Emerging therapies for treatment of agitation, psychosis, or apathy in Alzheimer's disease.

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.

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

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

Behavioral and psychological symptoms of dementia and mortality risk among people with cognitive impairment: an 8-year longitudinal study from the NCGG-STORIES.

BACKGROUND: 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. METHODS: This longitudinal study involved 1,065 males and 1,681 females (mean age: males = 77.1 years; females = 78.6 years) 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. RESULTS: 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 [95% confidence intervals] for the highest quartile score group = 1.59 [1.11-2.29] for males and 1.06 [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. CONCLUSIONS: The findings suggest a potential association between BPSD and poor prognosis among males with cognitive impairment.

Nurses' knowledge, attitude and practice regarding non-pharmacologic interventions for behavioral and psychological symptoms of dementia.

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.

Prevalence, treatment, and neural correlates of apathy in different forms of dementia: a narrative review.

OBJECTIVES: The aim of this review is to provide an overview on prevalence and clinical tools for the diagnosis of apathy, as well as on neurophysiological and neuroimaging findings obtained from studies in patients with apathy in different forms of dementia, including Alzheimer's disease (AD), vascular (VaD) and mixed dementia, frontotemporal dementia (FTD), and Parkinson's disease dementia (PDD). METHODS: Randomized controlled trials, non-randomized controlled trials, controlled before-after studies, and interrupted time series from four databases (WebOfScience, Scopus, Pubmed, and PsycINFO) addressing apathy in adults or older people aged over 65 years of age affected by dementia were included. RESULTS: The prevalence of apathy was 26-82% for AD, 28.6-91.7 for VaD, 29-97.5% in PDD, and 54.8-88.0 in FTD. The assessment of apathy was not consistent in the reviewed studies. Methylphenidate was the most successful pharmacological treatment for apathy. Neurobiological studies highlighted the relationship between both structural and functional brain areas and the presence or severity of apathy. CONCLUSION: Apathy is a very common disorder in all types of dementia, although it is often underdiagnosed and undertreated. Further studies are needed to investigate its diagnosis and management. A consensus on the different evaluation scales should be achieved.

Agitation in cognitive disorders: Progress in the International Psychogeriatric Association consensus clinical and research definition.

BACKGROUND: The International Psychogeriatric Association (IPA) published a provisional consensus definition of agitation in cognitive disorders in 2015. As proposed by the original work group, we summarize the use and validation of criteria in order to remove "provisional" from the definition. METHODS: This report summarizes information from the academic literature, research resources, clinical guidelines, expert surveys, and patient and family advocates on the experience of use of the IPA definition. The information was reviewed by a working group of topic experts to create a finalized definition. RESULTS: We present a final definition which closely resembles the provisional definition with modifications to address special circumstances. We also summarize the development of tools for diagnosis and assessment of agitation and propose strategies for dissemination and integration into precision diagnosis and agitation interventions. CONCLUSION: The IPA definition of agitation captures a common and important entity that is recognized by many stakeholders. Dissemination of the definition will permit broader detection and can advance research and best practices for care of patients with agitation.

Validation of the Japanese version of the Social Functioning in Dementia scale and COVID-19 pandemic's impact on social function in mild cognitive impairment and mild dementia.

OBJECTIVES: We aimed to psychometrically evaluate and validate a Japanese version of the Social Functioning in Dementia scale (SF-DEM-J) and investigate changes in social function in people with dementia during the coronavirus disease-19 (COVID-19) pandemic. DESIGN: We interviewed people with mild cognitive impairment (MCI) and mild dementia and their caregivers during June 2020-March 2021 to validate patient- and caregiver-rated SF-DEM-J and compared their scores at baseline (April 2020 to May 2020) and at 6-8 months (January 2021 to March 2021) during a time of tighter COVID-19 restrictions. SETTING: The neuropsychology clinic in the Department of Psychiatry at Osaka University Hospital and outpatient clinic in the Department of Psychiatry and Neurology at Daini Osaka Police Hospital, Japan. PARTICIPANTS: 103 dyads of patients and caregivers. MEASUREMENTS: SF-DEM-J, Mini-Mental State Examination, Neuropsychiatric Inventory, UCLA Loneliness Scale, and Apathy Evaluation Scale. RESULTS: The scale's interrater reliability was excellent and test-retest reliability was substantial. Content validity was confirmed for the caregiver-rated SF-DEM-J, and convergent validity was moderate. Caregiver-rated SF-DEM-J was associated with apathy, irritability, loneliness, and cognitive impairment. The total score of caregiver-rated SF-DEM-J and the score of Section 2, "communication with others," significantly improved at 6-8 months of follow-up. CONCLUSIONS: The SF-DEM-J is acceptable as a measure of social function in MCI and mild dementia. Our results show that the social functioning of people with dementia, especially communicating with others, improved during the COVID-19 pandemic, probably as a result of adaptation to the restrictive life.

Understanding and alleviating informal caregiver burden through the development and validation of a caregiver strain index-based model in Taiwan.

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.

Evaluating the Impact of Virtual Reality on the Behavioral and Psychological Symptoms of Dementia and Quality of Life of Inpatients With Dementia in Acute Care: Randomized Controlled Trial (VRCT).

BACKGROUND: Virtual reality (VR) is increasingly considered a valuable therapeutic tool for people with dementia. However, rigorous studies are still needed to evaluate its impact on behavioral and psychological symptoms of dementia (BPSDs) and quality of life (QoL) across care settings. OBJECTIVE: The primary aim of this study was to evaluate the impact of VR therapy on managing BPSDs, falls, length of stay, and QoL in inpatients with dementia admitted to an acute care hospital. The secondary aim was to evaluate the intervention's feasibility in terms of acceptability, safety, and patient experience. METHODS: A prospective, open-label, mixed methods, randomized controlled clinical trial was conducted between April 2019 and March 2020. A total of 69 participants (aged ≥65 years with a diagnosis of dementia and who did not meet the exclusion criteria) were randomly assigned to either the control (n=35, 51%) or VR (n=34, 49%) arm. Participants in the experimental (VR) arm were visited by a researcher and watched 360° VR films on a head-mounted display for up to 20 minutes every 1 to 3 days, whereas individuals in the control arm received standard of care. Instances of daily BPSDs and falls were collected from nurses' daily notes. QoL was measured through semistructured interviews and the Quality of Life in Late-Stage Dementia scale. Structured observations and semistructured interviews were used to measure treatment feasibility. The primary outcomes were analyzed at a 95% significance level based on the intention-to-treat method. RESULTS: VR therapy had a statistically significant effect on reducing aggressiveness (ie, physical aggression and loud vociferation; P=.01). Substantial impact of VR therapy was not found for other BPSDs (eg, apathy), falls, length of stay, or QoL as measured using the Quality of Life in Late-Stage Dementia scale. The average VR therapy session lasted 6.8 (SD 6.6; range 0-20) minutes, and the intervention was overall an acceptable and enjoyable experience for participants. No adverse events occurred as a result of VR therapy. CONCLUSIONS: Immersive VR therapy appears to have an effect on aggressive behaviors in patients with dementia in acute care. Although the randomized controlled trial was stopped before reaching the intended sample size owing to COVID-19 restrictions, trends in the results are promising. We suggest conducting future trials with larger samples and, in some cases, more sensitive data collection instruments. TRIAL REGISTRATION: ClinicalTrials.gov NCT03941119; https://clinicaltrials.gov/study/NCT03941119. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/22406.

Personality traits and measures of neuropsychiatric symptoms.

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.

Neuropsychiatric symptom burden in early-onset and late-onset Alzheimer's disease as a function of age.

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.

Influence of caregivers' psychological well-being on the anxiety and depression of care recipients with dementia.

This study was conducted to examine how caregivers' psychological well-being influences the anxiety or depression of care recipients with dementia. A secondary data analysis was conducted using 666 dyads of older adults with dementia and their caregivers. The odds that care recipients with dementia would experience anxiety increased when caregivers had a negative relationship with care recipients (OR = 1.22, p = 0.042), lower perception of the positive aspects of caregiving (OR = 0.86, p = 0.047), or anxiety (OR = 2.41, p = 0.036). The odds that care recipients with dementia would experience depression increased when caregivers had a greater perception of the negative aspects of caregiving (OR = 1.15, p = 0.023) or anxiety (OR = 2.21, p = 0.045). Since care recipients with dementia and their caregivers spend considerable time together daily, caregivers' psychological well-being can impact care recipients' anxiety and depression.

[Dementia with Lewy bodies: old and new knowledge-Part 2: treatment]. / Demenz mit Lewy-Körpern: alte und neue Erkenntnisse ­ Teil 2: Behandlung.

BACKGROUND: The treatment of patients with dementia with Lewy bodies (DLB) is multifaceted, as motor symptoms, cognitive symptoms, behavioral and psychological symptoms can occur in different constellations. In addition, the use of certain medications is limited (e.g., neuroleptics). OBJECTIVE: To summarize the main recent findings on the treatment of DLB. RESULTS: To date, there is no approved therapeutic option for the treatment of patients with DLB in Germany; moreover, the evidence base for pharmacological and non-pharmacological treatment is sparse. The currently consented treatment options are based on the treatment of motor symptoms in the same way as the treatment of Parkinson's disease and for behavioral symptoms based on the treatment for Alzheimer's disease. DISCUSSION: The treatment of DLB with its various symptoms is difficult and often can only be adequately achieved for the patient in close cooperation with a specialist.

The current status of apathy in patients with dementia and its factors: A systematic review.

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.

Person-centered care as a tool to reduce behavioral and psychological symptoms in older adults with dementia living in residential care facilities.

Among older adults living in dementia residential care facilities (RCF) behavioral and psychological symptoms (BPSD) are common, affecting the quality of life (QOL) for the residents as well as being challenging for the staff. The person-centered care (PCC) approach addresses BPSD by giving trained staff mandate to focus on the relation and to adapt the encounter and the environment to increase QoL for the person with dementia. The aims with this study were to improve PCC, decrease BPSD and improve QOL among older persons with dementia living in RCFs, and to explore leaders' and healthcare staff's experiences of a PCC intervention. An educational program was implemented at two RCFs. Data was collected through questionnaires, from national quality registries and through focus group interviews. A significant increase in PCC and QOL at three months was seen. However, no significant difference in BPSD was seen. The interviews showed the importance of a trust-based relationship, and support from an active management to improve PCC, as well as changing old patterns and recognising competence among staff. Factors that affect implementation of PCC in RCF are discussed in the article.

The Relationships between Caregiver Burden, Physical Frailty, Race, Behavioral and Psychological Symptoms (BPSD), and Other Associated Variables: An Exploratory Study.

Background and Objectives: For persons with dementia, the relationships between caregiver burden, physical frailty, race, behavioral and psychological symptoms (BPSD), and other associated variables are poorly understood. Only one prior study examined the relationships among these variables but did not include race, which is an important social determinant of health outcomes in the United States. To examine these interactions, we conducted a cross-sectional exploratory study based on a model by Sugimoto and colleagues. Materials and Methods: The sample comprised 85 patient-caregiver dyads (58% White) seen in four centers in diverse regions of New York State. All patients met DSM5 criteria for a major neurocognitive disorder, had a Clinical Dementia Rating sum score of ≥3, and Mini-Mental State Examination (MMSE) score of 10 to 26. Other measures included the SHARE-Frailty Instrument(FI), the Neuropsychiatric Inventory (NPI) to assess BPSD, Zarit's Caregiver Burden Interview (CBI), Lawton's Activities of Daily Living (ADL) Scale, the MMSE, the Cumulative Illness Rating Scale for Geriatrics (CIRSG), age, and gender. Results: In our sample, 59% met the criteria for prefrail/subsyndromal or frail/syndromal (SSF) on the SHARE-FI. SSF had significant direct effects on the NPI and significant indirect effects on the CBI mediated through the NPI; the NPI had significant direct effects on the CBI. Race (White) had significant direct effects on the CBI (higher) and SSF (lower) but did not have significant indirect effects on the CBI. MMSE, ADL, and CIRSG were not significantly associated with the NPI or the CBI. Conclusions: Our analysis demonstrated that frailty, race, BPSD, and caregiver burden may directly or indirectly influence one another, and therefore should be considered essential elements of dementia assessment, care, and research. These results must be viewed as provisional and should be replicated longitudinally with larger samples.

Ambivalent Feelings and Relationship Quality in Dementia Family Caregivers: Associations with Depressive Symptomatology.

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.

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

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

The association of physical activity and behavioral and psychological symptoms among a sample of hospitalized older adults living with dementia.

OBJECTIVES: The aims of this study were to: (1) describe the prevalence of behavioral and psychological symptoms of dementia in hospitalized older adults living with dementia and (2) examine the association of physical activity and behavioral and psychological symptoms of dementia among hospitalized older adults living with dementia, after controlling for covariates. METHODS: Physical activity was measured using the Physical Activity Survey and behavioral and psychological symptoms of dementia were measured using the Neuropsychiatric Inventory. Descriptive analysis and multiple linear regressions were run using baseline data on 294 older adults with dementia hospitalized on general medical units from an ongoing study entitled Function Focused Care for Acute Care Using the Evidence Integration Triangle. RESULTS: Participants performed an average of 7.92 (SD = 4.49) of 34 possible activities "in the last 24 h" prior to the Physical Activity Survey administration. A total of 132 participants (45.5%) had at least one behavioral and psychological symptom of dementia. We found that physical activity was not associated with behavioral and psychological symptoms of dementia (b = 0.01; p = 0.56), after controlling for covariates. CONCLUSIONS: Although this study found no evidence of an association between physical activity and behavioral and psychological symptoms of dementia, evidence of physical activity did not exacerbate these behaviors. Thus, given the benefits of physical activity, it is important to continue to encourage patients living with dementia to engage in activity.

The repetitive transcranial magnetic stimulation in Alzheimer's disease patients with behavioral and psychological symptoms of dementia: a case report.

BACKGROUND: Repetitive transcranial magnetic stimulation is a noninvasive intervention, can significantly reduce behavioral and psychological symptoms and cognitive impairment in AD patients. Only few cases have been reported the adverse reactions after the treatment. This report described the different adverse reactions after repetitive transcranial magnetic stimulation with different parameters. PATIENT PRESENTATION: This article reports a patient with dementia complicated with mental behavior disorder who was treated with repetitive transcranial magnetic stimulation (rTMS) in spite of poor drug response. First, 1 Hz rTMS was initiated. After 1 month, the patient showed improved symptoms of mental behavior, decreased cognitive function and prolonged sleep duration. After switched to 10 Hz rTMS, the patient's cognitive function and mental behavior abnormalities improved, and the sleep time returned to normal. However, epilepsy occurred after one session and was changed to 0.8 Hz rTMS treatment. The patient's symptoms improved and did not have seizure. CONCLUSION: Repetitive transcranial magnetic stimulation has a positive effect on cognitive function and Behavioral And Psychological Symptoms Of Dementia, and adverse reactions are inevitable. Playing personalized treatment according to the patients can reduce occurrence of adverse reactions.