Jeffrey Kaye

Jeffrey Kaye
Oregon Health and Science University | OHSU · Department of Neurology

About

608
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Publications

Publications (608)
Article
Full-text available
Genetics play an important role in late-onset Alzheimer’s Disease (AD) etiology and dozens of genetic variants have been implicated in AD risk through large-scale GWAS meta-analyses. However, the precise mechanistic effects of most of these variants have yet to be determined. Deeply phenotyped cohort data can reveal physiological changes associated...
Article
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Background The COVID-19 pandemic disrupted Alzheimer disease randomized clinical trials (RCTs), forcing investigators to make changes in the conduct of such trials while endeavoring to maintain their validity. Changing ongoing RCTs carries risks for biases and threats to validity. To understand the impact of exigent modifications due to COVID-19, w...
Article
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Klotho-VS heterozygosity (KL-VS het ) is associated with reduced risk of Alzheimer’s disease (AD). However, whether KL-VS het is associated with lower levels of pathologic tau, i.e., the key AD pathology driving neurodegeneration and cognitive decline, is unknown. Here, we assessed the interaction between KL-VS het and levels of beta-amyloid, a key...
Article
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Resting state functional connectivity (rs-fMRI) is impaired early in persons who subsequently develop Alzheimer’s disease (AD) dementia. This impairment may be leveraged to aid investigation of the pre-clinical phase of AD. We developed a model that predicts brain age from resting state (rs)-fMRI data, and assessed whether genetic determinants of A...
Article
Background/objectives: The COVID-19 global outbreak allowed a natural experiment to observe how older adults changed social patterns and how it affected their emotional well-being. We studied the frequency and modes of social contact and their effects on older adults' mood before and during the COVID-19 pandemic. Design: Phone-based surveys were...
Article
Changes in mobility are associated with cognitive decline in older adults. Mobility is frequently assessed in the clinic setting at episodic intervals. Passive sensors within a home‐based technology platform allow for unobtrusive collection of mobility and gait information over an extended time period. This method of high‐frequency data collection...
Article
Background: Social isolation is a risk factor for dementia, but the underlying mechanism is not well understood. It is possible that lack of social contacts negatively affects emotional well-being, which leads to cognitive decline. To shed light on this potential mediation mechanism, we examined changes in type and frequency of social contacts and...
Article
The Oregon Center for Aging & Technology (ORCATECH) has developed, refined, and deployed to hundreds of diverse older adults a home‐based research platform for providing assessment of cognition and multiple domains of function. The pandemic has brought to the forefront the necessity of this type of remotely conducted research. Even absent a pandemi...
Article
Blood levels of marine n‐3 PUFA (20:5; 22:6) are inversely associated with cerebral white matter lesion volume (WML), suggesting that n‐3 may offer one approach to reduce this major vascular contributor to cognitive impairment and dementia. This trial determined whether n‐3 slows WML progression and sustains white matter integrity over 3‐years in o...
Article
A diagnosis of Mild Cognitive Impairment (MCI) has been found to be associated with changes in emotional wellbeing and social relationships. Socially isolated older adults with MCI are at greater risk of developing Alzheimer's Disease and Related Dementias. Better understanding the emotional functioning of individuals with MCI could inform the deve...
Article
Given the COVID‐19 pandemic and necessary restrictions on older adults’ in‐person clinical and research exposure, there is an urgent need for validated cognitive measures that can be self‐administered remotely in the home to expand the reach of cognitive assessment. The current presentation describes the implementation, validity, and usability of t...
Article
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Background: Older adults spend a considerable amount of time inside their residences; however, most research investigates out-of-home mobility and its health correlates. We measured indoor mobility using room-to-room transitions, tested their psychometric properties, and correlated indoor mobility with cognitive and functional status. Materials and...
Article
Background: The ability to capture people's movement throughout their home is a powerful approach to inform spatiotemporal patterns of routines associated with cognitive impairment. The study estimated indoor room activities over 24 hours and investigated relationships between diurnal activity patterns and mild cognitive impairment (MCI). Methods...
Article
Metabolic deficits at brain–fluid barriers are an increasingly recognized feature of cognitive decline in older adults. At the blood–cerebrospinal fluid barrier, water is transported across the choroid plexus (CP) epithelium against large osmotic gradients via processes tightly coupled to activity of the sodium/potassium pump. Here, we quantify CP...
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Background: Increasing social interactions through communication technologies could offer a cost-effective prevention approach that slows cognitive decline and delays the onset of Alzheimer's disease. This paper describes the protocol of an active project named “Internet-based conversational engagement clinical trial (I-CONECT)” ( ClinicalTrials.go...
Article
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Abstract Primary age-related tauopathy (PART) is a form of Alzheimer-type neurofibrillary degeneration occurring in the absence of amyloid-beta (Aβ) plaques. While PART shares some features with Alzheimer disease (AD), such as progressive accumulation of neurofibrillary tangle pathology in the medial temporal lobe and other brain regions, it does n...
Article
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Neuroinflammation is associated with Alzheimer’s disease, but the application of cerebrospinal fluid measures of inflammatory proteins may be limited by overlapping pathways and relationships between them. In this work, we measure 15 cerebrospinal proteins related to microglial and T-cell functions, and show them to reproducibly form functionally-r...
Preprint
Full-text available
Primary age-related tauopathy (PART) is a form of Alzheimer-type neurofibrillary degeneration occurring in the absence of amyloid-beta (Aβ) plaques. While PART shares some features with Alzheimer disease (AD), such as progressive accumulation of neurofibrillary tangle pathology in the medial temporal lobe and other brain regions, it does not progre...
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Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we ident...
Article
Objectives To show the feasibility of using different unobtrusive activity-sensing technologies to provide objective behavioral markers of patients with dementia (PwD). Design Monitored the behaviors of two PwD living in memory care unit using the Oregon Center for Aging & Technology (ORCATECH) platform, and the behaviors of two PwD living in assi...
Article
Objectives: The aim of the study was to examine the unique contributions of age to objectively measure driving frequency and dangerous driving behaviors in healthy older adults after adjusting for executive function (EF). Method: A total of 28 community-dwelling older adults (mean age = 82.0 years, standard deviation [SD] = 7.5) without dementia...
Article
Introduction: Brief, Web-based, and self-administered cognitive assessments hold promise for early detection of cognitive decline in individuals at risk for dementia. The current study describes the design, implementation, and convergent validity of a fWeb-based cognitive assessment tool, the Survey for Memory, Attention, and Reaction Time (SMART)...
Article
Background: Computer use is a cognitively complex instrumental activity of daily living (IADL) that has been linked to cognitive functioning in older adulthood, yet little work has explored its capacity to detect incident mild cognitive impairment (MCI). Objective: To examine whether routine home computer use (general computer use as well as use...
Article
Introduction: Medication-taking is a routine instrumental activity of daily living affected by mild cognitive impairment (MCI) but difficult to measure with clinical tools. This prospective longitudinal study examined in-home medication-taking and transition from normative aging to MCI. Methods: Daily, weekly, and monthly medication-taking metri...
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Background and Objectives Many older adults remain inactive despite the known positive health implications of physical activity (improved mood, reduced mortality risk). Physical inactivity is an interdependent phenomenon in couples, but most research examines physical inactivity at the individual level. We estimated the average amount of prolonged...
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Introduction: The use of digital biomarker data in dementia research provides the opportunity for frequent cognitive and functional assessments that was not previously available using conventional approaches. Assessing high-frequency digital biomarker data can potentially increase the opportunities for early detection of cognitive and functional d...
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In Alzheimer’s diseases (AD), tau pathology is strongly associated with cognitive decline. Preclinical evidence suggests that tau spreads across connected neurons in an activity-dependent manner. Supporting this, cross-sectional AD studies show that tau deposition patterns resemble functional brain networks. However, whether higher functional conne...
Article
Background and objectives: Greater everyday decision-making involvement by persons living with dementia (PLWD) and congruent appraisal between PLWDs and their caregivers have been associated with better quality of life (QOL) for both members of the dyad. However, no study has examined the association between the appraisals of everyday decision-mak...
Conference Paper
Daily step counts from the Withings Activite were validated against those collected concurrently from the PiezoRxD Pedometer and the wGT3X-BT Actigraph worn on the waist and on the wrist in free-living conditions from 10 older adult volunteers. The Withings Activite underestimated step counts but showed good correlations with the other devices (Pea...
Article
Full-text available
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Article
BACKGROUND AND PURPOSE Transvascular water exchange plays a key role in the functional integrity of the blood–brain barrier (BBB). In white matter (WM), a variety of imaging modalities have demonstrated age‐related changes in structure and metabolism, but the extent to which water exchange is altered remains unclear. Here, we investigated the cumul...
Preprint
BACKGROUND Continuous in-home monitoring of older adults can provide rich and sensitive data capturing subtle behavioral and cognitive changes. Our previous work has identified multiple metrics that describe meaningful trends in daily activities over time. The continuous, multi-domain nature of this technology may also serve to inform caregivers of...
Article
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Causal Structure Discovery (CSD) is the problem of identifying causal relationships from large quantities of data through computational methods. With the limited ability of traditional association-based computational methods to discover causal relationships, CSD methodologies are gaining popularity. The goal of the study was to systematically exami...
Article
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Background: Research participation burden, despite being an integral concept in research ethics, is not well-conceptualized in the context of the use of technology in research. This knowledge gap is especially critical for the older adult population as new technology solutions are increasingly embedded in clinical trials for this demographic. Our...
Preprint
BACKGROUND Current clinical trial assessment methodology relies on a combination of self-report measures, cognitive and physical function tests, and biomarkers. This methodology is limited by recall bias and recency effects in self-report and by assessments that are brief, episodic, and clinic-based. Continuous monitoring of ecologically valid meas...
Article
Full-text available
Background: The current clinical trial assessment methodology relies on a combination of self-report measures, cognitive and physical function tests, and biomarkers. This methodology is limited by recall bias and recency effects in self-reporting and by assessments that are brief, episodic, and clinic based. Continuous monitoring of ecologically v...
Article
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Dementia severity can be quantitatively described by the latent dementia phenotype “δ” and its various composite “homologs”. We have explored δ’s blood-based protein biomarkers in the Texas Alzheimer’s Research and Care Consortium. However, it would be convenient to replicate them in the Alzheimer’s Disease Neuroimaging Initiative. To that end, we...
Article
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The Sharing History through Active Reminiscence and Photo-Imagery (SHARP) study aims to preserve African American cognitive health through neighborhood walking and social engagement in a way that celebrates Black culture. For 6 months, African Americans aged 55+ (2016 n=19; 2017 n=21) grouped in triads walked 1-mile routes accessible via the SHARP...
Article
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Culturally celebratory programming exceeds cultural relevancy, engaging participants in celebration-making and culture-creating. African Americans aged 55+ in the Sharing History through Active Reminiscence and Photo-imagery (SHARP) study celebrate their heritage in gentrifying neighborhoods through walking-reminiscence sessions; they create cultur...
Article
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Early studies of technology adoption and computer use identified a “digital divide” between older adults and the general population. As that gap has narrowed, other demographic variables have been identified as continuing to foster disparities in access to and use of computers and related technologies. For example, gender, socioeconomic status, edu...
Conference Paper
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Physical activity and sleep are behaviors that contribute to overall health, and are notoriously challenging to improve. For individuals co-residing as a couple, there is growing recognition of the importance of the interdependence between individuals’ behaviors (e.g. the physical activity and sleep habits of one’s partner has an influence on one’s...
Article
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A profusion of technologies and protocols have been developed to more effectively assess and deliver care to older adults with cognitive impairment, challenged health and declining function. These technologies take advantage of important developments in sensing and pervasive computing, wearable technologies, mobile and wireless communications, and...
Article
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Studies have shown that speech characteristics can aid in early-identification of those with mild cognitive impairment (MCI). We performed a linguistic analysis on spoken utterances of 41 participants (15 MCI, 26 healthy controls) from conversations with a trained interviewer using the Term Frequency-Inverse Document Frequency (TF-IDF) method. Data...
Article
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In our previous NIH-funded randomized controlled behavioral clinical trial, we developed a conversation-based social interaction cognitive stimulation protocol delivered by trained interviewers through webcams and a user-friendly interactive Internet interface. Daily 30 minute face-to-face video-chats were conducted for 6 weeks. Despite a short dur...
Conference Paper
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Agitation is a challenging dementia-related behavioral symptom and disconcertingly leads to an undesirable increase in pharmaceutical intervention. Agitation is primarily assessed subjectively by time-impoverished caregivers or clinicians, who may not be able to provide comprehensive or sensitive enough reporting to detect early signs of agitation...
Preprint
BACKGROUND Aging veterans are an important and growing population who are at an elevated risk for developing mild cognitive impairment (MCI) and Alzheimer’s dementia (AD), which emerge insidiously and progress gradually. Traditional clinic-based assessments are administered infrequently, making these visits less ideal to capture the earliest signal...
Article
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Background: Aging military veterans are an important and growing population who are at an elevated risk for developing mild cognitive impairment (MCI) and Alzheimer dementia, which emerge insidiously and progress gradually. Traditional clinic-based assessments are administered infrequently, making these visits less ideal to capture the earliest si...
Article
CpG‐related single nucleotide polymorphisms (CGS) have the potential to perturb DNA methylation; however, their effects on Alzheimer disease (AD) risk have not been evaluated systematically. We conducted a genome‐wide association study using a sliding‐window approach to measure the combined effects of CGSes on AD risk in a discovery sample of 24 Eu...
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Importance Oligomeric amyloid-β peptide binds to cellular prion protein on the neuronal cell surface, activating intracellular fyn kinase to mediate synaptotoxicity and tauopathy. AZD0530 is an investigational kinase inhibitor specific for the Src family, including fyn, that has been repurposed for the treatment of Alzheimer disease. Objective To...
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Aims: We explored the relationship between objective and subjective measures of burden prior to and after a telehealth-based caregiver intervention. One caregiver participated in two studies, one to assess the feasibility of objective, home-based monitoring (EVALUATE-AD), the second to assess the feasibility of a caregiver education telehealth-bas...