Evaluation of cognitive, functional, and behavioral effects observed in EMERGE, a phase 3 trial of aducanumab in people with early Alzheimer's disease.

Introduction: In EMERGE (NCT02484547), participants receiving aducanumab had significantly less progression versus placebo on all prespecified clinical endpoints at week 78. Here, we explicate the clinical meaningfulness of these treatment effects by analyzing item-level data and the persistence of treatment benefit.

Methods: Participants with early Alzheimer's disease (AD) were stratified by apolipoprotein E (APOE) ε4 status and randomized (1:1:1) to receive low- or high-dose aducanumab, or placebo.

A US-based practitioner's guide to diagnosis, evaluation, and evidence-based treatment of agitation in Alzheimer's dementia - recommendations of an expert, multispecialty advisory panel.

Background: Agitation in Alzheimer's dementia has a substantial impact on patients, caregivers/family, and healthcare systems. As new evidence surrounding the treatment of agitation emerges, a roundtable of multispecialty experts convened to review published literature (from a PubMed database search on 1 October 2024) and provide evidence-based clinical practice consensus recommendations for the diagnosis and management of agitation in Alzheimer's dementia for US-based primary care providers.

Aim: The main objective of this article is to summarize key recommendations from the roundtable on identification, differential diagnosis, current clinical practice, nonpharmacologic interventions, pharmacologic interventions, and treatment and communication considerations for residential care facilities/home care settings and caregivers.

Escitalopram for agitation in Alzheimer's dementia: a randomized controlled phase 3 trial.

Citalopram is effective in treating agitation in Alzheimer's dementia (AD), but it is associated with cognitive and cardiac risks, likely due to its R-enantiomer. Escitalopram, the S-enantiomer, may be an alternative. In this double-masked randomized (1:1) placebo-controlled trial, we assessed the efficacy and safety of escitalopram in treating agitation in AD after failure of a psychosocial intervention (PSI).

Cohen-mansfield agitation inventory total score as a measure of agitation and aggression in Alzheimer's disease: A factor analysis.

Background: Alzheimer's disease (AD) is often associated with agitation and aggression, which may impair function, impede care, and be a major source of stress for caregivers. The Cohen-Mansfield Agitation Inventory (CMAI) is often used to assess agitation and aggression. In its original, nursing-home version, it is a 29-item, caregiver-informed, clinician-administered 7-point scale that assesses the frequency of various agitation or aggressive behaviors.

Correlation between changes in apathy and cognition in Alzheimer's disease associated apathy: Analysis of the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2).

Background: Previous trials have shown improvements in both apathy and cognition with methylphenidate (MPH).

Objectives: To assess whether changes in apathy correlated with changes in cognition in the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2).

Participants: Mild to moderate AD patients with clinically significant apathy randomized to MPH (20 mg/day) or placebo for 6 months.

Smartwatch- and smartphone-based remote assessment of brain health and detection of mild cognitive impairment.

Consumer-grade mobile devices are used by billions worldwide. Their ubiquity provides opportunities to robustly capture everyday cognition. 'Intuition' was a remote observational study that enrolled 23,004 US adults, collecting 24 months of longitudinal multimodal data via their iPhones and Apple Watches using a custom research application that captured routine device use, self-reported health information and cognitive assessments.

Dynamic proportional loss of functional connectivity revealed change of left superior frontal gyrus in subjective cognitive decline: an explanatory study based on Chinese and Western cohorts.

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.

Measuring clinically relevant change in apathy symptoms in ADMET and ADMET 2.

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.

Brexpiprazole for Agitation Associated With Dementia Due to Alzheimer's Disease.

Alzheimer's disease (AD) is a prevalent neurodegenerative disease characterized by progressive cognitive and functional decline. Nearly all patients with AD develop neuropsychiatric symptoms (NPSs). Agitation is one of the most distressing and challenging NPS.

Adverse effects of methylphenidate for apathy in patients with Alzheimer's disease (ADMET2 trial).

Objectives: To examine clinically important adverse events (AEs) associated with methylphenidate (MPH) treatment of apathy in Alzheimer's Disease (AD) versus placebo, including weight loss, vital signs, falls, and insomnia.

Methods: The Apathy in Dementia Methylphenidate Trial 2 (ADMET2) trial was a multicenter randomized, placebo-controlled trial of MPH to treat apathy in individuals with apathy and AD. Participants in ADMET2 had vital signs and weight measured at monthly visits through 6 months.

Review of valiltramiprosate (ALZ-801) for the treatment of Alzheimer's disease: a novel small molecule with disease modifying potential.

Introduction: Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive deterioration, functional impairments, and neuropsychiatric symptoms. Valiltramiprosate is a tramiprosate prodrug being investigated as a novel treatment for AD.

Areas Covered: The online databases PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.

Effects of methylphenidate on neuropsychiatric symptoms in Alzheimer's disease: Evidence from the ADMET 2 study.

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.

Heterogeneity of Response to Methylphenidate in Apathetic Patients in the ADMET 2 Trial.

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.

Cost consequence analysis of Apathy in Dementia Methylphenidate Trial 2 (ADMET 2).

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.

A 2023 update on the advancements in the treatment of agitation in Alzheimer's disease.

Introduction: Neuropsychiatric symptoms (NPS) in Alzheimer's Disease (AD) are associated with negative outcomes for patients and their care partners. Agitation is a common and distressing NPS, without safe and effective treatments. Nonpharmacological interventions are first line treatment, but not effective or appropriate for every patient.

Effect of online tDCS to left somatomotor cortex on neuropsychiatric symptoms among older adults at risk for dementia.

Background: Neuropsychiatric symptoms (NPS) in mild cognitive impairment (MCI) cause distress to patients and caregivers, and accelerate progression to dementia. Transcranial direct current stimulation (tDCS) is a promising non-invasive treatment for NPS.

Objective/hypothesis: This pilot study assessed behavioral and neural effects of a 4-week anodal tDCS intervention targeting left sensorimotor cortex (LSMC: left precentral/postcentral gyri) during visual attention (compared to online sham tDCS), in 40 older adults (24 females, mean age = 71) with MCI.

Brain amyloid burden, sleep, and 24-hour rest/activity rhythms: screening findings from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration Studies.

Study Objectives: To examine in a subsample at the screening phase of a clinical trial of a β-amyloid (Aβ) antibody whether disturbed sleep and altered 24-hour rest/activity rhythms (RARs) may serve as markers of preclinical Alzheimer's disease (AD).

Methods: Overall, 26 Aβ-positive (Aβ+) and 33 Aβ-negative (Aβ-) cognitively unimpaired participants (mean age = 71.3 ± 4.

Effect of Methylphenidate on Apathy in Patients With Alzheimer Disease: The ADMET 2 Randomized Clinical Trial.

Importance: Apathy, characterized by diminished will or initiative and one of the most prevalent neuropsychiatric symptoms in individuals with Alzheimer disease, is associated with significant caregiver burden, excess disability, increased medical costs, and mortality.

Objective: To measure whether methylphenidate compared with placebo decreases the severity of apathy in individuals with Alzheimer disease.

Design, Setting, And Participants: This multicenter randomized placebo-controlled clinical trial was conducted from August 2016 to July 2020 in 9 US clinics and 1 Canadian clinic specializing in dementia care.

APOE ε4/ε4 homozygotes with early Alzheimer's disease show accelerated hippocampal atrophy and cortical thinning that correlates with cognitive decline.

Introduction: Hippocampal volume (HV) and cortical thickness are commonly used imaging biomarkers in Alzheimer's disease (AD) trials, and may have utility as selection criteria for enrichment strategies. Atrophy rates of these measures, in the high-risk apolipoprotein E (APOE) ε4/ε4 homozygous AD subjects are unknown.

Methods: Data from Alzheimer's Disease Neuroimaging Initiative (ADNI-1) and a tramiprosate trial were analyzed in APOE ε4/ε4 and APOE ε3/ε3 subjects with mild cognitive impairment (MCI) or mild AD.

Measuring Apathy in Alzheimer's Disease in the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2): A Comparison of Instruments.

Background: Diagnostic criteria for apathy have been published but have yet to be evaluated in the context of clinical trials. The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) operationalized the diagnostic criteria for apathy (DCA) into a clinician-rated questionnaire informed by interviews with the patient and caregiver.

Objective: The goal of the present study was to compare the classification of apathy using the DCA with that using the Neuropsychiatric Inventory-apathy (NPI-apathy) subscale in ADMET 2.

Neurobiologic Rationale for Treatment of Apathy in Alzheimer's Disease With Methylphenidate.

The public health burden of Alzheimer's disease (AD) is related not only to cognitive symptoms, but also to neuropsychiatric symptoms, including apathy. Apathy is defined as a quantitative reduction of goal-directed activity in comparison to a previous level of functioning and affects 30%-70% of persons with AD. Previous attempts to treat apathy in AD-both nonpharmacologically and pharmacologically-have been wanting.