Neuropsychiatric Inventory Scores Research Articles

Choroid plexus volume as a novel candidate neuroimaging marker of the Alzheimer’s continuum

BackgroundEnlarged choroid plexus (ChP) volume has been reported in patients with Alzheimer’s disease (AD) and inversely correlated with cognitive performance. However, its clinical diagnostic and predictive value, and mechanisms by which ChP impacts the AD continuum remain unclear.MethodsThis prospective cohort study enrolled 607 participants [healthy control (HC): 110, mild cognitive impairment (MCI): 269, AD dementia: 228] from the Chinese Imaging, Biomarkers, and Lifestyle study between January 1, 2021, and December 31, 2022. Of the 497 patients on the AD continuum, 138 underwent lumbar puncture for cerebrospinal fluid (CSF) hallmark testing. The relationships between ChP volume and CSF pathological hallmarks (Aβ42, Aβ40, Aβ42/40, tTau, and pTau181), neuropsychological tests [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), and Activities of Daily Living (ADL) scores], and multimodal neuroimaging measures [gray matter volume, cortical thickness, and corrected cerebral blood flow (cCBF)] were analyzed using partial Spearman’s correlation. The mediating effects of four neuroimaging measures [ChP volume, hippocampal volume, lateral ventricular volume (LVV), and entorhinal cortical thickness (ECT)] on the relationship between CSF hallmarks and neuropsychological tests were examined. The ability of the four neuroimaging measures to identify cerebral Aβ42 changes or differentiate among patients with AD dementia, MCI and HCs was determined using receiver operating characteristic analysis, and their associations with neuropsychological test scores at baseline were evaluated by linear regression. Longitudinal associations between the rate of change in the four neuroimaging measures and neuropsychological tests scores were evaluated on the AD continuum using generalized linear mixed-effects models.ResultsThe participants’ mean age was 65.99 ± 8.79 years. Patients with AD dementia exhibited the largest baseline ChP volume than the other groups (P < 0.05). ChP volume enlargement correlated with decreased Aβ42 and Aβ40 levels; lower MMSE and MoCA and higher NPI and ADL scores; and lower volume, cortical thickness, and cCBF in other cognition-related regions (all P < 0.05). ChP volume mediated the association of Aβ42 and Aβ40 levels with MMSE scores (19.08% and 36.57%), and Aβ42 levels mediated the association of ChP volume and MMSE or MoCA scores (39.49% and 34.36%). ChP volume alone better identified cerebral Aβ42 changes than LVV alone (AUC = 0.81 vs. 0.67, P = 0.04) and EC thickness alone (AUC = 0.81 vs.0.63, P = 0.01) and better differentiated patients with MCI from HCs than hippocampal volume alone (AUC = 0.85 vs. 0.81, P = 0.01), and LVV alone (AUC = 0.85 vs.0.82, P = 0.03). Combined ChP and hippocampal volumes significantly increased the ability to differentiate cerebral Aβ42 changes and patients among AD dementia, MCI, and HCs groups compared with hippocampal volume alone (all P < 0.05). After correcting for age, sex, years of education, APOE ε4 status, eTIV, and hippocampal volume, ChP volume was associated with MMSE, MoCA, NPI, and ADL score at baseline, and rapid ChP volume enlargement was associated with faster deterioration in NPI scores with an average follow-up of 10.03 ± 4.45 months (all P < 0.05).ConclusionsChP volume may be a novel neuroimaging marker associated with neurodegenerative changes and clinical AD manifestations. It could better detect the early stages of the AD and predict prognosis, and significantly enhance the differential diagnostic ability of hippocampus on the AD continuum.

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

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

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.

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

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

Temporal tau asymmetry spectrum influences divergent behavior and language patterns in Alzheimer‘s disease

Understanding the psychiatric symptoms of Alzheimer s disease (AD) is crucial for advancing precision medicine and therapeutic strategies. The relationship between AD behavioral symptoms and asymmetry in spatial tau PET patterns is not well-known. Braak tau progression implicates the temporal lobes early. However, the clinical and pathological implications of temporal tau laterality remain unexplored.This cross-sectional study investigated the correlation between temporal tau PET asymmetry and behavior assessed using the neuropsychiatric inventory and composite scores for memory, executive function, and language, using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. In the entire cohort, continuous right and left temporal tau contributions to behavior and cognition were evaluated, controlling for age, sex, education, and tau burden on the contralateral side. Additionally, a temporal tau laterality index was calculated to define “asymmetry-extreme” groups (individuals with laterality indices greater than two standard deviations from the mean).695 individuals (age = 73.9 ± 7.6 years, 372 (53.5 %) females) were included, comprising 281 (40%) cognitively unimpaired (CU) amyloid negative, 185 (27%) CU amyloid positive, and 229 (33%) impaired (CI) amyloid positive participants. In the full cohort analysis, right temporal tau was associated with worse behavior (B = 8.14, p-value = 0.007), and left temporal tau was associated with worse language (B = 1.4, p-value < 0.001). Categorization into asymmetry-extreme groups revealed 20 right- and 27 left-asymmetric participants. Within these extreme groups, there was additional heterogeneity along the anterior-posterior dimension.Asymmetrical tau burden is associated with distinct behavioral and cognitive profiles. Wide multi-cultural implementation of social cognition measures is needed to understand right-sided asymmetry in AD.

Systematic literature review with meta-analysis on essential oil interventions for agitated behavior in dementia patients

Introduction Essential oil treatment has been explored as a potential alternative medicine, as these therapies can induce calming and sedative effects by acting on the neuro-limbic system and upregulating neurotransmitter synthesis. Objectives This paper aims to assess the impact of essential oil interventions on aggressive behavior in people with dementia. Methods The literature search was carried out through six databases. The outcomes of interest were the survival risk and post-treatment score of the Cohen-Mansfield Agitation Inventory (CMAI), Neuropsychiatric Inventory (NPI), and Quality of Life (QoL). Quality appraisal was done using RoB 2.0, while meta-analysis was done using RevMan 5.4. This systematic review has been registered to the PROSPERO database (CRD42023476844). Results We analyzed 11 included studies with 1,418 patients. RoB 2.0 analysis resulted in eight low-risk-of-bias and three high-risk-of-bias studies. This study suggests that essential oil interventions lead to statistically significant improvements in survival risk with moderate heterogeneity [OR = 0.63 (95% CI: 0.41, 0.98, p = 0.04; I2 = 74%)]. This study also found a significant improvement in NPI scores following the use of essential oils [SMD = -2.97 (95% CI = -5.61, -0.32, p = 0.03; I2 = 98%)], but no statistically significant improvements were found in CMAI scores [SMD = 0.17 (95% CI = 0.37, 0.71, p = 0.53; I2 = 74%)]. The QoL assessment showed a trend favoring the control group after implementing essential oil treatments [SMD = 4.89 (95% CI = 1.51, 8.27, p = 0.005; I2 = 98%)]. Conclusions Essential oil is a potential approach in alleviating the agitated behavior of dementia patients considering its survival risk and some parameters, such as NPI, CMAI, and QoL score. However, more studies regarding essential oils on these parameters should be done, especially studies with specific main ingredients of the essential oil.

Clusterization of Behavioral and Psychological Symptoms of Dementia as Assessed by Neuropsychiatric Inventory: A Case Against the Use of Principal Component Analysis.

The term Behavioral and Psychological Symptoms of Dementia (BPSD) covers a group of phenomenologically and medically distinct symptoms that rarely occur in isolation. Their therapy represents a major unmet medical need across dementias of different types, including Alzheimer's disease. Understanding of the symptom occurrence and their clusterization can inform clinical drug development and use of existing and future BPSD treatments. The primary aim of the present study was to investigate the ability of a commonly used principal component analysis to identify BPSD patterns as assessed by Neuropsychiatric Inventory (NPI). NPI scores from the Aging, Demographics, and Memory Study (ADAMS) were used to characterize reported occurrence of individual symptoms and their combinations. Based on this information, we have designed and conducted a simulation experiment to compare Principal Component analysis (PCA) and zero-inflated PCA (ZI PCA) by their ability to reveal true symptom associations. Exploratory analysis of the ADAMS database revealed overlapping multivariate distributions of NPI symptom scores. Simulation experiments have indicated that PCA and ZI PCA cannot handle data with multiple overlapping patterns. Although the principal component analysis approach is commonly applied to NPI scores, it is at risk to reveal BPSD clusters that are a statistical phenomenon rather than symptom associations occurring in clinical practice. We recommend the thorough characterization of multivariate distributions before subjecting any dataset to Principal Component Analysis.

Difference of Cerebrospinal Fluid Biomarkers and Neuropsychiatric Symptoms Profiles among Normal Cognition, Mild Cognitive Impairment, and Dementia Patient.

The delineation of biomarkers and neuropsychiatric symptoms across normal cognition, mild cognitive impairment (MCI), and dementia stages holds significant promise for early diagnosis and intervention strategies. This research investigates the association of neuropsychiatric symptoms, evaluated via the Neuropsychiatric Inventory (NPI), with cerebrospinal fluid (CSF) biomarkers (Amyloid-β42, P-tau, T-tau) across a spectrum of cognitive states to enhance diagnostic accuracy and treatment approaches. Drawing from the National Alzheimer's Coordinating Center's Uniform Data Set Version 3, comprising 977 individuals with normal cognition, 270 with MCI, and 649 with dementia. To assess neuropsychiatric symptoms, we employed the NPI to understand the behavioral and psychological symptoms associated with each cognitive category. For the analysis of CSF biomarkers, we measured levels of Amyloid-β42, P-tau, and T-tau using the enzyme-linked immunosorbent assay (ELISA) and Luminex multiplex xMAP assay protocols. These biomarkers are critical in understanding the pathophysiological underpinnings of Alzheimer's disease and its progression, with specific patterns indicative of disease stage and severity. This study cohort consists of 1896 participants, which is composed of 977 individuals with normal cognition, 270 with MCI, and 649 with dementia. Dementia is characterized by significantly higher NPI scores, which are largely reflective of mood-related symptoms (p < 0.001). In terms of biomarkers, normal cognition shows median Amyloid-β at 656.0 pg/mL, MCI at 300.6 pg/mL, and dementia at 298.8 pg/mL (p < 0.001). Median P-tau levels are 36.00 pg/mL in normal cognition, 49.12 pg/mL in MCI, and 58.29 pg/mL in dementia (p < 0.001). Median T-tau levels are 241.0 pg/mL in normal cognition, 140.6 pg/mL in MCI, and 298.3 pg/mL in dementia (p < 0.001). Furthermore, the T-tau/Aβ-42 ratio increases progressively from 0.058 in the normal cognition group to 0.144 in the MCI group, and to 0.209 in the dementia group (p < 0.001). Similarly, the P-tau/Aβ-42 ratio also escalates from 0.305 in individuals with normal cognition to 0.560 in MCI, and to 0.941 in dementia (p < 0.001). The notable disparities in NPI and CSF biomarkers among normal, MCI and Alzheimer's patients underscore their diagnostic potential. Their combined assessment could greatly improve early detection and precise diagnosis of MCI and dementia, facilitating more effective and timely treatment strategies.

Assessment of Behavioral and Psychological Symptoms in Dementia, Associated Risk Factors and Clinical Correlates

Background: The presence of behavioral and psychological symptoms in dementia (BPSD) are associated with hospitalization, rapid cognitive decline, poor quality of life and higher caregiver burden. Thus, we aim to characterize the BPSD symptoms, its relationship to dementia-related risk factors and their predictive value, if any.Methodology: In 48 adults (mean age: 70.27 ± 10.08) with major neurocognitive disorder (MNCD) as per diagnostic and statistical manual of mental disorders, 5th edition and with Hindi mental status examination scores less than or equal to 23 were recruited. Patients were assessed for cognition by hindi Montreal cognitive assessment (HMOCA) and the clinical dementia rating scale (CDR). BPSD and caregiver burden were assessed using the neuropsychiatric inventory (NPI) and burden assessment schedule (BAS). The correlation of NPI scores with socio-demographic variables and clinical variables was assessed. A forward stepwise linear regression (using p-value &lt; .05) was used to identify possible predictors of the NPI scores.Results: The majority of participants were predominantly males, 25 (52.1%), from urban regions, belonged to middle-class socio-economic status and had severe grading (HMOCA (&lt; 10) of MNCD (25 (52.2%) but had moderate caregiver burden (25 (52.2%)). The most common MNCD type was due to Alzheimer’s disease (22 (45.8%)). Cortical atrophy and ischemic infarcts were the most common neuroimaging abnormalities reported (7 (14.9%)). Mean HMOCA, clinical dementia rating scale (CDR), NPI and BAS scores were 9.13 ± 6.96, 1.50 ± 1.05, 41.79 ± 27.06 and 68.65 ± 22.84, respectively. The most common BPSD domains were sleep disturbance (60.4%) and hallucinations (56.25%). Among the established risk factors, hypertension was present in the highest proportion (21 (43.8%)). As per the stepwise logistic regression model CDR scores, smoking status and HTN were predicted risk factors (R²: 0.452; p = 0.045).Conclusion: Irritability/agitation is most prevalent BPSD. The severity of MNCD, smoking and hypertension may help in the prediction of BPSD and their role may have to be explored in further studies.

Distribution of neuropsychiatric profiles and comorbid diseases in dementia subtypes

Objectives: Alzheimer’s disease (AH) is the most prevalent cause of dementia, followed closely by vascular dementia. Mixed vascular-Alzheimer’s dementia (MVAD) is more evident in individuals aged 80 and above. Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after AH. Vascular risk factors play important role in the pathogenesis of dementia syndromes. Behavioral and psychological symptoms represent a significant portion of the non-cognitive manifestations in dementia patients. This study aimed to evaluate the distribution of chronic diseases, behavioral disorders, psychiatric findings, and medication use in patients followed with different dementia diagnoses. Methods: Prevalance of chronic diseases, behavioral disorders, psychiatric findings as well as the usage of antidepressant and antipsychotic medications among patients followed up in dementia outpatient clinics with the diagnosis of AD, mild cognitive impairment (MCI), vascular dementia (VaD), FTD, and MVAD were investigated. Neuropsychiatric inventory (NPI) was applied to the patients. Results: Four hundred and fifty-five patients were accepted in the study. The patients were distributed as follows: AD (n=303, female/male: 187/115, age = 78±8 years), MCI (n=53, female/male: 31/22, age = 69±10 years), VaD (n=31, female/male: 18/13, age = 68±9 years), FTD (n=32, female/male: 17/15, age = 68±9 years), and MVAD (n=36, female/male: 16/20, age = 76±10 years). Both AD and MVAD groups were significantly older than the other groups (F = 23.2, P&amp;lt;0.0001). The ratio of comorbid chronic diseases was 80% in the AD group, 72% in the MCI group, 91% in the VaD group, 59% in the FTD group, and 93% in the MVAD group. In the whole group, antipsychotic drug use was 27.5% and antidepressant drug use was 28.9%. The mean NPI score was 32.9±28 in antipsychotic users and 16±19 in non-users (P&amp;lt;0.0001). The mean NPI of antidepressant users was 17.6±19 and 21.9±25 (P=0.055) in non-users. Conclusion: There is a comorbid chronic disease burden in all dementia subtypes, although at varying intensities, and as the chronic disease burden increases, behavioral disorders and psychotic findings increase, and accordingly, the use of antipsychotics also increases.

The relationship of neuropsychiatric symptoms with inflammatory markers in the hippocampus and cingulate cortex of bipolar disorder subjects: A post-mortem study

Increased levels of inflammation markers have been found in the peripheral tissue of individuals with bipolar disorder (BD), especially during mood episodes. Previous studies found distinctive inflammatory profiles across different brain regions, but potential associations with clinical symptoms are still lacking. This study aims to evaluate the association of neuropsychiatric symptoms with inflammatory markers in the hippocampus and cingulate of individuals with BD. Levels of IL-1β, IL-6, IL-17A, cortisol, and C-reactive protein (CRP) were measured in the hippocampus and anterior cingulate of 14 BD individuals and their non-psychiatric controls. Neuropsychiatric symptoms present in the three months before death were assessed using the Neuropsychiatric Inventory (NPI). In the BD group, greater NPI scores were associated with higher IL-6 in the hippocampus (p = 0.011) and cingulate (p = 0.038) and higher IL-1β (p = 0.039) in the hippocampus. After adjusting for age, sex and CDR, IL-1β and IL-6 were still associated with higher NPI in the hippocampus. In correlation analysis considering both BD and their controls, moderate positive associations were found between NPI and IL-6 and cortisol in the hippocampus (p < 0.001 and p = 0.006) and cingulate (p = 0.024 and p = 0.016), IL-1β (p < 0.001) and IL-17A in the hippocampus (p = 0.002). No difference in inflammatory markers was found according to type of psychotropic medication used. Hence, in individuals with BD, neuropsychiatric symptoms were differently associated with specific inflammatory cytokines and CRP in the hippocampus and cingulate. These results suggest that the neuroinflammatory changes occurring in BD may be more complex than previously expected and could be associated with clinical manifestations.

Validity and Reliability of the Turkish Version of Mild Behavioral Impairment Checklist in Patients With Cognitive Impairment.

The Mild Behavioral Impairment-Checklist (MBI-C) was developed to detect and standardize neuropsychiatric symptoms. The objective of this study was to evaluate the Turkish adaptation, validity, and reliability of the MBI-C. The sample of our study consisted of 80 patients with cognitive impairment and a control group with 113 participants whose cognitive impairment was not detected in standard tests. Participants were evaluated with the Standardized Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Geriatric Depression Scale-15 (GDS-15), MBI-C and Neuropsychiatric Inventory (NPI). In the reliability analysis, the Cronbach-alpha value for MBI-C was found to be .810. In the ROC analysis performed with the total MBI-C score, the area under the curve (AUC) was calculated as .821 and the cut-off score was determined as 8.5; sensitivity was calculated as .77 and specificity as .83. A strong positive correlation was found between test-retest MBI-C scores (r = .886, P < .0019). A strong positive correlation was found between MBI-C and NPI scores (r = .964, P < .001). MBI-C scores were significantly negatively correlated with MMSE and MoCA scores and positively correlated with GDS-15 scores. The results of our study showed that the Turkish version of the MBI-C is a valid and reliable measurement.

Clinical and neuroimaging association between neuropsychiatric symptoms and nutritional status across the Alzheimer's disease continuum: a longitudinal cohort study

ObjectivesTo investigate the association between neuropsychiatric symptoms (NPS) and nutritional status, and explore their shared regulatory brain regions on the Alzheimer’s disease (AD) continuum. DesignA longitudinal, observational cohort study. SettingData were collected from the Chinese Imaging, Biomarkers, and Lifestyle study between June 1, 2021 and December 31, 2022. ParticipantsOverall, 432 patients on the AD continuum, including amnestic mild cognitive impairment and AD dementia, were assessed at baseline, and only 165 patients completed the (10.37 ± 6.08) months’ follow-up. MeasurementsThe Mini-Nutritional Assessment (MNA) and Neuropsychiatric Inventory (NPI) were used to evaluate nutritional status and NPS, respectively. The corrected cerebral blood flow (cCBF) measured by pseudo-continuous arterial spin labeling of the dietary nutrition-related brain regions was analyzed. The association between the NPS at baseline and subsequent change in nutritional status and the association between the changes in the severity of NPS and nutritional status were examined using generalized linear mixed models. ResultsIncreased cCBF in the left putamen was associated with malnutrition, general NPS, affective symptoms, and hyperactivity (P < 0.05). The presence of general NPS (β = −1.317, P = 0.003), affective symptoms (β = −1.887, P < 0.001), and appetite/eating disorders (β = −1.714, P < 0.001) at baseline were associated with a decline in the MNA scores during follow-up. The higher scores of general NPI (β = −0.048), affective symptoms (β = −0.181), and appetite/eating disorders (β = −0.416; all P < 0.001) were longitudinally associated with lower MNA scores after adjusting for confounding factors. ConclusionsWe found that baseline NPS were predictors of a decline in nutritional status on the AD continuum. The worse the severity of affective symptoms and appetite/eating disorders, the poorer the nutritional status. Furthermore, abnormal perfusion of the putamen may regulate the association between malnutrition and NPS, which suggests their potentially common neural regulatory basis.

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

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

DEMENTIA STAGING, NEUROPSYCHIATRIC SYMPTOMS, AND DIVORCE OR SEPARATION IN LATE LIFE: A CASE CONTROL STUDY

Abstract Dementia can be difficult on marriages for many reasons, including but not limited to caregiving burden, loss of intimacy, and financial burden. This study examined the impact of dementia staging and neuropsychiatric behavioral symptoms on the likelihood of divorce or separation for older adult married couples. For this case-control study, we used data from the National Alzheimer’s Coordinating Center (NACC) Uniform dataset (UDS) versions 2 and 3. This dataset was from 2007 to 2021 and contains standardized clinical information submitted by NIA/NIH Alzheimer’s Disease Research Centers (ADRCs) across the United States (US). This data was from 37 ADRCs. We selected participants who were married or living as married/domestic partners at their initial visit. Cases were defined by a first divorce/separation occurring during the follow-up period, resulting in 291 participants. We selected 5 controls for each married/living as married case and matched on age. Conditional logistic regression estimated the association between overall Neuro Psychiatric Inventory (NPI) score and severity of NPI symptoms with case/control status, adjusted for education, the CDR® Dementia Staging Instrument score, living situation, symptom informant, sex, and race. Separate analyses were conducted for each symptom. Multiple comparisons were accounted for with the Hochberg method. Later stage of dementia was negatively associated with divorce/separation with an adjusted odds ratio. A higher overall NPI score was positively associated with divorce/separation. More severe ratings of agitation/aggression, depression/dysphoria, and disinhibition with divorce/separation were associated with greater odds of divorce/separation. Treating NPI symptoms may be away to protect relationships.

PHYSICAL ACTIVITY AND IMPACT ON PSYCHOLOGICAL AND BEHAVIOR SYMPTOMS ASSOCIATED WITH DEMENTIA

Abstract The aim of this study was to examine the impact of physical activity during hospitalization on behavioral and psychological symptoms of dementia among older adults, after controlling for covariates (age, gender, race, comorbidities, care interactions, and treatment group) and examine the association of physical and behavioral and psychological symptoms of dementia among hospitalized older adults living with dementia. Data from the first 365 participants in the FFC-AC-EIT study was used. Physical activity was measured over 24 hours and was based on the Physical Activity Survey which included the following activities: walking, wheeling, bathing, dressing, feeding, grooming, and toileting. Behavioral and psychological symptoms associated with dementia were based on the Neuropsychiatric Inventory (NPI). The mean age of participants was 83.18 years, the majority was female (63.6%) and White (69.4%), the mean NPI was 1.28(SD=1.85) and mean activities was 8(SD=5). A total of 16% of individuals performed no activity. The most common activity was eating and the least commonly performed was self-propelling in a wheelchair. A total of 40% engaged in walking and 60% performed some bathing and dressing while hospitalized. After controlling for covariates, physical activity explained an additional 2% of the variance in NPI scores (beta=-.13., p=.05). There was no evidence that engaging patients in physical activity resulted in behavioral symptoms and activity may help to decrease these symptoms. Continued focus is needed to engage older adults living with dementia when hospitalized to engage in routine physical activity by performing activities of daily living.

Predictors of live-in migrant caregiver employment for people with dementia in Taiwan.

With the increasing number of individuals with dementia, families have hired an increasing number of live-in migrant caregivers (LIMCs). Currently, limited evidence is available regarding the influence of long-term care resource utilization on the hiring of LIMCs for caring for individuals with dementia in Taiwan. We recruited individuals with dementia who did not hire LIMCs and their primary family caregivers from nine hospitals in Taiwan as baseline. Multivariable logistic regression was used to evaluate the utilization of long-term care resources for individuals with dementia and other factors that may affect the decision to hire LIMCs. The users of non-long-term care resources had the highest likelihood of hiring LIMCs (odds ratio [OR] = 4.24, 95% CI, 2.30-7.84). Compared with spouses, nonimmediate family caregivers (OR = 3.40, 95% CI, 1.16-9.90) were significantly more likely to hire LIMCs. A higher likelihood of hiring LIMCs was observed for those with Lewy body dementia compared with other individuals (OR = 2.31, 95% CI, 1.03-5.14). Compared with individuals who did not hire LIMCs, those who hired LIMCs exhibited higher scores on the Neuropsychiatric Inventory (NPI) and higher severity of individual NPI items. Hiring LIMCs is strongly correlated with the utilization of non-long-term care resources and is influenced by the dynamics between individuals with dementia and their primary family caregivers. A higher likelihood of hiring LIMCs was observed for individuals with Lewy body dementia and individuals with elevated NPI scores compared with their counterparts. Given these observations, various support strategies and interventions should be tailored to the specific requirements of individuals with dementia and their families.

BPSDiary study protocol: a multi-center randomized controlled trial to compare the efficacy of a BPSD diary vs. standard care in reducing caregiver's burden

Behavioral and Psychological Symptoms of Dementia (BPSD) are a heterogeneous set of psychological and behavioral abnormalities seen in persons with dementia (PwD), significantly impacting their quality of life and that of their caregivers. Current assessment tools, such as the Neuropsychiatric Inventory (NPI), are limited by recall bias and lack of direct observation. This study aims to overcome this limitation by making caregiver reports more objective through the use of a novel instrument, referred to as the BPSDiary. This randomized controlled trial will involve 300 caregiver-PwD dyads. The objective is to evaluate whether the use of the BPSDiary could significantly reduce caregiver burden, assessed using the Zarit Burden Interview (ZBI), compared to usual care. The study will include adult PwD, caregivers living with or close to the patient, and BPSD related to the HIDA (hyperactivity, impulsivity, irritability, disinhibition, aggression, agitation) domain. Caregivers randomized to the intervention arm will use the BPSDiary to record specific BPSD, including insomnia, agitation/anxiety, aggression, purposeless motor behavior, and delusions/hallucinations, registering time of onset, severity, and potential triggers. The primary outcome will be the change in ZBI scores at 3 months, with secondary outcomes including changes in NPI scores, olanzapine equivalents, NPI-distress scores related to specific BPSD domains, and caregiver and physician satisfaction. The study will be conducted in 9 Italian centers, representing diverse geographic and sociocultural contexts. While potential limitations include the relatively short observation period and the focus on specific BPSD disturbances, the BPSDiary could provide physicians with objective data to tailor appropriate non-pharmacological and pharmacological interventions. Additionally, it may empower caregivers by encouraging reflection on BPSD triggers, with the potential to improve the quality of life for both PwD and their caregivers.Trial registryNCT05977855.

Comparison of clinicopathologic features of Limbic and Diffuse Transactive Response DNA‐binding Protein 43 pathology in Alzheimer’s disease neuropathologic spectrum

AbstractBackgroundIncreasing evidence suggests that transactive response DNA‐binding protein 43 (TDP‐43) pathology in Alzheimer’s Disease (AD), or AD‐TDP, can be diffuse or limbic‐predominant. Understanding whether diffuse AD‐TDP has genetic, clinical, and pathological features that differ from limbic AD‐TDP could have clinical and research implications. We aimed to better characterize the clinicopathologic features of diffuse AD‐TDP and differentiate it from limbic‐predominant AD‐TDP pathology.MethodThree hundred sixty‐three participants were prospectively recruited and followed in the Mayo Clinic Study of Aging, Alzheimer’s Disease Research Center, and Neurodegenerative Research Group and died between May 1999 and August 2021. All underwent genetic, clinical, neuropsychologic, and neuropathologic evaluations. At postmortem evaluation, they showed Alzheimer’s disease neuropathologic changes and TDP‐43‐immunoreactive inclusions. The distribution of TDP‐43 pathology was assessed using the Josephs 6‐stage scheme. Participants with TDP‐43 stages 1‐3 were classified as Limbic, while those with stages 4‐6 were classified as Diffuse. Neuropathologically defined frontotemporal lobar degeneration cases were excluded. Multivariable logistic regression was used to identify clinicopathological features that predicted diffuse TDP‐43 pathology at postmortem. We hypothesized that the Diffuse group would show impairment in cognitive domains beyond episodic memory and more hippocampal sclerosis.ResultsThe cohort was 61% female and old at onset (median:76 years [IQR:70‐82]) and death (median:88 years [IQR:82‐92]). Fifty‐four percent (n = 197) were classified as Limbic and 46% (n = 166) as Diffuse. A “clinical” multivariate logistic regression fit to 85 participants with all clinical variables of interest showed that later age at onset (OR:1.09, 95%CI:1.01‐1.19;P = 0.03), longer disease duration (OR:1.17, 95%CI:1.02‐1.36;P = 0.03) and higher Neuropsychiatric Inventory scores (OR:1.14, 95%CI:1.01‐1.28;P = 0.03) all independently increased the odds of being Diffuse, while higher Trails Making Test‐B (OR:0.99, 95%CI:0.98‐0.99;P = 0.02) and Block Design Test scores (OR:0.91, 95%CI:0.85‐0.99;P = 0.023) independently decreased the odds of being Diffuse. A “pathology” multivariate logistic regression fit to 233 cases with all neuropathological data revealed that widespread amyloid‐β pathology corresponding to Thal phases 3‐5 all significantly decreased the odds of diffuse pathology by 80‐90%, while hippocampal sclerosis increased it sixfold (OR:6.18, 95% CI:2.93‐13.03;P&lt;0.001).ConclusionsDiffuse AD‐TDP shows clinicopathological features that differ from Limbic AD‐TDP, which could have public health implications relating to treatment and research on AD and dementia.

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.