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OBJECTIVES: Among participants with Alzheimer's disease (AD) we estimated the minimal clinically important difference (MCID) in apathy symptom severity on three scales. DESIGN: Retrospective anchor- and distribution-based analyses of change in apathy symptom scores. SETTING: Apathy in Dementia Methylphenidate Trial (ADMET) and ADMET 2 randomized controlled trials conducted at three and ten clinics specialized in dementia care in United States and Canada, respectively. PARTICIPANTS: Two hundred and sixty participants (60 ADMET, 200 ADMET 2) with clinically significant apathy in Alzheimer's disease. MEASUREMENTS: The Clinical Global Impression of Change in Apathy scale was used as the anchor measure and the MCID on the Neuropsychiatric Inventory - Apathy (NPI-A), Dementia Apathy Interview and Rating (DAIR), and Apathy Evaluation Scale-Informant (AES-I) were estimated with linear mixed models across all study visits. The estimated thresholds were evaluated with performance metrics. RESULTS: Among the MCID was a decrease of four points (95% CI: -4.0 to -4.8) on the NPI-A, 0.56 points (95% CI: -0.47 to -0.65) on the DAIR, and three points on the AES-I (95% CI: -0.9 to -5.4). Distribution-based analyses were largely consistent with the anchor-based analyses. The MCID across the three measures showed ∼60% accuracy. Sensitivity analyses found that MMSE scores and apathy severity at baseline influenced the estimated MCID. CONCLUSIONS: MCIDs for apathy on three scales will help evaluate treatment efficacy at the individual level. However, the modest correspondence between MCID and clinical impression of change suggests the need to consider other scales.

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Dementia is characterized by a progressive decline in cognition, behavioral and psychological symptoms (BPSD), and quality of life (QoL). The lack of curative therapies has led to a psychosocial discourse prioritizing QoL of people thriving with dementia (PTD). Group reminiscence therapy (RT) is a relatively inexpensive intervention, with music prompts being a preferred choice, owing to robust musical memory in the early disease stage. However, a synthesis of current evidence is needed to inform research and clinical use of group music RT in dementia care. Therefore, we conducted a systematic review on PubMed, Scopus, CINAHL, APA PsycInfo, and APA PsycArticles to critically appraise published randomized controlled trials examining group music RT to improve cognition, BPSD, and QoL in PTD. Of 14,725 articles, two RCTs involving 102 PTD were included. All studies used prerecorded music for group music RT. All studies were deemed of good quality, adhering to intention-to-treat analysis and assessor blinding. Based on the American Academy of Neurology guidelines, we assigned a Level C recommendation for group music RT for cognition and Level B recommendations for BPSD and QoL (ineffective). In conclusion, group music RT may be useful for symptomatic management in PTD. However, heterogeneous study designs, disease severity, dementia subtype, and outcome measures are likely barriers to meaningful clinical translation. Therefore, the rating of recommendations only serves as a point of reference. Future avenues include live performances as prompts for group music RT.

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Studies exploring the brain correlates of behavioral symptoms in the frontotemporal dementia spectrum (FTD) have mainly searched for linear correlations with single modality neuroimaging data, either structural magnetic resonance imaging (MRI) or fluoro-deoxy-D-glucose positron emission tomography (FDG-PET). We aimed at studying the two imaging modalities in combination to identify nonlinear co-occurring patterns of atrophy and hypometabolism related to behavioral symptoms. We analyzed data from 93 FTD patients who underwent T1-weighted MRI, FDG-PET imaging, and neuropsychological assessment including the Neuropsychiatric Inventory, Frontal Systems Behavior Scale, and Neurobehavioral Rating Scale. We used a data-driven approach to identify the principal components underlying behavioral variability, then related the identified components to brain variability using a newly developed method fusing maps of grey matter volume and FDG metabolism. A component representing apathy, executive dysfunction, and emotional withdrawal was associated with atrophy in bilateral anterior insula and putamen, and with hypometabolism in the right prefrontal cortex. Another component representing the disinhibition versus depression/mutism continuum was associated with atrophy in the right striatum and ventromedial prefrontal cortex for disinhibition, and hypometabolism in the left fronto-opercular region and sensorimotor cortices for depression/mutism. A component representing psychosis was associated with hypometabolism in the prefrontal cortex and hypermetabolism in auditory and visual cortices. Behavioral symptoms in FTD are associated with atrophy and altered metabolism of specific brain regions, especially located in the frontal lobes, in a hierarchical way: apathy and disinhibition are mostly associated with grey matter atrophy, whereas psychotic symptoms are mostly associated with hyper-/hypo-metabolism.

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BACKGROUND: A common challenge for individuals caring for people with Alzheimer disease and related dementias is managing the behavioral and psychological symptoms of dementia (BPSD). Effective management of BPSD will increase the quality of life of people living with dementia, lessen caregivers' burden, and lower health care cost. OBJECTIVE: In this review, we seek to (1) examine how indoor environmental quality parameters pertaining to light, noise, temperature, and humidity are associated with BPSD and how controlling these parameters can help manage these symptoms and (2) identify the current state of knowledge in this area, current gaps in the research, and potential future directions. METHODS: Searches were conducted in the CINAHL, Embase, MEDLINE, and PsycINFO databases for papers published from January 2007 to February 2024. We searched for studies examining the relationship between indoor environmental quality parameters pertaining to light, noise, temperature, and humidity and BPSD. RESULTS: A total of 3123 papers were identified in the original search in October 2020. After an additional 2 searches and screening, 38 (0.69%) of the 5476 papers were included. Among the included papers, light was the most studied environmental factor (34/38, 89%), while there were fewer studies (from 5/38, 13% to 11/38, 29%) examining the relationships between other environmental factors and BPSD. Of the 38 studies, 8 (21%) examined multiple indoor environmental quality parameters. Subjective data were the only source of environmental assessments in 6 (16%) of the 38 studies. The findings regarding the relationship between agitation and light therapy are conflicted, while the studies that examined the relationship between BPSD and temperature or humidity are all observational. The results suggest that when the environmental factors are deemed overstimulating or understimulating for an individual with dementia, the behavioral symptoms tend to be exacerbated. CONCLUSIONS: The findings of this scoping review may inform the design of long-term care units and older adult housing to support aging in place. More research is still needed to better understand the relationship between indoor environmental quality parameters and BPSD, and there is a need for more objective measurements of both the indoor environmental quality parameters and behavioral symptoms. One future direction is to incorporate objective sensing and advanced computational methods in real-time assessments to initiate just-in-time environmental interventions. Better management of BPSD will benefit patients, caregivers, and the health care system.

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Introduction: The Cohen-Mansfield Agitation Inventory (CMAI) quantifies the frequency of agitation behaviors in elderly persons. This post hoc analysis of data from the brexpiprazole clinical program aimed to determine a meaningful within-patient change (MWPC) threshold for CMAI Total score among patients with agitation associated with dementia due to Alzheimer's disease. Methods: Data were included from three 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-arm trials of brexpiprazole for the treatment of agitation associated with dementia due to Alzheimer's disease (ClinicalTrials.gov identifiers: NCT01862640, NCT01922258, NCT03548584). Change in CMAI Total score (range 29-203; higher scores indicate higher frequency of agitation behaviors) from baseline to Week 12 was the primary endpoint in each trial. MWPC thresholds were estimated from anchor-based mean change analyses and receiver operating characteristic (ROC) curves. The Clinical Global Impression-Severity of illness (CGI-S) and Clinical Global Impression-Improvement (CGI-I) scales, both as related to agitation, were used as anchors. Empirical cumulative distribution functions (eCDFs) and probability density functions (PDFs) were plotted as supportive evidence. Distribution-based methods were also employed. Results: Data from 898 patients were analyzed (mean age, 73.7 years; mean baseline CMAI Total score, 73.8). The mean CMAI Total score change corresponding to a difference of small improvement vs. stable (CGI-S one-point decrease vs. no change), or minimally improved vs. no change (CGI-I rating of 3 vs. 4), ranged from -10.6 to -13.5 points. The mean CMAI Total score change corresponding to a difference of moderate improvement vs. stable (CGI-S two-point decrease vs. no change), or much improved vs. no change (CGI-I rating of 2 vs. 4), ranged from -20.2 to -25.7 points. ROC curve analyses generally produced smaller estimates of meaningful change. eCDFs and PDFs showed good distribution and separation of CMAI Total score change between CGI-S/CGI-I categories. In distribution-based analyses, the minimal detectable change for CMAI Total score (10.5-11.8 points) was generally lower than anchor-suggested thresholds. Conclusion: Triangulation of evidence from anchor- and distribution-based analyses supports an MWPC threshold for CMAI Total score of -20 points, with a threshold range of -15 to -25 points, in patients with agitation associated with dementia due to Alzheimer's disease.

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BACKGROUND: Non-pharmacological interventions are considered the first-line treatment for managing the behavioral and psychological symptoms of dementia. Given the heterogeneous characteristics of these symptoms, which vary for each individual and tend to fluctuate, a symptom-specific approach is necessary for providing individualized non-pharmacological interventions for people with dementia. However, clear guidelines regarding the appropriate types of interventions for individual symptoms or clusters of behavioral and psychological symptoms of dementia are lacking. OBJECTIVES: The aim of this umbrella review was to summarize the current evidence on non-pharmacological interventions for behavioral and psychological symptoms of dementia and provide guidance for determining the appropriate types of interventions for each behavioral and psychological symptom of dementia. DESIGN: An umbrella review of systematic reviews and/or meta-analyses. METHODS: The Cochrane methodology for umbrella reviews was employed for this review, and the review protocol was registered. PubMed, CINAHL, Embase, PsycINFO, and Cochrane databases were searched for relevant reviews using the 'population, intervention, control, and outcomes' formulation. Two reviewers independently screened the extracted articles for eligibility. The quality of each selected review was independently assessed by the two reviewers using A Measurement Tool to Assess Systematic Reviews 2. The results were narratively synthesized and categorized according to each symptom. RESULTS: Thirty-five systematic reviews, 71 % of which were also meta-analyses, were included in this review. The methodologies employed in the included reviews were significantly heterogeneous. The qualities of the reviews ranged from low to moderate. Diverse types of non-pharmacological interventions were identified in the reviews, with music therapy being the most frequently discussed. Among the various symptoms, depression was most frequently addressed, followed by overall symptoms, agitation, anxiety, sleep problems, and apathy. Music therapy was found to be effective for improving both overall and specific symptoms, including depression and anxiety. Notably, relatively weak evidence supports the effectiveness of exercise in addressing each symptom. Aromatherapy could be considered for agitation, whereas reminiscence may be effective in managing overall and specific symptoms, such as depression. CONCLUSIONS: The results showed that the evidence of symptom-specific effectiveness of non-pharmacological interventions varied across the different behavioral and psychological symptoms of dementia, highlighting the need for a symptom-specific approach in future research. Furthermore, future research is needed to facilitate the development of symptom-specific guidelines that can enhance the quality of individualized dementia care. REGISTRATION: Registered with PROSPERO (number: CRD42022340930) on November 9, 2022.

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Dementia is frequent in nursing home (NH), affecting between 40 and 50 % of the residents and is associated in 90 % of the cases with behavioral and psychological symptoms (BPSD) which are detrimental to caregivers' working life and perceived health. We compared perceived health and working life between NHs that used or did not use nighttime personalized non-pharmacological therapies (PNPT) to address BPSD. This anonymous survey included 96 caregivers from 25 NHs which used (n = 69) or not (n = 27) nighttime PNPT. Perceived health, nursing and medical care, quality of care and internal motivation were significantly higher, stress symptoms and workload were significantly lower and there was a tendency to enhanced satisfaction with work in caregivers from NHs which used nighttime PNPT. Our present data open a new window on the benefits of PNPT.

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BACKGROUND AND OBJECTIVES: This study examined day-to-day variation in care-resistant behaviors (CRBs) exhibited by persons living with dementia during mouth healthcare and the potential influence of time of day on CRB trajectories. RESEARCH DESIGN AND METHODS: A secondary analysis was conducted on a sample of 75 nursing home-dwelling persons living with dementia who exhibited CRBs during mouth care activities. Over 21 days, CRBs were measured using the revised Resistiveness to Care scale (RTC-r) during morning and afternoon mouth care sessions. Group-based trajectory modeling was used to identify trajectory patterns and assess differences between morning and afternoon CRB patterns. RESULTS: Three trajectory patterns were identified: morning CRB trajectory patterns showed 50.6% of persons living with dementia had consistently low RTC-r scores, 37.5% of persons living with dementia exhibited fluctuating, moderate RTC-r scores, and 11.9% exhibited RTC-r scores that started high and then decreased over time. Similarly, CRB trajectory patterns during afternoon mouth care showed a consistently low RTC-r score for 54.5% and a fluctuating moderate RTC-r score for 38.6% of persons living with dementia. However, the third CRB trajectory group followed a high-increasing trajectory, with RTC-r scores starting high and continuing to increase for 6.9% of persons living with dementia. DISCUSSION AND IMPLICATIONS: CRBs are dynamic and vary within days and over time; however, the time of the day is often not considered in interventions to manage CRBs. Thus, it is important to consider the timing of providing mouth care for persons living with dementia. Based on the characteristics of the trajectories, we suggest that morning mouth activities may be more efficient.

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INTRODUCTION: We examined the burden of neuropsychiatric symptoms (NPSs) in early-onset (EO) and late-onset (LO) Alzheimer's disease (AD) and adjusted for age effects via the inclusion of cognitively unimpaired (CU) individuals. METHODS: Cross-sectional data from 2940 EOAD, 8665 LOAD, and 8775 age-stratified CU individuals (early-CU, n = 2433; late-CU, n = 6342) from the National Alzheimer's Coordinating Center database were included. Fisher's exact tests compared EOAD and LOAD on the presence and severity of NPSs. Multiple logistic regression models included an age*diagnosis interaction to examine age effects. RESULTS: Presence (ps < 0.0001) and severity (ps < 0.05) of NPS were greater in EOAD than in LOAD. However, after adjusting for base rates in NPS in CU individuals (age effects), only elation and eating behaviors were more frequent in EOAD (ps < 0.05) and nighttime behaviors more frequent and severe in LOAD (ps < 0.05). DISCUSSION: Few NPSs were specific to the EOAD versus LOAD. Previous findings of greater NPS burden in EOAD may partially reflect age effects. HIGHLIGHTS: Adjusting for age effect, elation and eating problems are more frequent in EOAD. Adjusting for age effect, sleep disturbances are more frequent and severe in LOAD. Age effects underlie higher neuropsychiatric symptom presentation in EOAD than in LOAD.

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Background: Neuropsychiatric symptoms are a robust risk factor for caregiver burden in family dementia caregivers. By grouping these symptoms, clinical interpretations regarding neuropsychiatric symptoms may facilitated because different groups of symptoms may require a different approach for intervention, thereby reducing caregiver burden. Objective: As clustering of neuropsychiatric symptoms could be clinically relevant, we aimed to explore the effects of these clusters on burden in family dementia caregivers. Methods: 152 family dementia caregivers were included. Caregiver burden was measured using the Ervaren Druk door Informele Zorg (EDIZ)/Self-Perceived Pressure from Informal Care, a Dutch questionnaire. Caregivers also reported the neuropsychiatric symptoms and functional impairments in daily activities of the people with dementia they cared for. Multiple regression analyses were used in this cross-sectional study. Results: Adjusted for functional impairments and sociodemographic variables, neuropsychiatric symptoms were associated with more caregiver burden (p < 0.001). However, this association did not differ between the three neuropsychiatric symptom clusters (p = 0.745). Conclusions: Neuropsychiatric symptoms were associated with more family caregiver burden, but no conclusive evidence was found that this association differed for the three clusters. Clustering of neuropsychiatric symptoms is, however, worth exploring further in future studies with more participants. If specific links are found, these could be targeted in clinical practice in order to prevent, reduce and/or postpone caregiver burden.

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OBJECTIVES: Caring for a spouse with Alzheimer's disease (AD) can elicit considerable distress but there are also positive moments. A growing body of work has examined caregivers' ambivalence in the care relationship and linked it to negative caregiver outcomes such as depression, but dyadic assessments of both parties' perspectives are missing. We examined ambivalence in both people with AD and their spousal caregivers, seeking to identify the correlates and well-being outcomes of such ambivalence in this unique context. METHODS: Participants included 72 couples managing early-stage AD. People with AD and spousal caregivers independently self-reported positive and negative relationship qualities (used to indirectly calculate their ambivalence) and life satisfaction. Caregivers reported both partners' demographic characteristics and their spouses' behavioral and psychological symptoms of dementia (BPSD), focusing on memory-related behaviors and psychological symptoms. RESULTS: Path analyses revealed that the number and frequency of psychological symptoms in people with AD were positively associated with their own and caregivers' ambivalence. Caregivers' distress ratings of memory-related behaviors and psychological symptoms were positively associated with their ambivalence. Greater ambivalence was associated with lower life satisfaction in both spouses. BPSD directly affected both spouses' life satisfaction but there were also indirect effects via ambivalence. DISCUSSION: This study utilizes a dyadic approach to assess ambivalence in dementia care. Findings reveal the conflicting emotions that couples experience as they cope with early-stage AD, identify sources of such ambivalence, and shed light on the development of dyadic interventions that can promote positive outcomes in both partners.

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OBJECTIVES: Changes in personality and behavioral symptoms are a core clinical criterion for the diagnosis of dementia. This study examines the association between caregiver-rated personality traits and multiple measures of neuropsychiatric symptoms. METHOD: Caregivers of individuals with dementia (N = 191) or cancer (N = 137) provided premorbid and concurrent personality trait ratings using the Big Five Inventory-2. Caregivers also completed the Mild Behavioral Impairment Checklist, Neuropsychiatric Inventory Questionnaire, and Revised Memory and Behavior Problems Checklist. RESULTS: In the combined sample, high concurrent neuroticism was associated with emotional dysregulation (r = 0.51), low agreeableness with impulse dyscontrol (r=-0.40), and low conscientiousness with decreased motivation (r=-0.42). Associations were similar across neuropsychiatric symptom scales, similar across cancer and dementia, but stronger with concurrent than premorbid personality ratings, and stronger for the individuals with mild than moderate-severe dementia. CONCLUSION: Personality was associated with neuropsychiatric symptoms, including with the measure for mild behavioral impairment. Personality had stronger associations when concurrently assessed, indicating that personality traits co-develop with neuropsychiatric symptoms. The associations were similar across cancer and dementia, suggesting transdiagnostic processes not limited to dementia. Neuropsychiatric symptoms are partly an expression of personality; accounting for personality traits could help with diagnosis and disease monitoring, tailoring interventions, and fostering person-centered care.

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BACKGROUND: To evaluate the knowledge, attitude and practice of nurses regarding non-pharmacologic therapies for behavioral and psychological symptoms of dementia (BPSD). METHODS: This cross-sectional, questionnaire-based study enrolled nurses at Peking Union Medical College Hospital (Beijing, China) between September 2022 and October 2022. Correlations between knowledge, attitude and practice scores were evaluated by Pearson correlation analysis. Factors associated with knowledge, attitude and practice scores were identified by multivariable linear regression. Based on a cross-sectional questionnaire survey, this study designed a questionnaire according to the Guidelines for Diagnosis and Treatment of Dementia in China, and randomly selected nurses from Peking Union Medical College Hospital to fill in the questions through the Wen-Juan-Xing online platform from September 2022 to October 2022. RESULTS: The analysis included 210 nurses (202 females). The average knowledge, attitude and practice scores were 11.06±2.61 (total score: 18), 53.51±5.81 (total score: 60) and 64.66 ± 10.35 (total score: 80) points, respectively. Knowledge score was positively correlated with attitude score (r = 0.416, P < 0.001) and practice score (r = 0.389, P < 0.001); attitude and practice scores were also positively correlated (r = 0.627, P < 0.001). Multivariable analysis demonstrated that age ≥ 40 years-old (vs. ≤30 years-old) was associated with higher knowledge score (ß = 1.48, 95% confidence interval [95%CI] = 0.42-2.54, P = 0.006). Age ≥ 40 years-old (ß = 1.43, 95%CI = 0.35-2.51, P = 0.010 vs. ≤30 years-old) and bachelor's degree or higher (ß = 1.11, 95%CI = 0.12-2.10, P = 0.028 vs. college degree or lower) were associated with higher practice score. CONCLUSIONS: Older age and higher education level were associated with higher knowledge, attitude and/or practice scores. The findings of this study may help guide the development and implementation of education and training programs to improve the management of BPSD by nurses in China.

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OBJECTIVES: Ambivalent feelings in dementia family caregivers have been found to be related to caregivers´ stress associated with the behavioral and psychological symptoms of dementia (BPSD-related stress), and depressive symptoms. Ambivalent feelings may also affect caregivers´ perceived quality of the relationship with the person living with dementia (PLwD), but this variable has been scarcely studied. This study analyzes the role of ambivalent feelings in the association between caregivers' BPSD-related stress, perceived quality of the relationship with the PLwD, and depressive symptomatology. METHODS: A theoretical model was developed and tested in a sample of 390 family caregivers. RESULTS: The obtained tested model had an excellent fit to the data, explaining 24% of the variance of depressive symptomatology. A significant association was found between caregivers' BPSD-related stress, ambivalent feelings, and depressive symptomatology. Also, an indirect effect in the association between ambivalent feelings and depressive symptomatology was found through the perceived quality of the relationship. CONCLUSIONS: Ambivalent feelings in dementia family caregivers are associated with caregivers' BPSD-related stress, perception of a lower relationship quality, and higher depressive symptomatology. CLINICAL IMPLICATIONS: Targeting caregivers' ambivalent feelings and the quality of the relationship in interventions for dementia family caregivers may decrease their distress.

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AIM: Brexpiprazole is the first FDA-approved treatment for agitation associated with dementia due to Alzheimer's disease. Agitation in Alzheimer's dementia (AAD) occurs in high prevalence and is a great burden for patients and caregivers. Efficacy, safety, and tolerability of brexpiprazole were demonstrated in the AAD clinical trials. To demonstrate the agitation-ameliorating effect of brexpiprazole in animals, we evaluated brexpiprazole in two AAD mouse models. METHODS: The resident-intruder test was conducted in 5- to 6-month-old Tg2576 mice, given vehicle or brexpiprazole (0.01 or 0.03 mg/kg) orally 1 h before the test. Locomotor activity was measured in 6-month-old APPSL-Tg mice given vehicle or brexpiprazole (0.01 or 0.03 mg/kg) orally the evening before the start of locomotor measurement for 3 days. RESULTS: In the resident-intruder test, Tg2576 mice showed significantly higher attack number and shorter latency to first attack compared to non-Tg mice. In the Tg mice, brexpiprazole treatment (0.03 mg/kg) significantly delayed the latency to first attack and showed a trend toward a decrease in attack number. APPSL-Tg mice (≧6 months old) showed significantly higher locomotion during dark period Phase II (Zeitgeber time [ZT] 16-20) and Phase III (ZT20-24) compared to non-Tg mice, correlating with the clinical observations of late afternoon agitation in Alzheimer's disease. Brexpiprazole treatment (0.01 and 0.03 mg/kg) significantly decreased hyperlocomotion during the Phase III in APPSL-Tg mice. CONCLUSION: The suppression of attack behavior and the reduction of nocturnal hyperlocomotion in these Tg mice may be indicative of the therapeutic effect of brexpiprazole on AAD, as demonstrated in the clinical trials.

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BACKGROUND: Quantifying the informal caregiver burden is important for understanding the risk factors associated with caregiver overload and for evaluating the effectiveness of services provided in Long-term Care (LTC). OBJECTIVE: This study aimed to develop and validate a Caregiver Strain Index (CSI)-based score for quantifying the informal caregiver burden, while the original dataset did not fully cover evaluation items commonly included in international assessments. Subsequently, we utilized the CSI-based score to pinpoint key caregiver burden risk factors, examine the initial timing of LTC services adoption, and assess the impact of LTC services on reducing caregiver burden. METHODS: The study analyzed over 28,000 LTC cases in Southern Taiwan from August 2019 to December 2022. Through multiple regression analysis, we identified significant risk factors associated with caregiver burden and examined changes in this burden after utilizing various services. Survival analysis was employed to explore the relationship between adopting the first LTC services and varying levels of caregiver burden. RESULTS: We identified 126 significant risk factors for caregiver burden. The most critical factors included caregiving for other disabled family members or children under the age of three (ß = 0.74, p < 0.001), the employment status of the caregiver (ß = 0.30-0.53, p < 0.001), the frailty of the care recipient (ß = 0.28-0.31, p < 0.001), and the behavioral symptoms of dementia in care recipients (ß = 0.28-2.60, p < 0.05). Generally, caregivers facing higher burdens sought LTC services earlier, and providing home care services alleviated the caregiver's burden. CONCLUSION: This comprehensive study suggests policy refinements to recognize high-risk caregivers better early and provide timely support to improve the overall well-being of both informal caregivers and care recipients.

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OBJECTIVE: To systematically evaluate the current status of apathy in dementia patients and its associated factors. METHODS: We searched Chinese and English databases to collect studies on the associated factors of apathy in patients with dementia from inception to March 14, 2023. Two researchers independently screened the literature, evaluated the quality, and extracted the data RESULTS: A total of 20 studies were included, and the incidence of apathy in patients with dementia ranged from 21 % to 90 %. According to the model of apathy proposed by Massimo in 2018, the associated factors were divided into individual factors for dementia patients, caregiver factors, and environmental factors. The individual factors of apathy in patients with dementia mainly include demographic characteristics, the severity of cognitive impairment, a combination of other behavioral and psychological symptoms of dementia, acute medical problems or adverse drug reactions, unmet needs, and malnutrition. Caregiver factors mainly include emotional expressions of hostility or criticism towards dementia patients and caregivers' expectations for a better life in the future. Environmental factors mainly include too high or too low stimulation and a lack of daytime activities CONCLUSIONS: Existing studies have shown that the incidence of apathy in dementia patients is high and is affected by multi-dimensional factors. There are more studies on individual factors in dementia patients and fewer studies on caregivers and environmental factors. In the future, a large number of high-quality studies are needed to demonstrate the mechanism of apathy in dementia patients and to find more related factors.

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INTRODUCTION: Agitation, psychosis, and apathy are prevalent and highly distressing neuropsychiatric symptoms (NPS) of Alzheimer's disease (AD) that have been linked to numerous negative outcomes, including increased mortality, worsened cognitive decline, and caregiver burden. Current treatments for AD-associated agitation, namely atypical antipsychotics, provide some benefits but may increase the risk of serious adverse events and death. Meanwhile, no pharmacotherapies have been approved by regulatory agencies for the treatment of psychosis or apathy in AD. Over the past decade, many new and repurposed drugs have emerged as potential therapeutic options for managing these challenging NPS. AREAS COVERED: This review aims to provide a comprehensive summary of pharmacotherapies that have recently been investigated in phase 2 and 3 clinical trials for the treatment of agitation, psychosis, or apathy in AD. EXPERT OPINION: Novel atypical antipsychotics, serotonergic antidepressants, cannabinoids, and dextromethorphan combination drugs have shown promising results for alleviating agitation. Pimavanserin appears to be the most effective emerging therapy for psychosis, while methylphenidate has demonstrated good efficacy for apathy. Further research on biomarkers of NPS severity and treatment response, as well as continued improvements in methodological approaches are needed to advance the field.