Aaron P. Schultz
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View article: Physical activity as a modifiable risk factor in preclinical Alzheimer’s disease
Physical activity as a modifiable risk factor in preclinical Alzheimer’s disease Open
Physical inactivity is a recognized modifiable risk factor for Alzheimer's disease (AD), yet its relationship with progression of AD pathology in humans remains unclear, limiting the effective translation into prevention trials. Using pedo…
View article: Independent effects of white matter lesion volume and <i>APOE ɛ4</i> on ARIA‐H in A4 Study
Independent effects of white matter lesion volume and <i>APOE ɛ4</i> on ARIA‐H in A4 Study Open
INTRODUCTION Increased white matter hyperintensity (WMH) volume is a common but non‐specific finding in AD. This study investigates the effect of baseline WMH volume and APO E ε4 on magnetic resonance imaging (MRI)‐visible hemorrhagic lesi…
View article: Estimating the preclinical Alzheimer's disease course with multimodal data
Estimating the preclinical Alzheimer's disease course with multimodal data Open
INTRODUCTION In observational studies of preclinical AD, an arbitrary “baseline” can obscure where an individual is located along a theoretical continuum. Optimizing longitudinal trajectories can distill multiple, non‐linearly distributed …
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). We examined whet…
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: 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: Rethinking the residual approach: leveraging statistical learning to operationalize cognitive resilience in Alzheimer’s disease
Rethinking the residual approach: leveraging statistical learning to operationalize cognitive resilience in Alzheimer’s disease Open
Cognitive resilience (CR) describes the phenomenon of individuals evading cognitive decline despite prominent Alzheimer's disease neuropathology. Operationalization and measurement of this latent construct is non-trivial as it cannot be di…
View article: Detecting early cognitive deficits in preclinical Alzheimer’s disease using a remote digital multi-day learning paradigm
Detecting early cognitive deficits in preclinical Alzheimer’s disease using a remote digital multi-day learning paradigm Open
Remote, digital cognitive testing on an individual's own device provides the opportunity to deploy previously understudied but promising cognitive paradigms in preclinical Alzheimer's disease (AD). The Boston Remote Assessment for NeuroCog…
View article: Rethinking the residual approach for estimating cognitive resilience and resistance to AD pathology
Rethinking the residual approach for estimating cognitive resilience and resistance to AD pathology Open
Background The residual approach has found wide application in researching cognitive resilience, a phenomenon conceptually understood as cognitive performance being better‐than‐typical for an individual, despite apparent AD pathology. The …
View article: Accelerated Temporal Cortex Tau Accumulation Mediates the Effects of Low Physical Activity on Faster Cognitive Decline in Preclinical Alzheimer's Disease
Accelerated Temporal Cortex Tau Accumulation Mediates the Effects of Low Physical Activity on Faster Cognitive Decline in Preclinical Alzheimer's Disease Open
Background Physically inactivity is associated with increased risk of dementia including Alzheimer’s disease (AD). Prior work from the Harvard Aging Brain Study (HABS) suggests that lower baseline physical activity in cognitively unimpaire…
View article: Left frontoparietal control network connectivity moderates the effect of amyloid on cognitive decline in preclinical Alzheimer’s disease
Left frontoparietal control network connectivity moderates the effect of amyloid on cognitive decline in preclinical Alzheimer’s disease Open
Background Stronger default mode (DMN) and bilateral frontoparietal control network (FPCN) resting‐state functional connectivity are associated with reduced β‐amyloid (Aβ)‐related cognitive decline in cognitively unimpaired older adults, w…
View article: Longitudinal Regional Flortaucipir Profiles in Preclinical Alzheimer’s Disease: Evaluation using A4 phase 3 trial with Solanezumab
Longitudinal Regional Flortaucipir Profiles in Preclinical Alzheimer’s Disease: Evaluation using A4 phase 3 trial with Solanezumab Open
Background The A4 Study (NCT02008357) was a multicenter, randomized, double‐blind, placebo‐controlled phase 3 trial, assessing the safety and efficacy of solanezumab in preclinical Alzheimer’s Disease (AD). We previously reported on the ba…
View article: Accelerated Temporal Cortex Tau Accumulation Mediates the Effects of Low Physical Activity on Faster Cognitive Decline in Preclinical Alzheimer’s Disease
Accelerated Temporal Cortex Tau Accumulation Mediates the Effects of Low Physical Activity on Faster Cognitive Decline in Preclinical Alzheimer’s Disease Open
Background Physically inactivity is associated with increased risk of dementia including Alzheimer’s disease (AD). Prior work from the Harvard Aging Brain Study (HABS) suggests that lower baseline physical activity in cognitively unimpaire…
View article: Lower resting‐state phasic LC activity is associated with cortical tau deposition and Aβ‐related cognitive decline in preclinical Alzheimer’s Disease
Lower resting‐state phasic LC activity is associated with cortical tau deposition and Aβ‐related cognitive decline in preclinical Alzheimer’s Disease Open
Background The locus coeruleus (LC) is one of the earliest regions accumulating tau pathology in Alzheimer’s Disease (AD). As the disease progresses, tau in the LC has been linked to increasing cortical tau and amyloid‐beta (Aβ) pathologie…
View article: Examining the impact of hormone therapy and Alzheimer’s disease risk factors on depressive symptoms in the Harvard Aging Brain Study
Examining the impact of hormone therapy and Alzheimer’s disease risk factors on depressive symptoms in the Harvard Aging Brain Study Open
Background Hormone therapy (HT) is often used to manage symptoms related to menopause, but its longer‐term effects on depressive symptoms in older women remains unclear. Previous literature reports inconclusive results on whether HT use is…
View article: Left frontoparietal control network connectivity moderates the effect of amyloid on cognitive decline in preclinical Alzheimer’s disease
Left frontoparietal control network connectivity moderates the effect of amyloid on cognitive decline in preclinical Alzheimer’s disease Open
Background Stronger default mode (DMN) and bilateral frontoparietal control network (FPCN) resting‐state functional connectivity are associated with reduced ß‐amyloid (Aß)‐related cognitive decline in cognitively unimpaired older adults, w…
View article: Longitudinal Regional Flortaucipir Profiles in Preclinical Alzheimer’s Disease: Evaluation using A4 phase 3 trial with Solanezumab
Longitudinal Regional Flortaucipir Profiles in Preclinical Alzheimer’s Disease: Evaluation using A4 phase 3 trial with Solanezumab Open
Background The A4 Study (NCT02008357) was a multicenter, randomized, double‐blind, placebo‐controlled phase 3 trial, assessing the safety and efficacy of solanezumab in preclinical Alzheimer’s Disease (AD). We previously reported on the ba…
View article: Latent change‐on‐change between amyloid accumulation and cognitive decline
Latent change‐on‐change between amyloid accumulation and cognitive decline Open
INTRODUCTION While the influence of cross‐sectional β‐amyloid (Aβ) on longitudinal changes in cognition is well established, longitudinal change‐on‐change between Aβ and cognition is less explored. METHODS A series of bivariate latent chan…
View article: Rethinking the residual approach: Leveraging machine learning to operationalize cognitive resilience in Alzheimer’s disease
Rethinking the residual approach: Leveraging machine learning to operationalize cognitive resilience in Alzheimer’s disease Open
Cognitive resilience describes the phenomenon of individuals evading cognitive decline despite prominent Alzheimer’s disease neuropathology. Operationalization and measurement of this latent construct is non-trivial as it cannot be directl…
View article: Spatial extent as a sensitive amyloid‐PET metric in preclinical Alzheimer's disease
Spatial extent as a sensitive amyloid‐PET metric in preclinical Alzheimer's disease Open
INTRODUCTION Spatial extent‐based measures of how far amyloid beta (Aβ) has spread throughout the neocortex may be more sensitive than traditional Aβ‐positron emission tomography (PET) measures of Aβ level for detecting early Aβ deposits i…
View article: Identifying longitudinal cognitive resilience from cross-sectional amyloid, tau, and neurodegeneration
Identifying longitudinal cognitive resilience from cross-sectional amyloid, tau, and neurodegeneration Open
View article: Amyloid beta–independent sleep markers associated with early regional tau burden and cortical thinning
Amyloid beta–independent sleep markers associated with early regional tau burden and cortical thinning Open
INTRODUCTION Sleep is crucial for memory consolidation and the clearance of toxic proteins associated with Alzheimer's disease (AD). We examined the association between sleep characteristics and imaging biomarkers of early amyloid beta (Aβ…
View article: Greater White Matter Hyperintensity Volume Is Associated with the Number of Microhemorrhages in Preclinical Alzheimer's Disease
Greater White Matter Hyperintensity Volume Is Associated with the Number of Microhemorrhages in Preclinical Alzheimer's Disease Open
These results indicate a strong association between WMH and MCH, a common manifestation of cerebral amyloid angiopathy and ARIA-H. These results suggest that increased WMH volume may represent an early sign of vessel amyloidosis, likely pr…
View article: Lower in vivo locus coeruleus integrity is associated with lower cortical thickness in older individuals with elevated Alzheimer’s pathology: a cohort study
Lower in vivo locus coeruleus integrity is associated with lower cortical thickness in older individuals with elevated Alzheimer’s pathology: a cohort study Open
Background Autopsy work indicates that the widely-projecting noradrenergic pontine locus coeruleus (LC) is among the earliest regions to accumulate hyperphosphorylated tau, a neuropathological Alzheimer’s disease (AD) hallmark. This early …
View article: Parental History of Memory Impairment and β-Amyloid in Cognitively Unimpaired Older Adults
Parental History of Memory Impairment and β-Amyloid in Cognitively Unimpaired Older Adults Open
Importance Studies have suggested that maternal history of late-onset Alzheimer disease, but not paternal, predisposes individuals to higher brain β-amyloid (Aβ) burden, reduced brain metabolism, and lower gray matter volumes. Objective To…
View article: Amyloid and tau burden relate to longitudinal changes in the performance of complex everyday activities among cognitively unimpaired older adults: results from the performance-based Harvard Automated Phone Task
Amyloid and tau burden relate to longitudinal changes in the performance of complex everyday activities among cognitively unimpaired older adults: results from the performance-based Harvard Automated Phone Task Open
Background Changes in everyday functioning constitute a clinically meaningful outcome, even in the early stages of Alzheimer's disease. Performance-based assessments of everyday functioning might help uncover these early changes. We aimed …
View article: Locus coeruleus integrity and left frontoparietal connectivity provide resilience against attentional decline in preclinical alzheimer’s disease
Locus coeruleus integrity and left frontoparietal connectivity provide resilience against attentional decline in preclinical alzheimer’s disease Open
Background Autopsy work reported that neuronal density in the locus coeruleus (LC) provides neural reserve against cognitive decline in dementia. Recent neuroimaging and pharmacological studies reported that left frontoparietal network fun…
View article: Atrophy links lower novelty‐related locus coeruleus connectivity to cognitive decline in preclinical AD
Atrophy links lower novelty‐related locus coeruleus connectivity to cognitive decline in preclinical AD Open
INTRODUCTION Animal research has shown that tau pathology in the locus coeruleus (LC) is associated with reduced norepinephrine signaling, lower projection density to the medial temporal lobe (MTL), atrophy, and cognitive impairment. We in…
View article: Plasma VEGFA and PGF impact longitudinal tau and cognition in preclinical Alzheimer’s disease
Plasma VEGFA and PGF impact longitudinal tau and cognition in preclinical Alzheimer’s disease Open
Vascular dysfunction is increasingly recognized as an important contributor to the pathogenesis of Alzheimer’s disease. Alterations in vascular endothelial growth factor (VEGF) pathways have been implicated as potential mechanisms. However…
View article: Estimating a clinically normal individual’s position along a preclinical Alzheimer’s disease continuum using cognitive and amyloid trajectories
Estimating a clinically normal individual’s position along a preclinical Alzheimer’s disease continuum using cognitive and amyloid trajectories Open
Background Optimizing longitudinal cognitive and biomarker trajectories can distill multiple observations from one individual into a single metric. Relative to other individuals, this metric can represent an individual’s distance from an a…