Role Of Neuropsychiatric Symptoms Research Articles

Associations Between Neuropsychiatric Symptoms and Inflammation in Neurodegenerative Dementia: A Systematic Review.

Neuropsychiatric symptoms are common in dementia and linked to adverse outcomes. Inflammation is increasingly recognized as playing a role as a driver of early disease progression in Alzheimer's disease (AD) and related dementias. Inflammation has also been linked to primary psychiatric disorders, however its association with neuropsychiatric symptoms in neurodegenerative dementias remains uncertain. We conducted a systematic literature review investigating associations between inflammation and neuropsychiatric symptoms in neurodegenerative dementias, including AD, Lewy body, Frontotemporal, Parkinson's (PD) and Huntington's disease dementias. Ninety-nine studies met our inclusion criteria, and the majority (n = 59) investigated AD and/or mild cognitive impairment (MCI). Thirty-five studies included PD, and only 6 investigated non-AD dementias. Inflammation was measured in blood, CSF, by genotype, brain tissue and PET imaging. Overall, studies exhibited considerable heterogeneity and evidence for specific inflammatory markers was inconsistent, with lack of replication and few longitudinal studies with repeat biomarkers. Depression was the most frequently investigated symptom. In AD, some studies reported increases in peripheral IL-6, TNF-a associated with depressive symptoms. Preliminary investigations using PET measures of microglial activation found an association with agitation. In PD, studies reported positive associations between TNF-a, IL-6, CRP, MCP-1, IL-10 and depression. Central and peripheral inflammation may play a role in neuropsychiatric symptoms in neurodegenerative dementias; however, the evidence is inconsistent. There is a need for multi-site longitudinal studies with detailed assessments of neuropsychiatric symptoms combined with replicable peripheral and central markers of inflammation.

Emotion regulation in people living with dementia and their spouses: the role of neuropsychiatric symptoms

Objectives People with dementia (PwD) and their care partners (CP) may have difficulties in emotion regulation, and individual differences in emotion regulation may be related to PwD’s neuropsychiatric symptoms. This study explores whether there is self-awareness of PwD’s difficulties in emotion regulation and whether CP’s emotion regulation relates to the PwD’s neuropsychiatric symptoms, potentially revealing bias or interpersonal effects. Method We used data from the Wish Outcome Obstacle Plan Study with a sample of 45 PwD and their spousal CP (n = 90 individuals). Multivariate linear regression models were used to investigate the associations between the CP-reported neuropsychiatric symptoms in PwD and self-reports of emotion regulation in both dyad members, net of sociodemographic and health factors. Separate analyses were conducted for each neuropsychiatric subsyndrome and each domain of difficulties in emotion regulation. Results Increasing severity of neuropsychiatric symptoms was associated with higher difficulties in emotion regulation in PwD (ß = 1.23, p < 0.05), but not with CP’s difficulties in emotion regulation. When CP reported more severe neuropsychiatric symptoms in PwD, PwD reported that they had difficulties in accepting emotions, controlling impulses, goal-directed behaviors, and accessing emotion regulation strategies, but not in emotion awareness and clarification. Proxy-reports of hyperactivity and psychosis subsyndromes are significantly related to PwD’s self-reported difficulties in emotion regulation. Conclusion PwD reported difficulties in emotion regulation at the early stage of dementia. Proxy-reported neuropsychiatric symptoms may capture PwD’s emotion regulation capability and not be biased by CP’s difficulties in emotion regulation.

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.

Emotion Regulation in Dementia Caregiving: The Role of Neuropsychiatric Symptoms and Attachment Orientation.

Family caregivers are usually the main source of support for persons living with dementia, being exposed to a loved one's suffering, which can lead to experiencing strong and negative emotions. This study aimed to identify factors capable of explaining individual differences in the way caregivers regulate their emotions. This cross-sectional study included 78 informal caregivers (M = 64.84years; SD = 13.32) and 84 controls (non-caregivers) (M = 77years; SD = 7.59). Neuropsychiatric symptoms (NPS), attachment orientations, and emotion regulation were measured using self-report scales. Caregivers of persons living with dementia used more expressive suppression in comparison to non-caregivers. NPS and attachment avoidance were associated with expressive suppression. Moderation analyses showed that NPS only predicted expressive suppression when attachment avoidance was low or medium. The present study showed that caregivers are more likely to suppress their emotions in the presence of NPS, especially those with lower/middle levels of attachment avoidance. Psychological interventions targeting emotion regulation should be offered especially to caregivers that face NPS of persons living with dementia and present lower/middle levels of attachment avoidance.

Temporal Dynamic Alterations of Regional Homogeneity in Parkinson's Disease: A Resting-State fMRI Study.

Brain activity is time varying and dynamic, even in the resting state. However, little attention has been paid to the dynamic alterations in regional brain activity in Parkinson's disease (PD). We aimed to test for differences in dynamic regional homogeneity (dReHo) between PD patients and healthy controls (HCs) and to further investigate the pathophysiological meaning of this altered dReHo in PD. We included 57 PD patients and 31 HCs with rs-fMRI scans and neuropsychological examinations. Then, ReHo and dReHo were calculated for all subjects. We compared ReHo and dReHo between PD patients and HCs and then analyzed the associations between altered dReHo variability and clinical/neuropsychological measurements. Support vector machines (SVMs) were also used to assist in differentiating PD patients from HCs using the classification values of dReHo. The results showed that PD patients had increased ReHo in the bilateral medial temporal lobe and decreased ReHo in the right posterior cerebellar lobe, right precentral gyrus, and supplementary motor area, compared with controls. The coefficient of variation (CV) of dReHo was considerably higher in the precuneus in PD patients compared with HCs, and the CV of dReHo in the precuneus was found to be highly associated with HAMD, HAMA, and NMSQ scores. Multiple linear regression analysis controlling for demographic, clinical, and neuropsychiatric variables confirmed the association between altered dReHo and HAMD. Using the leave-one-out cross validation procedure, 98% (p < 0.001) of individuals were properly identified using the SVM classifier. These results provide new evidence for the aberrant resting-state brain activity in the precuneus of PD patients and its role in neuropsychiatric symptoms in PD.

Impact on Quality of Life After Parathyroidectomy for Asymptomatic Primary Hyperparathyroidism

BackgroundPrimary hyperparathyroidism (PHPT) is associated with a poorer quality of life. The role of neuropsychiatric symptoms in asymptomatic patients who do not display classical features of PHPT remains undefined. It is unclear whether parathyroidectomy provides immediate benefit beyond the long-term risk reduction of adverse effects. The aim of the study is to assess the effect on quality of life in patients with asymptomatic PHPT undergoing parathyroidectomy. MethodsConsecutive patients with PHPT undergoing parathyroidectomy by a single surgeon were recruited from a single center between 2014 and 2019. All patients prospectively completed the validated EQ-5D-3L health status questionnaire preoperatively and postoperatively, comprising two components: (i) five domains including physical and mental health and (ii) visual analog scale (VAS). Biochemical and clinical indices were recorded. ResultsSeventy-eight patients were included, 72% female (n = 56), median age 62 y (interquartile range (IQR): 52-70), and 28 (36%) asymptomatic. A global improvement in health-related quality of life was observed with a VAS score increase from 70 (IQR: 50-80) to 80 (IQR: 70-90); P < 0.001. VAS scores also improved significantly in asymptomatic patients increasing from 77 to 85 (P = 0.014), with an overall improvement in all five domains of quality of life. The symptomatic group showed a significant improvement in anxiety/depression levels (P < 0.01), although this was not the primary complaint in any of the cases. ConclusionsParathyroidectomy is associated with a significant improvement in the quality of life of patients with asymptomatic PHPT. In symptomatic patients, this includes a reduction in anxiety and depression. Benefits are observed as early as 2 mo postoperatively, and results suggest a potentially important cognitive and social aspect of this disease.

Effect of positive and negative symptoms on schizophrenia related quality of life of hospitalized schizophrenic patients at Sargodha and Lahore: Moderating role of neuropsychiatric symptoms.

The purpose of the study was to find out the moderating effect of neuropsychiatric symptoms in the relationship between positive-negative symptoms of schizophrenia with quality of life of schizophrenic patients. This cross-sectional study was conducted at Lahore and Sargodha, Pakistan. Data was collected by administering the Positive and Negative of Schizophrenia Questionnaire, Quality of Life of Schizophrenia Scale and Neuropsychiatry Inventory. SPSS-23 was used for data analysis. The study was completed in one year. The data was collected from September 4, 2017 to November 1, 2018 after 10am. The findings indicated that positive symptoms had significant positive correlation with negative symptoms (p < 0.001) and neuropsychiatric symptoms (p < 0.001) with significant negative correlation with schizophrenia quality of life (p < 0.001). Negative symptoms had significant positive correlation with neuropsychiatric symptoms (p < 0.001) and significant negative correlation with schizophrenia related quality of life (p <0.001). Neuropsychiatric symptoms had significant negative correlation with schizophrenia quality of life (p <0.001) in the study. Moreover, neuropsychiatric symptoms moderated between negative symptoms and schizophrenia related quality of life. In this study, findings suggested that negative symptoms and neuropsychiatric symptoms have positive association with quality of life of schizophrenic patients whereas positive symptoms have inverse relationship. The study also revealed that neuropsychiatric symptoms enhanced the effect of negative symptoms on quality of life of schizophrenic patients.

Differences in Assessment of Everyday Preferences Between People With Cognitive Impairment and Their Care Partners: The Role of Neuropsychiatric Symptoms

ObjectiveAs cognitive impairment progresses, people with dementia increasingly rely on surrogate decision-makers for everyday activities. Yet, little is known about concordance on everyday preferences between persons with cognitive impairment and their care partners. MethodsThe sample included 69 dyads of persons with cognitive impairment (Clinical Dementia Rating Scale ≥0.5) and their care partners. We used the Preferences for Everyday Living Inventory (PELI) to assess preferences for activities and lifestyle choices among persons with cognitive impairment. The PELI was concurrently but separately administered to care partners, who answered as surrogate decision-makers. Factor analysis was used to ascertain factor structure of the PELI; reliability measures were computed within the sample. Paired sample t-tests were used to estimate differences in scores of corresponding PELI items for each factor. Multiple regression models were used to relate predictors, including neuropsychiatric symptoms, to agreement levels. ResultsFour factors were identified from the PELI: autonomous choice, social engagement, personal growth, and keeping a routine. Significant participant-care partner discrepancy was found in “social engagement” preferences (e.g., regular contact with family, meeting new people, volunteering). Geriatric Depression Scale-15 score and care partner sex were significantly associated with participant-care partner discrepancies in “social engagement” preferences. ConclusionThis study yields new insights regarding the most important preferences for persons with cognitive impairment and clarifies a path to optimizing surrogate decision-making around everyday preferences by highlighting areas of apparent disagreement and identifying potential predictors of discrepancy.

Examining the Link Between Cardiovascular Risk Factors and Neuropsychiatric Symptoms in Mild Cognitive Impairment and Major Depressive Disorder in Remission.

Cardiovascular risk factors (CVRFs) have been linked to both depression and cognitive decline but their role in neuropsychiatric symptoms (NPS) has yet to be clarified. Understanding the role of CVRFs in the etiology of NPS for prospective treatments and preventive strategies to minimize these symptoms. We examined the distribution of NPS using the Neuropsychiatric Inventory (NPI) scores in three cohorts from the Prevention of Alzheimer's Dementia with Cognitive Remediation Plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression (PACt-MD) study: older patients with a lifetime history of major depressive disorder (MDD) in remission, patients with mild cognitive impairment (MCI), and patients with combined MCI and MDD. We also examined the link between individual NPS and CVRFs, Framingham risk score, and Hachinski ischemic score in a combined sample. Analyses were based on a sample of 140 subjects, 70 with MCI, 38 with MCI plus MDD, and 32 with MDD. There was no effect of age, gender, education, cognition, or CVRFs on the presence (NPI >1) or absence (NPI = 0) of NPS. Depression was the most prevalent affective NPS domain followed by night-time behaviors and appetite changes across all three diagnostic groups. Agitation and aggression correlated negatively while anxiety, disinhibition, night-time behaviors, and irritability correlated positively with CVRFs (all p-values <0.05). Other NPS domains showed no significant association with CVRFs. CVRFs are significantly associated with individual NPI sub-scores but not with total NPI scores, suggesting that different pathologies may contribute to different NPS domains.

Neuropsychiatric subsyndromes and brain metabolic network dysfunctions in early onset Alzheimer's disease.

Neuropsychiatric symptoms (NPSs) often occur in early-age-of-onset Alzheimer's disease (EOAD) and cluster into sub-syndromes (SSy). The aim of this study was to investigate the association between 18 F-FDG-PET regional and connectivity-based brain metabolic dysfunctions and neuropsychiatric SSy. NPSs were assessed in 27 EOAD using the Neuropsychiatric Inventory and further clustered into four SSy (apathetic, hyperactivity, affective, and psychotic SSy). Eighty-five percent of EOAD showed at least one NPS. Voxel-wise correlations between SSy scores and brain glucose metabolism (assessed with 18 F-FDG positron emission tomography) were studied. Interregional correlation analysis was used to explore metabolic connectivity in the salience (aSN) and default mode networks (DMN) in a larger sample of EOAD (N = 51) and Healthy Controls (N = 57). The apathetic, hyperactivity, and affective SSy were highly prevalent (>60%) as compared to the psychotic SSy (33%). The hyperactivity SSy scores were associated with increase of glucose metabolism in frontal and limbic structures, implicated in behavioral control. A comparable positive correlation with part of the same network was found for the affective SSy scores. On the other hand, the apathetic SSy scores were negatively correlated with metabolism in the bilateral orbitofrontal and dorsolateral frontal cortex known to be involved in motivation and decision-making processes. Consistent with these SSy regional correlations with brain metabolic dysfunction, the connectivity analysis showed increases in the aSN and decreases in the DMN. Behavioral abnormalities in EOAD are associated with specific dysfunctional changes in brain metabolic activity, in particular in the aSN that seems to play a crucial role in NPSs in EOAD. Hum Brain Mapp 37:4234-4247, 2016. © 2016 Wiley Periodicals, Inc.

Neuroimmune interactions in obesity: Role in neuropsychiatric symptoms

Neuroimmune interactions in obesity: Role in neuropsychiatric symptoms

The role of neuropsychiatric symptoms as predictors of dementia

The role of neuropsychiatric symptoms as predictors of dementia

The relation of cytokines TH1, TH2 and TH17 in childhood-onset systemic lupus erythematosus

Serum IL-6 (p=0.001), IL-10 (p=0.006), IL-12 (p=0.027) and IL-17 (p=0.0001) levels were increased in cSLE patients when compared to healthy controls. IL-6 levels were significantly increased in patients whit active disease (p=0.008). IL-6 (p=0.032) and IL-12 (p=0.028) levels were significantly increased in patients with active nephritis. We observed that IL-17 was associated with migraine (p=0.045), IL-6 with thrombocytopenia (p=0.022) and IL-12 with the presence of anxiety (p=0.048). No association between cytokine levels and SDI scores or medication was observed. Conclusion Cytokines play a central role in cSLE, IL-6 is associated with SLEDAI and may be a biomarker of disease activity, Th1 and Th2 responses may play ar ole in lupus nephritis and Th1 and Th17 may play a role in neuropsychiatric symptoms in cSLE. Longitudinal studies are necessary to confirm their ability to predict SLE related manifestations.

Effects of a caloric restriction weight loss diet on tryptophan metabolism and inflammatory biomarkers in overweight adults

Recent data suggest that chronic low-grade inflammation, a characteristic of obesity, is associated with altered tryptophan (Trp) and tyrosine (Tyr) metabolism and plays a role in neuropsychiatric symptoms. The present study assessed the effect of an extreme short-term diet on Trp breakdown and inflammatory biomarkers in overweight adults. Thirty-eight overweight participants (16 women, 22 men; average body mass index: 29 kg/m², mean age 52.8 years) were randomized into two diet groups: a very low kcal diet group (VLCD; Ø 600 kcal/day, n = 21) and a low kcal diet group (LCD; Ø 1,200 kcal/day, n = 17). Assays included the measurement of Trp, kynurenine (Kyn), and their ratio, neopterin, phenylalanine (Phe), Tyr, as biologic markers; leptin, plasma insulin, glucose, and homeostatic model assessment-insulin resistance; and interleukin 6, tumor necrosis factor alpha, and C-reactive protein, as biochemical and inflammatory markers at baseline and after 2 weeks of treatment. Weight loss diet lowered leptin levels in both groups by 46%, although not reaching significance. Trp and Kyn decreased significantly by 21 and 16% for VLCD and by 15 and 17% for the LCD group, respectively. A significant reduction in Phe was only seen after VLCD. Inflammatory biomarkers, neopterin, and Tyr were not significantly altered during the study period. Leptin was significantly correlated with Trp breakdown before and after the intervention (P < 0.02). Since disturbed metabolism of Trp affects biosynthesis of serotonin and might be associated with increased susceptibility for mood disturbances and carbohydrate craving, strategies to supplement Trp while dieting could be highly useful in treating uncontrolled weight gain or in preventing neuropsychiatric symptoms.

Chronic Low-Grade Inflammation in Elderly Persons Is Associated with Altered Tryptophan and Tyrosine Metabolism: Role in Neuropsychiatric Symptoms

Neuropsychiatric symptoms are common complaints of elderly persons. Recent data suggest that chronic low-grade inflammation, a fundamental characteristic of aging, plays a role. Effects might rely on the influence of inflammation on the activity of two enzymatic pathways, the indoleamine-2,3-dioxygenase (IDO) and the guanosine-triphosphate-cyclohydrolase-1 (GTP-CH1) pathways, which are involved in the biosynthesis of monoamines. The present study assessed this possibility in 284 healthy elderly subjects drawn from the Three-City cohort. Assays included the measurement of serum interleukin-6 and C-reactive-protein, as inflammatory markers; tryptophan, kynurenine, and their ratio as index of IDO activity; and neopterin, phenylalanine, tyrosine, and nitrite, as markers of GTP-CH1 activity. In addition, structured assessments of depressive symptomatology, fatigue, and general behavioral/neurovegetative symptoms were performed. As expected, age correlated significantly with concentrations of immune markers and neuropsychiatric symptoms. Increased inflammation was related to reduced tryptophan concentrations and increased kynurenine levels, suggestive of IDO-induced increased tryptophan catabolism. In addition, inflammation was associated with increases in neopterin and nitrite levels and in phenylalanine concentrations at the expense of tyrosine. Interestingly, increased tryptophan catabolism was associated with the depressive symptoms of lassitude, reduced motivation, anorexia, and pessimism. In contrast, variations in markers of GTP-CH1 activity correlated more with neurovegetative symptoms, including sleep disturbance, digestive symptoms, fatigue, sickness, and motor symptoms. These findings show that chronic low-grade inflammation in aging is associated with alterations in enzymatic pathways involved in monoamine metabolism and suggest that these alterations might participate in the pathophysiology of neuropsychiatric symptoms in elderly persons.