Use of Safety Net Enclosures as an Additional Treatment of Neuropsychiatric Symptoms in Dementia: A Prospective Cohort Study.

Degenerative dementia is characterized by progressive cognitive decline and neuropsychiatric symptoms. People with Alzheimer's disease (AD), the most common cause of dementia, show synaptic loss and disruption of functional brain networks along with neuritic plaques and neurofibrillary tangles. Electroencephalography (EEG) directly reflects synaptic activity, and among patients with AD it is associated with slowing of background activity. The purpose of this study was to identify associations between neuropsychiatric symptoms and EEG in patients with dementia and to determine whether EEG parameters could be used for clinical assessment of pharmacological treatment of neuropsychiatric symptoms in dementia (NPSD) with galantamine or risperidone. Seventy-two patients with EEG recordings and a score ≥10 on the Neuropsychiatric Inventory (NPI) were included. Clinical assessments included administration of the NPI, the Mini-Mental State Examination (MMSE), and the Cohen-Mansfield Agitation Inventory (CMAI). Patients underwent EEG examinations at baseline and after 12 weeks of treatment with galantamine or risperidone. EEG frequency analysis was performed. Correlations between EEG and assessment scale scores were statistically examined, as were EEG changes from baseline to the week 12 visit and the relationship with NPI, CMAI, and MMSE scores. Significant correlations were found between NPI agitation and delta EEG frequencies at baseline and week 12. No other consistent and significant relationships were observed between NPSD and EEG at baseline, after NPSD treatment, or in the change in EEG from baseline to follow-up. The limited informative findings in this study suggest that there exists a complex relationship between NPSD and EEG; hence, it is difficult to evaluate and use EEG for clinical assessment of pharmacological NPSD treatment.

The authors aim to determine if a history of traumatic brain injury (TBI) assessed before dementia onset is associated with a higher risk of neuropsychiatric symptoms after dementia onset. A population-based incident series of people with dementia were assessed for TBI prior to onset of dementia and for neuropsychiatric symptoms after the onset, using the Neuropsychiatric Inventory. Participants with predementia TBI were more likely to exhibit disinhibition (12.7% versus 5.4%, OR=2.8, p=0.02), but not other neuropsychiatric symptoms. Traumatic brain injury may increase the risk of disinhibition in patients with dementia.

Neuropsychiatric symptoms (NPS) in dementia are frequent and challenging for patients, carers, and the health care system, but few long-term studies exist. We analyse the longitudinal course of NPS in patients with mild dementia. A longitudinal cohort study of 223 patients with mild dementia and annual assessments using the Neuropsychiatric Inventory (NPI) for 5years. A total 1043 NPI assessments, representing 97% of all possible measurements of living cohort members, were analysed. Neuropsychiatric symptoms were common at baseline, and only a moderate increase in total NPS score from 15 to 17 with no increase in the proportion with high NPI total scores. Ninety seven percent scored ≥16, and 49% scored ≥36 on NPI total score at least once during follow-up. Individual NPS fluctuated and often reappeared. The most common symptoms ever reported was apathy (83%), depression (63%), appetite (63%), and aberrant motor behavior (60%). Cognitive decline was associated with higher NPI total score and several NPI items, but only the frequency of apathy increased significantly with time. Lewy body dementia was associated with higher NPI total score and psychotic symptoms. Alzheimer's disease was associated with increase in apathy. Severe NPS are already common at time of dementia diagnosis, and the increase in overall severity over 5years was moderate. Individual symptoms tend to fluctuate over time within patients and correspond to states rather than traits. These findings highlight the need to focus on, and plan for, NPS as part of dementia pathway, and are relevant for clinical trial design.

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BackgroundThe underlying disease mechanism of neuropsychiatric symptoms (NPS) in dementia remains unclear. Cerebrospinal fluid (CSF) biomarkers for synaptic and axonal degeneration may provide novel neuropathological information for their occurrence. The aim was to investigate the relationship between NPS and CSF biomarkers for synaptic (neurogranin [Ng], growth-associated protein 43 [GAP-43]) and axonal (neurofilament light [NFL]) injury in patients with dementia.MethodsA total of 151 patients (mean age ± SD, 73.5 ± 11.0, females n = 92 [61%]) were included, of which 64 had Alzheimer’s disease (AD) (34 with high NPS, i.e., Neuropsychiatric Inventory (NPI) score > 10 and 30 with low levels of NPS) and 18 were diagnosed with vascular dementia (VaD), 27 with mixed dementia (MIX), 12 with mild cognitive impairment (MCI), and 30 with subjective cognitive impairment (SCI). NPS were primarily assessed using the NPI. CSF samples were analyzed using enzyme-linked immunosorbent assays (ELISAs) for T-tau, P-tau, Aβ1–42, Ng, NFL, and GAP-43.ResultsNo significant differences were seen in the CSF levels of Ng, GAP-43, and NFL between AD patients with high vs low levels of NPS (but almost significantly decreased for Ng in AD patients < 70 years with high NPS, p = 0.06). No significant associations between NPS and CSF biomarkers were seen in AD patients. In VaD (n = 17), negative correlations were found between GAP-43, Ng, NFL, and NPS.ConclusionOur results could suggest that low levels of Ng may be associated with higher severity of NPS early in the AD continuum (age < 70). Furthermore, our data may indicate a potential relationship between the presence of NPS and synaptic as well as axonal degeneration in the setting of VaD pathology.

Polypharmacy is common in older individuals with Alzheimer's disease and related dementia (ADRD) who present with neuropsychiatric symptoms (NPS). While it is associated with increased fall risk, specific impact of psychotropic and general medication use on fall risk in this population is not clear. We evaluated fall risk associated with psychotropic and general medication use in patients with ADRD and NPS while controlling for other clinical factors. We used the following data from participants with a clinical diagnosis of AD and clinically significant NPS in the Standardizing Care for Neuropsychiatric Symptoms and Quality of Life in Dementia (StaN) study (ClinicalTrials.gov/NCT03672201): number of psychotropic and general medications and scores on the Cohen Mansfield Agitation Inventory (CMAI) scores, Cumulative Illness Rating Scale-Geriatric (CIRSG), Functional Assessment Staging Tool (FAST). and Morse Fall Scale (MFS). Linear regression analyses evaluated the associations between psychotropic or general medication use and fall risk (MFS) while adjusting for age, CIRS-G, CMAI, and FAST scores. 185 participants (female: 96 (52.5%)) were included, with mean (SD) age of 80.5 (9.8) years, mean FAST score of 9.1 (SD: 0.65; median stage: 6e). Psychotropic or general medications and CMAI or CIRS-G scores were not significantly associated with MFS, but FAST stage of dementia was. Fall risk in AD may be influenced more by functional and cognitive impairment than by medication use. These findings should be considered in the context of unique characteristics of this cohort that include a severe stage of dementia and the presence of significant NPS, and may inform fall risk management strategies in this population. References Gallagher, E., Mehmood, M., Lavan, A., Kenny, R. A., & Briggs, R. (2023). Psychotropic medication use and future unexplained and injurious falls and fracture amongst community-dwelling older people: Data from TILDA. European Geriatric Medicine, 14(4), 455-463. Zarei S, Choudhury S, Burhan AM, Chu L, Colman S, Derkach P, et al. Determinants of polypharmacy in patients with behavioral and psychological symptoms of dementia. Alzheimers Dement. 2021;17(S6).

PHS31 - Healthcare Resource Utilisation and Costs of Agitation in People with Demetia Living in Care Homes - The Managing Agitation and Raising Quality of Life in Dementia (MARQUE) Study

This aim of this study was to examine the mechanisms underlying the neuropsychiatric symptoms in dementia with Lewy bodies by investigating regional cerebral blood flow. Participants were 27 patients who fulfilled the diagnostic criteria for probable dementia with Lewy bodies. All subjects underwent single-photon emission computed tomography scans using technetium-99 m hexamethylpropyleneamine oxime. Neuropsychiatric symptoms were evaluated by neuropsychiatric inventory. Multiple regression analyses using neuropsychiatric inventory and voxel-based analyses of covariance of the regional cerebral blood flow images between subjects with or without each neuropsychiatric symptom were performed. Additionally, similar voxel-based analyses of covariance between subjects with each neuropsychiatric symptom and normal subjects were performed. There were no significant correlations in any psychiatric symptoms in multiple regression analyses. All subjects had hallucination but none had euphoria. We analyzed eight neuropsychiatric symptom scores with the exception of hallucination and euphoria using voxel-based analyses of covariance. Significant differences of regional cerebral blood flow were shown in groups with agitation, disinhibition, and irritability. Subjects with agitation showed hypoperfusion in the parietal lobule, the precuneus, and the angular gyrus, and hyperperfusion in the fusiform gyrus, the lingual gyrus, and the thalamus. Subjects with disinhibition showed hypoperfusion in the left frontal gyrus. Subjects with irritability showed hyperperfusion in the right frontal gyrus. There were no significant differences in regional cerebral blood flow between subjects with any neuropsychiatric symptoms and normal subjects. This study reveals that dysfunction of specific brain regions is associated with various neuropsychiatric symptoms in dementia with Lewy bodies.

The purpose of this research was to assess the frequency and severity of neuropsychiatric and behavioral symptoms and to examine the association between preexisting medical conditions and specific neuropsychiatric symptoms in demented individuals. We studied 211 demented subjects (87.7 percent male) who were participants in epidemiological studies of dementia. Using the Neuropsychiatric Inventory (NPI), we assessed the frequency and severity of neuropsychiatric symptoms. We collected medical history information during a structured telephone interview. Our analyses focused on determining prevalence of neuropsychiatric symptoms by dementia diagnosis and severity. We also examined the association of history of head injury, alcohol abuse, and stroke with development of neuropsychiatric symptoms. We found that neuropsychiatric symptoms were common, with approximately three-fourths of the subjects exhibiting at least one symptom during the preceding month. Apathy (39.3 percent), agitation (31.8 percent), and aberrant motor behavior (31.1 percent) were the most frequent symptoms. Frequency and severity of symptoms were similar for the all-dementia and Alzheimer's disease-only groups, neuropsychiatric symptoms varied by severity of dementia, but generally not in a consistent ordinal pattern. History of alcohol abuse, head injury, or stroke was associated with presence of specific neuropsychiatric symptoms in dementia. While psychiatric symptoms are common in dementia, they also vary by type and severity of dementia. The finding that certain medical conditions may increase risk for specific types of neuropsychiatric symptoms expands our knowledge of the natural history of dementia and should improve management of dementia in medically ill patients. Our results may also shed light on mechanisms that underlie neuropsychiatric symptoms.

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.

Neuropsychiatric symptoms (NPS) such as aggression, apathy, agitation, and wandering may occur in up to 90%of dementia cases. International guidelines have suggested that non-pharmacological interventions are as effective as pharmacological treatments, however without the side effects and risks of medications. An occupational therapy method, called Tailored Activity Program (TAP), was developed with the objective to treat NPS in the elderly with dementia and has been shown to be effective. Evaluate the efficacy of the TAP method (outpatient version) in the treatment of NPS in individuals with dementia and in the burden reduction of their caregivers. This is a randomized, double-blind, controlled clinical trial for the treatment of NPS in dementia. Outcome measures consisted of assessing the NPS of individuals with dementia, through the Neuropsychiatric Inventory-Clinician rating scale (NPI-C), and assessing the burden on their caregivers, using the Zarit Scale. All the participants were evaluated pre-and post-intervention. 54 individuals with dementia and caregivers were allocated to the experimental (n = 28) and control (n = 26) groups. There was improvement of the following NPS in the experimental group: delusions, agitation, aggressiveness, depression, anxiety, euphoria, apathy, disinhibition, irritability, motor disturbance, and aberrant vocalization. No improvement was observed in hallucinations, sleep disturbances, and appetite disorders. The TAP method for outpatient settings was also clinically effective in reducing burden between caregivers of the experimental group. The use of personalized prescribed activities, coupled with the caregiver training, may be a clinically effective approach to reduce NPS and caregiver burden of individuals with dementia.

To understand the relationship between social determinants of health (SDoH) and neuropsychiatric symptoms (NPS) of dementia and mild cognitive impairment (MCI) such as depression, agitation, psychosis, and apathy. The study extracted data from papers published before January 27, 2025, from PubMed, PsycINFO, and Embase. A total of 2034 articles were identified, and after critical assessment, 18 articles were included in our narrative review. Of the 18 studies, 14 assessed the relationship between NPS and SDoH in participants with dementia, one studied participants with MCI, and three studied those with either dementia or MCI. The majority of the studies (n = 10) had a cross-sectional design, while others had a longitudinal design. Most studies (n = 13) used the Neuropsychiatric Inventory (NPI) or its variants for measuring NPS. Education (n = 8) was the most studied SDoH, with studies overall showing that more education is associated with less NPS (n = 4), although some studies showed mixed (n = 1), null (n = 1), and reverse (n = 2) associations. Studies showed that increased social connectedness and marriage overall was associated with decreased NPS (4 out of 6 studies). Two studies showed that increased religiosity and spirituality was associated with decreased NPS. Poor nutrition, and immigrant status/speaking English as a second language were associated with increased NPS. This narrative review shows that while several studies report an association between SDoHs and NPS in dementia and MCI, more studies are needed to understand the relationship, particularly elucidating how it affects different symptoms of NPS. That could inform clinical practice and public policy. Future studies also need to focus on understanding the causality of the relationship and possible interventions.

INTRODUCTION:Neuropsychiatric symptoms in dementia (NPS) collectively refer to behavioral and psychological symptoms affecting individuals with mild cognitive impairment (MCI) or Alzheimer’s disease or related dementia (ADRD). NPS are among the most troubling aspects of living with dementia and their treatments have limited efficacy. We aim to investigate genetic variants contributing to NPS to identify new therapeutic targets.METHODS:We performed a genome-wide association study (GWAS) for nine NPS domains measured by the NPI-Q in 12,800 participants of European ancestry with MCI or ADRD recruited by Alzheimer’s disease research centers across the U.S.RESULTS:We found genome-wide significant signals for agitation, anxiety, apathy, delusions, and hallucinations in the APOE locus that were driven by the APOE ε4 allele. We replicated these findings in two independent datasets. Mediation analyses revealed that MCI/ADRD severity only partially mediated the GWAS signals, except for apathy.DISCUSSION:These findings suggest the APOE ε4 allele influences NPS independently of and beyond its effect on ADRD.

Patients with dementia may be unable to describe their symptoms, and caregivers frequently suffer emotional burden that can interfere with judgment of the patient's behavior. The Neuropsychiatric Inventory-Clinician rating scale (NPI-C) was therefore developed as a comprehensive and versatile instrument to assess and accurately measure neuropsychiatric symptoms (NPS) in dementia, thereby using information from caregiver and patient interviews, and any other relevant available data. The present study is a follow-up to the original, cross-national NPI-C validation, evaluating the reliability and concurrent validity of the NPI-C in quantifying psychopathological symptoms in dementia in a large Brazilian cohort. Two blinded raters evaluated 312 participants (156 patient-knowledgeable informant dyads) using the NPI-C for a total of 624 observations in five Brazilian centers. Inter-rater reliability was determined through intraclass correlation coefficients for the NPI-C domains and the traditional NPI. Convergent validity included correlations of specific domains of the NPI-C with the Brief Psychiatric Rating Scale (BPRS), the Cohen-Mansfield Agitation Index (CMAI), the Cornell Scale for Depression in Dementia (CSDD), and the Apathy Inventory (AI). Inter-rater reliability was strong for all NPI-C domains. There were high correlations between NPI-C/delusions and BPRS, NPI-C/apathy-indifference with the AI, NPI-C/depression-dysphoria with the CSDD, NPI-C/agitation with the CMAI, and NPI-C/aggression with the CMAI. There was moderate correlation between the NPI-C/aberrant vocalizations and CMAI and the NPI-C/hallucinations with the BPRS. The NPI-C is a comprehensive tool that provides accurate measurement of NPS in dementia with high concurrent validity and inter-rater reliability in the Brazilian setting. In addition to universal assessment, the NPI-C can be completed by individual domains.

Neuropsychiatric symptoms (NPS) are key clinical manifestations across the Alzheimer's disease (AD) continuum and predict worse clinical outcomes, yet their biological correlates remain incompletely understood. It remains unclear whether biomarkers of neuroaxonal injury and astrocytic activation, namely neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP), are associated with NPS independently of amyloid-β (Aβ) pathology or through downstream structural brain changes. We conducted a cross-sectional study of 478 individuals from the First Affiliated Hospital of the University of Science and Technology of China, spanning the cognitive spectrum from cognitively unimpaired (CU) to mild cognitive impairment (MCI), AD dementia, and non-AD dementia. NPS were assessed using the Neuropsychiatric Inventory Questionnaire (NPIQ). We measured core AD biomarkers (Aβ42/40, pTau181, and pTau217) and serum NFL and GFAP using single-molecule array (Simoa) assays. Aβ status was determined by amyloid PET or CSF Aβ42/Aβ40 ratio, and cortical thickness was derived from 3D T1-weighted MRI. NPS burden was substantially higher in both AD dementia and non-AD dementia than in CU or MCI, highlighting the transdiagnostic nature of NPS in dementia syndromes. Associations between serum biomarkers and NPS differed by Aβ status. In Aβ - individuals, serum NFL was associated with global NPIQ burden and multiple symptom domains, whereas in Aβ + individuals, serum GFAP was associated with global NPIQ burden and several symptom domains. Formal interaction analyses confirmed significant effect modification by Aβ status for serum NFL, but not for serum GFAP. Sensitivity analyses excluding extreme NFL values yielded unchanged results. These findings support an Aβ-dependent dissociation in biomarker correlates of NPS, with stronger NFL-related associations in Aβ - individuals and stronger GFAP-related associations in Aβ + individuals. Our results suggest that biologically distinct pathways may underlie neuropsychiatric manifestations across the cognitive continuum and support biomarker-informed subtyping of NPS in aging and dementia.