Disclosure of elevated amyloid status is not associated with long‐term suicidality in a preclinical AD trial DOI Creative Commons
Joshua D. Grill, Rema Raman,

Charlene Flournoy

и другие.

Alzheimer s & Dementia, Год журнала: 2025, Номер 21(2)

Опубликована: Фев. 1, 2025

Abstract INTRODUCTION The long‐term implications of disclosing Alzheimer's disease (AD) biomarker information to cognitively unimpaired individuals are unknown. METHODS We compared participants who disclosed their elevated amyloid imaging result in a preclinical AD trial those not and enrolled an observational cohort that underwent parallel assessments. Our primary outcome was score > 0 on the Columbia Suicidality Severity Rating Scale (CSSRS) at any visit; we also considered suicidal behaviors (CSSRS 5). RESULTS Among 1707 total (68% amyloid, mean [standard deviation] age 71.5 [4.7], 60% female, 90% non‐Hispanic White), followed for 218 (74.1) weeks, there were no suicides few indications thoughts ( n = 124 [7%]) or 13 [<1%]). In generalized estimating equation model controlling covariates, observed effect status CSSRS (odds ratio 1.6, 95% confidence interval 0.76, 3.37). DISCUSSION With structured approach, brain results can be returned safely. Highlights Anti‐Amyloid Treatment Asymptomatic study among first largest studies include disclosure population without cognitive impairment. Routine psychological assessment provided novel impact this sample. Learning through protocolized approach associated with matched learned they did have amyloid. Future research will needed ensure similar safety more real‐world settings.

Язык: Английский

INTERCEPT-AD, a phase 1 study of intravenous sabirnetug in participants with mild cognitive impairment or mild dementia due to Alzheimer's disease DOI Creative Commons
Eric Siemers,

Todd Feaster,

Gopalan Sethuraman

и другие.

The Journal of Prevention of Alzheimer s Disease, Год журнала: 2025, Номер 12(1), С. 100005 - 100005

Опубликована: Янв. 1, 2025

Soluble species of multimeric amyloid-beta including globular oligomers (AβOs) and linear protofibrils are toxic to neurons. Sabirnetug (ACU193) is a humanized monoclonal antibody, raised against soluble AβO, that has over 650-fold greater binding affinity for AβOs monomers appears have relatively little amyloid plaque. To assess safety, pharmacokinetics, exploratory measures target engagement, biomarker effects, clinical efficacy sabirnetug in participants with early symptomatic Alzheimer's disease (AD; defined as mild cognitive impairment dementia due AD). Randomized, double-blind, placebo-controlled, ascending dose first-in-human phase 1 study. Fifteen study centers the United States. Sixty-five AD. Participants received one infusion 2 mg/kg, 10 25 60 or placebo (Part A) three infusions B). Safety, tolerability, serum central engagement single multiple doses sabirnetug, cerebrospinal fluid (CSF) concentrations plaque load, determined by positron emission tomography. was generally well tolerated. A larger percentage receiving (56.3%) versus (42.9%) had at least treatment emergent adverse event, approximately 29% each group considered related drug. Most events were mild-to-moderate severity. Of 48 given five developed imaging abnormalities - edema/effusion, instance mildly participant who mg/kg. Notably, none six apolipoprotein E Ɛ4 homozygotes edema/effusion hemorrhage/hemosiderin deposition. Infusion reactions, such rash, pain, erythema, not frequent (6.3% 0.0% placebo). exposure proportional both CSF. Target drug bound CSF, shown be dependent. Over months, 25% 20% reduction plaques, respectively, observed mg/kg every four weeks two weeks. The Phase INTERCEPT-AD provided dosing, data supported design ongoing ALTITUDE-AD (NCT06335173).

Язык: Английский

Процитировано

1
Detecting early cognitive deficits in preclinical Alzheimer’s disease using a remote digital multi-day learning paradigm DOI Creative Commons
Roos J. Jutten, Daniel Soberanes, Cassidy Molinare

и другие.

npj Digital Medicine, Год журнала: 2025, Номер 8(1)

Опубликована: Янв. 13, 2025

Remote, digital cognitive testing on an individual's own device provides the opportunity to deploy previously understudied but promising paradigms in preclinical Alzheimer's disease (AD). The Boston Remote Assessment for NeuroCognitive Health (BRANCH) captures a personalized learning curve same information presented over seven consecutive days. Here, we examined BRANCH multi-day curves (MDLCs) 167 cognitively unimpaired older adults (age = 74.3 ± 7.5, 63% female) with different amyloid-β (A) and tau (T) biomarker profiles positron emission tomography. MDLC scores decreased across ascending groups, A + T- group performing numerically worse (β –0.24, 95%CI[–0.55,0.07], p 0.128) T+ significantly –0.58, 95%CI[–1.06,–0.10], 0.018) than A-T- group. Further, lower were associated greater cortical thinning 0.18, 95%CI[0.04,0.34], 0.013). Our results suggest that diminished MDLCs track advanced AD pathophysiology, demonstrate how paradigm can provide novel insights about decline during AD.

Язык: Английский

Процитировано

1
Cognivue Clarity® characterizes amyloid status and preclinical Alzheimer's disease in biomarker confirmed cohorts in the Bio-Hermes Study DOI Creative Commons
James E. Galvin, Michael J. Kleiman,

Paul W. Estes

и другие.

Journal of Alzheimer s Disease, Год журнала: 2025, Номер unknown

Опубликована: Янв. 26, 2025

Cognivue Clarity® is an FDA-cleared computerized cognitive test to screen for impairment included in the Bio-Hermes Study blood-based and digital biomarkers' ability mild (MCI) Alzheimer's disease (AD). A subset of cognitively normal individuals have amyloid deposition (Preclinical AD) but no current assessment can identify these absence expensive biomarkers. We examined differences Clarity performance between positive negative whether could differentiate True Controls (cognitively normal/amyloid negative), Preclinical AD positive), MCI due (MCI-AD, impaired/amyloid positive). was administered all participants who also had PET Performance compared biomarker-defined groups: (n = 297), 95), MCI-AD 113). global scores distinguished from (p < 0.001) differentiated versus 0.014) 0.001). Three subtests [Shape Discrimination 0.004), Visual Salience 0.008), Adaptive Motor Control 0.004)] 3-test mean AD. The composite correlated with Amyloid (r -0.433) pTau217 -0.400). identified both White Black participants. Clarity, a 10-min battery, screens impairment, characterizes individuals, identifies This has great potential as cost- time-effective strategy enroll prevention trials.

Язык: Английский

Процитировано

1
Immune Modulation in Alzheimer’s Disease: From Pathogenesis to Immunotherapy DOI Creative Commons
Sahar Balkhi,

Antimo Di Spirito,

Alessandro Poggi

и другие.

Cells, Год журнала: 2025, Номер 14(4), С. 264 - 264

Опубликована: Фев. 12, 2025

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia, affecting significant proportion elderly population. AD characterized by cognitive decline functional impairments due to pathological hallmarks like amyloid β-peptide (Aβ) plaques neurofibrillary tangles (NFTs) composed hyperphosphorylated tau. Microglial activation, chronic neuroinflammation, disruptions in neuronal communication further exacerbate disease. Emerging research suggests that immune modulation could play key role treatment given involvement neuroinflammatory processes. This review focuses on recent advancements immunotherapy strategies aimed at modulating responses AD, with specific emphasis microglial behavior, clearance, tau pathology. By exploring these immunotherapeutic approaches, we aim provide insights into their potential alter progression improve patient outcomes, contributing evolving landscape treatment.

Язык: Английский

Процитировано

1
Disclosure of elevated amyloid status is not associated with long‐term suicidality in a preclinical AD trial DOI Creative Commons
Joshua D. Grill, Rema Raman,

Charlene Flournoy

и другие.

Alzheimer s & Dementia, Год журнала: 2025, Номер 21(2)

Опубликована: Фев. 1, 2025

Abstract INTRODUCTION The long‐term implications of disclosing Alzheimer's disease (AD) biomarker information to cognitively unimpaired individuals are unknown. METHODS We compared participants who disclosed their elevated amyloid imaging result in a preclinical AD trial those not and enrolled an observational cohort that underwent parallel assessments. Our primary outcome was score > 0 on the Columbia Suicidality Severity Rating Scale (CSSRS) at any visit; we also considered suicidal behaviors (CSSRS 5). RESULTS Among 1707 total (68% amyloid, mean [standard deviation] age 71.5 [4.7], 60% female, 90% non‐Hispanic White), followed for 218 (74.1) weeks, there were no suicides few indications thoughts ( n = 124 [7%]) or 13 [<1%]). In generalized estimating equation model controlling covariates, observed effect status CSSRS (odds ratio 1.6, 95% confidence interval 0.76, 3.37). DISCUSSION With structured approach, brain results can be returned safely. Highlights Anti‐Amyloid Treatment Asymptomatic study among first largest studies include disclosure population without cognitive impairment. Routine psychological assessment provided novel impact this sample. Learning through protocolized approach associated with matched learned they did have amyloid. Future research will needed ensure similar safety more real‐world settings.

Язык: Английский

Процитировано

1