The increasing prevalence of dementia within an ageing global population, combined with prolonged life expectancy, accentuates Alzheimer's disease (AD) as a multifaceted healthcare challenge. This challenge is further compounded by the limited therapeutic options currently available. Addressing the intricacies of AD management, the mitigation of comorbidities has emerged as a pivotal facet of treatment. Comorbid conditions, such as neurobehavioral symptoms, play a role in shaping the clinical course, management, and outcomes of this pathology; highlighting the importance of comprehensive care approaches for affected individuals. Exploration of psychedelic compounds in psychiatric and palliative care settings has recently uncovered promising therapeutic potential, enhancing neuroplasticity, emotional processing and connection. These effects are particularly relevant in the context of AD, where psychedelic therapy offers hope not only for mitigating core symptoms but also for addressing the array of comorbidities associated with this condition. The integration of this comprehensive method offers a chance to significantly enhance the care provided to those navigating the intricate landscape of AD. Therefore, the current paper reviews the intricate link between more frequent additional health conditions that may coexist with dementia, particularly in the context of AD, and explores the therapeutic potential of psychedelic compounds in addressing these concurrent conditions.

Non-pharmacological interventions (NPIs) are the primary approaches to the management of behavioural and psychological symptoms of dementia (BPSD), but studies have indicated that there is a suboptimal implementation. Although there are several studies on the factors influencing NPI implementation for BPSD at residential aged-care homes (RACHs), there has not been a comprehensive qualitative systematic review on the topic.

This systematic review aimed to examine the qualitative studies that investigate the factors influencing the implementation of NPIs for managing BPSD in RACHs.

Systematic searches were conducted up until 31 December 2023 using five databases: MEDLINE, EMCARE, EMBASE, CINAHL complete and APA PsycINFO.

This systematic review included qualitative studies and qualitative data from mixed-method studies on the implementation of NPIs for RACH residents with dementia experiencing BPSD. The research question and inclusion criteria for this review included the components of PICo: Population (aged-care residents with dementia), Phenomenon of interest (factors influencing implementation of NPIs) and Context/setting (RACHs).

After screening and extracting the data, the methodological limitations were assessed using the Joanna Briggs Institute System for the Unified Management, Assessment, and Review of Information (JBI SUMARI) quality assessment tool. JBI SUMARI meta-aggregative synthesis was used to synthesise the data. The extracted findings were categorised into the 10 Theoretical Domain Framework domains: knowledge, skills, environmental context and resources, social influences, reinforcement, emotions, intentions, beliefs about consequences, social and professional roles and beliefs about capability. Confidence in the output of qualitative research synthesis (CONQual) was used to assess the credibility and dependability of the synthesised findings.

Twenty-four studies were included, from which factors influencing NPI implementation were extracted. Study participants included RACH managers, RACH care staff, families of aged-care residents with dementia and volunteers. Amongst the studies specifying the gender of participants, there were 352 females (84.4%) and 46 males (15.6%). The method of data collection for the included studies consisted of eighteen interviews, five focus group discussions and one qualitative survey. All except one study had a quality assessment score of at least 60% based on the JBI SUMARI quality assessment tool. However, all studies were included regardless of the result of the quality assessment result. These studies spanned the period from 2010 to 2022 and were mostly conducted in the United Kingdom, Australia, the United States and Canada. Twenty-four synthesised findings were identified (13 high, 7 moderate and 4 low ConQual scores). Examples of factors influencing the implementation of NPIs were collaboration amongst care staff and families of residents with dementia, belief in the efficacy of interventions, staffing, staff time constraints, funding, familiarity with the interventions, organisational support, communication amongst the care staff and with families of residents with dementia, education and training for the care staff and families of residents with dementia and familiarity with the residents with dementia.

This systematic review highlights and synthesises factors influencing the implementation of NPIs for managing BPSD in RACHs. Key factors include collaboration amongst staff and families, organisational support, staffing, education and staff familiarity with both the interventions and residents. Strengthening these areas could enhance the care outcomes for aged-care residents with dementia. For decision-makers, these insights suggest the need for comprehensive strategies to improve NPI implementation. This could include ensuring appropriate staffing levels, enhancing collaboration, allocating adequate funds, providing training, strengthening organisational support and improving the quality of information exchange amongst care staff, between care staff and volunteers and families of residents with dementia. For researchers, the findings from this systematic review could provide valuable insights including the need to explore strategies to overcome barriers to NPI implementation, especially investigating innovative models for staffing and collaborative practice, examining the effectiveness of different education and training approaches, and exploring organisational policies and support mechanisms that can enhance the implementation of NPIs.

Neuropsychiatric symptoms (NPS) are very common and associated with high levels of distress, both in dementia patients and their caregivers. Especially at more advanced dementia disease stages, NPS rarely occur in isolation and the presence of two or more NPS may affect disease severity as well as the response to therapy. There is limited quantitative information on prevalence of specific symptom combinations in the general population, as well as in the populations recruited for symptom-specific investigations. We performed cross-sectional analyses of data from two longitudinal studies (Aging, Demographics, and Memory Study (ADAMS) and the National Alzheimer's Coordinating Center data (NACC)). In both studies and all Mini Mental State Examination (MMSE) strata, we observed every possible pair combination, from commonly recognized and discussed associations (e.g., hallucinations and delusions) to what might be seen as rather counter-intuitive patterns (e.g., apathy and agitation). In conclusion, prevalence of symptom pairs cannot be readily predicted based on prevalence of individual symptoms. Further, the presence of cognitive deficit and degree of cognitive impairment is associated with increased prevalence of all symptoms and symptom pairs, albeit to different degrees. The present study illustrates that, while there is the possibility of any combination of neuropsychiatric symptoms presenting during the course of dementia, their co-occurrence cannot be readily predicted based on the prevalence of individual symptoms. Thus, our study results serve as a source of reference information to inform the design and recruitment strategies for future clinical studies and epidemiological research on neuropsychiatric symptoms in people with dementia.

We performed a systematic review evaluating evidence regarding whether/which 24-h sleep-wake characteristics (e.g. sleep, activity levels, and 24-h rhythms) related to worse BPSDs. We searched PubMed for cross-sectional observational studies of people with dementia examining relationships between actigraphy-measured sleep/wake factors and BPSDs (search completed June 2024). We used the JBI checklists to assess the risk of bias and summarize results within subcategories of sleep/wake (sleep, activity level, and rhythm) and BPSD (composite, agitation, apathy, and mood/affect) dimensions. Thirteen articles met inclusion criteria. Measures of inactivity were most frequently examined and correlated with: (a) greater apathy (6/6 studies); (b) worse depression (only in bivariate analyses in 1 study); (c) more agitation (2/3 studies); and (d) higher composite BPSD scores (1/2 studies). All six studies measuring sleep duration failed to identify associations with BPSDs. Studies examining sleep continuity measures generally found associations, i.e. with a BPSD composite (1 study), agitation (1 study), apathy (1/2 studies), and mood (only in bivariate analyses in 1 study). Studies examining rhythm variables found associations with mood (1 study), mixed evidence for associations with apathy (1 study), and no evidence for association with a BPSD composite (1 study). Actigraphy measures of inactivity are associated with apathy in people with dementia. Due to relatively low numbers of articles, future studies are needed to confirm if inactivity, sleep continuity issues, rhythm disruption, and timing independently relate to BPSDs, and if changes in objective sleep/wake measures, e.g. increase in activity following intervention, signal/mediate improvements in BPSDs.

Objectives: Music offers a promising nonpharmacological alternative for managing agitation in people with Alzheimer's disease and other dementias (ADRD). We report resident and nursing home (NH) characteristics associated with uptake of a personalized music intervention. Design: Post hoc analysis of a cluster-randomized embedded pragmatic clinical trial (ePCT) involving delivering resident-preferred music to manage agitated behaviors. Setting and Participants: A total of 463 residents with ADRD in 27 NHs randomized to receive the intervention. Methods: We obtained resident and NH characteristics from Minimum Data Set and Long-Term Care FocUS data. In addition, we created a study-specific engagement measure, which describes the proportion of enrolled residents in a given NH with any nursing staff use of the intervention. We used hierarchical models to estimate associations between resident and NH characteristics and (1) any exposure to the personalized music intervention and (2) minutes of music received per study day. Results: This post hoc analysis included 463 residents from 27 NHs (mean age: 80 years (standard deviation, SD: 12.2), 68.5% female, and 25.3% Black or African American). Resident characteristics associated with a greater likelihood of any exposure to the music included being Black or African American (p=0.02). NH characteristics were associated with greater likelihood of any exposure included higher quality star ratings (p=0.01) and nursing staff engagement with the intervention (p=0.01). Among those exposed to the music, younger residents (p=0.02), Black residents (p=0.03), and those with less health instability (p=0.03) received greater doses. Residents living in NHs with high nursing staff engagement also received higher doses (p ≤ 0.001). Conclusions and Implications: Black race was associated with a greater probability of exposure and more use of a personalized music intervention, after controlling for NH quality. Nursing staff engagement with a personalized music intervention increased uptake. These findings are useful for future ePCTs of behavioral interventions in NHs. Trial Registration: Clinicaltrials.gov Identifier: NCT03821844.

To improve assessment of neuropsychiatric symptoms (NPS) by expanding the measurement properties of the Neuropsychiatric Inventory Questionnaire (NPI-Q).

Multicenter, longitudinal observational study.

Several Alzheimer's Disease Research Centers (ADRCs).

Individuals (n = 45,274) who presented to an ADRC with a collateral and completed the NPI-Q.

The NPI-Q total severity score, four NPI-Q subscales, dementia stage, expert NPS rating, consensus rating of dementia syndrome, global cognitive screening, collateral rating of daily functioning, and self-rating of depression.

There was strong evidence of criterion validity with both dementia stage and expert NPS rating for the NPI-Q total severity index, which informed cutoffs and interpretive ranges. Furthermore, subscales had adequate classification of dementia syndromes and appropriate convergent relationships with cognition, daily functioning, and mood. There was good-to-excellent evidence of reliability for the NPI-Q total severity index over several years, and subscales had adequate-to-good reliability.

This is the first study to provide empirically established cutoffs, interpretive ranges, and evidence of reliability over a period longer than a month on the NPI-Q and its subscales. This will improve assessment of NPS in clinical and research contexts.

Neuropsychiatric symptoms of neurodegeneration are increasingly understood as early disease markers with tremendous functional impact later in disease, but are often missed or misdiagnosed. The most common measure of these symptoms, the Neuropsychiatric Inventory Questionnaire (NPI-Q), does not have clinically actionable guidance, which this article provided. We established cutscores for several conditions and test-retest reliability over longer periods for the total score and subscales using a multicenter database.

The purpose of this study was to identify, map, summarize, and clarify the existing literature on the effects of behavioral and psychological symptoms of dementia (BPSD) an individual's autonomy across all types of dementia diagnoses. The study aimed to determine whether there is a correlation between BPSD and a decrease in a person's autonomy, as this relationship is important for improving dementia care through effective interventions. To achieve this goal, a scoping review was conducted using the Joanna Briggs Institute's methodology for scoping reviews and the PRISMA extension for scoping reviews checklist. The inclusion criteria were: (i) population: participants with a clinical diagnosis of any type of dementia; (ii) concept: examining the relationship between one or more neuropsychiatric symptoms or BPSD and the individual's autonomy; (iii) context: the progress of any type and any stage of dementia. The database search yielded 74 records, of which 41 fully met the pre-established eligibility criteria. Most studies in this review focused on participants with Alzheimer's disease and analysed their functional abilities. Most studies in this review showed significant outcomes regarding the impact of BPSD on a person's autonomy. The main BPSD investigated in the studies were depression, apathy, irritability, agitation, aggression, disinhibition, and lability. Apathy had a recurrent association with reduced autonomy in persons with dementia, while depression and psychosis were also found to have an impact on individuals' autonomy.

Psychotropic drugs are frequently prescribed for challenging behavior in residents with dementia in nursing homes. Recommendations on psychotropic drug use for challenging behavior are described in the Dutch multidisciplinary guideline "Problem behavior in dementia." This study aimed to gain insight into the adherence to guideline recommendations on drug type and timing of evaluations of different types of psychotropic drugs for challenging behavior in a national sentinel network of Dutch nursing homes.

Prospective observational study.

Data on psychotropic drug use of residents in a sentinel network of 22 nursing homes across the Netherlands were collected during a 3-month measurement period in 2021.

Physicians completed registration forms integrated into the electronic health record after reporting on psychotropic drug use in progress notes. Prescribed drug type(s), type of drug intervention (start/stop/change in dosage/evaluation), and drug indications were recorded. Adherence to guideline recommendations on drug type was achieved if prescribed psychotropic drugs were recommended for the specified indication. Adherence to guideline recommendations on timing of evaluations was achieved if evaluations were reported within 7 days after starting.

A total of 1279 forms on psychotropic drug use for specified challenging behaviors in 599 residents were collected. Recommended psychotropic drugs were used in 57% of all forms. The highest rate of recommended psychotropic drugs was for psychotic behavior (80%), followed by agitation (48%). Adherence was lowest for nighttime restlessness (22%). Of all newly started prescriptions, 17% were evaluated within the recommended 7 days after starting.

Adherence to guideline recommendations on drug type was present in just over half of the cases. Frequently, evaluations were not reported or were performed after the recommended time frame. Further research is needed to determine the reasons for non-recommended psychotropic drug use, low evaluation reporting rates, and factors that influence adherence. The use of a sentinel network may increase awareness and adherence.

To estimate the immediate and long-term effects of a visitor restriction policy on antipsychotic use in nursing home (NH) residents with Alzheimer's disease and related dementias (ADRD) during COVID-19.

A repeated cross-sectional study time series analysis was conducted using NH electronic health records (EHRs) from January 1, 2020, to December 31, 2021.

A large, multistate sample of NH residents living with ADRD.

We calculated weekly changes in facility-level prevalence of antipsychotic use using interrupted time series (ITS) to compare level and slope changes in antipsychotic use before, during, and after NH visitation restrictions. Generalized linear models with generalized estimating equations, logit link, binomial distribution, and AR-1 correlation structure were used for all ITS analyses. Final models were stratified by long- and short-stay residents and adjusted for NH-level covariates including resident demographics, clinical diagnoses, and nurse staffing.

We observed more than 8500 long-stay and 2700 short-stay NH residents with ADRD. Among long-stay residents, the weekly prevalence of antipsychotic use increased from 18.9% as of January 7, 2020, to 24.9% by December 31, 2021. For short-stay residents, antipsychotic use increased from 21.1% to 26.6% over this same window. The ITS analysis showed no meaningful changes in the relative rate of change in antipsychotic use during and after visitor restrictions, relative to pre-policy trends.

The Centers for Medicare and Medicaid Services visitation restriction policy had no meaningful impact on antipsychotic use among NH residents with ADRD. However, antipsychotic use increased over time for both long- and short-stay residents and remained above pre-pandemic levels by the end of 2021. Our findings emphasize the potential for increased reliance on pharmacotherapy to manage resident symptoms during public health emergencies. Future infection control efforts should prioritize safe interpersonal care delivery and consider policies that improve vigilance of medication utilization changes among high-risk populations.

Dementia diseases represent a major burden for the directly affected people, their relatives and modern society. Despite considerable efforts in recent years, early and accurate disease diagnosis and monitoring is still a challenge while no cure is available in most cases. New drugs, in particular disease-modifying therapies, and recent technological advancements offer promising perspectives. The integration of novel biomarkers, artificial intelligence and digital health tools has the potential to transform dementia care, making it more personalised, efficient and adapted to the living conditions and needs of older people. In November 2023, the 7th Dementia Summit convened a panel of experts from geriatrics, neurology, neuropsychology, psychiatry, ethics as well as general medicine to discuss interdisciplinary challenges, advancements and their implications for the future of dementia care in Switzerland. The conference underscored the importance of a multidisciplinary approach to successfully integrate new technologies in both clinical-translational research and dementia prevention, diagnosis and care. While recent innovations represent major steps forward, their implementation also comes with important challenges including questions on healthcare system preparedness and adaptation, ethical aspects, technology literacy, acceptance and appropriate use.

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.

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.

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.

The Persian version of BEHAVE-AD and E-BEHAVE-AD is valid and reliable for the assessment of BPSD in patients with AD.

Studies in cognitively normal individuals on associations between psychiatric symptomatology and incident dementia have not reliably differentiated psychiatric syndromes from neuropsychiatric symptoms (NPS) that represent neurodegeneration. Conventional modelling often overlooks symptom natural history. Mild behavioural impairment (MBI) is a syndrome that leverages later-life emergent and persistent NPS to identify a high-risk group for incident dementia.

We aimed to explore associations of MBI, and conventionally-measured NPS (NPS-not-MBI), with incident dementia in cognitively normal individuals and the cognitively normal subset with subjective cognitive decline (SCD).

Using National Alzheimer's Coordinating Center data, MBI was operationalised by the absence of past psychiatric disorders (symptom emergence) and the presence of symptoms at >2/3 of pre-dementia visits (symptom persistence). Kaplan-Meier survival curves and Cox proportional hazards regressions modelled dementia incidence across NPS groups and MBI domains, adjusted for age, gender, education, race, APOE-ε4, and cognitive status.

The sample comprised 1408 MBI (age 75.2 ± 9.5; 54.3% female), 5625 NPS-not-MBI (age 71.6 ± 8.8; 65.5% female) and 5078 No-NPS (age 71.2 ± 8.9; 67.6% female) participants. Compared with No-NPS, MBI participants had lower dementia-free survival (P < 0.0001) and 2.76-fold greater adjusted dementia incidence rate (95% CI: 2.27-3.35, P < 0.001); incidence rate in NPS-not-MBI did not differ from No-NPS (hazard ratio 0.97, 95% CI: 0.82-1.14, P = 0.687). Of those with MBI who progressed to dementia, 76.0% developed Alzheimer's disease. Similarly, in the SCD subsample (n = 3485), persons with MBI had 1.99-fold greater dementia incidence versus No-NPS (95% CI: 1.46-2.71, P < 0.001) while NPS-not-MBI did not differ from No-NPS (hazard ratio 0.92, 95% CI: 0.70-1.19, P = 0.511).

Incorporating natural history into assessment of psychiatric symptoms in accordance with MBI criteria enhances dementia prognostication and modelling.

Mild behavioral impairment (MBI) represents a recently introduced diagnostic concept that focuses on behavioral and personality changes occurring in late life and associated with cognitive decline. Nevertheless, the relationship between these dimensions remains unclear. This systematic review and meta-analysis aim to analyze the relationship between MBI and cognitive functioning. The review process was conducted according to the PRISMA-Statement. Restrictions were made, selecting the studies published in peer-review journals, including at least one cognitive measure and presenting the measurement of MBI. Studies that included participants with neurological disorders, dementia, or psychiatric disorders or that only did a neuroimaging or genetic study were excluded. Twenty-two studies were included in the systematic review, while in the meta-analysis seventeen studies featured data to be included in the analyses. The results were classified according to the following cognitive domains: global cognitive functioning, memory, language, attention executive functions, visuospatial skills, and processing speed. In the quantitative analysis, only global cognitive functioning, executive function, attention, and memory were evaluated. The results of both qualitative and quantitative analysis indicate that individuals with MBI exhibited diminished performance on cognitive tasks when compared to those without MBI symptoms. These results are stronger when evaluating the various domains individually (particularly memory and executive functions) than when a global assessment was made. These findings highlight the potential role of MBI symptoms as early indicators of neurodegenerative processes, reinforcing the necessity for comprehensive assessments that encompass both behavioral and cognitive evaluations. The early detection of these symptoms in prodromal phases can be very useful for the development of non-pharmacological interventions and may provide relevant guidelines for clinicians in the management and diagnosis of neurodegenerative disorders.

There has been no systematic analysis of coping strategies for behavioral and psychological symptoms of dementia (BPSD) using large-scale cumulative data. We preliminarily examined the characteristics of successful and unsuccessful coping strategies for BPSD.

We employed a deductive and inductive analysis (hybrid approach) of the data derived from "Ninchisho Chienowa-net," a web-based system that collects caregivers' coping strategies for BPSD. Antecedent control procedure and consequence manipulation in applied behavior analysis (ABA) were used as theory-driven codes for deductive classification.

We targeted 1049 cases except "others" among BPSD's categories submitted from January 2016 to January 2019, and finally, 1027 were selected.

Subsequently, nine sub-codes of coping strategies were inductively generated through a trial classification in the first BPSD category, applying these to remaining categories.

Success frequencies varied significantly across coping strategy sub-codes: strategies "assisting the person in performing other activities," "addressing setting events," "listening to the person and accepting her/his challenges," and "multi-coping strategies" had higher success frequencies than expected. Conversely, "explaining reality" and "inhibiting BPSD" had higher failure frequencies than expected. As for the BPSD category "problems due to forgetting," "prompting the person to do an appropriate behavior" was more successful than other coping strategies.

This investigation systematically elucidated the efficacy of various coping strategies, delineating successful ones from those that were not. The discerned patterns across all categories of BPSD and within each individual category will provide valuable insights for caregivers.

Neurodegenerative disorders present significant therapeutic challenges, particularly due to the complex nature of drug delivery to the central nervous system. This review investigates the applications of various biopolymers in neuroprotection and their potential role in treating neurodegeneration. We present a critical analysis of natural and synthetic biopolymers, focusing primarily on chitosan, fish collagen/gelatin, and alginate as key therapeutic agents. The review examines the fundamental mechanisms of brain development and neurodegeneration, establishing a framework for understanding how these biopolymers interact with neural tissues. By analyzing recent experimental studies, we evaluate the effectiveness of different biopolymer-based delivery systems in crossing the blood-brain barrier and their subsequent neuroprotective effects. Additionally, promising materials, including lignin, poly lactic-co-glycolic acid, and glucose-modified bovine serum albumin/procyanidin complexes, are briefly explored to provide a comprehensive overview of current developments in the field. Our analysis reveals that biopolymer-based approaches offer unique advantages in both neuroprotection and drug delivery, potentially opening new avenues for treating neurodegenerative conditions. This review synthesizes current knowledge and identifies promising directions for future research in biopolymer-based therapeutic strategies.

Dementia prevalence within the European Union (EU) is expected to double by 2050. Behavioural and Psychological Symptoms of Dementia (BPSD) are common, causing burden to patients and caregivers. This pragmatic scoping review aims to synthesize recommendations of European BPSD management guidelines and literature, highlighting areas of consensus and disagreement.

An electronic literature search, including Medline, PsychINFO, and CINAHL, and Internet search for grey literature were undertaken to identify published BPSD guidelines from the EU, European Economic Area (EEA) and UK, supplemented by contacting EU member countries of European Geriatric Medicine Society (EuGMS).

The literature search found 11 papers describing BPSD management. Of the 32 countries of interest, 22 guidelines were sourced (five confirmed no guidelines, five did not respond). There was a general consensus between the guidelines, as all recommended comprehensive assessment and individualised approaches, with non-pharmacological therapies as first line, but there was disagreement around specific therapies. Psycho-education was most commonly recommended (15 countries). There was general agreement that pharmacological treatment should be used as an adjunct to non-pharmacological interventions, but recommendations differed between medication groups. Short-term atypical antipsychotics were most commonly recommended, especially risperidone (18 countries). 15 countries recommended acetylcholinesterase inhibitors and 12 memantine. 16 countries recommended the use of SSRIs. Recommendations for the use of sedative medications and antiepileptics varied.

This study provides a broad, inclusive overview of current European guidelines for the management of BPSD, demonstrating significant variability. Clinical practice in dementia care throughout Europe needs to be optimised and standardised.

Neuropsychiatric symptoms (NPS) present in older adults with Alzheimer's disease (AD) and other dementias are related to mortality. Research on the relationship between NPS and mortality in a non-dementia population is limited. This study examines NPS as a predictor of six-year mortality among community dwelling Mexican Americans aged 80 years and older. Data included 466 cognitively normal participants from Wave 7 of the Hispanic Established Population for the Epidemiological Study of Elderly. NPS were measured using the Neuropsychiatric inventory (NPI). Cox proportional hazard models were used to estimate the hazard ratio (HR) of mortality. The HR of death at 6 years was 1.02 (95% Confidence Interval-CI [1.00, 1.04]) as a function of NPI score and 1.09 (95% CI [1.02, 1.17]) for the number of NPI conditions, controlling for demographic and health characteristics. Apathy, irritability, and aberrant motor behavior were all independently predictors of mortality. NPS may be modifiable risk factors to increase survival time or may be indicative of underlying health problems. NPS may be related to underlying health conditions among older adults with normal cognitive functioning.

The presence of psychosis in Alzheimer's disease (AD) is suggested to be associated with distinct molecular and neuropathological profiles in the brain.

We assessed brain DNA methylation in AD donors with psychosis (AD+P) and without psychosis (AD-P) using the EPIC array. Weighted gene correlation network analysis identified modules of co-methylated genes in a discovery cohort (PITT-ADRC: N = 113 AD+P, N = 40 AD-P), with validation in an independent cohort (BDR: N = 79 AD+P, N = 117 AD-P), with Gene Ontology and cell-type enrichment analysis. Genetic data were integrated to identify methylation quantitative trait loci (mQTLs), which were co-localized with GWAS for related traits.

We replicated one AD+P associated module, which was enriched for synaptic pathways and in excitatory and inhibitory neurons. mQTLs in this module co-localized with variants associated with schizophrenia and educational attainment.

This represents the largest epigenetic study of AD+P to date, identifying pleiotropic relationships between AD+P and related traits.

DNA methylation was assessed in the prefrontal cortex in subjects with AD+P and AD-P. WGCNA identified six modules of co-methylated loci associated with AD+P in a discovery cohort. One of the modules was replicated in an independent cohort. This module was enriched for synaptic genes and in excitatory and inhibitory neurons. mQTLs mapping to genes in the module co-localized with GWAS loci for schizophrenia and educational attainment.

The objective of this research was to examine the association between precuneus cortex thickness and mild behavioral impairment (MBI) in patients with mild stroke. Seventy-two patients were evaluated by high-resolution 3 T magnetic resonance and the mild behavioral impairment checklist (MBI-C). To determine the association between precuneus cortex thickness and MBI, we adjusted for demographics, vascular risk factors, and laboratory examination indicators in logistic regression analysis. In addition, we used mendelian randomization to further study the association through genetic databases. Of the 72 mild stroke patients in this study, 26 had MBI. We found a strong negative connection between precuneus cortex thickness and MBI after adjusting for any confounding variables. In patients with an initial mild stroke, the thinner the precuneus cortex, the higher the risk of MBI (OR: 0.02; 95% CI: 0.00-0.39; P < 0.05). Our study has uncovered a significant negative association between the thickness of the precuneus cortex and MBI. This finding provides a novel viewpoint for the radiological diagnosis of MBI, thereby augmenting the contribution of imaging to the diagnostic process of MBI and advancing the prediction of dementia. Specifically, in patients who have suffered mild stroke, a reduction in the cortical thickness of the precuneus has been pinpointed as crucial radiographic evidence of preclinical cognitive impairment. This insight could potentially facilitate earlier detection and intervention strategies for cognitive decline.

Traumatic Brain Injury (TBI) may contribute additional complexity to the clinical picture of mild behavioral impairment (MBI). MBI, a behavioral analog to mild cognitive impairment (MCI), is comprised of five neuropsychiatric domains: decreased motivation, affective dysregulation, impulse dyscontrol, social inappropriateness, and abnormal perception/thought content. We investigated (1) if cross-sectional associations of cognitive status with MBI symptoms differ by TBI status and (2) if prospective associations of MBI domain positivity with incident dementia risk differ by TBI status.

2246 participants without dementia from the Atherosclerosis Risk in Communities Study were included (mean age = 75.6 years, 59.0% female). TBI was defined by self-report/ICD-9/10 codes, MBI via an established algorithm based on the Neuropsychiatric Inventory Questionnaire, and baseline cognitive status/incident dementia using neuropsychological tests, informant interviews, and hospital/death certificate codes.

Cross-sectionally, although MCI status was associated with greater odds of MBI, this did not differ based on TBI status (MCI with TBI: OR = 2.04, 95% CI = 1.44-2.88, MCI without TBI: OR = 1.60, 95% CI = 1.20-2.14). Individuals with MCI (with or without TBI) were more likely to have decreased motivation, affective dysregulation, and impulse dyscontrol. Prospectively, positivity in 1+ MBI domains was associated with increased risk of incident dementia, not differing by TBI status (no TBI and MBI: HR = 2.15, 95% CI = 1.55-2.99, TBI and MBI: HR = 2.62, 95% CI = 1.81-3.80).

Neither cross-sectional associations between cognitive status and MBI domain positivity nor prospective associations of MBI domain positivity with incident dementia risk differed by TBI status. How TBI may relate to neuropsychiatric symptomatology in the context of neurodegenerative processes requires further clarification.

Alzheimer's disease is characterized by progressive amyloid deposition and cognitive decline, yet the pathological mechanisms and treatments remain elusive. Here we report the therapeutic potential of low-intensity 40 hertz blue light exposure in a 5xFAD mouse model of Alzheimer's disease. Our findings reveal that light treatment prevents memory decline in 4-month-old 5xFAD mice and motivation loss in 14-month-old 5xFAD mice, accompanied by restoration of glial water channel aquaporin-4 polarity, improved brain drainage efficiency, and a reduction in hippocampal lipid accumulation. We further demonstrate the beneficial effects of 40 hertz blue light are mediated through the activation of the vLGN/IGL-Re visual circuit. Notably, concomitant use of anti-Aβ antibody with 40 hertz blue light demonstrates improved soluble Aβ clearance and cognitive performance in 5xFAD mice. These findings offer functional evidence on the therapeutic effects of 40 hertz blue light in Aβ-related pathologies and suggest its potential as a supplementary strategy to augment the efficacy of antibody-based therapy.

Previous studies on neuroimaging findings in Alzheimer's disease (AD) patients with hallucinations and delusions have yielded inconsistent results. We aimed to systematically review neuroimaging findings of delusions and hallucinations in AD patients to describe the most prominent neuroimaging features.

We performed a comprehensive search in three online databases, including PubMed, Scopus, and Web of Science in June 2023. We included studies that reported neuroimaging features of AD patients with delusion, hallucination, or psychosis.

After the screening, 34 studies with 2241 AD patients were eligible to be included in our qualitative synthesis. On the basis of the included studies, there are significant changes in the volume and perfusion levels of broad brain areas, including the hippocampus, amygdala, insula, cingulate, occipital, frontal, prefrontal, orbitofrontal, temporal, and parietal cortices in these patients. Moreover, AD patients with psychosis, hallucinations, or delusions reflected different EEG waves compared to AD patients without these disorders.

The results of our review provided evidence about the neuroimaging alterations in AD patients suffering from psychosis, hallucinations, and delusions using different imaging methods. AD patients with psychosis, hallucinations, or delusions have significant differences in the volume and perfusion levels of various brain regions along with alterations in EEG waves and biological molecules compared to patients with only AD.

Neuropsychiatric symptoms affect the majority of dementia patients. Past studies report high rates of potentially inappropriate prescribing of psychotropic medications in this population. We investigate differences in neuropsychiatric diagnoses and psychotropic medication prescribing in a local US cohort by sex and race.

We utilize Medicare claims and prescription fill records in a cohort of 100% Medicare North and South Carolina beneficiaries ages 50 and above for the year 2017 with a dementia diagnosis. We identify dementia and quantify diagnosis of anxiety, depression and psychosis using validated coding algorithms. We search Medicare claims for antianxiety, antidepressant and antipsychotic medications to determine prescriptions filled.

Anxiety and depression were diagnosed at higher rates in White patients; psychosis at higher rates in Black patients. (P < .001) Females were diagnosed with anxiety, depression and psychosis at higher rates than males (P < .001) and filled more antianxiety and antidepressant medications than males. (P < .001) Black and Other race patients filled more antipsychotic medications for anxiety, depression and psychosis than White patients. (P < .001) Antidepressants were prescribed at higher rates than antianxiety or antipsychotic medications across all patients and diagnoses. Of patients with no neuropsychiatric diagnosis, 11.4% were prescribed an antianxiety medication, 22.8% prescribed an antidepressant and 7.6% prescribed an antipsychotic.

The high fill rate of antianxiety (benzodiazepine) medications in dementia patients, especially females is a concern. Patients are prescribed psychotropic medications at high rates. This practice may represent potentially inappropriate prescribing. Patient/caregiver education with innovative community outreach and care delivery models may help decrease medication use.

Clinical distinction between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) poses significant challenges due to pathological comorbidity. Similar ages of onset and overlapping cognitive and psychiatric symptoms can lead to diagnostic inaccuracy and inappropriate treatment recommendations.

Identify the best combination of clinical and neuropsychological predictors of AD, DLB, and mixed DLB/AD neuropathology in dementia patients.

Using the National Alzheimer's Coordinating Center dataset, we selected either pure AD (n = 189), DLB (n = 21), or mixed DLB/AD (n = 42) patients on autopsy. Neuropsychological and clinical predictors, including core clinical features of DLB, were entered into multivariable logistic regressions.

Gait disturbances (odds ratio (OR) = 19.32; p = 0.01), visual-spatial complaints (OR = 6.06; p = 0.03), and visual hallucinations (OR = 31.06; p = 0.002) predicted DLB compared to AD, along with better memory (OR = 3.42; p = 0.003), naming (OR = 3.35; p = 0.002), and worse processing speed (OR = 0.51; p = 0.01). When comparing DLB to DLB/AD, gait disturbances (OR = 6.33; p = 0.01), increased depressive symptoms (OR = 1.44; p = 0.03), and better memory (OR = 3.01; p = 0.004) predicted DLB. Finally, rapid eye movement sleep behavior disorder (RBD) (OR = 6.44; p = 0.004), parkinsonism severity (OR = 1.07; p = 0.02), and lower depressive symptoms (OR = 0.70; p = 0.006) and memory impairment (OR = 0.57; p = 0.02) distinguished DLB/AD from AD.

Our study converges with prior research suggesting specific neuropsychological and clinical features can help distinguish DLB from AD. Neuropsychological differentiation becomes more challenging among mixed pathologies and in advanced cognitive impairment, although the presence of RBD and parkinsonism distinguished DLB. Earlier clinical assessment and incorporation of in vivo and postmortem biomarkers should enhance diagnostic accuracy and understanding of disease characteristics, offering significant relevance for disease-modifying treatments.

In a response to the lack of public awareness of dementia, 'ageing in place' and 'dementia-friendly community' policies have been proposed, and a number of relevant studies have been carried out.

To map the evidence of public help for people with dementia in the community.

A scoping review.

A comprehensive search of nine databases was conducted to find studies from the inception of the databases to January 2024. We developed our inclusion criteria to identify studies about public help for people with dementia in the community. Data from included studies were charted (purposively designed template) and narrated synthesis in relation to the study's research questions.

Of 34 studies included, we found that difficult situations were encountered by people with dementia after developing cognitive, behavioural and psychological symptoms. We identified three types of helping behaviour, namely, formal planned, informal planned and spontaneous helping behaviour, which were influenced by general demographic characteristics, knowledge, attitudes, responsibilities and understanding. Fourteen studies proposed interventions to promote public help for people with dementia in the community, covering three categories of teaching, practical and web-based methods.

It is necessary to develop a systematic intervention to promote public helping behaviour according to the characteristics of people with dementia and the modifiable influencing factors of helping behaviour.

No patient or public contribution. This is a Scoping Review.

Mental health issues are widespread and significant among individuals with serious illness. Among patients receiving palliative care (PC), psychiatric comorbidities are common and impact patient quality of life. Despite their prevalence, PC clinicians face challenges in effectively addressing the intricate relationship between medical and psychiatric disorders due to their complex, intertwined and bidirectionally influential nature. This article, created collaboratively with a team of psychiatric-palliative care experts, is the second in a two-part series examining the bidirectional relationship between medical and psychiatric illness in PC. This article explores 10 prevalent psychiatric manifestations associated with severe illness and its treatment. Building upon the first article, which focused on 10 common physical manifestations of psychiatric illness among patients receiving PC, these two articles advocate for an integrated approach to PC that prioritizes mental and emotional wellbeing across the continuum of serious illness.

The coexistence of dementia and depression in older populations presents a complex clinical challenge, with each condition often exacerbating the other. Cognitive decline can intensify mood disturbances, and untreated or recurring depression accelerates neurodegenerative processes. As depression is a recognized risk factor for dementia, it is crucial to address both conditions concurrently to prevent further deterioration. Antidepressants are frequently used to manage depression in dementia patients, with some studies suggesting they offer neuroprotective benefits. These benefits include promoting neurogenesis, enhancing synaptic plasticity, and reducing neuroinflammation, potentially slowing cognitive decline. Additionally, antidepressants have shown promise in addressing Alzheimer's-related pathologies by reducing amyloid-beta accumulation and tau hyperphosphorylation. However, treatment-resistant depression remains a significant challenge, particularly in older adults with cognitive impairment. Many do not respond well to standard antidepressant therapies due to advanced neurodegenerative changes. Conflicting findings from studies add to the uncertainty, with some research suggesting that antidepressants may increase dementia risk, especially when used in patients with undiagnosed early-stage dementia. This article aims to explore the intricate relationship between depression and dementia, examining the benefits and risks of antidepressant use. We highlight the urgent need for personalized, comprehensive treatment strategies that balance mental health improvement with cognitive protection.

Psychotic symptoms (hallucinations and delusions) are a type of neuropsychiatric symptom found during Alzheimer's Disease (AD).

This systematic review aims to comprehensively capture, analyse, and evaluate the body of evidence that has investigated associations between brain regions/networks and psychotic symptoms in AD.

The protocol, created according to the PRISMA guidelines, was pre-registered on OSF (https://osf.io/tg8xp/). Searches were performed using PubMed, Web of Science and PsycInfo. A partial coordinate-based meta-analysis (CBMA) was performed based on data availability.

Eighty-two papers were selected: delusions were found to be associated mainly with right fronto-temporal brain regions and the insula; hallucinations mainly with fronto-occipital areas; both were frequently associated with the anterior cingulate cortex. The CBMA, performed on the findings of fourteen papers on delusions, identified a cluster in the frontal lobe, one in the putamen, and a smaller one in the insula.

The available evidence highlights that key brain regions, predominantly in the right frontal lobe, the anterior cingulate cortex, and temporo-occipital areas, appear to underpin the different manifestations of psychotic symptoms in AD and MCI. The fronto-temporal areas identified in relation to delusions may underpin a failure to assimilate correct information and consider alternative possibilities (which might generate and maintain the delusional belief), and dysfunction within the salience network (anterior cingulate cortex and insula) may suggest a contribution for how internal and external stimuli are identified; the fronto-occipital areas linked to hallucinations may indicate diminished sensory processing and non-optimal predictive processing, that together contribute to misinterpretation of stimuli and misperceptions; the fronto-temporal and occipital areas, as well as the anterior cingulate cortex were linked to the psychotic cluster.

Behavioral and psychological symptoms of dementia (BPSD) are common among people with dementia from the early stages and can appear even in mild cognitive impairment (MCI). However, the prognostic impact of BPSD is unclear. This study examined the association between BPSD and mortality among people with cognitive impairment.

This longitudinal study involved 1,065 males and 1,681 females (mean age: 77.1 years for males and 78.6 years for females) with MCI or dementia diagnosis from the National Center for Geriatrics and Gerontology-Life Stories of People with Dementia (NCGG-STORIES), a single-center memory clinic-based cohort study in Japan that registered first-time outpatients from 2010-2018. Information about death was collected through a mail survey returned by participants or their close relatives, with an up to 8-year follow-up. BPSD was assessed using the Dementia Behavior Disturbance Scale (DBD) at baseline.

During the follow-up period, 229 (28.1%) male and 254 (15.1%) female deaths occurred. Cox proportional hazards regression analysis showed that higher DBD scores were significantly associated with increased mortality risk among males, but not females (compared with the lowest quartile score group, hazard ratios for the highest quartile score group were 1.59; 95% confidence interval, [CI] 1.11-2.29 for males and 1.06; 95% CI, 0.66-1.70 for females). Among the DBD items, lack of interest in daily living, excessive daytime sleep, and refusal to receive care had a higher mortality risk.

The findings suggest a potential association between BPSD and poor prognosis among males with cognitive impairment.

Behavioral and psychological symptoms of dementia (BPSD) are common in people with dementia. Aromatherapy may reduce the frequency and severity of BPSD. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of aromatherapy in relieving BPSD and improving functional ability in people with dementia.

Systematic review and meta-analysis.

Patients with dementia receiving aromatherapy.

A literature search was conducted using PubMed, Embase, and Cochrane Library for RCTs published before March 2024 comparing aromatherapy with control treatments in patients with dementia.

There were 15 trials involving 821 patients. Overall, significant reduction in BPSD was observed after 1 month of aromatherapy treatment. Among 15 trials, 9 reported the Cohen-Mansfield Agitation Inventory (CMAI) score, and 7 evaluated the Neuropsychiatric Inventory (NPI) score. The meta-analysis showed significant improvement in CMAI score [weighted mean difference (WMD) -6.31, 95% CI -9.52 to -3.11] and NPI score (WMD -8.07, 95% CI -13.53 to -2.61) in patients receiving 3 to 4 weeks of aromatherapy compared with the control group. Four of the 15 trials reported improvement in depressive mood and 3 trials reported no significant improvement in functional ability.

In conclusion, aromatherapy is a safe and viable nonpharmacologic treatment to improve BPSD in people with dementia and its combination with massage showed higher efficacy.

According to scientific literature, some 99% of patients affected by Alzheimer's disease (AD) suffer from behavioral and psychological symptoms of dementia (BPSD), also known as neuropsychiatric symptoms (NPSs). In particular, agitation is one of the most difficult disorders to treat. States of agitation represent a very serious problem as they make these subjects dangerous for themselves and others and worsen as the disease advances. To date, there are no specific solutions for treating agitation. The only authorized drug is risperidone (as well as brexpiprazole, approved by the FDA on 11 May 2023), which can be used for no longer than 6-12 weeks because it increases the risk of death-owing to cardiocerebrovascular accidents-by 1.6-1.7 times.

In order to address the latter noteworthy unmet medical need, NanoBEO was produced. The aim of the present work is to generate the health technology assessment (HTA) of this nanotechnological device. The latter consists of a controlled release system, based on solid lipid nanoparticles loaded with bergamot essential oil (BEO).

The results of the present research assessed the current evidence in the field of non-pharmacological treatments for this condition, including relevant primary preclinical and clinical data studies supporting the use of this device and the production of the operative plan for its launch on the market. The findings offer recommendations for decision-making on its implementation in dementia.

NanoBEO represents a public-worth innovation in this neglected area, marking a significant advancement in the history of dementia, moving from academic research to product development.

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.

With the rising demand for medical services and the associated burden, work-related stress and mental health issue have garnered increased attention among healthcare workers. Anxiety, cognitive impairment, and their comorbidities severely impact the physical and mental health as well as the work status of healthcare workers. The network analysis method was used to identify the anxiety and cognitive impairment among mental healthcare workers using the Generalized Anxiety Disorder Scale (GAD-7) and the Perceived Deficit Questionnaire for Depression (PDQ-D). We sought to identify the core symptoms associated with the comorbidity of anxiety and cognitive impairment in mental healthcare workers.

The study was conducted by Shandong Daizhuang Hospital and Qingdao Mental Health Center in China from September 13, 2022, to October 25, 2022, involving a total of 680 healthcare workers as participants. GAD-7 and PDQ-D were utilized to assess anxiety and cognitive impairment, respectively. Regularized partial correlation network analysis was employed to examing the expected influence and predictability of each item within the network. Statistical analysis and visualization of the network were performed using R software.

The mean total score for anxiety was 3.25, while the mean total score for cognitive symptoms was 15.89. PDQ17 "Remembering numbers", PDQ12 "Trouble get started" and PDQ20 "Trouble make decisions" emerged as central symptoms in the anxiety-cognition network. GAD6 "Irritable", GAD5 "Restlessness" and GAD1 "Nervousness or anxiety" were identified as the most critical bridge symptoms connecting anxiety and cognition. Gender was found to be unrelated to the global strength of the network, edge weight distribution, or individual edge weights.

Utilizing central and bridge symptoms (i.e., Remembering numbers, Trouble get started, Trouble make decisions, Irritable, Restlessness and Nervousness or anxiety) as primary intervention points may aid in mitigating the serious health consequences of anxiety, cognitive impairment, and comorbidities anxiety and cognitive impairment for mental healthcare workers.

The pathological hallmarks of Alzheimer's disease (AD), amyloid, tau, and associated neurodegeneration, are present in the cortical gray matter (GM) years before symptom onset, and at significantly greater levels in carriers of the apolipoprotein E4 (APOE4) allele. Their respective biomarkers, A/T/N, have been found to correlate with aspects of brain biochemistry, measured with magnetic resonance spectroscopy (MRS), indicating a potential for MRS to augment the A/T/N framework for staging and prediction of AD. Unfortunately, the relationships between MRS and A/T/N biomarkers are unclear, largely due to a lack of studies examining them in the context of the spatial and temporal model of T/N progression. Advanced MRS acquisition and post-processing approaches have enabled us to address this knowledge gap and test the hypotheses, that glutamate-plus-glutamine (Glx) and N-acetyl-aspartate (NAA), metabolites reflecting synaptic and neuronal health, respectively, measured from regions on the Braak stage continuum, correlate with: (i) cerebrospinal fluid (CSF) p-tau181 level (T), and (ii) hippocampal volume or cortical thickness of parietal lobe GM (N). We hypothesized that these correlations will be moderated by Braak stage and APOE4 genotype.

We conducted a retrospective imaging study of 34 cognitively unimpaired elderly individuals who received APOE4 genotyping and lumbar puncture from pre-existing prospective studies at the NYU Grossman School of Medicine between October 2014 and January 2019. Subjects returned for their imaging exam between April 2018 and February 2020. Metabolites were measured from the left hippocampus (Braak II) using a single-voxel semi-adiabatic localization by adiabatic selective refocusing sequence; and from the bilateral posterior cingulate cortex (PCC; Braak IV), bilateral precuneus (Braak V), and bilateral precentral gyrus (Braak VI) using a multi-voxel echo-planar spectroscopic imaging sequence. Pearson and Spearman correlations were used to examine the relationships between absolute levels of choline, creatine, myo-inositol, Glx, and NAA and CSF p-tau181, and between these metabolites and hippocampal volume or parietal cortical thicknesses. Covariates included age, sex, years of education, Fazekas score, and months between CSF collection and MRI exam.

There was a direct correlation between hippocampal Glx and CSF p-tau181 in APOE4 carriers (Pearson's r = 0.76, p = 0.02), but not after adjusting for covariates. In the entire cohort, there was a direct correlation between hippocampal NAA and hippocampal volume (Spearman's r = 0.55, p = 0.001), even after adjusting for age and Fazekas score (Spearman's r = 0.48, p = 0.006). This relationship was observed only in APOE4 carriers (Pearson's r = 0.66, p = 0.017), and was also retained after adjustment (Pearson's r = 0.76, p = 0.008; metabolite-by-carrier interaction p = 0.03). There were no findings in the PCC, nor in the negative control (late Braak stage) regions of the precuneus and precentral gyrus.

Our findings are in line with the spatially- and temporally-resolved Braak staging model of pathological severity in which the hippocampus is affected earlier than the PCC. The correlations, between MRS markers of synaptic and neuronal health and, respectively, T and N pathology, were found exclusively within APOE4 carriers, suggesting a connection with AD pathological change, rather than with normal aging. We therefore conclude that MRS has the potential to augment early A/T/N staging, with the hippocampus serving as a more sensitive MRS target compared to the PCC.

Neuropsychiatric symptoms (NPSs) in Alzheimer's disease (AD) constitute multifaceted behavioral manifestations that reflect processes of emotional regulation, thinking, and social behavior. They are as prevalent in AD as cognitive impairment and develop independently during the progression of neurodegeneration. As studying NPSs in AD is clinically challenging, most AD research to date has focused on cognitive decline. In this opinion article we summarize emerging literature on the prevalence, time course, and the underlying genetic, molecular, and pathological mechanisms related to NPSs in AD. Overall, we propose that NPSs constitute a cluster of core symptoms in AD, and understanding their neurobiology can lead to a more holistic approach to AD research, paving the way for more accurate diagnostic tests and personalized treatments embracing the goals of precision medicine.

Neuropsychiatric symptoms (NPS) are common in older people, may occur early in the development of dementia disorders, and have been associated with faster cognitive decline. Here, our objectives were to investigate whether plasma levels of neurofilament light chain (NfL), glial fibrillary acid protein (GFAP), and tau phosphorylated at threonine 181 (pTau181) are associated with current NPS and predict future NPS in non-demented older people. Furthermore, we tested whether the presence of NPS combined with plasma biomarkers are useful to predict Alzheimer's disease (AD) pathology and cognitive decline.

One hundred and fifty-one participants with normal cognition (n = 76) or mild cognitive impairment (n = 75) were examined in a longitudinal brain aging study at the Memory Centers, University Hospital of Lausanne, Switzerland. Plasma levels of NfL, GFAP, and pTau181 along with CSF biomarkers of AD pathology were measured at baseline. NPS were assessed through the Neuropsychiatric Inventory Questionnaire (NPI-Q), along with the cognitive and functional performance at baseline and follow-up (mean: 20 months). Different regression and ROC analyses were used to address the associations of interest.

None of the three plasma biomarker was associated with NPS at baseline. Higher GFAP levels were associated with the presence of NPS at follow-up (OR = 2.8, p = .002) and both, higher NfL and higher GFAP with an increase in the NPI-Q severity score over time (β = 0.25, p = .034 and β = 0.30, p = .013, respectively). Adding NPS and the plasma biomarkers to a reference model improved the prediction of future NPS (AUC 0.72 to 0.88, p = .002) and AD pathology (AUC 0.78 to 0.87, p = .010), but not of cognitive decline (AUC 0.79 to 0.85, p = .081).

Plasma NfL and GFAP are both associated with future NPS and NPS severity change. Considering the presence of NPS along with blood-based AD-biomarkers may improve the prediction of clinical progression of NPS over time and inform clinical decision-making in non-demented older people.