Reisa A. Sperling
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View article: Divergent latent classes of cognitive decline in the A4 and LEARN studies
Divergent latent classes of cognitive decline in the A4 and LEARN studies Open
Importance Alzheimer disease biomarkers in cognitively unimpaired older adults are associated with later cognitive and clinical decline, yet substantial heterogeneity in the timing and rate of decline remains insufficiently characterized. …
View article: Cognitive screening biases in a secondary prevention Alzheimer’s disease clinical trial
Cognitive screening biases in a secondary prevention Alzheimer’s disease clinical trial Open
INTRODUCTION Alzheimer’s disease (AD) prevention trials have multiple screening steps to identify cognitively unimpaired individuals with AD biomarker evidence. Cognitive/functional screening tests may be biased in underrepresented groups,…
View article: <i>APOE, ABCA7</i> , and <i>RASGEF1C</i> are associated with earlier onset of amyloid deposition from more than 4000 harmonized positron emission tomography images
<i>APOE, ABCA7</i> , and <i>RASGEF1C</i> are associated with earlier onset of amyloid deposition from more than 4000 harmonized positron emission tomography images Open
INTRODUCTION New methods estimate amyloid positivity onset age (EAOA) from amyloid positron emission tomography (PET). We explore the genetics of EAOA to identify molecular factors underlying the earliest Alzheimer's disease (AD) changes. …
View article: Prognostic performance across Alzheimer’s biomarkers, multi-modal physiological measures, and clinical history in asymptomatic individuals
Prognostic performance across Alzheimer’s biomarkers, multi-modal physiological measures, and clinical history in asymptomatic individuals Open
Importance Evaluating prognostic performance of Alzheimer’s biomarkers, multi-modal physiological measures, and clinical history in asymptomatic individuals versus established risk factors in asymptomatic individuals is can inform effcient…
View article: Associations of lifestyle factors with amyloid pathology in persons without dementia
Associations of lifestyle factors with amyloid pathology in persons without dementia Open
Background The association between lifestyle factors and Alzheimer's disease (AD) pathophysiology remains incompletely understood. Objective The aim of this study was to assess the association of alcohol consumption, smoking behavior, slee…
View article: Prognostic value of plasma glial fibrillary acidic protein in cognitively unimpaired older adults: Results from the A4 study
Prognostic value of plasma glial fibrillary acidic protein in cognitively unimpaired older adults: Results from the A4 study Open
INTRODUCTION Plasma glial fibrillary acidic protein (GFAP), a marker of astrocytic activation, has been linked to Alzheimer's disease; however, its prognostic value in cognitively unimpaired (CU) individuals remains unclear. METHODS We inc…
View article: Using memory recall response time on digital cognitive testing to detect subtle cognitive changes among cognitively unimpaired older adults
Using memory recall response time on digital cognitive testing to detect subtle cognitive changes among cognitively unimpaired older adults Open
INTRODUCTION We investigated whether memory recall response time (RT) on remote digital testing reflects decrements in memory function linked to Alzheimer's disease (AD) biomarkers. METHODS One hundred seventy‐five cognitively unimpaired p…
View article: Tau biology, biomarkers, and therapeutics
Tau biology, biomarkers, and therapeutics Open
As Alzheimer's disease (AD) research advances, tau has emerged as both a critical biomarker and a promising therapeutic target, central to understanding disease mechanisms, tracking progression, and guiding treatment development. The Fall …
View article: Continuum of Core 1 Biomarkers in Preclinical Alzheimer’s Disease
Continuum of Core 1 Biomarkers in Preclinical Alzheimer’s Disease Open
Background and Objectives Biological Staging for Alzheimer’s disease (AD) in clinically unimpaired (CU) individuals is critical for early detection efforts. In this study, we evaluated whether Core 1 biomarkers (plasma ptau-217 and amyloid…
View article: Prognostic Value of Plasma Glial Fibrillary Acidic Protein in Cognitively Unimpaired Older Adults: Results from the A4 Study
Prognostic Value of Plasma Glial Fibrillary Acidic Protein in Cognitively Unimpaired Older Adults: Results from the A4 Study Open
INTRODUCTION Plasma glial fibrillary acidic protein (GFAP), a marker of astrocytic activation, has been linked to Alzheimer’s disease; however, its prognostic value in cognitively unimpaired (CU) individuals remains unclear. METHODS We inc…
View article: Concurrent Changes in Plasma Phosphorylated Tau 217, Tau PET, and Cognition in Preclinical Alzheimer Disease
Concurrent Changes in Plasma Phosphorylated Tau 217, Tau PET, and Cognition in Preclinical Alzheimer Disease Open
Importance Developing disease-modifying treatments is a priority for Alzheimer disease research. Objective To determine the potential of plasma phosphorylated tau 217 (p-tau217) and tau positron emission tomography (PET) to assess disease …
View article: Modernizing diagnosis of Alzheimer's disease: A review of global trends and Asia‐specific perspectives
Modernizing diagnosis of Alzheimer's disease: A review of global trends and Asia‐specific perspectives Open
The landscape of Alzheimer's disease (AD) and related dementias (ADRD) diagnosis is evolving rapidly, driven by advances in disease understanding, biomarker tools, and disease‐modifying therapies. Modern diagnostic approaches emphasize bio…
View article: BrainAge moderates associations between Alzheimer’s disease biomarkers and cognitive decline: a meta-analysis across A4/LEARN, HABS and ADNI cohorts
BrainAge moderates associations between Alzheimer’s disease biomarkers and cognitive decline: a meta-analysis across A4/LEARN, HABS and ADNI cohorts Open
BrainAge delta, the difference between a person’s predicted brain age and their chronological age, is a promising marker of the accumulation of neurodegeneration that may increase vulnerability to Alzheimer’s disease (AD). In this study we…
View article: Relationship between BrainAge Polygenetic Risk Score and plasma biomarkers in the A4/LEARN studies
Relationship between BrainAge Polygenetic Risk Score and plasma biomarkers in the A4/LEARN studies Open
Background and Objectives To examine the association between genetic predisposition to accelerated brain aging—measured with polygenic risk scores (PRS) derived from BrainAge models—and plasma biomarkers of Alzheimer’s disease (AD), with a…
View article: Revisiting Centiloids using AI
Revisiting Centiloids using AI Open
The Centiloid scale is the standard for Amyloid (Aβ) PET quantification, widely used in research, clinical settings, and trial stratification. However, variability between tracers and scanners remains a challenge. This study introduces Dee…
View article: Sex-Specific Genetic Drivers of Memory, Executive Functioning, and Language Performance in Older Adults
Sex-Specific Genetic Drivers of Memory, Executive Functioning, and Language Performance in Older Adults Open
We previously identified sex-specific genetic loci associated with memory performance, a strong Alzheimer’s disease (AD) endophenotype. Here, we expand on this work by conducting sex-specific, cross-ancestral, genome-wide meta-analyses of …
View article: Localization of Network-Level Atrophy in Preclinical Alzheimer's Disease
Localization of Network-Level Atrophy in Preclinical Alzheimer's Disease Open
Brain atrophy may precede symptoms in Alzheimer's disease (AD), but it remains unclear whether atrophy in this preclinical stage falls within a distinct brain network or is associated with transitional cognitive changes. We investigated co…
View article: Relationship between use of anti‐platelet agents, oral anti‐coagulants, and Aβ burden with cerebral microhemorrhages in cognitively asymptomatic adults
Relationship between use of anti‐platelet agents, oral anti‐coagulants, and Aβ burden with cerebral microhemorrhages in cognitively asymptomatic adults Open
INTRODUCTION Cerebral microhemorrhages (CMHs) are detectable by magnetic resonance imaging (MRI). CMHs in deep brain regions are linked to hypertensive vasculopathy, while those in lobar regions with amyloid beta (Aβ) deposition in blood v…
View article: Tau-PET pathology in the subregions of the amygdala and its associations with cognitive performance and neuropsychiatric symptoms in autosomal dominant Alzheimer’s disease
Tau-PET pathology in the subregions of the amygdala and its associations with cognitive performance and neuropsychiatric symptoms in autosomal dominant Alzheimer’s disease Open
These findings suggest that in autosomal dominant AD, tau accumulation in the amygdala begins early in the basal nucleus, while both the basal and the lateral nuclei are associated with early cognitive deficits and depressive symptoms. The…
View article: Amyloid-Related Imaging Abnormalities With Donanemab in Early Symptomatic Alzheimer Disease
Amyloid-Related Imaging Abnormalities With Donanemab in Early Symptomatic Alzheimer Disease Open
Importance Amyloid-related imaging abnormalities (ARIA) are the major adverse event associated with amyloid-targeting immunotherapy. Identifying clinical features and individual risk factors for ARIA could facilitate effective prediction a…
View article: Associations between hormone therapy use and tau accumulation in brain regions vulnerable to Alzheimer’s disease
Associations between hormone therapy use and tau accumulation in brain regions vulnerable to Alzheimer’s disease Open
Elucidating the downstream impact of exogenous hormones on the aging brain will have far-reaching consequences for understanding why Alzheimer’s disease (AD) predominates in women almost twofold over men. We tested the extent to which meno…
View article: Disclosure of elevated amyloid status is not associated with long‐term suicidality in a preclinical AD trial
Disclosure of elevated amyloid status is not associated with long‐term suicidality in a preclinical AD trial Open
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…
View article: Depressive Symptoms and Amyloid Pathology
Depressive Symptoms and Amyloid Pathology Open
Importance Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association betwee…
View article: Validation of the multi-day Boston remote assessment of neurocognitive health (BRANCH) among cognitively impaired & unimpaired older adults
Validation of the multi-day Boston remote assessment of neurocognitive health (BRANCH) among cognitively impaired & unimpaired older adults Open
Findings suggest that a remotely administered web-based assessment of multi-day learning is feasible and valid in participants with and without cognitive impairment.