Michelle E. Farrell
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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: 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: Leveraging a multi‐day learning paradigm to reveal early amyloid‐ and tau‐ related cognitive deficits in preclinical Alzheimer’s disease
Leveraging a multi‐day learning paradigm to reveal early amyloid‐ and tau‐ related cognitive deficits in preclinical Alzheimer’s disease Open
Background Individuals with preclinical Alzheimer’s disease (AD) show reduced practice effects on annually repeated neuropsychological testing, suggesting a decreased ability to learn over repeated exposures. Remote, digital testing enable…
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: 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…
View article: Spatial Extent as a more sensitive amyloid biomarker for early stages of Alzheimer’s disease
Spatial Extent as a more sensitive amyloid biomarker for early stages of Alzheimer’s disease Open
Background Despite considerable advances in beta amyloid (Aβ)‐PET imaging over the last decade, the standard approach of estimating the average neocortical Aβ burden remains largely unchanged. However, as research and clinical trials incre…
View article: Locus coeruleus integrity exhibits distinct anatomic vulnerabilities to regional tau and amyloid accumulation: parallel and intersecting mechanisms?
Locus coeruleus integrity exhibits distinct anatomic vulnerabilities to regional tau and amyloid accumulation: parallel and intersecting mechanisms? Open
Background The locus coeruleus (LC) is one of the first regions to accumulate tau in Alzheimer’s disease (AD). As the disease progresses, tau in the LC has been related to increasing allocortical tau. Recent autopsy work reported that LC n…
View article: Predicting change in depressive symptoms using longitudinal regional amyloid and cognition in cognitively unimpaired older adults
Predicting change in depressive symptoms using longitudinal regional amyloid and cognition in cognitively unimpaired older adults Open
Background Depression is a neuropsychiatric symptom of Alzheimer’s disease (AD) and has been linked to greater cortical amyloid burden in preclinical AD. We sought to examine whether amyloid accumulation in brain regions subserving emotion…
View article: Examining the influence of changes in amyloid burden on both contemporaneous and subsequent cognitive decline: using a latent change score approach
Examining the influence of changes in amyloid burden on both contemporaneous and subsequent cognitive decline: using a latent change score approach Open
Background A critical question for understanding the natural history of preclinical Alzheimer’s disease (AD) is the extent to which changes in pathology affect contemporaneous and/or subsequent (lagged) cognitive manifestations of the dise…
View article: Contribution of extracerebral tracer retention and partial volume effects to sex differences in Flortaucipir-PET signal
Contribution of extracerebral tracer retention and partial volume effects to sex differences in Flortaucipir-PET signal Open
Clinically normal females exhibit higher 18 F-flortaucipir (FTP)-PET signal than males across the cortex. However, these sex differences may be explained by neuroimaging idiosyncrasies such as off-target extracerebral tracer retention or p…
View article: A longitudinal analysis of depressive symptoms in relation to repeated measurements of regional tau
A longitudinal analysis of depressive symptoms in relation to repeated measurements of regional tau Open
Background Depressive symptoms are commonly observed early in Alzheimer’s disease (AD), but their temporal association with progression along the AD continuum is less clear. We sought to determine if initial measurements of regional tau we…
View article: AD‐causing variants that affect <i>PSEN1</i> transmembrane domains are associated with faster neurodegeneration and cognitive decline compared to those affecting cytoplasmic domains
AD‐causing variants that affect <i>PSEN1</i> transmembrane domains are associated with faster neurodegeneration and cognitive decline compared to those affecting cytoplasmic domains Open
Background Rates of cognitive and biomarker change in Autosomal Dominant Alzheimer disease (ADAD) vary substantially across individuals. Prior cross‐sectional work suggests that the location of the pathogenic variant within PSEN1 , specifi…
View article: AD‐causing variants that affect <i>PSEN1</i> transmembrane domains are associated with faster neurodegeneration and cognitive decline compared to those affecting cytoplasmic domains.
AD‐causing variants that affect <i>PSEN1</i> transmembrane domains are associated with faster neurodegeneration and cognitive decline compared to those affecting cytoplasmic domains. Open
Background Rates of cognitive and biomarker change in Autosomal Dominant Alzheimer disease (ADAD) vary substantially across individuals. Prior cross‐sectional work suggests that the location of the pathogenic variant within PSEN1 , specifi…
View article: Kinetic evaluation and assessment of longitudinal changes in reference region and extracerebral [<sup>18</sup>F]MK-6240 PET uptake
Kinetic evaluation and assessment of longitudinal changes in reference region and extracerebral [<sup>18</sup>F]MK-6240 PET uptake Open
[ 18 F]MK-6240 meningeal/extracerebral off-target binding may impact tau quantification. We examined the kinetics and longitudinal changes of extracerebral and reference regions. [ 18 F]MK-6240 PET was performed in 24 cognitively-normal an…
View article: Opportunities for Community Pharmacists to Counsel Patients With Epilepsy and Seizure Clusters to Overcome Barriers and Foster Appropriate Treatment
Opportunities for Community Pharmacists to Counsel Patients With Epilepsy and Seizure Clusters to Overcome Barriers and Foster Appropriate Treatment Open
Some patients with epilepsy experience seizure clusters, which may be defined as 2 or more seizures occurring within 24 hours. Left untreated, seizure clusters increase the risk for physical injury and may progress to status epilepticus, i…
View article: Sequential early cognitive changes sensitive to rising beta‐amyloid and tau pathology in preclinical AD
Sequential early cognitive changes sensitive to rising beta‐amyloid and tau pathology in preclinical AD Open
Background AD clinical trials are increasingly looking towards intervention at the earliest stage of preclinical AD, when beta‐amyloid (Aβ) is emerging and tau pathology remains restricted to the MTL. While some evidence suggests subtle co…
View article: Longitudinal associations between amyloid and tau‐PET: Impact for prevention trials
Longitudinal associations between amyloid and tau‐PET: Impact for prevention trials Open
Background In Alzheimer’s disease, cognitive decline is associated with a rapid increase in tau pathology, making tau‐PET a potentially useful outcome in prevention trials. To identify individuals most at‐risk of tau accumulation, we inves…
View article: The relationship of functional hippocampal activity, amyloid deposition, and longitudinal memory decline to memory complaints in cognitively healthy older adults
The relationship of functional hippocampal activity, amyloid deposition, and longitudinal memory decline to memory complaints in cognitively healthy older adults Open
We evaluated whether self-reports of worse cognition in older adults with normal cognitive function reflected actual memory decline, amyloid pathology, and subtle vulnerabilities in hippocampal function. We measured subjective cognitive de…
View article: Estimating an individual's placement on a theoretical continuum using longitudinal cognitive trajectories: Relationships with longitudinal amyloid and Tau‐PET
Estimating an individual's placement on a theoretical continuum using longitudinal cognitive trajectories: Relationships with longitudinal amyloid and Tau‐PET Open
Background Theoretical models of the Alzheimer’s disease (AD) continuum posit a curvilinear trajectory of declining cognition, with accumulating AD pathology catalyzing an accelerated rate of decline. Assuming this continuum can be modelle…
View article: Distinct contributions of longitudinal tau and amyloid to decline in various cognitive domains in preclinical AD
Distinct contributions of longitudinal tau and amyloid to decline in various cognitive domains in preclinical AD Open
Background We sought to assess the preclinical contributions of longitudinal Aβ and tau accumulation at different baseline Aβ levels to decline across multiple cognitive domains. Method 124 clinically normal older adults from the Harvard A…
View article: Longitudinal hippocampal atrophy is associated with an amyloid‐independent entorhinal tauopathy and an amyloid‐dependent neocortical tauopathy
Longitudinal hippocampal atrophy is associated with an amyloid‐independent entorhinal tauopathy and an amyloid‐dependent neocortical tauopathy Open
Background Hippocampal atrophy is observed in Alzheimer’s disease (AD), but also in older adults with no evidence of amyloid‐β (Aβ) plaques. To understand the pathophysiology of hippocampal volume (HV) loss, we investigated the association…
View article: Faster rates of tau accumulation in FTP‐PET in females relative to males, and a cross‐sectional influence on faster cognitive decline: Preliminary findings from HABS and ADNI
Faster rates of tau accumulation in FTP‐PET in females relative to males, and a cross‐sectional influence on faster cognitive decline: Preliminary findings from HABS and ADNI Open
Background Clinically normal older females exhibit higher cross‐sectional 18 F‐Flortaucipir (FTP)‐PET signal, but not Aβ‐PET, than males, particularly in temporal regions. What remains unclear is the extent to which these findings represen…
View article: Defining the Lowest Threshold for Amyloid-PET to Predict Future Cognitive Decline and Amyloid Accumulation
Defining the Lowest Threshold for Amyloid-PET to Predict Future Cognitive Decline and Amyloid Accumulation Open
This study provides Class II evidence that among clinically normal individuals a specific Aβ-PET threshold is predictive of cognitive decline.
View article: P4‐568: HISTORY OF MILD TRAUMATIC BRAIN INJURY APPEARS UNRELATED TO CHANGES IN AMYLOID ACCUMULATION IN NORMAL AGING
P4‐568: HISTORY OF MILD TRAUMATIC BRAIN INJURY APPEARS UNRELATED TO CHANGES IN AMYLOID ACCUMULATION IN NORMAL AGING Open
Interest in concussion or mild traumatic brain injury (mTBI) has increased dramatically in the past decade. Evidence continues to mount that there is not only a link between mTBI and later cognitive impairment, but also higher levels of ce…
View article: Association of Amyloid and Tau With Cognition in Preclinical Alzheimer Disease
Association of Amyloid and Tau With Cognition in Preclinical Alzheimer Disease Open
We identified sequential changes in normal older adults, from Aβ to tau to cognition, after which the participants with high Aβ with greater tau increase met clinical criteria for mild cognitive impairment. These findings highlight the imp…
View article: Actual memory as a mediator of the amyloid‐subjective cognitive decline relationship
Actual memory as a mediator of the amyloid‐subjective cognitive decline relationship Open
Introduction Amyloid pathology in cognitively normal adults is associated with subjective cognitive decline, potentially reflecting awareness of Alzheimer's‐related memory deficits. To clarify the mechanism underlying this relationship, we…
View article: Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults
Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults Open
Early tau deposition was elevated in women compared with men in individuals on the Alzheimer disease trajectory. These findings lend support to a growing body of literature that highlights a biological underpinning for sex differences in A…