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.

Care-resistant Behavior Trajectories during Mouth Care among Nursing Home Residents with Dementia.

BACKGROUND AND OBJECTIVES: This study examined day-to-day variation in care-resistant behaviors (CRBs) exhibited by persons living with dementia during mouth health care 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.

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.

Brexpiprazole: A new option in treating agitation in Alzheimer's dementia-Insights from transgenic mouse models.

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.

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.

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.

Correlation of behavioral and psychological symptoms of dementia with patients' sociodemographic & clinical details and caregivers' distress.

Background: Behavioral and psychological symptoms of dementia (BPSD) influence dementia care significantly. BPSD can be affected by factors related to the patient's illness and socio-cultural background. Aim: This study aimed to find a relationship between BPSD with patients' socio-demographic and clinical profiles and their caregivers' distress in a tertiary care center. Materials and Methods: In this hospital-based cross-sectional study, the purposive sampling technique was used to select 100 dementia patients. A comprehensive record of socio-demographic and clinical details was made on a self-prepared semi-structured data sheet. The Neuropsychiatric Inventory Questionnaire was the principal tool to find the BPSD and related caregivers' distress. Results: The sample comprised predominantly Hindu (91%) male patients (66%) with Alzheimer's dementia (76%) coming from rural backgrounds (74%) and joint familial systems (96%), with a mean age of 71.77 ± 7.41 years. Patients' main caregivers were their children/children-in-law (65%). The severity of an overall BPSD and its variable individual domains were directly related to the duration of dementia, patients' age, their cognitive decline, and related decline in activities of living, as well as their caregivers' distress. In comparison to Alzheimer's disease patients, those with other dementia types had more impairment in cognitive functions and activities of daily living and they had a higher number and severity of BPSD. Conclusion: The advancing age, increased duration of dementia, and decline in cognition and related activities of daily living of the patients, as well as their caregivers' distress, are important correlates of BPSD. The findings are essential for the better management of dementia patients.

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.

Using AI-Based Technologies to Help Nurses Detect Behavioral Disorders: Narrative Literature Review.

BACKGROUND: The behavioral and psychological symptoms of dementia (BPSD) are common among people with dementia and have multiple negative consequences. Artificial intelligence-based technologies (AITs) have the potential to help nurses in the early prodromal detection of BPSD. Despite significant recent interest in the topic and the increasing number of available appropriate devices, little information is available on using AITs to help nurses striving to detect BPSD early. OBJECTIVE: The aim of this study is to identify the number and characteristics of existing publications on introducing AITs to support nursing interventions to detect and manage BPSD early. METHODS: A literature review of publications in the PubMed database referring to AITs and dementia was conducted in September 2023. A detailed analysis sought to identify the characteristics of these publications. The results were reported using a narrative approach. RESULTS: A total of 25 publications from 14 countries were identified, with most describing prospective observational studies. We identified three categories of publications on using AITs and they are (1) predicting behaviors and the stages and progression of dementia, (2) screening and assessing clinical symptoms, and (3) managing dementia and BPSD. Most of the publications referred to managing dementia and BPSD. CONCLUSIONS: Despite growing interest, most AITs currently in use are designed to support psychosocial approaches to treating and caring for existing clinical signs of BPSD. AITs thus remain undertested and underused for the early and real-time detection of BPSD. They could, nevertheless, provide nurses with accurate, reliable systems for assessing, monitoring, planning, and supporting safe therapeutic interventions.

Guideline Recommendations on Behavioral and Psychological Symptoms of Dementia: A Systematic Review.

OBJECTIVE: To synthesize recommendations on assessing and managing behavioral and psychological symptoms of dementia (BPSDs) in existing clinical practice guidelines on dementia care to learn from and adapt recommendations to a Canadian context and language for describing BPSDs. DESIGN: Systematic review. SETTING AND PARTICIPANTS: Moderate to high-quality clinical practice guidelines on dementia care that made 1 or more recommendations on BPSD assessment or management. METHODS: We searched MEDLINE, Embase, JBI EBM, PsycINFO, AgeLine, and gray literature for clinical practice guidelines on dementia care making recommendations on BPSD, published between January 1, 2011, and October 13, 2022. Two independent reviewers conducted study screening and data abstraction. Four independent reviewers completed quality appraisal using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool; included guidelines had a mean overall AGREE II score ≥4. RESULTS: Our systematic review identified 23 moderate to high-quality clinical practice guidelines (264 recommendations). The mean overall quality score on the AGREE II tool ranged from 4 to 6.5. Recommendations were clearly presented (mean clarity of presentation score 73.5%), but guideline applicability was not consistently addressed (mean applicability score 39.3%). BPSD was the most prevalent term describing neuropsychiatric symptoms (number of guidelines [n] = 14). People with lived experience contributed to 6 guidelines (26.1%). Ten guidelines (43.5%) described 1 or more health equity considerations. Guidelines made recommendations for assessing and managing agitation (n = 12), aggression (n = 10), psychosis (n = 11), depression (n = 9), anxiety (n = 5), apathy (n = 6), inappropriate sexual behavior (n = 3), nighttime behavior (n = 5), and eating disturbances (n = 3). There was substantial variability in recommendation statements, evidence quality assigned to each statement, and strength of recommendations. CONCLUSIONS AND IMPLICATIONS: There are several moderate to high-quality clinical practice guidelines making recommendations on BPSD assessment and management, but variability in recommendation statements across guidelines and insufficient consideration of guideline applicability may hamper guideline dissemination and implementation in clinical practice.

Diagnoses and Treatment of Behavioral and Psychological Symptoms of Dementia Among Racially and Ethnically Diverse Persons Living with Dementia.

Background: Behavioral and psychological symptoms of dementia (BPSD) and prescribed central nervous system (CNS) active drugs to treat them are prevalent among persons living with Alzheimer's disease and related dementias (PLWD) and lead to negative outcomes for PLWD and their caregivers. Yet, little is known about racial/ethnic disparities in diagnosis and use of drugs to treat BPSD. Objective: Quantify racial/ethnic disparities in BPSD diagnoses and CNS-active drug use among community-dwelling PLWD. Methods: We used a retrospective cohort of community-dwelling Medicare Fee-for-Service beneficiaries with dementia, continuously enrolled in Parts A, B and D, 2017-2019. Multivariate logistic models estimated rates of BPSD diagnosis and, conditional on diagnosis, CNS-active drug use. Results: Among PLWD, 67.1% had diagnoses of an affective, psychosis or hyperactivity symptom. White (68.3%) and Hispanic (63.9%) PLWD were most likely, Blacks (56.6%) and Asians (52.7%) least likely, to have diagnoses. Among PLWD with BPSD diagnoses, 78.6% took a CNS-active drug. Use was highest among whites (79.3%) and Hispanics (76.2%) and lowest among Blacks (70.8%) and Asians (69.3%). Racial/ethnic differences in affective disorders were pronounced, 56.8% of white PLWD diagnosed; Asians had the lowest rates (37.8%). Similar differences were found in use of antidepressants. Conclusions: BPSD diagnoses and CNS-active drug use were common in our study. Lower rates of BPSD diagnoses in non-white compared to white populations may indicate underdiagnosis in clinical settings of treatable conditions. Clinicians' review of prescriptions in this population to reduce poor outcomes is important as is informing care partners on the risks/benefits of using CNS-active drugs.

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.

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.

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.

Examining Frontal Lobe Asymmetry and Its Potential Role in Aggressive Behaviors in Early Alzheimer's Disease.

Background: Neuropsychiatric symptoms (NPS) in patients with dementia lead to caregiver burdens and worsen the patient's prognosis. Although many neuroimaging studies have been conducted, the etiology of NPS remains complex. We hypothesize that brain structural asymmetry could play a role in the appearance of NPS. Objective: This study explores the relationship between NPS and brain asymmetry in patients with Alzheimer's disease (AD). Methods: Demographic and MRI data for 121 mild AD cases were extracted from a multicenter Japanese database. Brain asymmetry was assessed by comparing the volumes of gray matter in the left and right brain regions. NPS was evaluated using the Neuropsychiatric Inventory (NPI). Subsequently, a comprehensive assessment of the correlation between brain asymmetry and NPS was conducted. Results: Among each NPS, aggressive NPS showed a significant correlation with asymmetry in the frontal lobe, indicative of right-side atrophy (r = 0.235, p = 0.009). This correlation remained statistically significant even after adjustments for multiple comparisons (p < 0.01). Post-hoc analysis further confirmed this association (p < 0.05). In contrast, no significant correlations were found for other NPS subtypes, including affective and apathetic symptoms. Conclusions: The study suggests frontal lobe asymmetry, particularly relative atrophy in the right hemisphere, may be linked to aggressive behaviors in early AD. These findings shed light on the neurobiological underpinnings of NPS, contributing to the development of potential interventions.

Pangenomics: A new era in the field of neurodegenerative diseases.

A pangenome is composed of all the genetic variability of a group of individuals, and its application to the study of neurodegenerative diseases may provide valuable insights into the underlying aspects of genetic heterogenetiy for these complex ailments, including gene expression, epigenetics, and translation mechanisms. Furthermore, a reference pangenome allows for the identification of previously undetected structural commonalities and differences among individuals, which may help in the diagnosis of a disease, support the prediction of what will happen over time (prognosis) and aid in developing novel treatments in the perspective of personalized medicine. Therefore, in the present review, the application of the pangenome concept to the study of neurodegenerative diseases will be discussed and analyzed for its potential to enable an improvement in diagnosis and prognosis for these illnesses, leading to the development of tailored treatments for individual patients from the knowledge of the genomic composition of a whole population.