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BACKGROUND The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. METHODS In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we as-signed extremely preterm infants (gestational age, <28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care. The primary outcome was a composite of death or severe brain injury on cerebral ultrasonography at 36 weeks' postmenstrual age. Serious adverse events that were assessed were death, severe brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and late-onset sepsis. RESULTS A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative risk with cerebral oximetry, 1.03; 95% confidence interval, 0.90 to 1.18; P=0.64). The incidence of serious adverse events did not differ between the two groups. CONCLUSIONS In extremely preterm infants, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth was not associated with a lower incidence of death or severe brain injury at 36 weeks' postmenstrual age than usual care. (Funded by the Elsass Foundation and others; SafeBoosC-III ClinicalTrials.gov number, NCT03770741.) [ABSTRACT FROM AUTHOR]

Brain network dynamics have been extensively explored in patients with subjective cognitive decline (SCD). However, these studies are susceptible to individual differences, scanning parameters, and other confounding factors. Therefore, how to reveal subtle SCD-related subtle changes remains unclear. Cross-sectional and longitudinal resting-state functional magnetic resonance imaging data from both Chinese and Western populations were analyzed. We proposed a framework of dynamic proportional loss of functional connectivity (DPLFC). After its stability was validated, the optimal parameters were applied for the clinical diagnosis of SCD. DPLFC yielded a relatively high intraclass correlation coefficient. In particular, the DPLFC of the left superior frontal gyrus (SFG) progressively decreased along the Alzheimer's disease (AD) continuum. Compared with the traditional index, the DPLFC had better classification performance between cognitively normal controls and patients with SCD. Furthermore, DPLFC was related to Aβ deposition and scale scores. Patients with lower DPLFC values had a greater risk of cognitive decline. Decreased DPLFC in the left SFG may be a potential AD-related neuroimaging biomarker at an early stage., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to American Aging Association.)

Background/Objectives : The goal of this commentary is to highlight several key components of the inflammatory process as it relates to amyloid toxicity in Alzheimer's disease (AD), including the role of neuroinflammatory factors and peripheral inflammatory events. Methods : Google Scholar and PubMed were used to find articles with the following keywords: Alzheimer's disease, amyloids, neuroinflammation, peripheral inflammation, microglia, cytokines, and treatments. Sources that were case reports, not peer-reviewed, or older than 30 years were excluded. Abstracts were reviewed first for their relevance before the full text was considered. Methods sections were reviewed to ensure the interventional papers included were randomized controlled trials, meta-analyses, or systematic reviews; however, several literature reviews were also included due to the relevance of their background information. Results : Based on the literature review, we chose to concentrate on microglia, cytokine signaling, and peripheral inflammation markers. We found that microglia activation and subsequent microglia-driven inflammation play a pivotal role in the pathomechanism of AD. Additionally, cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-a) appear to contribute to amyloid accumulation and cell damage. Finally, the increased permeability of the blood-brain barrier (BBB) allows for the peripheral inflammatory process to contribute to the inflammation of the central nervous system (CNS) and amyloid-beta (Aβ) accumulation. Conclusions : Current evidence suggests that the immune system plays a pivotal role in the pathogenesis of AD, both in the CNS and the periphery.

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

Infants requiring admission to the neonatal intensive care unit (NICU) are particularly vulnerable to developing brain injury. The severity of the underlying clinical conditions and the complexity of care call for continuous, cot-side, non-invasive monitoring tools. Near-infrared spectroscopy (NIRS) measures the regional tissue oxygen saturation of hemoglobin (rStO 2 ) and provides continuous information on the net-result of several factors. Cerebral rStO 2 correlates with echocardiography-derived measures of blood flow. Cerebral fractional tissue oxygen extraction provides information on the balance between oxygen supply and demand and can be continuously derived from the combined use of cerebral rStO 2 and arterial oxygen saturation. Information on cerebral blood flow autoregulatory capacity can be obtained from combining cerebral rStO 2 and invasive blood pressure monitoring by appropriate software. Cerebral rStO 2 provides real-time, end-organ information on perfusion-oxygenation, and when interpreted in the clinical context based on pathophysiological principles may be used as a help to guide interventions in the NICU. In this review we will discuss how to optimize NIRS monitoring for application in the NICU, with a particular focus on the preterm infant. IMPACT: Near-infrared spectroscopy (NIRS) provides cot-side, real-time information on blood and oxygen supply to the brain. Therefore, it is a valuable tool to better understand the pathophysiology underlaying disease processes. Current evidence suggests that NIRS-guided treatment in extremely preterm infants during transitional circulation does not improve clinical outcomes. Specific training is needed to maximize potential performance. Pathophysiological interpretation of cerebral NIRS data in the given clinical context may help in decision-making. Appropriate use of this monitoring technique, interpreted concurrently with other routine parameters, is a potential clinical tool to guide interventions in the NICU setting., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Alzheimer's disease (AD) is the most common cause of dementia, and the gradual deterioration of brain function eventually leads to death. Almost all AD patients suffer from neuropsychiatric symptoms (NPS), the emergence of which correlates with dysfunctional serotonergic systems. Our aim is to generate hindbrain organoids containing serotonergic neurons using human induced Pluripotent Stem Cells (iPSCs). Work presented here is laying the groundwork for the application of hindbrain organoids to evaluate individual differences in disease progression, NPS development, and pharmacological treatment response. Human peripheral blood mononuclear cells (PBMCs) from healthy volunteers (n = 3), an AD patient without NPS (n = 1), and AD patients with NPS (n = 2) were reprogrammed into iPSCs and subsequently differentiated into hindbrain organoids. The presence of serotonergic neurons was confirmed by quantitative reverse transcription PCR, flow cytometry, immunocytochemistry, and detection of released serotonin (5-HT). We successfully reprogrammed PBMCs into 6 iPSC lines, and subsequently generated hindbrain organoids from 6 individuals to study inter-patient variability using a precision medicine approach. To assess patient-specific treatment effects, organoids were treated with different concentrations of escitalopram oxalate, commonly prescribed for NPS. Changes in 5-HT levels before and after treatment with escitalopram were dose-dependent and variable across patients. Organoids from different people responded differently to the application of escitalopram in vitro. We propose that this 3D platform might be effectively used for drug screening purposes to predict patients with NPS most likely to respond to treatment in vivo and to understand the heterogeneity of treatment responses., (© 2024. The Author(s).)

Perioperative applications of near-infrared spectroscopy (NIRS) to monitor regional tissue oxygenation and perfusion in cardiac and noncardiac surgery are of increasing interest in neonatal care. Complex neonatal surgery can impair adequate oxygen delivery and tissue oxygen consumption and increase the risk of neurodevelopmental delay. Coupled with conventional techniques, NIRS monitoring may enable targeted hemodynamic management of the circulation in both cardiac and noncardiac surgical procedures. In this narrative review, we discuss the application of perioperative NIRS in specific neonatal interventions, including surgical intervention for congenital heart defects, definitive closure of the patent ductus arteriosus, neurological and gastrointestinal disorders, and use of extracorporeal membrane oxygenation. We identified areas for future research within disease-specific indications and offer a roadmap to aid in developing evidence-based targeted diagnostic and management strategies in neonates. IMPACT: There is growing recognition that perioperative NIRS monitoring, used in conjunction with conventional monitoring, may provide critical hemodynamic information that either complements clinical impressions or delivers novel physiologic insight into the neonatal circulatory and perfusion pathways., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Cerebral oxygenation monitoring utilising near-infrared spectroscopy (NIRS) is increasingly used to guide interventions in clinical care. The objective of this systematic review with meta-analysis and Trial Sequential Analysis is to evaluate the effects of clinical care with access to cerebral NIRS monitoring in children and adults versus care without., Methods: This review conforms to PRISMA guidelines and was registered in PROSPERO (CRD42020202986). Methods are outlined in our protocol (doi: 10.1186/s13643-021-01660-2)., Results: Twenty-five randomised clinical trials were included (2606 participants). All trials were at a high risk of bias. Two trials assessed the effects of NIRS during neonatal intensive care, 13 during cardiac surgery, 9 during non-cardiac surgery and 1 during neurocritical care. Meta-analyses showed no significant difference for all-cause mortality (RR 0.75, 95% CI 0.51-1.10; 1489 participants; I 2  = 0; 11 trials; very low certainty of evidence); moderate or severe, persistent cognitive or neurological deficit (RR 0.74, 95% CI 0.42-1.32; 1135 participants; I 2  = 39.6; 9 trials; very low certainty of evidence); and serious adverse events (RR 0.82; 95% CI 0.67-1.01; 2132 participants; I 2  = 68.4; 17 trials; very low certainty of evidence)., Conclusion: The evidence on the effects of clinical care with access to cerebral NIRS monitoring is very uncertain., Impact: The evidence of the effects of cerebral NIRS versus no NIRS monitoring are very uncertain for mortality, neuroprotection, and serious adverse events. Additional trials to obtain sufficient information size, focusing on lowering bias risk, are required. The first attempt to systematically review randomised clinical trials with meta-analysis to evaluate the effects of cerebral NIRS monitoring by pooling data across various clinical settings. Despite pooling data across clinical settings, study interpretation was not substantially impacted by heterogeneity. We have insufficient evidence to support or reject the clinical use of cerebral NIRS monitoring., (© 2022. The Author(s).)

Background: The aim of this systematic qualitative review was to give an overview of reference ranges defined as normal values or centile charts of regional tissue oxygen saturation measured by near-infrared spectroscopy (NIRS) in term and preterm neonates., Methods: A systematic search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials was performed. Additional articles were identified by manual search of cited references. Only human studies in neonates were included., Results: Nineteen studies were identified. Eight described regional tissue oxygen saturation during fetal-to-neonatal transition, six during the first 3 days after birth, four during the first 7 days after birth, and one during the first 8 weeks after birth. Nine described regional tissue oxygen saturation in term, nine in preterm neonates, and one in both. Eight studies published centile charts for cerebral regional tissue oxygen saturation, and only five included large cohorts of infants. Eleven studies described normal values for cerebral, muscle, renal, and abdominal regional tissue oxygen saturation, the majority with small sample sizes. Four studies of good methodological quality were identified describing centile charts of cerebral regional tissue oxygen saturation., Conclusions: In clinical settings, quality centile charts are available and should be the preferred method when using NIRS monitoring., Impact: Near-infrared spectroscopy (NIRS) enables a bed-side non-invasive continuous monitoring of tissue oxygenation. When using NIRS monitoring in a clinical setting, centile charts with good quality are available and should be preferred to normal values. High-quality reference ranges of regional tissue oxygenation in term and preterm born neonates are an important step toward routine clinical application of NIRS., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

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.

Objectives: To develop an agitation reduction and prevention algorithm is intended to guide implementation of the definition of agitation developed by the International Psychogeriatric Association (IPA)., Design: Review of literature on treatment guidelines and recommended algorithms; algorithm development through reiterative integration of research information and expert opinion., Setting: IPA Agitation Workgroup., Participants: IPA panel of international experts on agitation., Intervention: Integration of available information into a comprehensive algorithm., Measurements: None., Results: The IPA Agitation Work Group recommends the Investigate, Plan, and Act (IPA) approach to agitation reduction and prevention. A thorough investigation of the behavior is followed by planning and acting with an emphasis on shared decision-making; the success of the plan is evaluated and adjusted as needed. The process is repeated until agitation is reduced to an acceptable level and prevention of recurrence is optimized. Psychosocial interventions are part of every plan and are continued throughout the process. Pharmacologic interventions are organized into panels of choices for nocturnal/circadian agitation; mild-moderate agitation or agitation with prominent mood features; moderate-severe agitation; and severe agitation with threatened harm to the patient or others. Therapeutic alternatives are presented for each panel. The occurrence of agitation in a variety of venues-home, nursing home, emergency department, hospice-and adjustments to the therapeutic approach are presented., Conclusions: The IPA definition of agitation is operationalized into an agitation management algorithm that emphasizes the integration of psychosocial and pharmacologic interventions, reiterative assessment of response to treatment, adjustment of therapeutic approaches to reflect the clinical situation, and shared decision-making.

Background: Improving neonatal abstinence syndrome (NAS) management is an important concern, and objective measures of its physiologic impact remain elusive. We sought to determine whether near-infrared spectroscopy (NIRS)-derived tissue oxygenation (rSO2) and fractional tissue oxygen extraction (FTOE) demonstrated physiologically plausible changes correlating with standard NAS scoring., Methods: Thirty subjects (mean 39 weeks' GA and 3 127 g BW) underwent cerebral and peripheral muscle NIRS monitoring on Days of Life (DOL) Three, Five, and Seven. We examined correlations between NAS scores and FTOE and assessed the impact of non-pharmacologic swaddling and cuddling., Results: No statistically significant correlations between NAS scores and FTOE were observed; however, plausible trends were demonstrated between NAS scores and cerebral measurements. Buprenorphine-exposed babies (57%) showed significantly lower FTOE when swaddled (DOL7)., Conclusions: Tissue oxygenation monitoring demonstrates potential to provide objective, clinically relevant physiologic information on infants at risk for NAS. Further study is required to determine whether NIRS-derived measures could assist in individualizing NAS care.

This position statement of the Expert Panel on Brain Health of the American Association for Geriatric Psychiatry (AAGP) emphasizes the critical role of life course brain health in shaping mental well-being during the later stages of life. Evidence posits that maintaining optimal brain health earlier in life is crucial for preventing and managing brain aging-related disorders such as dementia/cognitive decline, depression, stroke, and anxiety. We advocate for a holistic approach that integrates medical, psychological, and social frameworks with culturally tailored interventions across the lifespan to promote brain health and overall mental well-being in aging adults across all communities. Furthermore, our statement underscores the significance of prevention, early detection, and intervention in identifying cognitive decline, mood changes, and related mental illness. Action should also be taken to understand and address the needs of communities that traditionally have unequal access to preventive health information and services. By implementing culturally relevant and tailored evidence-based practices and advancing research in geriatric psychiatry, behavioral neurology, and geroscience, we can enhance the quality of life for older adults facing the unique challenges of aging. This position statement emphasizes the intrinsic link between brain health and mental health in aging, urging healthcare professionals, policymakers, and a broader society to prioritize comprehensive strategies that safeguard and promote brain health from birth through later years across all communities. The AAGP Expert Panel has the goal of launching further activities in the coming months and years., (Copyright © 2023 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) found that methylphenidate was effective in treating apathy with a small-to-medium effect size but showed heterogeneity in response. We assessed clinical predictors of response to help determine individual likelihood of treatment benefit from methylphenidate., Design: Univariate and multivariate analyses of 22 clinical predictors of response chosen a priori., Setting: Data from the ADMET 2 randomized, placebo controlled multi-center clinical trial., Participants: Alzheimer's disease patients with clinically significant apathy., Measurements: Apathy assessed with the Neuropsychiatric Inventory apathy domain (NPI-A)., Results: In total, 177 participants (67% male, mean [SD] age 76.4 [7.9], mini-mental state examination 19.3 [4.8]) had 6-months follow up data. Six potential predictors met criteria for inclusion in multivariate modeling. Methylphenidate was more efficacious in participants without NPI anxiety (change in NPI-A -2.21, standard error [SE]:0.60) or agitation (-2.63, SE:0.68), prescribed cholinesterase inhibitors (ChEI) (-2.44, SE:0.62), between 52 and 72 years of age (-2.93, SE:1.05), had 73-80 mm Hg diastolic blood pressure (-2.43, SE: 1.03), and more functional impairment (-2.56, SE:1.16) as measured by the Alzheimer's Disease Cooperative Study Activities of Daily Living scale., Conclusion: Individuals who were not anxious or agitated, younger, prescribed a ChEI, with optimal (73-80 mm Hg) diastolic blood pressure, or having more impaired function were more likely to benefit from methylphenidate compared to placebo. Clinicians may preferentially consider methylphenidate for apathetic AD participants already prescribed a ChEI and without baseline anxiety or agitation., (Copyright © 2023 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: This paper used data from the Apathy in Dementia Methylphenidate Trial 2 (NCT02346201) to conduct a planned cost consequence analysis to investigate whether treatment of apathy with methylphenidate is economically attractive., Methods: A total of 167 patients with clinically significant apathy randomized to either methylphenidate or placebo were included. The Resource Utilization in Dementia Lite instrument assessed resource utilization for the past 30 days and the EuroQol five dimension five level questionnaire assessed health utility at baseline, 3 months, and 6 months. Resources were converted to costs using standard sources and reported in 2021 USD. A repeated measures analysis of variance compared change in costs and utility over time between the treatment and placebo groups. A binary logistic regression was used to assess cost predictors., Results: Costs were not significantly different between groups whether the cost of methylphenidate was excluded ( F (2,330) = 0.626, η p 2 = 0.004, p = 0.535) or included ( F (2,330) = 0.629, η p 2 = 0.004, p = 0.534). Utility improved with methylphenidate treatment as there was a group by time interaction ( F (2,330) = 7.525, η p 2 = 0.044, p < 0.001)., Discussion: Results from this study indicated that there was no evidence for a difference in resource utilization costs between methylphenidate and placebo treatment. However, utility improved significantly over the 6-month follow-up period. These results can aid in decision-making to improve quality of life in patients with Alzheimer's disease while considering the burden on the healthcare system.

Background: The SafeBoosC project aims to test the clinical value of non-invasive cerebral oximetry by near-infrared spectroscopy in newborn infants. The purpose is to establish whether cerebral oximetry can be used to save newborn infants' lives and brains or not. Newborns contribute heavily to total childhood mortality and neonatal brain damage is the cause of a large part of handicaps such as cerebral palsy. The objective of the SafeBoosC-IIIv trial is to evaluate the benefits and harms of cerebral oximetry added to usual care versus usual care in mechanically ventilated newborns., Methods/design: SafeBoosC-IIIv is an investigator-initiated, multinational, randomised, pragmatic phase-III clinical trial. The inclusion criteria will be newborns with a gestational age more than 28 + 0 weeks, postnatal age less than 28 days, predicted to require mechanical ventilation for at least 24 h, and prior informed consent from the parents or deferred consent or absence of opt-out. The exclusion criteria will be no available cerebral oximeter, suspicion of or confirmed brain injury or disorder, or congenital heart disease likely to require surgery. A total of 3000 participants will be randomised in 60 neonatal intensive care units from 16 countries, in a 1:1 allocation ratio to cerebral oximetry versus usual care. Participants in the cerebral oximetry group will undergo cerebral oximetry monitoring during mechanical ventilation in the neonatal intensive care unit for as long as deemed useful by the treating physician or until 28 days of life. The participants in the cerebral oximetry group will be treated according to the SafeBoosC treatment guideline. Participants in the usual care group will not receive cerebral oximetry and will receive usual care. We use two co-primary outcomes: (1) a composite of death from any cause or moderate to severe neurodevelopmental disability at 2 years of corrected age and (2) the non-verbal cognitive score of the Parent Report of Children's Abilities-Revised (PARCA-R) at 2 years of corrected age., Discussion: There is need for a randomised clinical trial to evaluate cerebral oximetry added to usual care versus usual care in mechanically ventilated newborns., Trial Registration: The protocol is registered at www., Clinicaltrials: gov (NCT05907317; registered 18 June 2023)., (© 2023. The Author(s).)

Background: In the SafeBoosC-III trial, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth did not reduce the incidence of death or severe brain injury in extremely preterm infants at 36 weeks' postmenstrual age, as compared with usual care. Despite an association between severe brain injury diagnosed in the neonatal period and later neurodevelopmental disability, this relationship is not always strong. The objective of the SafeBoosC-III follow-up study is to assess mortality, neurodevelopmental disability, or any harm in trial participants at 2 years of corrected age. One important challenge is the lack of funding for local costs for a trial-specific assessment., Methods: Of the 1601 infants randomised in the SafeBoosC-III trial, 1276 infants were alive at 36 weeks' postmenstrual age and will potentially be available for the 2-year follow-up. Inclusion criteria will be enrollment in a neonatal intensive care unit taking part in the follow-up study and parental consent if required by local regulations. We aim to collect data from routine follow-up programmes between the ages of 18 and 30 months of corrected age. If no routine follow-up has been conducted, we will collect informal assessments from other health care records from the age of at least 12 months. A local co-investigator blinded to group allocation will classify outcomes based on these records. We will supplement this with parental questionnaires including the Parent Report of Children's Abilities-Revised. There will be two co-primary outcomes: the composite of death or moderate or severe neurodevelopmental disability and mean Bayley-III/IV cognitive score. We will use a 3-tier model for prioritisation, based on the quality of data. This approach has been chosen to minimise loss to follow-up assuming that little data is better than no data at all., Discussion: Follow-up at the age of 2 years is important for intervention trials in the newborn period as only time can show real benefits and harms later in childhood. To decrease the risk of generalisation and data-driven biased conclusions, we present a detailed description of the methodology for the SafeBoosC-III follow-up study. As funding is limited, a pragmatic approach is necessary., Trial Registration: ClinicalTrials.gov NCT05134116 . Registered on 24 November 2021., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Methylphenidate has been shown to improve apathy in patients with Alzheimer's disease (AD). The authors evaluated the impact of methylphenidate on neuropsychiatric symptoms (NPS) of AD, excluding apathy, using data from the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) study., Methods: A secondary analysis was conducted on data from the ADMET 2 study to determine the effect of methylphenidate on Neuropsychiatric Inventory (NPI) scores outside of apathy. Caregiver scores were compared from baseline to month 6 in 199 participants receiving methylphenidate (20 mg/day) or placebo regarding the presence or absence of individual neuropsychiatric symptoms, emergence of new symptoms, and individual domain scores., Results: No clinically meaningful improvement was observed in any NPI domain, excluding apathy, in participants treated with methylphenidate compared to placebo after 6 months. A statistical difference between groups was appreciated in the domains of elation/euphoria ( P = 0.044) and appetite/eating disorders ( P = 0.014); however, these findings were not considered significant., Discussion: Methylphenidate is a selective agent for symptoms of apathy in patients with AD with no meaningful impact on other NPS. Findings from this secondary analysis are considered exploratory and multiple limitations should be considered when interpreting these results, including small sample size and use of a single questionnaire. HIGHLIGHTS: Methylphenidate was not associated with significant improvement on the Neuropsychiatric Inventory in domains outside of apathy.Methylphenidate did not show a statistically significant emergence of new neuropsychiatric symptoms (NPS) throughout the 6-month treatment period compared to placebo.Methylphenidate appears to be a highly selective agent for apathy in Alzheimer's disease, potentially supporting catecholaminergic dysfunction as the driving force behind this presentation of symptoms., Competing Interests: Dr. Brawman‐Mintzer receives grant funding from the National Institute on Aging, Merck, Alzheimer's Trials Research Institute and Alzheimer's Cooperative Trials Consortium, and the Department of Defense. Dr. Brawman‐Mintzer has served as a steering committee member for the Alzheimer's Disease Cooperative Study and as an associate steering committee member with the Alzheimer's Clinical Trials Consortium. Dr. Brawman‐Mintzer has received payment or honoraria from Medscape. Dr. Clark reports grants to her institution for clinical trials from Alzheon and Biogen. Dr. Lanctôt reports grants from Alzheimer's Association (PTC‐18‐543823, PTCG‐20‐ 700751), Alzheimer Society of Canada, Alzheimer's Drug Discovery Foundation (Grant No: 2016354), Canadian Institutes Health Research (PJ2‐179752, PJT‐183584), National Institute on Aging (R01AG046543), and Weston Brain Institute; consulting fees from BioXcel Therapeutics, Bright Minds, Cerevel Therapeutics, Eisai Co. Ltd, Exciva, ICG Pharma, Jazz Pharmaceuticals, Kondor Pharma, H Lundbeck A/S, Merck, Novo Nordisk, Praxis Therapeutics, Sumitomo Pharma Co. Ltd; stock options from Highmark Interactive outside the submitted work. Krista Lanctôt is the Bernick Chair in Geriatric Psychopharmacology of Sunnybrook Health Sciences Centre and University of Toronto's Temerty Faculty of Medicine. Dr. Lerner receives research grant support from the National Institutes of Health and National Institute on Aging (P30AG072959), Alzheimer's Clinical Trials Consortium, the Elisabeth S. Prentiss Foundation. He receives honoraria for consulting from Premier Inc (PINC AI Applied Sciences). He has received book royalties from Elsevier. He is a steering committee member of the Alzheimer's Clinical Trials Consortium. Dr. Jacobo Mintzer is a consultant and Governance Committee Member for AARP's Global Council on Brain Health and a consultant and Scientific Advisor for AARP's Staying Sharp Scientific Advisory Committee. He is a consultant for ACADIA, AiOmed, Corium, Exciva, Genentech (affiliate of F. Hoffmann‐La Roche Ltd), Ironshore Pharmaceuticals, Lundbeck, Praxis Bioresearch, and Sygnature Discovery. Dr. Mintzer is a Steering Committee Member for the Alzheimer's Clinical Trials Consortium, Alzheimer's Disease Cooperative Study, and the Elder Court. He is a Board Member for the Alzheimer's Association, SC Chapter and the Technology Accelerator Company as well as an Association Member of the International Psychogeriatric Association. He is a Scientific Advisory Board Member for Exciva and Advisory Board Member for ACADIA. Dr. Mintzer is a stockholder and the VP for Clinical Affairs for NeuroQuest, a majority owner of Biopharma Connex, and a majority partner for Recruitment Partners. Dr. Mintzer has received payment or honoraria from ACADIA. He is receiving support for specific clinical trials from Cerevel Therapeutics, LLC, Eisai Inc., Eli Lilly and Company, the Alzheimer's Association, the Alzheimer's Drug Discovery Foundation, the National Institute on Aging, the National Institutes of Health, and the National Endowment for the Arts. Dr. Mintzer has received support for attending meetings and/or travel from AARP Global Council on Brain Health (GCBH), AiOmed, and Alzheimer's Clinical Trials Consortium. Finally, he has served as a DSMB member for NAB‐It: Nabilone for Agitation Blinded Intervention Trial. Dr. Padala receives support for his time from the Department of Veterans Affairs and the National Institutes of Health. Dr. Perin received grant support for the present manuscript from the National Institutes of Health (Grant R01AG046543). Dr. Rosenberg has received research grants from the National Institute on Aging, Alzheimer's Association, Alzheimer's Clinical Trials Consortium, Alzheimer's Trials Research Institute and Alzheimer's Cooperative Trials Consortium, Richman Family Precision Medicine Center of Excellence on Alzheimer's Disease, Eisai, Functional Neuromodulation, and Lilly; honoraria from consulting for GLG, Leerink, Cerevel, Cerevance, Bioxcel, Sunovion, Acadia, Medalink, Novo Nordisk, Noble Insights, TwoLabs, Otsuka, Lundbeck, Biogen, MedaCorp, ExpertConnect, and HMP Global. He participates on an advisory board for Synaptogenix. He has received honoraria for presentations from Medscape and Neurology Week, and has received support for travel for a consultation meeting from Lundbeck. Dr. David Shade received grant support for the present manuscript from the National Institutes of Health. Dr. van Dyck serves as a scientific advisor for Eisai, Roche, Ono, and Cerevel and reports grant support for clinical trials from Biogen, Biohaven, Cerevel, Eisai, Eli Lilly, Genentech, Janssen, Roche, and UCB. He also participates as a member of the Medical and Scientific Advisory Group for the Alzheimer's Association. Dr. Porsteinsson reports DSMB membership fees from Acadia, Cadent, Cognitive Research Corp, Functional Neuromodulation, Neurim, Novartis, and Tetra Discovery Partners; consulting fees from Athira, Avanir, Biogen, BioXcel, Eisai, Grifols, IQVIA, Lundbeck, Maplight Therapeutics, Merck, ONO Pharmaceuticals, Pfizer, and Toyama; grants for clinical trials from the National Institute on Aging, National Institute on Mental Health, the Department of Defense, Alector, AstraZeneca, Athira, Avanir, Biogen, Biohaven, Cassava, Eisai, Eli Lilly, Genentech/Roche, Janssen, Merck, Novartis, Toyama, and Vaccinex outside the submitted work. Dr. Herrmann declares no conflicts of interest. Susie Sami declares no conflicts of interest. This research did not receive any specific grant from funding agencies in the public, commercial, or not‐for‐profit sectors. Author disclosures are available in the supporting information., (© 2023 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Purpose: Research about the prevalence of dementia among older adults in the incarceration system is currently lacking, and further investigation is warranted. Considering the high level of healthcare needs, unique behavioural issues and difficulty to rehabilitate within the system due to its punitive approach and lack of effective rehabilitation programs, further investigation is warranted to characterize and determine the number of incarcerated older adults with dementia. The purpose of this study is to estimate the prevalence of individuals with dementia in the prison system while also describing the incarceration, demographic and offence-related characteristics of this unique population., Design/methodology/approach: South Carolina (SC) Alzheimer's Disease and Related Dementias Registry (1992-2016) and South Carolina Department of Corrections (SCDC) data (Fiscal years 1992-2019) were cross-referenced. The prevalence of Alzheimer's disease and related dementias (ADRD) cases in the corrections system was calculated using South Carolina Alzheimer's Disease (SC AD) SC ADRD Registry and SCDC data. Pearson's correlation coefficients were calculated to determine strength and direction of relationships between year of incarceration and frequency of ADRD cases both prior to and after incarcerations, respectively. Significant differences by age group, race, gender and dementia type were determined using a two-tailed pooled t -test and Bonferroni approach where appropriate. Count data for types of crimes committed are also presented., Findings: The linkage showed that there were 2,171 individuals within the SC AD Registry who have been in the corrections system, about 1% of those in the Registry. Of these individuals, 1,930 cases were diagnosed with ADRD after incarceration and 241 prior to incarceration. In 2016, 317 individuals with ADRD were incarcerated. For ages 55 and above in South Carolina, the prevalence of ADRD is 6.7% in the general, non-incarcerated population compared to 14.4% in the incarcerated population. Additional results showed that those diagnosed with ADRD between 55 and 65 years of age had a significantly lower mean age at first incarceration (34.6 years of age) than those diagnosed between 66 and 74 years of age (55.9 years of age), indicating that those incarcerated earlier in life had an earlier dementia diagnosis. Additionally, African Americans had a significantly lower mean age at first incarceration (43.4 years of age) than Whites (46.2 years of age) and females had significantly lower mean age at first incarceration (42.9 years of age) than males (45 years of age). When investigating trends, results showed a significant positive linear association between year and frequency of ADRD diagnoses ( p -value < 0.05) for those with ADRD diagnosis prior to incarceration and a significant decreasing linear association ( p -value < 0.0001) in the number of individuals with an ADRD diagnosis after corrections. Findings also showed that a large percentage of older adults with ADRD in prison did not commit a violence offence., Originality/value: This study links a population-based Alzheimer's disease registry and state-wide corrections data to estimate the prevalence of individuals with dementia in the prison system. This linkage presents an opportunity to fill in significant gaps and contribute to the body of literature on dementia among people in prison in the USA., (© Emerald Publishing Limited.)