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This systematic review analyzes the research evidence on the psychosocial risks faced by graduates of Neonatal Intensive Care Units (NICUs) during childhood. NICUs hold enormous value in uniting preterm or critically ill infants and their families; however, excess NICU exposure affects infants in numerous negative psychosocial ways. Developmental, behavioral, emotional, and social issues faced by NICU graduates are the focus of this systematic review, which aims to summarize the available evidence from published literature. It points to the incidence of such problems and how they emerged, and it insists on the importance of early detection, complex interference, and constant assistance to children and their families dealing with such issues. The review uses the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework to assess methodological quality and includes data from various electronic databases. This review emphasizes the concurrent applications of family-centered care, early neurodevelopmental screens, and specialized intervention strategies and also, explains the different types of childhood psychosocial problems in NICU graduates.

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INTRODUCTION: This study aimed to examine baseline risk factors in Alzheimer's Disease (AD) and Vascular dementia (VaD) patients with neuropsychiatry symptoms (NPS), and determine whether specific risk factors differ by subtypes of dementia for AD and VaD patients with NPS. METHODS: A retrospective data analysis was conducted to evaluate similarities and differences in the risk factors for AD and VaD with NPS. The analysis included 2949 patients with VaD and 6341 patients with clinical confirmation of AD and VaD with or without NPS collected between February 2016 and August 2021. The multivariate logistic regression analysis was used to determine the risk factors associated with AD and VaD with NPS, by predicting the increasing odds (odds ratios (ORs) of an association of a specific baseline risk factor with AD or VaD with NPS. The validity of the regression models was tested using a Hosmer-Lemeshow test, while the Receiver Operating Curve (ROC) was used to test the sensitivity of the models. RESULTS: In the adjusted analysis TSH (OR = 1.781, 95 % CI, p = 0.0025) and CHF (OR = 1.620, 95 %, p = 0.016) were associated with VaD with NPS, while a history of emergency department(ED) admission (OR = 0.277, 95 % CI, p = 0.003) likely to be associated with VaD patients without NPS. For AD patients, a history of CVA (OR = 1.395, 95 % CI, p = 0.032) and cancer (OR = 1.485, 95 % CI, p = 0.013) were associated with AD patients with NPS. DISCUSSION: The findings of this study indicate that an abnormal thyroid gland and CHF were linked to VaD patients with behavioral disturbances, while CVA and cancer were linked to AD patients with behavioral disturbances. These findings suggest the need to develop management strategies for the care of patients with AD and VaD with NPS.

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Background: Neuropsychiatric symptoms (NPS) are often overlooked and under-identified symptoms associated with dementia, despite their significant impact on the prognosis of individuals living with the disease. The specific role of certain NPS in functional prognosis remains unclear. Aims: To determine the association of different NPS with functional decline in people living with Alzheimer's disease (AD) or Lewy body dementia (LBD). Methods: This is an analysis of data from the Dementia Study of Western Norway (DemVest) with 196 patients included of which 111 had AD and 85 LBD. The Neuropsychiatric Inventory (NPI) and the Rapid Disability Rating Scale (RDRS-2) for activities of daily living were administered annually for 5 years. NPI total score and individual items with RDRS-2 trajectories were analyzed with linear mixed models. Results: The LBD group exhibited higher levels of functional impairment and a greater burden of NPS at baseline. Over the 5-year follow-up, hallucinations, aggression, depression, anxiety, apathy, disinhibition, aberrant motor behavior, nighttime behavior disturbances, and abnormal eating patterns were significantly associated with the decline in functional abilities in individuals with AD, as well as irritability and aberrant motor behavior in those with LBD. Discussion: These results highlight the relevance of early detection and intervention of these particularly relevant NPS, due to its potential of also impacting physical function. Better detection and management of these NPS could improve functional prognosis in people living with dementia. Conclusion: Specific NPS demonstrate relevant distinct associations with Longitudinal trajectories of functional decline in AD and LBD.

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Sucralose (SUC) and acesulfame-k (ACE-K) are widely used artificial sweeteners worldwide; however, they are frequently detected in aquatic environments due to their low metabolism and inadequate removal during wastewater treatment. The harmful effects of these compounds on hydrobionts have yet to be fully understood, as data on their toxicity is limited and inconclusive. This research aimed to determine the impact of SUC (50, 75, 125 µg/L) and ACE-K (50, 75, 125 µg/L), individually and in combination, on fish's swimming behavior, acetylcholinesterase activity, and oxidative stress response after four months of exposure. Following exposure, adult Danio rerio displayed anxiety-like behavior, as evidenced by increased freezing time and decreased swimming activity. Additionally, analysis of fish brain tissue revealed a disruption of REDOX homeostasis, leading to oxidative stress, which may be responsible for the observed inhibition of AChE activity. The results indicated that ACE-K was more toxic than SUC, and the mixture of both compounds produced a more detrimental effect than when each compound was administered alone. These findings highlight the hazardous impacts of SUC and ACE-K on fish in environmentally relevant concentrations, suggesting that these compounds should be added to the priority pollutant list.

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Ammonium ion (NH4 + ) is the major suspected molecule responsible for neurological complications of hepatic encephalopathy (HE). No specific pharmacological action for NH4 + -induced brain injury exists so far. Excitotoxicity is a well-known phenomenon in the brain of hyperammonemic cases. The hyperactivation of the N-Methyl- d-aspartate (NMDA) receptors by agents such as glutamate, an NH4 + metabolite, could cause excitotoxicity. Excitotoxicity is connected with events such as oxidative stress and neuroinflammation. Hence, utilizing NMDA receptor antagonists could prevent neurological complications of NH4 + neurotoxicity. In the current study, C57BL6/J mice received acetaminophen (APAP; 800 mg/kg, i.p) to induce HE. Hyperammonemic animals were treated with ketamine (0.25, 0.5, and 1 mg/kg, s.c) as an NMDA receptor antagonist. Animals' brain and plasma levels of NH4 + were dramatically high, and animals' locomotor activities were disturbed. Moreover, several markers of oxidative stress were significantly increased in the brain. A significant increase in brain tissue levels of TNF-α, IL-6, and IL-1ß was also detected in hyperammonemic animals. It was found that ketamine significantly normalized animals' locomotor activity, improved biomarkers of oxidative stress, and decreased proinflammatory cytokines. The effects of ketamine on oxidative stress biomarkers and inflammation seem to play a key role in its neuroprotective mechanisms in the current study.

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PUS7 gene pathogenic variants cause a deficiency in an RNA-independent pseudouridine synthase, which results in a neurodevelopmental phenotype characterized by various degrees of psychomotor delay, acquired microcephaly, aggressive behavior, and intellectual disability. Since 2018, PUS7 deficiency has been described in 15 patients with different pathogenic variants but similar clinical phenotypes. We describe the case of a male infant with a homozygous truncating pathogenic variant in the PUS7 gene (c.329_332delCTGA; p.Thr110Argfs*4) who, in addition to the previously mentioned features, displays self-injurious behavior, sleep disturbances and motor stereotypies.

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Commonly reported in dementia, neuropsychiatric symptoms (NPS), cognitive decline, and sleep disturbances indicate dementia progression. With the growing dementia burden, identifying protective factors that may slow dementia progression is increasingly essential. Religion and spirituality are associated with better mental and physical health, yet few studies have been reported in older adults with dementia. This study examines associations between religious service attendance and symptoms of dementia progression. Using data from the Health and Retirement Study in 2000, 2006, and 2008 and the sub-study, Aging, Demographics, and Memory Study in 2001-2003, 2006-2007, and 2008-2009, we examined the association of religious attendance with neuropsychiatric symptoms, cognitive function, and sleep disturbances among U.S. older adults aged 70 years and older with all-cause dementia (N = 72) using Spearman's partial Rho correlation controlling for social interaction. Significant associations were identified for religious attendance and NPS (rs (97) = -0.124, 95% CI [-0.129, -0.119], p < 0.0005); cognitive function, rs (97) = -0.018, 95% CI [-0.023, -0.013], p < 0.001); and sleep disturbances, rs (97) = -0.275, 95% CI [-0.280, -0.271], p < 0.0005). Beyond adjusting for social interaction, increased religious attendance was associated with lower NPS, better cognitive function, and fewer sleep disturbances. Clinical trials and longitudinal studies with a larger sample size examining religion and spirituality factors with dementia progression are warranted.

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Behavioral and psychological symptoms of dementia (BPSD) may occur in most patients with dementia. Symptoms such as agitation, aggression, and psychosis often lead to higher rates of hospitalization, morbidity, and mortality. Despite the prevalence of BPSD, safe and effective treatment options are limited. This often leads to off-label prescribing and trends toward polypharmacy. Notwithstanding modest efficacy in BPSD, antipsychotics seem to be one of the most commonly prescribed medications in its treatment. Polypharmacy with antipsychotics is particularly troublesome due to the increased risk of potentially lethal adverse effects. As such, their use should be judiciously monitored with the goal of gradual dose reduction.

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Background: Aggression is one manifestation of behavioral disturbances in neurodegenerative disease with emerging literature suggesting a high prevalence in Parkinson's disease and related disorders (PDRD). Objectives: Our aim was to describe characteristics, associated factors, and consequences of aggression towards caregivers in PDRD. Methods: This is a convergent mixed methods study, leveraging data from 296 PDRD patient-caregiver dyads in a clinical trial of palliative care and semi-structured interviews with a subgroup of 14 caregivers who reported aggression. The primary outcome was baseline caregiver-reported aggression. Using multivariate linear regression, baseline dyad characteristics (eg, measures of disease, psychosocial issues, caregiver strain) were examined to identify factors associated with aggression. Thematic analysis of interviews was used to augment these findings. Results: Associated variables included disease duration (r = 0.15, P < 0.05), patient grief (r = 0.22, P< 0.001), symptom burden (r = 0.18, r < 0.01), resistance to care (r = 0.40, P < 0.01), caregivers' depression (r = 0.16, P < 0.05), and caregiving burden (r = 0.34, P < 0.001). We identified five themes: (1) Aggressive behaviors range from verbal abuse to threats of physical violence; (2) Caregivers believe that aggressive behaviors result from the difficulty patients experience in coping with disease progression and related losses; (3) Caregivers' stress and mental health are worsened by aggressive behaviors; (4) Aggressive behaviors negatively affect patient-caregiver relationships; (5) Caregivers are ill-prepared to manage aggressive behaviors and cope with the consequences on their own. Conclusions: Aggression in PDRD is driven by diverse factors (eg, grief, fluctuations in cognition) with serious consequences for caregivers. Neurologists and movement specialists should consider screening for aggression while prioritizing caregiver education and wellbeing.

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The cerebellum is classically linked with control of motor function, such as coordination, balance, and regulation of movement. There is an increasing awareness, now, of the non-motor functions of the cerebellum, and the occurrence of behavioral anomalies with cerebellar disorders. We present the first report of Schmahmann syndrome (cerebellar cognitive affective syndrome [CCAS]) occurring secondary to posterior fossa meningioma excision. A 35-year-old lady with a posterior fossa meningioma developed an infarct of the right posterosuperior cerebellar hemisphere and ipsilateral superior vermis, following suboccipital craniotomy and tumor resection. Few days after the surgery, she presented with aggressive and emotional behavior, irrelevant talk, and emotional lability. The CCAS scale was administered, and she scored poorly on almost all parameters. A neuropsychological evaluation was also done. The occurrence of CCAS, posterior fossa syndrome (PFS), and behavioral abnormalities like abnormal pathological laughter/crying provides further clinical evidence of the "affective" functions of the cerebellum, modulated mainly by the posterior lobe and vermis of the cerebellum.

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Background: Almost 90% of patients with dementia suffer from some type of neurobehavioral symptom, and there are no approved medications to address these symptoms. Objective: To evaluate the safety and efficacy of the medical cannabis oil "Avidekel" for the reduction of behavioral disturbances among patients with dementia. Materials and methods: In this randomized, double-blind, single-cite, placebo-controlled trial conducted in Israel (ClinicalTrials.gov: NCT03328676), patients aged at least 60, with a diagnosis of major neurocognitive disorder and associated behavioral disturbances were randomized 2:1 to receive either "Avidekel," a broad-spectrum cannabis oil (30% cannabidiol and 1% tetrahydrocannabinol: 295 mg and 12.5 mg per ml, respectively; n = 40) or a placebo oil (n = 20) three times a day for 16 weeks. The primary outcome was a decrease, as compared to baseline, of four or more points on the Cohen-Mansfield Agitation Inventory score by week 16. Results: From 60 randomized patients [mean age, 79.4 years; 36 women (60.0%)], 52 (86.7%) completed the trial (all eight patients who discontinued treatment were from the investigational group). There was a statistically significant difference in the proportion of subjects who had a Cohen-Mansfield Agitation Inventory score reduction of ≥ 4 points at week 16: 24/40 (60.0%) and 6/20 (30.0%) for investigational and control groups, respectively (χ2 = 4.80, P = 0.03). There was a statistically significant difference in the proportion of subjects who had a Cohen-Mansfield Agitation Inventory score reduction of ≥ 8 points at week 16: 20/40 (50%) and 3/20 (15%), respectively (χ2 = 6.42, P = 0.011). The ANOVA repeated measures analysis demonstrated significantly more improvement in the investigational group compared to the control group at weeks 14 and 16 (F = 3.18, P = 0.02). Treatment was mostly safe, with no significant differences in the occurrence of adverse events between the two groups. Conclusion: In this randomized controlled trial, 'Avidekel' oil significantly reduced agitation over placebo in patients suffering from behavioral disturbances related to dementia, with non-serious side-effects. Further research is required with a larger sample size.

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Introduction: Following the Covid-19 epidemic affecting 76 of the 97 residents (78.3 %) in a French nursing home, we assessed the impact of this cluster period on the physical and psycho-cognitive health of the residents, expecting in particular to observe effects that were dependent on their state of cognitive-behavioural dependence. Methods: We retained twenty-two variables, 5 relating to demographic data, 6 to the specific care linked to Covid-19 infection, 6 to somatic pathologies and psycho-behavioural disturbances before the epidemic and 5 to the period following it. Results: Eleven residents among those diagnosed positive died. Nine were transferred to a Covid unit, and 35 were asymptomatic. The main consequences of the period of infections were in particular behavioural, nutritional, and motor. A history of disruptive behaviours before the appearance of the cluster increased the risk of an aggravation of these behaviours by four (RR = 3.9, IC95 % = 1.38­11.02, p = 0.0042). Twenty per cent of the residents presented under-nutrition at the end of lockdown, but no specific risk factors could be identified. However, states of under-nutrition for the whole of 2020 were significantly more frequent than in 2019, in particular severe cases (χ² = 5.43, p = 0.02). A history of under-nutrition in the previous year increased twofold the likelihood of under-nutrition in the following year (RR = 2.07, IC95 % = 1.14­3.74, p = 0.02). The Covid cluster period also had an effect on the functional autonomy of certain patients. Conclusion: Our main hypothesis relating to cognitive-behavioural dependence was not completely validated. The impact of the occurrence of the cluster remained moderate, in particular because of the care resources afforded by the nursing home. The advantages of a "medicalised" facility, and the problems associated with the restrictions of lockdown, are viewed in the light of ethical considerations.

Introduction: Suite à une épidémie de Covid-19 ayant affecté 76 des 97 résidents d'un Ehpad, nous avons évalué l'impact de cette période de cluster sur la santé physique et psycho-cognitive des résidents pronostiquant notamment une altération en fonction de leur dépendance cognitivo-comportementale. Méthodes: Nous avons retenus vingt-deux variables relatives : aux données démographiques (5) ; aux prises en charge spécifiques liées à l'infection (6) ; aux pathologies somatiques et troubles psycho-comportementaux avant l'épidémie (6) et après la période de cluster (5). Résultats: Onze résidents diagnostiqués positifs sont décédés. Neuf ont été transférés en unité Covid et 35 étaient asymptomatiques. Les troubles consécutifs à la période de cluster concernaient la majoration des comportements perturbateurs et la dénutrition lorsque des antécédents existaient déjà (respectivement : RR = 3,9, IC95 % = 1,38­11,02, p = 0,0042 ; RR = 2,07, IC95 % = 1,14­3,74, p = 0,02), ainsi que la réduction des capacités motrices. Nous n'avons pu objectiver d'autres facteurs explicatifs spécifiques à ces altérations. Conclusion: Notre hypothèse principale en lien avec la dépendance cognitivo-comportementale n'apparaît pas totalement validée. L'impact de la période de cluster est resté modéré notamment grâce aux moyens médico-soignants dont l'Ehpad disposait. L'avantage d'un dispositif médicalisé et l'inconvénient des restrictions liées au confinement est discuté au regard de questions éthiques.

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INTRODUCTION: Acute behavioral disturbances in psychosis, including agitation, comprise a heterogeneous group of manifestations varying in intensity and duration they last for. They require rapid, non-coercive treatments ranging from verbal de-escalation to the calming effect of pharmacological agents. The treatment goals are reduction of patient suffering and prevention of disease deterioration. Stabilizing rather than sedating is preferred to ensure improved compliance and a stronger therapeutic alliance. Furthermore, animal pharmacology and clinical studies on agitation reveal the robust calming and anxiolytic properties of loxapine. AREAS COVERED: This review covers the pharmacological and clinical history of loxapine along with research developments. It emphasizes the advantages of its multiple formulations ranging from injectable forms and tablets to orally inhaled forms to attain rapid and fine-tuned tranquilization. EXPERT OPINION: Rapid tranquillization is achieved within 2-6 hours using liquid orally-consumed loxapine, and within an hour or less with its IM or orally inhaled forms. Loxapine has been adopted in the management of a wide range of acute disturbances, such as agitation in psychosis. In the context of personalized medicine, key cellular and molecular elements of the schizophrenia phenotype were recently shown to be improved with loxapine.

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What is the value of assessing the biological age and frailty and predicting residual lifespan and health status? The benefit is obvious if we have means to alter the pace of aging and the development of frailty. So far, limited but increasing examples of interventions altering the predicted status indicate that, at least in some cases, this is possible through interventions spanning from the economic-social through drug treatments. Thus, why searching for biological markers, when some clinical and socio-economic indicators do already provide sufficiently accurate predictions? Indeed, the search of frailty biomarkers and of their biological clocks helps to build up a mechanistic frame that may orientate the design of interventions and the time window of their efficacy. Among the candidate biomarkers identified, several studies converge to indicate epigenetic clocks as a promising sensitive biomarker of the aging process. Moreover, it will help to establish the relationship between personal aging and health trajectories and to individuate the check points beyond which biological changes are irreversible.

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BACKGROUND: Cognitive impairment and behavioral changes associated with Alzheimer's disease and related dementias (ADRDs) can impair safe firearm handling ability, an issue that can be challenging for ADRD caregivers to address. In this qualitative analysis, we sought to explore behavioral disruptions that raise concerns about firearm access in dementia and how caregivers react and respond. METHODS: Secondary qualitative analysis using data from semi-structured, one-on-one interviews originally conducted as part of a study to develop firearm safety educational materials for ADRD caregivers. Interviewees were English-speaking adults (≥18 years) from three stakeholder groups: ADRD caregivers (professional or informal), medical professionals (geriatricians, neurologists), and firearm professionals (retailers, range employees, instructors). For secondary analysis, transcripts of interviews were recoded and analyzed after an inductive-deductive thematic analysis process. RESULTS: Among 24 participants, 17 (70%) were female and 20 (83%) white; 13 (54%) had personal or professional experience with ADRD caregiving; and 5 (21%) had a firearm affiliation. Major themes were: (1) behavioral disturbances that make caregivers concerned about firearm access; (2) caregiver emotional responses to and difficulties associated with these disturbances; and (3) caregiver actions (planned or actual) to limit firearms access. CONCLUSION: Various behavioral disturbances and emotional burdens can trigger ADRD caregiver concern about firearms access, but strategies exist for restricting or safeguarding firearms in the home. Study findings suggest a need for caregiver support on this topic, including counseling by healthcare providers, advance planning for older firearm owners, and development of community resources.

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BACKGROUND: The neuropsychiatric symptoms (NPS) in patients with neurocognitive disorders (NCD) increases the risk of exhibiting significant cognitive and functional decline. However, to the best of our knowledge, few studies have evaluated to what extent the presence of chronic and early NPS impacts cognition and functionality in patients with minor or major stages of NCD. OBJECTIVE: We aimed to assess the interplay between early and chronic NPS and cognitive and functional presentation of patients with mild and major forms of NCD. METHODS: We used two NPS tools tracking early and late NPS and assessed to what extent they determine cognitive and functional outcomes in patients with mild and major forms of NCD. RESULTS: We found an inverse relationship between the presence of NPS, as measured by the Neuropsychiatric Inventory and Mild Behavioral Impairment Checklist (MBI-C), and cognitive and functional variables in major forms of NCD. In contrast, the minor stage of NCD was associated with increased MBI-C scores. CONCLUSION: Our results revealed that NPS are associated with cognitive and functional outcomes in mild and chronic forms of NCD. Crucially our results suggest that NPS could be considered as a pathological marker of the clinical course of dementia. Additionally, our study calls to study early and late forms of NPS as both impact cognition and functionality of NCD.

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People with intellectual disability (ID) have a greater frequency of psychiatric illnesses, ranging from 10% to 80%, as compared to the general population. It has been proven that mood stabilizers are beneficial in the management of behavior issues in people with ID. Here, we report a series of five cases with mild and moderate ID with behavioral disturbances including mood and psychotic symptoms managed successfully with sodium valproate as the part of the treatment.

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INTRODUCTION: Peripheral and central nervous system inflammation have been linked to the classic symptoms of Parkinson's disease (PD) and Alzheimer's disease (AD). However, it remains unclear whether the analysis of routine systemic inflammatory markers could represent a useful prediction tool to identify clinical subtypes in patients with Parkinson's and Alzheimer's at higher risk of dementia-associated symptoms, such as behavioral and psychological symptoms of dementia (BPSD). METHODS: We performed a multivariate logistic regression using the 2016 and 2017 National Inpatient Sample with International Classification of Diseases 10th edition codes to assess if pro-inflammatory white blood cells (WBCs) anomalies correlate with dementia and BPSD in patients with these disorders. RESULTS: We found that leukocytosis was the most common WBC inflammatory marker identified in 3.9% of Alzheimer's and 3.3% Parkinson's patients. Leukocytosis was also found to be an independent risk factor for Parkinson's dementia. Multivariate analysis of both cohorts showed that leukocytosis is significantly decreased in patients with BPSD compared to patients without BPSD. CONCLUSIONS: These results suggest a link between leukocytosis and the pathophysiology of cognitive dysfunction in both PD and AD. A better understanding of the role of systemic neuroinflammation on these devastating neurodegenerative disorders may facilitate the development of cost-effective blood biomarkers for patient's early diagnosis and more accurate prognosis.

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BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) are quite challenging problems during the dementia course. Special Care Units for people with dementia (PwD) and BPSD (SCU-B) are residential medical structures, where BPSD patients are temporarily admitted, in case of unmanageable behavioral disturbances at home. OBJECTIVE: RECage (REspectful Caring for AGitated Elderly) aspires to assess the short and long-term effectiveness of SCU-Bs toward alleviating BPSD and improving the quality of life (QoL) of PwD and their caregivers. METHODS: RECage is a three-year, prospective study enrolling 500 PwD. Particularly, 250 community-dwelling PwDs presenting with severe BPSD will be recruited by five clinical centers across Europe, endowed with a SCU-B, for a short period of time; a second similar group of 250 PwD will be followed by six other no-SCU-B centers solely via outpatient visits. RECage's endpoints include short and long-term SCU-B clinical efficacy, QoL of patients and caregivers, cost-effectiveness of the SCU-B, psychotropic drug consumption, caregivers' attitude toward dementia, and time to nursing home placement. RESULTS: PwD admitted in SCU-Bs are expected to have diminished rates of BPSD and better QoL and their caregivers are also expected to have better QoL and improved attitude towards dementia, compared to those followed in no-SCU-Bs. Also, the cost of care and the psychotropic drug consumption are expected to be lower. Finally, PwD followed in no-SCU-Bs are expected to have earlier admission to nursing homes. CONCLUSION: The cohort study results will refine the SCU-B model, issuing recommendations for implementation of SCU-Bs in the countries where they are scarce or non-existent.

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INTRODUCTION: Neuropsychiatric symptoms (NPS) in dementia are associated with poor cognitive outcomes in longitudinal studies. Whether this is due to differences in symptom burden between persons (BP) or changes within persons (WP) is unknown. METHODS: Patients with mild Alzheimer's disease (AD, n = 111) and Lewy-body dementia (LBD, n = 85) were assessed annually for 8 years. We modelled the association between NPS assessed by the Neuropsychiatric Inventory (NPI) and Mini-Mental State Examinations (MMSE) using Tobit mixed-effects model with NPS as individual means over time (BP) and its deviance (WP). RESULTS: The association between higher NPS and poorer cognitive outcomes was mostly due to BP differences for the NPI-total score, and in particular for delusions, hallucinations, agitation, aberrant motor behavior, and apathy scores. DISCUSSION: The NPS trait (BP) effect on cognitive decline is considerably stronger than the state effect (WP). Clinically, long-term rather than episodic NPS better identifies patients with poor cognitive outcomes.