Neuropsychiatric Inventory Questionnaire Scores Research Articles

A - 109 Neuropsychiatric Inventory Questionnaire Subfactors and Cognition in Parkinson’s Disease

Abstract Objective Patients with Parkinson’s disease (PD) commonly experience neuropsychiatric symptoms, often garnered through informant interview, that may be associated with poorer cognitive functioning. Recently, the Neuropsychiatric Inventory Questionnaire (NPI-Q) was found to have three factors with differential association to cognition in patients with PD. We sought to further examine this relationship in those with the condition. Method A sample of 42 patients with PD were seen for neuropsychological evaluation (85.7% male, 97.6% White, mean age 70.88 [SD = 7.16], mean years education 15.74 [SD = 2.99]). A knowledgeable informant completed the NPI-Q. Spearman correlations examined relationships between cognition (Digit Span, BVMT-R, CVLT-3, BNT-2, D-KEFS Color-Word Interference, COWAT, Animal Fluency, Trail Making Test), NPI-Q Total Severity, and severity for three factors (Mood [depression, anxiety, apathy, motor, nighttime behaviors, eating]; Hyperactivity [mania, aggression/agitation, disinhibition, irritability]; Psychotic Symptoms [delusions, hallucinations]). Results NPI-Q total severity was generally low (mean = 3.90, SD = 5.12). Total severity and severity of Mood and Hyperactivity were unrelated to cognition. More severe Psychotic Symptoms were related to worse Digit Span (r = −0.41, p = 0.008), BVMT-R Learning (r = −0.33, p = 0.03) and Delayed Recall (r = −0.34, p = 0.03), and D-KEFS Inhibition Time (r = 0.44, p = 0.006). Conclusions In a modest sample of patients with PD, severity of psychotic symptoms was related to worse auditory attention/working memory, visual learning and memory, and inhibition. No other NPI-Q score was associated with cognitive functioning. Findings support the utility of the NPI-Q in PD and the importance of considering specific neuropsychiatric factors and their implications for cognitive functioning.

Shoulder joint range of Motion related to Dementia.

Dementia is caused by various diseases, including Alzheimer's disease dementia (ADD) and Dementia with Lewy bodies (DLB). We often encounter patients with dementia who have limited shoulder joint range of motion (ROM), especially those with behavioral and psychological symptoms of dementia (BPSD). But the relationship between the diseases of dementia and restricted shoulder joint ROM is currently unclear. We examined cognitive function and shoulder joint ROM in 234 new outpatients at 7 memory clinics in Japan. We assessed cognitive function using the Mini-Mental State Examination (MMSE) and Revised Hasegawa Dementia Scale (HDS-R), and BPSD using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Patients were categorized by dementia diagnosis (ADD, DLB, other dementia, and control). Right, left, and total shoulder joint ROM was assessed using validated the Japanese Orthopaedic Association (JOA) score. We found significant associations of lower right, left, and total shoulder joint ROM scores with male sex, advanced age, higher NPI-Q score, lower HDS-R and MMSE scores. Little difference was found between right and left shoulder joint ROM scores. Restricted shoulder joint ROM was related to serial 7, verbal frequency domain scores on the HDS-R and repeat score on the MMSE. It was also related to the hallucinations, irritability/lability and nighttime disturbances scores on the NPI-Q. Furthermore, the dementia groups, especially the DLB group, showed worse shoulder joint ROM than the control group. Dementia was significantly related to restricted shoulder joint ROM. Maintaining communication and social interaction may help to maintain shoulder joint ROM.

CAPS: a simple clinical tool for β-amyloid positivity prediction in clinical Alzheimer syndrome.

With the advent of anti-β-amyloid therapies, clinical distinction between Aβ + and Aβ- in cognitive impairment is becoming increasingly important for stratifying referral and better utilization of biomarker assays. Cognitive profile, rate of decline, neuropsychiatric inventory questionnaire (NPI-Q), and imaging characteristics were collected from 52 subjects with possible/probable AD. Participants with Aβ+ status had lower baseline MMSE scores (24.50 vs. 26.85, p = 0.009) and higher total NPI-Q scores (2.73 vs. 1.18, p < 0.001). NPI-Q score was found to be the only independent predictor for β-amyloid positivity (p = 0.008). A simple scoring system, namely Clinical β-Amyloid Positivity Prediction Score (CAPS), was developed by using the following parameters: NPI-Q, rapidity of cognitive decline, and white matter microangiopathy. Data from 48 participants were included in the analysis of accuracy of CAPS. CAP Score of 3 or 4 successfully classified Aβ + individuals in 86.7% cases. Clinical β-Amyloid Positivity Prediction Score is a simple clinical tool for use in primary care and memory clinic settings to predict β-amyloid positivity in individuals with clinical Alzheimer Syndrome can potentially facilitate referral for Anti Aβ therapies.

Plasma Neurofilament Light Relates to Divergent Default and Salience Network Connectivity in Alzheimer's Disease and Behavioral Variant Frontotemporal Dementia.

Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) show differential vulnerability to large-scale brain functional networks. Plasma neurofilament light (NfL), a promising biomarker of neurodegeneration, has been linked in AD patients to glucose metabolism changes in AD-related regions. However, it is unknown whether plasma NfL would be similarly associated with disease-specific functional connectivity changes in AD and bvFTD. Our study examined the associations between plasma NfL and functional connectivity of the default mode and salience networks in patients with AD and bvFTD. Plasma NfL and neuroimaging data from patients with bvFTD (n = 16) and AD or mild cognitive impairment (n = 38; AD + MCI) were analyzed. Seed-based functional connectivity maps of key regions within the default mode and salience networks were obtained and associated with plasma NfL in these patients. We demonstrated divergent associations between NfL and functional connectivity in AD + MCI and bvFTD patients. Specifically, AD + MCI patients showed lower default mode network functional connectivity with higher plasma NfL, while bvFTD patients showed lower salience network functional connectivity with higher plasma NfL. Further, lower NfL-related default mode network connectivity in AD + MCI patients was associated with lower Montreal Cognitive Assessment scores and higher Clinical Dementia Rating sum-of-boxes scores, although NfL-related salience network connectivity in bvFTD patients was not associated with Neuropsychiatric Inventory Questionnaire scores. Our findings indicate that plasma NfL is differentially associated with brain functional connectivity changes in AD and bvFTD.

P.002 Distinct neuropsychiatric symptom trajectories in frontotemporal dementia across genetic mutations

Background: Frontotemporal dementia (FTD) often presents with varying neuropsychiatric symptoms (NPS), which may differ based on genetic mutations. We hypothesized distinct NPS trajectories in FTD progression among carriers of chromosome 9 open reading frame 72 (C9orf72), progranulin (GRN), and microtubule-associated protein tau (MAPT) mutations. Methods: We analyzed 1662 participants from ALLFTD, including 342 C9orf72, 148 GRN, 168 MAPT mutation carriers, and 1004 noncarriers. We categorized participants into four stages based on CDR plus NACC FTLD global scores: 1) Presymptomatic (consistent CDR=0), 2) Early conversion (CDR increasing from 0 to 0.5), 3) Advanced conversion (CDR increasing from 0.5 to ≥1.0), and 4) Symptomatic (CDR&gt;1.0). The Neuropsychiatric Inventory-Questionnaire (NPI-Q) assessed NPS changes, analyzed using a mixed-effects model, accounting for age and baseline scores. Results: Our results indicated similar NPS trajectories in the presymptomatic stage for all groups. Notably, during early conversion, C9orf72 and GRN carriers exhibited significantly higher NPI-Q score increases than MAPT carriers, primarily in psychosis and hyperactivity domains. In later stages, increases in NPS were similar across groups. Conclusions: This study suggests familial FTD progression, particularly in TDP-43 pathology, may involve more severe NPS like psychosis or hyperactivity, differing from tau pathology or sporadic FTD. Further research is needed to explore these distinct trajectories.

Delirium in acute stroke is associated with increased cognitive and psychiatric symptoms over time: The Nor-COAST study

BackgroundDelirium, an acute and fluctuating mental disturbance of attention, cognition, and consciousness, commonly occurs in acute stroke. Research on long-term outcomes of stroke patients experiencing delirium is limited, especially regarding cognitive and psychiatric symptoms. MethodsAs part of the Nor-COAST study, 373 patients were screened for delirium using the Confusion Assessment Method (CAM) in the acute phase of stroke. Patients were included in the mixed-model linear regression analyses if they had available data from the follow-ups at three, 18 or 36 months, totaling 334 (44.6 % women, mean (SD) age: 72.1 (12.5) years, 17 (5.1 %) diagnosed with delirium). Global cognition was measured using the Montreal Cognitive Assessment (MoCA). Psychiatric symptoms were measured using the Hospital Anxiety and Depression Scale (HADS) and the Neuropsychiatric Inventory-Questionnaire (NPI-Q). ResultsAt three months, delirium was associated with a higher NPI-Q score (Mean (SD) 2.9 (3.6) vs 1.4 (2.2)). At 18 and 36 months, delirium was associated with a lower MoCA score (Mean (SD) 19.7 (6.6) vs 24.3 (5.0), and 20.6 (7.6) vs 24.6 (4.8)), higher HADS anxiety symptoms (5.0 (4.3) vs 3.3 (3.3), and 5.9 (4.1) vs 3.4 (3.6)), higher HADS depression symptoms (7.2 (4.7) vs 3.4 (3.3), and 6.6 (5.1) vs 3.7 (3.7)), and higher NPI-Q score (2.4 (4.4) vs 1.7 (2.3), 2.6 (4.5) vs 1.0 (1.9)). Delirium significantly predicted the psychiatric symptoms hallucinations and agitation. ConclusionsPatients with delirium in the acute phase of stroke may be particularly vulnerable to developing cognitive and psychiatric symptoms in the chronic phase.

Home-based family caregiver-delivered music and reading interventions for people living with dementia (HOMESIDE trial): an international randomised controlled trial

Music interventions provided by qualified therapists within residential aged care are effective at attenuating behavioural and psychological symptoms (BPSD) of people with dementia (PwD). The impact of music interventions on dementia symptom management when provided by family caregivers is unclear. We implemented a community-based, large, pragmatic, international, superiority, single-masked randomised controlled trial to evaluate if caregiver-delivered music was superior to usual care alone (UC) on reducing BPSD of PwD measured by the Neuropsychiatric Inventory-Questionnaire (NPI-Q). The study included an active control (reading). People with dementia (NPI-Q score ≥6) and their caregiver (dyads) from one of five countries were randomly allocated to caregiver-delivered music, reading, or UC with a 1:1:1 allocation stratified by site. Caregivers received three online protocolised music or reading training sessions delivered by therapists and were recommended to provide five 30-min reading or music activities per week (minimum twice weekly) over 90-days. The NPI-Q severity assessment of PwD was completed online by masked assessors at baseline, 90- (primary) and 180-days post-randomisation and analysed on an intention-to-treat basis using a likelihood-based longitudinal data analysis model. ACTRN12618001799246; ClinicalTrials.govNCT03907748. Between 27th November 2019 and 7th July 2022, we randomised 432 eligible of 805 screened dyads (music n=143, reading n=144, UC n=145). There was no statistical or clinically important difference in the change from baseline BPSD between caregiver-delivered music (-0.15, 95% CI-1.41 to 1.10, p=0.81) or reading (-1.12, 95% CI-2.38 to 0.14, p=0.082) and UC alone at 90-days. No related adverse events occurred. Our findings suggested that music interventions and reading interventions delivered by trained caregivers in community contexts do not decrease enduring BPSD symptoms. Our funding was provided by National Health and Medical Research Council, Australia; The Research Council of Norway; Federal Ministry of Education and Research, Germany; National Centre for Research and Development, Poland; Alzheimer's Society, UK, as part of the Joint Programme for Neurodegenerative Diseases consortia scheme.

Unique contributions of specific neuropsychiatric symptoms to caregiver burden in informal caregivers family members of patients with dementia

ABSTRACT Introduction We aimed to evaluate how the presence of individual neuropsychiatric symptoms in non-institutionalised patients with dementia is associated with caregiver burden of their informal caregivers, family members. Methods We performed a cross-sectional study on a total of 131 pairs of one informal caregiver family member and non-institutionalised patient with dementia in a family medicine practices in a city of Zagreb, Croatia. Caregiver measures included Zarit Burden Interview (ZBI) whereas patient measures included Mini mental state examination (MMSE), Barthel index and Neuropsychiatric Inventory Questionnaire (NPI-Q). Results Total NPI-Q score explained 21% of overall burden. In order of strength of the association, after adjustments for age, sex, MMSE and Barthel index, overall burden was significantly associated with higher NPI-Q scores for agitation/aggression, apathy/indifference, irritability/lability, disinhibition, motor disturbance, appetite/eating, depression/dysphoria, anxiety, elation/euphoria and nighttime behaviours. When evaluating mutually independent contribution of unique NPI-Q symptoms to caregiver burden, agitation/aggression and apathy/indifference remained only two mutually independently associated symptoms, each explaining 5% of overall burden in this context. Conclusions Informal caregivers who provide for family members with dementia suffering from agitation/aggression or apathy/indifference should be recognised as under special risk for the development of caregiver burden and considered as candidates for early targeted interventions.

Contribution of amyloid and putative Lewy body pathologies in neuropsychiatric symptoms.

Neuropsychiatric symptom could be useful for detecting patients with prodromal dementia. Similarities and differences in the NPSs between preclinical/prodromal Alzheimer's disease (AD) and prodromal Parkinson's disease dementia (PDD)/Dementia with Lewy bodies (DLB) may exist. This study aimed to compare the NPSs between preclinical/prodromal AD and prodromal PDD/DLB. One hundred and three participants without dementia aged ≥50years were included in this study. The mild behavioral impairment (MBI) total score and the MBI scores for each domain were calculated using the neuropsychiatric inventory questionnaire score. Participants were divided into five groups based on the clinical diagnosis by neurologists or psychiatrists in each institution based on the results of the amyloid positron emission tomography and dopamine transporter single photon emission computed tomography (DAT-SPECT): Group 1: amyloid-positive and abnormal DAT-SPECT, Group 2: amyloid-negative and abnormal DAT-SPECT, Group 3: amyloid-positive and normal DAT-SPECT, Group 4: mild cognitive impairment unlikely due to AD with normal DAT-SPECT, and Group 5: cognitively normal with amyloid-negative and normal DAT-SPECT. The MBI abnormal perception or thought content scores were significantly higher in Group 1 than Group 5 (Bonferroni-corrected p=0.012). The MBI total score (Bonferroni-corrected p=0.011) and MBI impulse dyscontrol score (Bonferroni-corrected p=0.033) in Group 4 were significantly higher than those in Group 5. The presence of both amyloid and putative Lewy body pathologies may be associated with psychotic symptoms.

Cognitive impairments predict the behavioral and psychological symptoms of dementia.

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

Neuropsychiatric inventory questionnaire scores are predictive of dementia progression

AbstractBackgroundIn ageing adults, the most common form of dementia is Alzheimer’s disease (AD). AD pathogenesis involves the accumulation of beta‐amyloid (Aβ) protein aggregation in plaques and tau proteins in neurofibrillary tangles that are associated with a decreased number of synapses in the brain, altered neuronal function and cell death via neurotoxicity, as well as learning and memory deficits. Clinically, the presence and severity of neuropsychiatric symptoms that AD patients present with can be reliably measured by the Neuropsychiatric Inventory Questionnaire (NPIQ). This study aims to explore the association between baseline mental health and the severity of AD progression.MethodTo measure baseline mental health, NPIQ scores were used while the change in deq was used to represent the severity of AD progression within the TARCC cohort. deq is a homolog of d, a reliable latent dementia proxy that represents cognitive correlates of functional status and is specific for distinguishing cases with AD from other dementia‐related presentations. Most crucially, the deq homolog has been adjusted for equivalence across ethnicities. Using stratified analysis and structured equation models, the association between baseline mental health and change in was investigated.ResultThe first model exploring NPIQ and the change in deq was only adjusted for baseline deq; it showed NPIQ explaining 19% of the variance in delta deq and was statistically significant at p = 0.016 for Non‐Hispanic Whites. With the second model, age, sex, and education were adjusted for in addition to baseline deq. NPIQ was shown to explain 25% of the variance in delta deq while being statistically significant at p = 0.037 for Non‐Hispanic Whites. This model was replicated in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort; NPIQ was shown to be predictive for delta deq at p = 0.013.ConclusionIn Non‐Hispanic Whites, worse baseline mental health has been shown to predict increased severity and progression of AD. This makes it a clinical therapeutic target with the possible benefit of impacting the course of AD in patients. The fascinating interplay between mental health and its relationship to Alzheimer’s disease should be studied further with an additional focus on ethnicity.

MBI‐apathy, ApoEɛ2, and risk for Alzheimer disease dementia

AbstractBackgroundApathy, characterized by decreased interest, initiative, and emotional reactivity, is amongst the most common neuropsychiatric symptoms in dementia. However, apathy can emerge before dementia and constitutes a domain of mild behavioral impairment (MBI), an at‐risk state for incident cognitive decline and dementia. MBI‐apathy is the de novo emergence of persistent apathy in dementia‐free older adults and may be a driving factor in dementia risk conferred by MBI. Apolipoprotein E (ApoE) is a risk marker for Alzheimer disease (AD) dementia. Compared to ApoEɛ3 homozygotes, ApoEɛ2 carriers are 40% less likely to develop AD while ApoEɛ4 carriers are 3.2‐14.9 times more likely. We investigated the association between MBI‐apathy, ApoE, and incident dementia. We hypothesized that ɛ2 would have protective effects for MBI‐apathy associated risk, compared to ɛ3 and ɛ4.MethodDementia‐free participants in the National Alzheimer’s Coordinating Centre were stratified as MBI‐apathy and no‐NPS until dementia diagnosis, based on Neuropsychiatric Inventory Questionnaire scores at 2 consecutive visits. ApoE genotypes were categorized by ɛ2 (ɛ2/ɛ2, ɛ2/ɛ3), ɛ3 (ɛ3/ɛ3), and ɛ4 (ɛ4/ɛ3, ɛ4/ɛ4) alleles. Group characteristics were contrasted to determine covariate inclusion in regression modelling. Cox regressions assessed risk of incident dementia and included an interaction term for MBI‐apathy and ApoE allele.ResultsOf the 3,644 participants (3,022 Normal‐Cognition); 314 had MBI‐apathy (Table 1). Significant main effects were found for MBI‐apathy and incident dementia (HR:2.51, 95% CI:1.99‐3.17, p&lt;0.001) as well as interaction effects with ApoE. In MBI‐apathy (ɛ3 as reference), the ɛ2 group had a 60% lower dementia risk (adjusted HR:0.40, 95% CI:0.19‐0.85) while ɛ4 had a 16% higher risk (adjusted HR:1.16, 95% CI:0.80‐1.69) (Figure 1). Of the 125 participants with apathy who progressed to dementia, 80.8% had AD. In the no‐NPS group (ɛ3 as reference), ɛ2 individuals had a 17% lower dementia risk (adjusted HR:0.83, 95% CI:0.52‐1.33) while ɛ4 individuals had a 177% higher risk (adjusted HR:2.77, 95% CI:2.13‐3.59) (Figure 2).ConclusionTo our knowledge, this is the first study examining the relationship between MBI‐apathy and ApoE status in determining dementia risk. Results suggest that ApoE modifies the association between MBI‐apathy and incident dementia with the ɛ2 allele acting as a protective factor.

Sex as a moderator of the association between frailty and mild behavioral impairment

AbstractBackgroundFrailty and mild behavioral impairment (MBI) are associated with dementia and sex differences are recognized in both. Each can facilitate early detection and treatment. This study investigated the association between frailty and MBI and whether this association is moderated by sex.MethodCross‐sectional data from 219 participants (48.9% female; mean and SD of age = 72.2 ± 6.5 years, and education = 15.8 ± 3.5 years) from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS‐ND) study was analyzed. No participants had dementia: 58 (26.5%) were cognitively normal and 161 (73.5%) had mild cognitive impairment. Frailty was measured using the frailty index (FI); higher scores indicate more health deficits/greater frailty. MBI symptoms were derived from Neuropsychiatric Inventory Questionnaire scores using a published algorithm with a cut‐off of &gt;0 indicating MBI symptom presence. As with the FI, greater MBI severity was indicated by higher scores. Multivariable logistic and linear regressions adjusted for age, sex, education, and cognitive diagnosis were used to test the association between FI and MBI symptom presence and severity, respectively, with MBI as the outcome variable. An FI‐by‐sex interaction term was included in the linear regression model to test for sex‐dependent effects.ResultThe FI mean and SD across the entire cohort was 0.14 ± 0.06 (median = 0.14, IQR = 0.09–0.17, range = 0.02–0.38). Approximately half (51.6%) showed MBI symptoms (mean and SD of severity = 1.8 ± 2.7). Higher FI scores were associated with the presence of MBI symptoms both globally and in the domains of decreased motivation, affective dysregulation, and psychosis (Table 1). Higher FI scores were also associated with more severe MBI symptoms in a sex‐dependent manner: both sexes reported similarly low MBI symptom severity at low (‐1 SD) levels of FI but males reported 1.9x higher MBI symptom severity relative to females at high (+1 SD) levels of FI (Figure 1).ConclusionThe FI is associated with both the presence and severity of MBI, especially for males. These findings suggest that patients with frailty should be assessed for MBI and that patients with MBI should be assessed for frailty.

Associations between neuropsychiatric symptoms, pathology, and survival in an autopsy-confirmed cohorts of Alzheimer’s disease, Alzheimer’s disease with Lewy bodies and Dementia with Lewy bodies (S39.008)

Associations between neuropsychiatric symptoms, pathology, and survival in an autopsy-confirmed cohorts of Alzheimer’s disease, Alzheimer’s disease with Lewy bodies and Dementia with Lewy bodies (S39.008)

Association Between Cerebrospinal Fluid Biomarkers of Amyloid and Tau and Neuropsychiatric Symptoms Among Participants from the National Alzheimer’s Coordinating Center Uniform Data Set (P10-6.004)

Association Between Cerebrospinal Fluid Biomarkers of Amyloid and Tau and Neuropsychiatric Symptoms Among Participants from the National Alzheimer’s Coordinating Center Uniform Data Set (P10-6.004)

Validation study of the Persian version of behavioral pathology in Alzheimer’s Disease Rating scale (BEHAVE-AD) and the empirical BHAVE-AD (E-BEHAVE-AD)

Introduction Behavioral and psychological symptoms of dementia (BPSD) are observed in more than 90% of patients with Alzheimer’s disease (AD). BPSDs are remediable if detected early and managed appropriately. Behavioral Pathology in Alzheimer’s disease Rating Scale (BEHAVE-AD) and Empirical BEHAVE-AD (E-BEHAVE-AD) were designed to identify BPSD. The aim of this study is to validate and prepare BEHAVE-AD and E-BEHAVE-AD in Persian language for clinical and research applications. Method 120 patients were selected through a combination of intentional and convenience sampling. All participants should fulfill the NINCDS-ADRDA Work Group criteria for a clinical diagnosis of Alzheimer’s disease. Functional Assessment Staging Tool (FAST) was used to determine the rate of AD progression. All patients were evaluated using the BEHAVE-AD and E-BEHAVE-AD questionnaires, as well as the Persian version of the Neuropsychiatric Inventory Questionnaire (NPI-Q) and Mini-Mental State Examination (MMSE). The Content Validity Index (CVI) is determined based on the compatibility of the Persian and the original version of the two scales according to the opinion of expert panels. Correlation of MMSE with BEHAVE-AD and E-BEHAVE-AD as well as the BPSD pattern on AD progression continuum by FAST were considered as indices of construct validity. Concurrent validity was estimated by correlating NPI-Q scores with BEHAVE-AD and E-BEHAVE-AD scores. For both scales, interrater reliability was extracted as a reliability index. Results Pearson correlation coefficients for the BEHAVE-AD scale were as follows: with NPI-Q (r = 0.77, p-value <0.01), with MMSE (r = −0.34, p-value <0.01), indicating concurrent and construct validity, respectively. The result for E-BEHAVE-AD was as follows: with NPI-Q-total (r = 0.59, p-value <0.01), and with MMSE (r = 0.31, p-value <0. 01). BEHAVE-AD and E-BEHAVE-AD scores increased in parallel with AD severity according to FAST, but not on the most severe AD stage. The area under the curve was estimated to be 0.84 (p-value <0.001) for BEHAVE-AD and 0.78 (p-value <0.001) for E-BEHAVE-AD. Correlation between BEHAVE-AD and E-BEHAVE-AD scores ranged from 0.45 to 0.63. The inter-rater reliability index ranged from 0.88 to 0.99 for BEHAVE-AD and from 0.74 to 0.95 for E-BEHAVE-AD. Conclusions The Persian version of BEHAVE-AD and E-BEHAVE-AD is valid and reliable for the assessment of BPSD in patients with AD.

Reducing Behavioral and Psychological Symptoms of Dementia in Acutely Ill Patients via Patient Engagement Specialists: A Pilot Feasibility Study.

Behavioral and psychological symptoms of dementia (BPSD) are common in hospitalized persons living with dementia (PLWD). This pilot aimed to test the feasibility of an innovative model of care, PES-4-BPSD (a dementia unit staffed with Patient Engagement Specialists, PES). Non-randomized pilot feasibility trial was conducted, enrolling N = 158 patients to the intervention unit (n = 79, a 10-bed dementia unit, staffed with nursing assistants, NAs, with mental health backgrounds, PES) and an enhanced control unit (n = 79, 40-bed medicine unit, staffed with NAs). All NAs/PES (N = 63) received dementia training, with completion rate of 82.5%. Overall, patients had ~1 NPI-Q (Neuropsychiatric Inventory Questionnaire) assessment/48 hr. 97% (n = 153) of PLWD exhibited at least one behavior. Average NPI-Q scores did not differ across intervention (5.36) and control (3.87) units (p = .23). Patients on the intervention unit had 88% (p = .002) shorter duration of constant observation. A dementia care unit staffed by PES is an innovative model requiring further research.

Persisting neuropsychiatric symptoms, Alzheimer’s disease, and cerebrospinal fluid cortisol and dehydroepiandrosterone sulfate

IntroductionNeuropsychiatric symptoms are important treatment targets in the management of dementia and can be present at very early clinical stages of neurodegenerative diseases. Increased cortisol has been reported in Alzheimer’s disease (AD) and has been associated with faster cognitive decline. Elevated cortisol output has been observed in relation to perceived stress, depression, and anxiety. Dehydroepiandrosterone sulfate (DHEAS) has known anti-glucocorticoid effects and may counter the effects of cortisol.ObjectivesWe aimed to examine whether CSF cortisol and DHEAS levels were associated with (1) neuropsychiatric symptoms at baseline, (2) changes in neuropsychiatric symptoms over 3 years, and (3) whether these associations were related to or independent of AD pathology.MethodsOne hundred and eighteen participants on a prospective study in a memory clinic setting, including patients with cognitive impairment (n = 78), i.e., mild cognitive impairment or mild dementia, and volunteers with normal cognition (n = 40), were included. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). CSF cortisol and DHEAS, as well as CSF AD biomarkers, were obtained at baseline. Neuropsychiatric symptoms were re-assessed at follow-up visits 18 and 36 months from baseline. We constructed linear regression models to examine the links between baseline neuropsychiatric symptoms, the presence of AD pathology as indicated by CSF biomarkers, and CSF cortisol and DHEAS. We used repeated-measures mixed ANCOVA models to examine the associations between the neuropsychiatric symptoms’ changes over time, baseline CSF cortisol and DHEAS, and AD pathology.ResultsHigher CSF cortisol was associated with higher NPI-Q severity scores at baseline after controlling for covariates including AD pathology status (B = 0.085 [0.027; 0.144], p = 0.027; r = 0.277). In particular, higher CSF cortisol was associated with higher baseline scores of depression/dysphoria, anxiety, and apathy/indifference. Elevated CSF cortisol was also associated with more marked increase in NPI-Q scores over time regardless of AD status (p = 0.036, η2 = 0.207), but this association was no longer significant after controlling for BMI and the use of psychotropic medications. CSF DHEAS was associated neither with NPI-Q scores at baseline nor with their change over time. Cortisol did not mediate the association between baseline NPI-Q and changes in clinical dementia rating sum of boxes over 36 months.ConclusionHigher CSF cortisol may reflect or contribute to more severe neuropsychiatric symptoms at baseline, as well as more pronounced worsening over 3 years, independently of the presence of AD pathology. Our findings also suggest that interventions targeting the HPA axis may be helpful to treat neuropsychiatric symptoms in patients with dementia.

Blood plasma protein profiles of neuropsychiatric symptoms and related cognitive decline in older people.

Neuropsychiatric symptoms (NPS) severely affect patients and their caregivers, and are associated with worse long-term outcomes. This study tested the hypothesis that altered protein levels in blood plasma could serve as biomarkers of NPS; and that altered protein levels are associated with persisting NPS and cognitive decline over time. We performed a cross-sectional and longitudinal study in older subjects with cognitive impairment and cognitively unimpaired in a memory clinic setting. NPS were recorded through the Neuropsychiatric Inventory Questionnaire (NPI-Q) while cognitive and functional impairment was assessed using the clinical dementia rating sum of boxes (CDR-SoB) score at baseline and follow-up visits. Shotgun proteomic analysis based on liquid chromatography-mass spectrometry was conducted in blood plasma samples, identifying 420 proteins. The presence of Alzheimer's Disease (AD) pathology was determined by cerebrospinal fluid biomarkers. Eighty-five subjects with a mean age of 70 (±7.4) years, 62% female and 54% with mild cognitive impairment or mild dementia were included. We found 15 plasma proteins with altered baseline levels in participants with NPS (NPI-Q score > 0). Adding those 15 proteins to a reference model based on clinical data (age, CDR-SoB) significantly improved the prediction of NPS (from receiver operating characteristic area under the curve [AUC] 0.75 to AUC 0.91, p= 0.004) with a specificity of 89% and a sensitivity of 74%. The identified proteins additionally predicted both persisting NPS and cognitive decline at follow-up visits. The observed associations were independent of the presence of AD pathology. Using proteomics, we identified a panel of specific blood proteins associated with current and future NPS, and related cognitive decline in older people. These findings show the potential of untargeted proteomics to identify blood-based biomarkers of pathological alterations relevant for NPS and related clinical disease progression.

Neuropsychiatric Inventory Questionnaire Associated with Cognitive Function, Age, and Duration of Education in Patients with Alzheimer’s Disease

Introduction: Alzheimer’s disease (AD) is the most common cognitive disease, and behavioral and psychological symptoms of dementia (BPSD) can place a heavy burden on families. The presence of these symptoms related to AD is commonly assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). This study sought to clarify the relationship between scores on the 12-domain NPI-Q and individual factors in patients with AD. Methods: Participants were 218 new outpatients with AD at five memory clinics. Cognitive function was assessed using the Revised Hasegawa Dementia Scale (HDS-R) and Mini-Mental State Examination (MMSE). We examined which individual factors were associated with the total NPI-Q score and the number of domains. We also examined which domains were associated with the factors identified. Results: A higher total NPI score was significantly associated with lower scores on both cognitive assessments and a longer duration of education. Exhibiting symptoms on a greater number of domains was significantly associated with lower scores on both cognitive assessments, longer duration of education, and advanced age. The nighttime disturbances domain was significantly associated with lower scores on both cognitive assessments and advanced age. The delusions domain was significantly associated with lower education. Conclusions: BPSD may appear more easily with reduced quality of life and ongoing dissatisfaction. Effective individualized services are important for patients with AD, and therefore, we should account for age, cognitive function, and duration of education in the services provided.