longitudinally for a median of three years. NPS identified at baseline by the Neuropsychiatric Inventory (NPI) were included as predictors in linear regressions and linear mixed effects models to assess the relationship between NPS and performance on a range of cognitive tests both at baseline and longitudinally.ResultsAt baseline, NPS were most prevalent and severe among the MCI‐LB group (49% with NPI score &gt;4 in at least one symptom) and least prevalent in controls (7% with NPI score &gt;4). Total NPI score was not related to baseline cognitive function in any domain in any group. Greater baseline total NPI score was associated with steeper rates of decline among PD‐MCI patients on a measure of processing speed (p = .01). Among healthy adults, only sleep disturbance was associated with steeper rates of decline on global cognition (p = .005). None of the patient groups showed any association between individual NPS and decline on a measure of global cognitive function.ConclusionsThe lack of a significant relationship found between NPS and either global cognitive function or decline in global cognition seen among MCI patients suggests that at this prodromal stage of disease, NPS appear to be of limited clinical impact and indicates that the mechanisms of cognitive and neuropsychiatric symptoms may differ in early Lewy body disease. Future work will investigate these mechanisms using multimodal imaging data from this cohort.

Fortasyn Connect Improves Neuropsychiatric Symptoms in Patients with Mild Cognitive Impairment and Dementia: Results from a Retrospective Real-World Study.

Behavioral and psychological symptoms of dementia (BPSD) manifest in the early stages of the disease and impair patients' and caregivers' quality of life. To assess the effectiveness of the nutritional supplement Fortasyn Connect on BPSD for 12 months in people with mild cognitive impairment (MCI) and dementia in clinical practice. Retrospective, national, single-center study of 236 patients (158 MCI and 78 dementia; 55.1% of AD etiology). BPSD were assessed with the Neuropsychiatric Inventory (NPI) at month 3, 6, and 12. Cognition (Mini-Mental State Examination, MMSE), depression (Geriatric Depression Scale, GDS), and everyday functioning (Blessed Dementia Scale, BLS-D; Rapid Disability Rating Scale 2, RDRS2) were also evaluated. Total NPI score, caregiver impact, and symptoms of depression, anxiety, apathy, and irritability improved after 3, 6, and 12 months from Fortasyn Connect initiation (p < 0.001). NPI decreases were more pronounced when baseline NPI score was higher than > 20 points (p < 0.001). The benefit was independent of gender, age, diagnosis, etiology, or concomitant treatment (p < 0.0001), although larger decreases in NPI total score were observed in MCI patients (p < 0.0001). After 12 months, GDS scores decreased (p = 0.042), and MMSE, BLS-D, and RDRS 2 scores remained stable. Fortasyn Connect improved BPSD over at least a year in patients with MCI and dementia. Depression, anxiety, apathy, and irritability were the symptoms that improved the most. The benefit was independent of patients' characteristics and treatment but was greater if prescribed early and when baseline NPI scores were higher.

Efficacy and safety of negative allosteric modulators of 5-hydroxytryptamine 2A receptors in the treatment of Alzheimer's disease psychosis: A systematic review and meta-analysis.

Psychosis is a very common feature of Alzheimer's disease (AD) that can emerge as the neurodegenerative disease progresses. The 5-hydroxytryptamine (5-HT2A) receptors are located postsynaptically to serotonergic neurons in the frontal cortex and mediate both excitatory and inhibitory neurotransmissions. However, the effectiveness and tolerance of negative modulators of 5-HT2A receptors in Alzheimer's disease psychosis (ADP) are uncertain. To detect the negative modulators of the 5-HT2A receptor as a cure for ADP. The primary outcome indicator was the total Neuropsychiatric Inventory (NPI) score. Other prognostic indicators included Mini-Mental State Examination (MMSE), the Katz Index of Independence in Activities of Daily Living (KATZ), the discontinuation rate, and adverse events. Compared to placebo, 5-HT2A inverse agonists significantly reduced the NPI total score, the KATZ and the MMSE score. The pooled odds ratio (OR) was 1.64 (95% confidence interval (95% CI): 1.01-2.65) and the heterogeneity variance was estimated at Tau2 = 0.52 with an I2 value of 90%, a χ2 value of 111.31, p = 0.04, and z-value of 2.01. The risk difference (RD) between the 5-HT2A receptor negative modulators and placebo groups was 0.12 (95% CI: 0.00-0.24) and the heterogeneity was estimated at Tau2 = 0.03, χ2 value of 127.23, degrees of freedom (df) value of 9, I2 value of 93%, z-value of 1.92, and p-value of 0.01 (<0.05). Our results suggest that negative modulators of 5-HT2A receptors are beneficial and well-tolerated in the treatment of ADP.

Immunotherapy Responsiveness and Risk of Relapse in Down Syndrome Regression Disorder (S34.003)

<h3>Objective:</h3> This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation in persons with Down Syndrome Regression Disorder (DSRD). <h3>Background:</h3> Down syndrome regression disorder (DSRD) is a clinical symptom cluster consisting of neuropsychiatric regression without an identifiable cause. Although presumably polyfactorial, a minority of individuals with this condition have been found to have inflammatory biomarkers and are immunotherapy responsive. This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation. <h3>Design/Methods:</h3> A prospective, multi-center, non-randomized, observational study was performed. Patients met criteria for DSRD and were treated with IVIg. All patients underwent a standardized wean off therapy after 9–12 months of treatment. Baseline, on therapy, and relapse scores of the Neuropsychiatric Inventory Total Score (NPITS), Clinical Global Impression-Severity (CGI-S), and the Bush-Francis Catatonia Rating Scale (BFCRS) were used to track clinical symptoms. <h3>Results:</h3> Eighty-two individuals were enrolled in this study. Patients had lower BFCRS (MD: −6.68; 95% CI: −8.23, −5.14), CGI-S (MD: −1.27; 95% CI: −1.73, −0.81), and NPITS scores (MD: −6.50; 95% CI: −7.53, −5.47) while they were on therapy compared to baseline. Approximately 46% of the patients (n = 38) experienced neurologic relapse with wean of IVIg. Patients with neurologic relapse were more likely to have any abnormal neurodiagnostic study (χ2 = 11.82, p = 0.001), abnormal MRI (χ2 = 7.78, p = 0.005), and abnormal LP (χ2 = 5.45, p = 0.02), and a personal history of autoimmunity (OR: 6.11, p&lt;0.001) compared to patients without relapse. <h3>Conclusions:</h3> IVIg was highly effective in the treatment of DSRD. Individuals with a history of personal autoimmunity or neurodiagnostic abnormalities were more likely to relapse following weaning of immunotherapy, indicating the potential for, a chronic autoimmune etiology in some cases of DSRD. <b>Disclosure:</b> Dr. Santoro has received personal compensation for serving as an employee of UCB. Dr. Santoro has received personal compensation for serving as an employee of Cycle Pharma. Dr. Spinazzi has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Zalkin Law Firm. The institution of Dr. Spinazzi has received research support from Konica Minolta. The institution of an immediate family member of Dr. Filipink has received research support from NIH . Dr. Filipink has received personal compensation in the range of $0-$499 for serving as a Author with Medlink. Dr. Hayati Rezvan has nothing to disclose. The institution of Dr. Kammeyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. The institution of Dr. Kammeyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Kammeyer has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Ogborn-Mihm Trial Lawyers. The institution of Dr. Kammeyer has received research support from Rocky Mountain Multiple Sclerosis Center. Dr. Patel has nothing to disclose. The institution of Dr. Sannar has received research support from Colorado Department of Public Health and Environment. The institution of Dr. Sannar has received research support from National Institute of Health. Dr. Dwyer has nothing to disclose. Dr. Banerjee has nothing to disclose. Dr. Khoshnood has nothing to disclose. Dr. Jafarpour has nothing to disclose. Ms. Boyd has nothing to disclose. Dr. Partridge has nothing to disclose. The institution of Dr. Gombolay has received research support from CDC. The institution of Dr. Gombolay has received research support from NIH. Dr. Christy has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for SAGE Publishing. Dr. Christy has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for The Becker Law Firm . The institution of Dr. Christy has received research support from Biohaven. Dr. ORTEGA BERNARDO has nothing to disclose. Dr. Manning has nothing to disclose. Dr. Van Mater has nothing to disclose. Dr. Worley has nothing to disclose. Dr. Franklin has nothing to disclose. The institution of Dr. Stanley has received research support from NIH. The institution of Dr. Stanley has received research support from NIH. Dr. Brown has nothing to disclose. The institution of George Capone has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ACImmune. The institution of George Capone has received research support from LuMind. Dr. Quinn has nothing to disclose. Dr. Rafii has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AC Immune. Dr. Rafii has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Keystone Bio. Dr. Rafii has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alzheon.

Neuropsychiatric Symptoms and Caregiver Stress in Parkinson's Disease with Cognitive Impairment, Alzheimer's Disease, and Frontotemporal Dementia.

A better understanding of factors associated with caregiver burden might facilitate the construction of coping strategies to improve their clinical outcomes and the comprehensive care model for dementia. To investigate the cognitive and neuropsychiatric domains that contribute to caregiver burden in three types of neurodegenerative disorders: Parkinson's disease (PD), Alzheimer's disease (AD), and frontotemporal disease (FTD). Eight hundred and fourteen patients and their caregivers were invited to participate; among them, 235 had PD with cognitive impairment; 429 had AD, and 150 had FTD. The evaluation protocol included the Neuropsychiatric Inventory (NPI), the Mini-Mental State Examination, the Chinese Version Verbal Learning Test, the modified Trail Making Test B, semantic fluency, and a geriatric depression score. Statistical comparisons of the cognitive tests, NPI total scores, and caregiver burden among the three diagnosed types of dementia, matched for a Clinical Dementia Rating (CDR) of 0.5 or 1, were performed, and multivariate linear regression models were used to evaluate the parameter significance. Caregivers for patients with PD and FTD showed significant burden increments when the CDR scores changes from 0.5 to 1. For CDR = 0.5, the PD group had significantly lower caregiver burdens than the AD group, but the NPI total scores were significantly higher. Factors related to caregiver burden were the presence of delusion among all diagnosis groups, while the impact of NPI total scores related to caregiver burden was the highest in FTD, followed by AD and PD. At the mild to moderate stages, our results suggested different degrees of significance in terms of the cognitive test scores or NPI subdomains for predicting caregiver stress among the three types of dementia.