Neuropsychiatric Inventory Questionnaire Scores Research Articles

Association Between Serum Vitamins and the Risk of Alzheimer's Disease in Chinese Population.

Alzheimer's disease (AD) is a chronic and fatal neurodegenerative disease; accumulating evidence suggests that vitamin deficiency is associated with the risk of AD. However, studies attempting to elucidate the relationship between vitamins and AD varied widely. This study aimed to investigate the relationship between serum vitamin levels and AD in a cohort of the Chinese population. A total of 368 AD patients and 574 healthy controls were recruited in this study; serum vitamin A, B1, B6, B9, B12, C, D, and E were measured in all participants. Compared with the controls, vitamin B2, B9, B12, D, and E were significantly reduced in AD patients. Lower levels of vitamin B2, B9, B12, D, and E were associated with the risk of AD. After adjusting for age and gender, low levels of vitamin B2, B9, and B12 were still related to the risk of AD. In addition, a negative correlation was determined between vitamin E concentration and Activity of Daily Living Scale score while no significant association was found between serum vitamins and age at onset, disease duration, Mini-Mental State Examination, and Neuropsychiatric Inventory Questionnaire score. We conclude that lower vitamin B2, B9, B12, D, and E might be associated with the risk of AD, especially vitamin B2, B9, and B12. And lower vitamin E might be related to severe ability impairment of daily activities.

The severity of neuropsychiatric symptoms is higher in early-onset than late-onset Alzheimer's disease.

The faster rates of cognitive decline and predominance of atypical forms in early-onset Alzheimer's disease (EOAD) suggest that neuropsychiatric symptoms could be different in EOAD compared to late-onset AD (LOAD); however, prior studies based on non-biomarker-diagnosed cohorts show discordant results. Our goal was to determine the profile of neuropsychiatric symptoms in EOAD and LOAD, in a cohort with biomarker/postmortem-confirmed diagnoses. Additionally, the contribution of co-pathologies was explored. In all, 219 participants (135 EOAD, 84 LOAD) meeting National Institute on Aging and Alzheimer's Association criteria for AD (115 amyloid positron emission tomography/cerebrospinal fluid biomarkers, 104 postmortem diagnosis) at the University of California San Francisco were evaluated. The Neuropsychiatric Inventory-Questionnaire (NPI-Q) was assessed at baseline and during follow-up. The NPI-Q mean comparisons and regression models adjusted by cognitive (Mini-Mental State Examination) and functional status (Clinical Dementia Rating Sum of Boxes) were performed to determine the effect of EOAD/LOAD and amnestic/non-amnestic diagnosis on NPI-Q. Regression models assessing the effect of co-pathologies on NPI-Q were performed. At baseline, the NPI-Q scores were higher in EOAD compared to LOAD (p<0.05). Longitudinally, regression models showed a significant effect of diagnosis, where EOAD had higher NPI-Q total, anxiety, motor disturbances and night-time behavior scores (p<0.05). No differences between amnestics/non-amnestics were found. Argyrophilic grain disease co-pathology predicted a higher severity of NPI-Q scores in LOAD. Anxiety, night-time behaviors and motor disturbances are more severe in EOAD than LOAD across the disease course. The differential patterns of neuropsychiatric symptoms observed between EOAD/LOAD could suggest a pattern of selective vulnerability extending to the brain's subcortical structures. Further, co-pathologies such as argyrophilic grain disease in LOAD may also play a role in increasing neuropsychiatric symptoms.

Neuropsychiatric symptoms and mortality among patients with mild cognitive impairment and dementia due to Alzheimer's disease

Neuropsychiatric symptoms (NPS) could increase mortality risk in people with dementia due to Alzheimer's disease (AD). However, whether NPS affects mortality risk in people with mild cognitive impairment (MCI) and whether any specific syndrome of NPS influences this risk are still unclear. In total, 984 participants with dementia due to AD, 338 with MCI, and 365 controls were enrolled. Over a mean of 5-year follow-up, cause of death data were obtained from the Ministry of Health and Welfare in Taiwan. NPS were assessed using Neuropsychiatric Inventory Questionnaire (NPI-Q), and psychosis, mood, and frontal domain scores were determined. Survival analyses were conducted to determine the hazard ratio (HR) of death. In controlled analyses, HR of death for AD was 2.19 (95% confidence interval [CI]=1.29-3.71) compared with the control group, whereas no statistical significance was noted for the MCI group. A high NPI-Q score (above the median score) increased mortality risk for both the MCI and AD groups, with HRs of 2.32 (95% CI=1.07-5.03) and 2.60 (95% CI=1.51-4.47), respectively. Among NPI-Q domain scores, only high mood domain, but not psychosis or frontal domain, scores increased death risk for both the MCI (HR=2.89, 95% CI=1.00-8.51) and AD (HR=2.59, 95% CI=1.47-4.55) groups. Mortality risk is high for patients with AD. Not only for AD, patients with MCI presenting with NPS, particularly mood symptoms, have high death risk.

Abdominal acupoint thread embedding therapy based on "brain-intestinal connection" for mild-to-moderate Alzheimer's disease and its effects on serum levels of APP and Aβ1-42

To compare the clinical efficacy of abdominal acupoint thread embedding therapy based on "brain-intestinal connection" combined with donepezil hydrochloride tablets and oral donepezil hydrochloride tablets alone for mild-to-moderate Alzheimer's disease (AD) and observe its effects on amyloid precursor protein (APP) and β-amyloid protein1-42 (Aβ1-42). Sixty patients with AD were randomly divided into an observation group (30 cases, 3 cases dropped off) and a control group (30 cases, 3 cases dropped off). The patients in the control group were treated with donepezil hydrochloride tablets (5 mg per day); based on the treatment in the control group, the patients in the observation group were treated with abdominal acupoint thread embedding therapy at Zhongwan (CV 12), Xiawan (CV 10), Huaroumen (ST 24), Wailing (ST 26), Daheng (SP 15), etc., once every 10 days. Both groups were treated for 2 months. The mini-mental state examination (MMSE), Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog), activity of daily living scale (ADL), neuropsychiatric inventory questionnaire (NPI) as well as the serum levels of APP and Aβ1-42 were observed before and after treatment in the two groups. After treatment, the MMSE scores in the two groups were higher than those before treatment (P<0.05), and the ADAS-Cog, ADL and NPI scores were lower than those before treatment (P<0.05). After treatment, the MMSE score in the observation group was higher than that in the control group (P<0.05), and the ADAS-Cog, ADL and NPI scores were lower than those in the control group (P<0.05). After treatment, the serum levels of APP and Aβ1-42 were lower than those before treatment (P<0.05), and the serum levels of APP and Aβ1-42 in the observation group was lower than those in the control group (P<0.05). The abdominal acupoint thread embedding therapy based on the theory of "brain-intestinal connection" combined with donepezil hydrochloride tablets can improve cognitive function, self-care ability of daily life and mental behavior, and reduce the serum levels of APP and Aβ1-42 in patients with mild-to-moderate AD, which have superior clinical effect to donepezil hydrochloride tablets alone.

A-3 History of Traumatic Brain Injury and the Course of Neuropsychiatric Symptoms among those with Autopsy-Confirmed Alzheimer’s Disease

Abstract Objective We explored the course of neuropsychiatric symptoms (NPS) in autopsy-confirmed Alzheimer’s disease (ad) subjects with and without a history of TBI (TBI+ vs. TBI-), expecting that TBI history may be associated with NPS severity over time. Method Data from 1532 individuals (age 50+) with autopsy-confirmed ad were obtained from the National Alzheimer’s Coordinating Center (Mean visits = 3.69). Those with other tau pathology and significant Lewy pathology were removed. Neuropsychiatric Inventory Questionnaire (NPI-Q) and the 15-item Geriatric Depression Scale (GDS) scores were used to examine NPS. Multilevel zero-inflated binomial regression models assessed if NPS severity differed between TBI+ (N = 154) and TBI- (N = 1378) groups over time. Covariates included: years from baseline visit, demographics, MMSE, Functional Activities Questionnaire score, and psychotropic treatment. Results The groups did not differ at baseline in NPI-Q (p = 0.36) or GDS (p = 0.07) scores. NPI-Q scores mildly decreased in the TBI+ group (trend = −0.03), whereas the TBI- group remained stable over time (trend = 0.001), 95% CI for the trend [0.01, 0.07]. GDS scores increased more rapidly in the TBI+ group (trend = 0.08) than the TBI- group (trend = 0.02), 95% CI for the trend [0.02, 0.10]. Conclusions This preliminary study suggests that NPS course in ad may differ depending on TBI history, though effect sizes were small. Over the course of ad, individuals with a history of TBI may experience less NPS overall (as measured by NPI-Q scores) but may experience marginally more depressive symptoms (as measured by GDS scores). Future investigations evaluating the relationship between TBI and the course of neurodegenerative disease are needed.

A-1 Neuropsychiatric Symptoms over Time in Autopsy-Confirmed Alzheimer’s Disease, Lewy Body Disease, and Mixed Pathology

Abstract Objective Neuropsychiatric symptoms (NPS) are common in neurodegenerative disease, but longitudinal studies using large autopsy-confirmed samples are lacking. Our primary aim was to investigate progression of NPS over time in autopsy-confirmed Alzheimer’s disease (ad), Lewy body disease (LBD), and mixed (ad+LBD) cohorts. Methods Data on individuals (age &amp;gt; =50) with autopsy-confirmed ad (N = 1568), ad+LBD (N = 349), and LBD (N = 142) was obtained from the National Alzheimer’s Coordinating Center (Mean visits = 2.61). Neuropsychiatric Inventory Questionnaire (NPI-Q) and 15-item Geriatric Depression Scale (GDS) scores were used to measure NPS. Multilevel zero-inflated binomial regression models were used to assess if NPI-Q and GDS scores differed among ad, ad+LBD, and LBD groups over time. Covariates included: years from baseline to final visit, cognitive status at baseline (i.e., normal, MCI, or dementia), demographic characteristics, MMSE, Functional Activities Questionnaire, and psychotropic treatment of psychiatric conditions. Results Higher NPI-Q and GDS scores were observed at baseline in the LBD group compared to ad (p’s &amp;lt; 0.001). NPI-Q scores increased over time in the LBD group compared to ad+LBD and ad groups (90% CI). GDS scores differed among all groups at baseline (95% CI), with more rapid increase in the LBD group vs. ad and ad+LBD groups. Conclusions Overall, the course of NPS differs among disease pathologies. Those with pure LBD appear to have more severe NPS over time compared to those with ad and ad+LBD. Depressive symptoms increased more in LBD and ad+LBD compared to ad over time. Future research examining clinical outcomes related to NPS burden (care needs, caregiver burden, and life expectancy) is needed.

Neurobehavioral Characteristics of FDG-PET Defined Right-Dominant Semantic Dementia: A Longitudinal Study

Introduction: Semantic dementia (SD) is characterized by fluent speech, anomia, and loss of word and object knowledge with varying degrees of right and left anterior-medial temporal lobe hypometabolism on [¹⁸F] fluorodeoxyglucose (FDG)-PET. We assessed neurobehavioral features in SD patients across 3 FDG-PET-defined metabolic patterns and investigated progression over time. Methods: Thirty-four patients with SD who completed FDG-PET were classified into a left- and right-dominant group based on the degree of hypometabolism in each temporal lobe. The left-dominant group was further subdivided depending on whether hypometabolism in the right temporal lobe was more or less than 2 standard deviations from controls (left+ group). Neurobehavioral characteristics determined using the Neuropsychiatric Inventory Questionnaire (NPI-Q) were compared across groups. Progression of NPI-Q scores and FDG-PET hypometabolism was assessed in 14 patients with longitudinal follow-up. Results: The right-dominant group performed worse on the NPI-Q and had a greater frequency of abnormal behaviors and more severe disinhibition compared to the left-dominant group. Performance on the NPI-Q and severity of disinhibition correlated with right medial and lateral, but not left, temporal lobe hypometabolism. Severity of abnormal behaviors worsened over time in most left-dominant and left+ patients but appeared to improve in the 2 right-dominant patients with longitudinal follow-up. All groups showed progressive worsening of metabolism in both temporal lobes over time, with hypometabolism spreading from anteromedial to posterior temporal regions. However, the degree of temporal lobe asymmetry remained relatively constant over time. Conclusion: In SD, neurobehavioral features, especially disinhibition, are associated with right medial and lateral temporal lobe hypometabolism and commonly develop over time even in patients that present with left-dominant patterns of hypometabolism.

Assessment and Documentation of Neuropsychiatric Symptoms in Hospitalized Patients with Dementia

<h3>Introduction</h3> Nursing assessment and documentation of neuropsychiatric symptoms (NPS) for patients with dementia are critical processes for symptom management, treatment and discharge planning. Lack of standardization and inadequate documentation may lead to poor symptom management, prolonged hospitalization, or denial of admission to care facilities following discharge. Nursing observations may become buried in the progress notes, which can make it difficult to provide appropriate clinical management. The purpose of this quality improvement (QI) project was to improve clinical management of dementia, by implementing an evidence-based protocol for standardized assessment and documentation of NPS, using the Neuropsychiatric Inventory-Questionnaire (NPI-Q). <h3>Methods</h3> This QI project was implemented over 12 weeks in late 2020 on a 14-bed inpatient behavioral health unit (BHU) with an average daily census of 1-2 patients with dementia. During the baseline phase (weeks 1-3), the clinical site representative (CSR) accessed Epic, the electronic health record, to capture information needed to anticipate staffing demands. A core group of nurses (n=9) were trained for proper NPI-Q administration and their competency was documented. During the implementation phase (weeks 4-12), registered nurses administered the NPI-Q at admission, discharge, and 3 times per week (Monday, Wednesday and Friday) between 4 pm and 5 pm. A paper version of the NPI-Q was used due to delays in programming the instrument into Epic. The CSR captured data for analysis, including age, gender, admission and discharge dates, plus an indication (Yes/No) of whether the NPI-Q was administered on admission and discharge and on each M-W-F during the hospitalization. These data were used to determine adherence to the protocol (whether each person with dementia received the prescribed number of NPI-Q assessments per hospitalization) and patient outcomes (improvements in NPI-Q total and domain scores from admission to discharge). <h3>Results</h3> During implementation weeks 4-12, only eight patients with dementia were admitted to the inpatient behavioral health unit. The average age of these patient was 73 years (range 65 to 85 years); gender was equally distributed. Their average length-of-stay was 7 days (range 1 to 12 days). Of these patients, 86% were assessed using the NPI-Q at admission, and 75% were assessed using the NPI-Q on the day of discharge. Seventy-four percent of patients received the targeted number of NPI-Q during their hospitalization. Additionally, 71% of patients who received both admission and discharge NPI-Qs had improved NPI-Q scores at discharge. <h3>Conclusions</h3> Using a structured, validated instrument is likely to improve assessment and documentation of NPS among patients with dementia in an inpatient BHU. Although the number of assessed patients was small, it appears that this practice change was well accepted by nurses, is sustainable, and may improve quality of care, as evidenced by improved NPI-Q scores from admission to discharge. <h3>Funding</h3> Not applicable.

Behavioural symptoms in Alzheimer’s disease are associated with white matter lesions (WML) volume and are independent of atrophy and hypometabolism

AbstractBackgroundBehavioral and psychological symptoms of dementia (BPSD) are highly prevalent in Alzheimer’s disease (AD) and associated with adverse outcomes. There is increasing interest in identifying the risk factors for developing BPSD among AD patients. However, the pathophysiological mechanisms underlying BPSD remain poorly understood. Here we evaluated whether BPSD are associated with WMLs volume, brain atrophy and brain metabolism in AD subjects.Method130 AD subjects form the Evaluating Liraglutide in Alzheimer's Disease (ELAD) trial (NCT01843075) were enrolled. The presence of BPSD was evaluated with the Neuropsychiatric Inventory Questionnaire (NPI). FLAIR and T1‐weighted imaging were performed on 3T scans. WMLs was determined on FLAIR images using the Lesion Segmentation Tool (LST) in SPM12. Hippocampal and grey matter volumes were estimated using the FreeSurfer analysis on T1 MRI. Glucose metabolism (rCMRGlc) was calculated by parametric images generated using spectral analysis with an arterial plasma input function.ResultIn this AD population, NPI scores were correlated with WMLs volume (Spearman's rho=.197, p=.02), also after correcting for age. NPI scores were not correlated to hippocampal or grey matter volume and to rCMRGlc in frontal, temporal, parietal or occipital lobes. When looking at the NPI sub‐scores, WMLs volume was significantly associated with agitation/aggression (Spearman's rho=.177, p=.05) and with appetite and eating disorders (Spearman's rho=.233, p=.00).ConclusionIn this study of a clinical AD population, BPSD were associated with WMLs but not with brain atrophy and hypometabolism. This suggests that vascular changes and the prevention of vascular risk factors might play an important role in reducing the impact of BPSD in AD dementia.

Neuropsychiatric Symptoms as a Reliable Phenomenology of Cerebellar Ataxia.

While cerebellar ataxia (CA) is a neurodegenerative disease known for motor impairment, changes in mood have also been reported. A full account of neuropsychiatric symptomology in CA may guide improvements in treatment regimes, measure the presence and severity of sub-clinical neuropsychiatric disturbance symptomology in CA, and compare patient versus informant symptom recognition. Neuropsychiatric phenomena were gathered from CA patients with genetic and unknown etiologies and their informants (e.g., spouse or parent). Information was obtained from in-person interviews and the Center for Epidemiologic Studies Depression Scale. Responses were converted to the Neuropsychiatric Inventory-Questionnaire (NPI-Q) scores by consensus ratings. Patient NPI-Q scores were evaluated for symptom prevalence and severity relative to those obtained from healthy controls. Patient-informant NPI-Q score disagreements were evaluated. In this cohort, 95% of patients presented with at least one neuropsychiatric symptom and 51% of patients with three or more symptoms. The most common symptoms were anxiety, depression, nighttime behaviors (e.g., interrupted sleep), irritability, disinhibition, abnormal appetite, and agitation. The prevalence of these neuropsychiatric symptoms was uniform across patients with genetic versus unknown etiologies. Patient and informant symptom report disagreements reflected that patients noted sleep impairment and depression, while informants noted irritability and agitation. Neuropsychiatric disturbance is highly prevalent in patients with CA and contributes to the phenomenology of CA, regardless of etiology. Clinicians should monitor psychiatric health in their CA patients, considering that supplemental information from informants can help gauge the impact on family members and caregivers.

Assessment of neuropsychiatric symptoms in dementia: validity and reliability of the Lebanese version of the neuropsychiatric inventory questionnaire

This study aims to examine the psychometric properties of an Arabic version of the Neuropsychiatric Inventory Questionnaire (NPI-Q) that evaluates neuropsychiatric symptoms in patients with dementia. A cross-sectional study was carried out with a sample of 136 Lebanese demented patients aged 63–98 years. NPI-Q was completed by the patients’ primary caregiver and standard NPI was administered through personal interview by an experienced research assistant to the same caregiver. The internal consistencies of the Arabic NPI-Q total and distress scale were 0.680 and 0.684 respectively. One week test-retest reliability of the total NPI-Q and distress scores were 0.991 and 0.988 respectively (p-value <0.0001 for both). The NPI-Q correlated significantly with the standard NPI in individual and total symptom scores as well as caregiver distress scores. Exploratory factor analysis extracted five factors that explained 64.7% of variances. The prevalence of analogous symptoms reported on the NPI and NPI-Q differed on average by 3% while moderate or severe symptom ratings differed on average by 1%. The Arabic version of the NPI-Q showed evidence of good psychometric properties indicating that it is a suitable tool for the routine assessment of neuropsychiatric symptoms for Lebanese patients with dementia in clinical settings.

Responder Analysis of a Multicomponent Non-Pharmacological Intervention (MAKS) for People With Cognitive Impairment in the German Day-Care Study (DeTaMAKS).

Background: Multicomponent non-pharmacological therapies have been shown to be effective at reducing cognitive symptoms and slowing deterioration in abilities to perform activities of daily living (ADL) in individuals with cognitive impairment. However, little is known about response rates and predictors of response. Methods: We used data from the German day-care study (DeTaMAKS; De = dementia, Ta = Tagespflege/day-care, M = motor stimulation, A = activities of daily living stimulation, K = k/cognitive stimulation, S = social stimulation; n = 362), which was based on a cluster-randomized trial of the non-pharmacological, multicomponent, anti-dementia MAKS therapy for people with cognitive impairment in day-care centers. We investigated response (defined as improvement or no deterioration) for three different response criteria: cognition via Mini-Mental State Examination (MMSE) score, ADL via Erlangen Test of Activities of Daily Living in Persons with Mild Dementia or Mild Cognitive Impairment (ETAM) score, and behavioral and psychological symptoms of dementia (BPSD) via Neuropsychiatric Inventory Questionnaire (NPI-Q) score. In addition, we calculated the number needed to treat (NTT) and response rates according to net gain analyses. Results: For all three criteria, the response rates were higher in the intervention group than in the control group (chi2 test: p = 0.058 to p = 0.003). Compared with non-responders, responders according to cognition had higher ETAM scores (= better ADL abilities) at baseline; responders according to ADL had lower ETAM scores (= poorer ADL abilities) at baseline; and responders according to BPSD had higher NPI-Q scores (= more BPSD) at baseline. Classification rates based on these predictors ranged from 60.6 to 68.3%. Discussion: The response rates to the non-pharmacological MAKS therapy were greater than those reported for anti-dementia drugs. There were only a few differences between responders and non-responders. Because of the low classification rates, these variables had only a small impact on response predictions. Therefore, there are no empirically substantiated selection criteria for the application of MAKS therapy in facilities. Clinical Trial Registration: www.ClinicalTrials.gov, identifier ISRCTN16412551.

Advanced dementia: an integrated homecare programme

ObjectivesWe established an integrated palliative homecare programme for advanced dementia. This study explores patients’ symptoms and quality-of-life and their association with enteral feeding, evaluates the impact of the programme on...

EXAMINING THE IMPACT OF CARDIOVASCULAR RISK FACTORS ON NEUROPSYCHIATRIC SYMPTOMS IN THE PACT-MD STUDY

Introduction Although cardiovascular risk factors (CVRFs) have been identified as important risk factors for both major depression and cognitive decline in later life, their association with neuropsychiatric symptoms (NPS) has not been fully elucidated. Furthermore, CVRFs, particularly hypertension, hypercholesterolemia, and diabetes, may ultimately lead to physical conditions such as small vessel disease known to disrupt cognition, thereby leading to the onset of NPS. Thus, a better understanding of the association between CVRFs and NPS could improve the development of treatments and preventative measures for NPS. Methods Using baseline data from the Prevention of Alzheimer's Dementia with Cognitive Remediation plus Transcranial Direct Current Stimulation (PACt-MD) study, a multi-site intervention study targeting older patients with depression and cognitive decline, we analysed the distribution of CVRFs (Framingham risk scores; Hachinski ischemic score; presence of hypertension, hypercholesterolemia, hyperlipidemia, diabetes, and smoking) in patients with and without NPS as determined by a score of 1 and above or 0 on the Neuropsychiatric Inventory-Questionnaire (NPI-Q). Participants fell into one of the following three diagnosis groups: Mild Cognitive Impairment (MCI) with a lifetime history of major depression (MDD); MCI without MDD; and MDD without MCI. Comparisons of distributions of CVRFs between NPI positive and negative groups were conducted using the non-parametric Mann-Whitney U test at a significance level of Results In a combined sample of 140 participants, there were no significant differences in any CVRF between positive and negative total NPI groups. However, some NPI subscale scores, notably agitation/aggression, anxiety, disinhibition, irritability, and night-time behaviour were significantly associated with increased CVRFs (p Conclusions None of the CVRFs were associated with overall total NPI-Q scores, however, these preliminary analyses suggest that some specific CVRFs were associated with certain NPI-Q subdomains. This suggests that CVRFs contribute to specific NPS domains rather than overall NPS burden. This research was funded by This project has been made possible by Brain Canada through the Canada Brain Research Fund, with the financial support of Health Canada and the Chagnon Family.

Decreased perfusion of the posterior cingulate gyri shown by a cingulate island score is a possible marker of vulnerability to behavioural and psychological symptoms of Alzheimer's disease: a pilot study.

The cingulate island score (CIScore), which indicates the Z-score ratio of the posterior cingulate gyri to the medial occipital area, has been shown to be useful for differentiating dementia with Lewy bodies from Alzheimer's disease (AD). Our aim was to investigate associations between the clinical symptoms of AD and the CIScore as an index of the relative decrease in perfusion of the posterior cingulate gyri that occurs in the early stages of AD. Seventeen patients with early-stage AD and 13 patients with amnesic mild cognitive impairment were examined. Z-score maps of technetium-99m ethyl cysteinate dimer single-photon emission computed tomography images acquired from the patients were converted, and the CIScore was determined by using the easy Z-score imaging system. The relationships between the CIScore and clinical symptom scores were tested. A significant correlation was identified between the CIScore and the Neuropsychiatric Inventory Questionnaire score. No significant correlations were identified between the CIScore and other measures of cognitive function. Based on a CIScore of 0.39, we correctly differentiated patients with and without behavioural and psychological symptoms of dementia (BPSD), with a sensitivity of 72.2% and specificity of 75.0%. Using technetium-99m ethyl cysteinate dimer single-photon emission computed tomography, we observed that decreased posterior cingulate gyri perfusion, relative to the medial occipital area, in prodromal and early AD was closely associated with behavioural and psychological symptoms of dementia. Therefore, our findings suggest that CIScore is not only useful for discriminating dementia with Lewy bodies from AD, but it can also be clinically used as a specific indicator of the vulnerability to behavioural and psychological symptoms of dementia in the early stages of AD.

Psychiatric symptom burden in older people living with HIV with and without cognitive impairment: the UCSF HIV over 60 cohort study

ABSTRACTPsychiatric comorbidities are common in people living with HIV (PLWH) and adversely affect life satisfaction, treatment adherence and disease progression. There are few data to inform the burden of psychiatric symptoms in older PLWH, a rapidly growing demographic in the U.S. We performed a cross-sectional analysis to understand the degree to which symptom burden was associated with cognitive disorders in PLWH over age 60. Participants completed a standardized neuropsychological battery and were assigned cognitive diagnoses using Frascati criteria. We captured psychiatric symptom burden using the Geriatric Depression Scale (GDS) and proxy-informed Neuropsychiatric Inventory-Questionnaire (NPI-Q). Those diagnosed with HIV-associated neurocognitive disorders (HAND, n = 39) were similar to those without HAND (n = 35) by age (median = 67 years for each group, p = 0.696), education (mean = 16 years vs. 17 years, p = 0.096), CD4+ T-lymphocyte counts (mean = 520 vs. 579, p = 0.240), duration of HIV (median = 21 years for each group, p = 0.911) and sex (92% male in HAND vs. 97% in non-HAND, p = 0.617). Our findings showed similarities in HAND and non-HAND groups on both NPI-Q (items and clusters) and GDS scores. However, there was a greater overall symptom burden in HIV compared to healthy elder controls (n = 236, p < 0.05), with more frequent agitation, depression, anxiety, apathy, irritability and nighttime behavior disturbances (p < 0.05). Our findings demonstrate no differences in psychiatric comorbidity by HAND status in older HIV participants; but confirm a substantial neurobehavioral burden in this older HIV-infected population.

The Role of Cerebrovascular Disease on Cognitive and Functional Status and Psychosis in Severe Alzheimer's Disease.

Background: The pathophysiology behind psychosis in patients with Alzheimer’s disease (AD) remains unknown. Recently, vascular risk factors have been recognized as important modifiers of the clinical presentation of AD.Objective: The purpose of our study is to investigate the mechanism through which vascular risk factors mediate psychosis and whether or not it involves cerebrovascular lesions.Methods: Data was provided by the National Alzheimer’s Coordinating Centre. The Uniform Data Set was used to collect information on subject-reported history of vascular risk factors, clinician-reported state of cognitive performance, and presence of psychosis based on the Neuropsychiatric Inventory Questionnaire (NPI-Q). The Neuropathology Data Set was used to evaluate the presence of vascular lesions and the severity of AD pathology. Subjects with high probability of AD based on the NIA/AA Reagan criteria were included in the analysis.Results: We identified 1,459 patients with high probability of AD and corresponding NPI-Q scores. We confirmed the association between hypertension and diabetes on psychosis, specifically in delusions and the co-occurrence of delusions and hallucinations. Furthermore, the presence of white matter rarefaction based on pathological evaluation was associated with hallucinations. A history of vascular risk factors was positively associated with vascular lesions. However, vascular lesions in the presence of vascular risk factors did not increase the likelihood of psychosis. Furthermore, vascular lesions were not associated with greater cognitive or functional impairments in this group with severe AD pathology.Conclusion: Vascular risk factors and vascular lesions are independently associated with psychosis in patients with severe AD. However, vascular lesions are not the mechanism through which vascular risk factors mediate psychosis.

Efficacy of memantine on neuropsychiatric symptoms associated with the severity of behavioral variant frontotemporal dementia: A six-month, open-label, self-controlled clinical trial

Previous studies have focused on the curative effects of memantine in patients with mild-to-moderate frontotemporal lobar degeneration (FTLD); however, its benefits in patients with moderate-to-severe FTLD have not been investigated. The present study explores the behavioral, cognitive and functional effects of memantine on behavioral variant frontotemporal dementia (bvFTD) in patients with mild and moderate-to-severe stage bvFTD. A total of 42 patients with bvFTD completed a 6-month treatment plan of 20 mg memantine daily in an open-label, self-controlled clinical trial. Patients were divided into two groups according to their Mini-Mental State Examination (MMSE) score: Mild (score, 21-26); and moderate-to-severe (score, 4-20). Primary endpoints included Neuropsychiatric Inventory Questionnaire (NPI-Q) and Clinic Dementia Rating (CDR) scores, and secondary endpoints comprised Neuropsychiatric Inventory Caregiver Distress Scale (NPI-D), MMSE, Montreal Cognitive Assessment (MoCA), Activity of Daily Life (ADL) and Hamilton Depression Rating Scale (HAMD) scores. Memantine treatment had no effect on overall NPI-Q scores, with the exception of the agitation subdomain in all patients with bvFTD. However, patients with moderate-to-severe bvFTD exhibited a better performance than patients with mild bvFTD, demonstrated by improved NPI-Q total scores and subscales of agitation, depression, apathy and disinhibition. In the moderate-to-severe group, CDR and HAMD scores remained stable, but MMSE, MoCA and ADL scores were reduced after 6 months of treatment. Memantine was well-tolerated in patients. In conclusion, patients with moderate-to-severe bvFTD responded significantly better to memantine in comparison to patients with mild bvFTD with regard to their neuropsychiatric scores, while memantine did not present any cognitive or functional benefits in patients with mild bvFTD. A randomized, double-blind, placebo-controlled clinical trial with a larger number of patients is required to verify these promising results for patients with moderate-to-severe bvFTD.

Mood Changes in Cognitively Normal Older Adults are Linked to Alzheimer Disease Biomarker Levels

To evaluate whether cerebrospinal fluid (CSF) and PET Pittsburgh Compound B (PiB) biomarkers of underlying Alzheimer disease (AD) pathology (β-amyloid42 [Aβ42], tau, phosphorylated tau181 [ptau181], tau/Aβ42, ptau181/Aβ42 and mean cortical binding potential [MCBP] for PET-PiB) predict changes in mood in cognitively normal older adults. Knight Alzheimer's Disease Research Center (ADRC) at Washington University (WU). Participants, 65 years of age or older, were enrolled from longitudinal studies at the WU Knight ADRC. CSF, PET-PiB biomarkers, Clinical Dementia Rating (CDR), Mini-Mental State Examination (MMSE), Profile of Mood States-Short Form (POMS-SF), the Geriatric Depression Scale (GDS), and Neuropsychiatric Inventory Questionnaire (NPI-Q). Data from 118 participants at baseline and 66 participants at one-year follow-up were analyzed. CSF and PET biomarkers were not associated cross-sectionally with any mood disturbances at baseline (p > 0.05). Changes in mood as indicated by the total mood disturbance score on the POMS-SF, selected POMS-SF subscales, GDS, and NPI-Q scores from baseline to one-year follow-up were associated with (p < 0.05) CSF and PET-PiB biomarkers. There was no statistically significant decline in cognitive functioning. Generally, higher values of CSF and PET-PiB biomarkers are associated with more changes in mood in cognitively normal older adults. Further work is needed to understand the temporal development of mood changes over several years during the phase of preclinical AD. Evaluating mood as a noncognitive outcome may provide further insight into the development of preclinical AD in cognitively normal older adults.

Cognitive and Functional Correlates of NPI-Q Scores and Symptom Clusters in Mildly Demented Alzheimer Patients.

Previous research has demonstrated an association between the emotional and behavioral symptoms of dementia, known as neuropsychiatric symptoms, and cognitive and functional decline among patients with Alzheimer disease (AD). The present study aimed to identify associations between neuropsychiatric symptoms as measured by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) and cognitive and functional performance. Participants were 256 AD patients enrolled in the Alzheimer's Disease and Memory Disorders Center at Baylor College of Medicine. An exploratory factor analysis of the NPI-Q indicated a 2-factor structure consisting of Negative/Oppositional and Anxiety/Restlessness factors. Regression analyses revealed significant associations between greater total severity of neuropsychiatric symptoms and poorer performance on basic and Instrumental Activities of Daily Living. Greater severity of Anxiety/Restlessness symptoms was associated with poor performance on measures of visuospatial functioning and basic and instrumental activities of daily living. The Negative/Oppositional factor was not related to cognition or functioning. In summary, neuropsychiatric symptoms (particularly Anxiety/Restlessness symptoms) were related to cognition and everyday functioning. Proper assessment and treatment of these symptoms is essential for improving cognition and functioning in AD patients.