Jeffrey Kaye

Oregon Health and Science University | OHSU · Department of Neurology

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background The gold standard method for assessing the efficacy of dementia treatments, the Alzheimer’s Disease (AD) Assessment Scale‐Cognitive Subscale (ADAS‐Cog), has limitations of use based on the level of cognitive decline of a patient, the need for an in‐person evaluation, and the sampling of a time point in the patient experience. However, me...

Aging is a significant contributor to changes in sleep patterns, which has compounding consequences on cognitive health. A modifiable factor contributing to poor sleep is inadequate and/or mistimed light exposure. However, methods to reliably and continuously collect light levels long-term in the home, a necessity for informing clinical guidance, a...

Background and Objective Care partners of people living with dementia require support to knowledgeably navigate decision making about how and when to use monitoring technologies for care purposes. We conducted a pilot study of a novel self-administered intervention, “Let’s Talk Tech,” for people living with mild dementia and their care partners. Th...

(1) Background: The development of assistive technologies has become a key solution to reduce caregiver burden. The objective of this study was to survey caregivers on perceptions and beliefs about the future of modern technology in caregiving. (2) Methods: Demographics and clinical caregiver characteristics were collected via an online survey alon...

Objective: Given growing interest in companion robots to mitigate loneliness, large-scale studies are needed to understand peoples' perspectives on the use of robots to combat loneliness and attendant ethical issues. This study examines opinions about artificial companion (AC) robots regarding deception with dementia and impact on loneliness. Met...

BACKGROUND Describing changes in health and behavior that precede and follow a sentinel health event, like a cancer diagnosis, is challenging because of a lack of longitudinal, objective measurements that are collected frequently enough to capture varying trajectories of change leading up to and following the event. A continuous passive assessment...

Background Describing changes in health and behavior that precede and follow a sentinel health event, such as a cancer diagnosis, is challenging because of the lack of longitudinal, objective measurements that are collected frequently enough to capture varying trajectories of change leading up to and following the event. A continuous passive assess...

Octogenarians are the fastest growing segment of the population worldwide, but are often excluded from pharmacological intervention trials. Slowing cognitive decline and delaying the onset of dementia even for a few years among this age group could reduce prevalent dementia significantly. Behavioral intervention targeting the older old, which can b...

Voluntary, self-administered online assessment platforms have gained popularity in monitoring cognition and lifestyle behaviors. This study used the AARP Staying Sharp online brain health assessment platform to estimate the progression of a cognitive composite and correlate it with six modifiable lifestyle behaviors (physical activity, diet, sleep,...

Amyloid (Aβ) clearance is disturbed in late‐onset Alzheimer’s disease (AD), and a local relationship between Aβ clearance and gray (GM) and white matter (WM) perivascular spaces (PVS) is presumed. Most in vivo primate work has focused on MRI‐visible PVS in WM, described as pathological and enlarged, while nearly all in vivo mechanistic work in anim...

For older adults in community settings, predicting undesired outcomes (needing higher levels of care or death) is important for advancing preventative care and achieving successful aging. We examined whether a combination of baseline characteristics (demographic, clinical) and a continuous digital measure of general mobility and socialization (time...

Among prominent unmet needs of the Alzheimer’s disease and related dementia (ADRD) research community is the ability to leverage opportunities to improve the assessments of persons with and at risk for ADRD. This vision can be realized by providing the tools and infrastructure to transform dementia assessment using remote sensing and digital techno...

Remote delivery of dementia caregiver interventions can decrease delivery costs, and make it more feasible to provide evidence-based interventions to caregivers across the country. As the science behind remote delivery develops, new technologies and their applications can ensure preservation of important intervention components and principles, as w...

The out-of-pocket costs to care for individuals living with dementia are high, and is exacerbated by the expense of managing behavioral and psychological symptoms of dementia (BPSD) (e.g., depression, irritability). STELLA (Support via TEchnology: Living and Learning with Advancing AD) is a telehealth-based intervention that provides a personalized...

Mobility features are important for health. In this study, we quantified in-home mobility and explored potential health and environmental correlates. Participants included community-dwelling older adults living alone (n=139). Two indoor mobility features were developed (frequency; interdaily stability) using passive, room-level (bathroom; bedroom;...

Timely and objective knowledge regarding behavioral and psychological symptoms (BPS) in older adults with cognitive impairment or dementia residing in the community setting is challenging to obtain. The Monitoring Dementia-Related Agitation using Technology Evaluation (MODERATE) Study aims to identify longitudinal changes of agitation and related s...

Many people living with Alzheimer’s disease and related dementias (ADRD) never receive a formal disease diagnosis. This compromises wellbeing and increases health services utilization and care costs. Wider screening and assessment for ADRD may increase access to supportive care, improve allocation of medical care, and foster interventions that prev...

Background: For older adults in community settings, predicting undesired outcomes (needing higher levels of care or death) is important for advancing preventative care and achieving successful aging. We examined whether a combination of baseline characteristics (demographic, clinical) and a continuous digital measure of general mobility and social...

Background: Home-based sensor technologies can detect information on daily activities, such as sleep, activity level, and time spent together. This is relevant information for care partners of individuals with cognitive impairment as it can detect early changes in daily activities and cognition. The challenge is how to present thousands of data po...

Background: Among prominent unmet needs of the Alzheimer's disease and related dementia (ADRD) research community is the ability to leverage opportunities to improve the assessments of persons with and at risk for ADRD. This vision can be realized by providing the tools and infrastructure to transform dementia assessment using remote sensing and d...

Home‐based sensor technologies can detect information on daily activities, such as sleep, activity level, and time spent together. This is relevant information for care partners of individuals with cognitive impairment as it can detect early changes in daily activities and cognition. The challenge is how to present thousands of data points to care...

Introduction: During the COVID-19 pandemic, in-person research study visits were moved to an online format using a variety of communication platforms (e.g., Webex and Zoom). Increased technology use among older adults allowed for greater insight regarding the remote research study visit format. Methods: A survey developed by the National Alzheim...

Introduction: Examining the emotional functioning of individuals with mild cognitive impairment (MCI) could help describe their cognitive status and inform the development of interventions. This study compared the emotional characteristics of socially isolated older adults with and without MCI. Methods: We used baseline data from the Internet-ba...

Postmortem (PM) magnetic resonance imaging (MRI) can serve as a bridge between in vivo imaging and histology by connecting MRI observed macrostructural findings to histological staining and microstructural changes. Data were acquired from 20 formalin-fixed brains including T2, T1, PD, and T2*-weighted images of left hemispheres and 6-mm-thick coron...

For optimal design of anti-amyloid-β (Aβ) and anti-tau clinical trials, we need to better understand the pathophysiological cascade of Aβ- and tau-related processes. Therefore, we set out to investigate how Aβ and soluble phosphorylated tau (p-tau) relate to the accumulation of tau aggregates assessed with PET and subsequent cognitive decline acros...

Objectives: We aimed to examine the impact of COVID-19 pandemic-related stay-at-home orders on weekly reports of mood and activity before and during COVID-19 in a sample of older Veterans and their cohabitants. Methods: Urban and rural Veterans and their cohabitants living in the Pacific Northwest ≥62 years old were enrolled as part of the Collabor...

Objective The objective of this study was to examine associations between level of depressive symptoms in older adult spouse/partner couples and their physical health and social factors (social activity and number of close friends). Methods Using data from 116 community-dwelling couples (age 76.2 ± 8.5), we simultaneously analyzed associations bet...

The process of identifying suitable genome-wide association (GWA) studies and formatting the data to calculate multiple polygenic risk scores on a single genome can be laborious. Here, we present a centralized polygenic risk score calculator currently containing over 250,000 genetic variant associations from the NHGRI-EBI GWAS Catalog for users to...

Objective The Survey for Memory, Attention, and Reaction Time (SMART) was recently introduced as a brief (<5 min), self-administered, web-based measure of cognitive performance in older adults. The purpose of this study was threefold: (1) to develop preliminary norms on the SMART; (2) to examine the relationship between demographic variables (i.e....

Sleep disturbances are common in older adults and may contribute to disease progression in certain populations (e.g., Alzheimer’s disease). Light therapy is a simple and cost-effective intervention to improve sleep. Primary barriers to light therapy are: (1) poor acceptability of the use of devices, and (2) inflexibility of current devices to deliv...

Objective: To determine the sensitivity and specificity of α-synuclein seed amplification assay (αSyn-SAA) in antemortem and postmortem CSF of autopsy-confirmed patients with different distributions of pathological αSyn, co-pathologies, and clinical diagnoses. Methods: αSyn-SAA was used to test antemortem CSF samples from 119 subjects with a var...

Changes in the levels of circulating proteins are associated with Alzheimer’s disease (AD), whereas their pathogenic roles in AD are unclear. Here, we identified soluble ST2 (sST2), a decoy receptor of interleukin-33–ST2 signaling, as a new disease-causing factor in AD. Increased circulating sST2 level is associated with more severe pathological ch...

Studies find that older adults want control over how technologies are used in their care, but how it can be operationalized through design remains to be clarified. We present findings from a large survey (n=825) of a well-characterized U.S. online cohort that provides actionable evidence of the importance of designing for control over monitoring te...

Background/aims There is a close link between iron and polyamine biosynthesis and metabolism. In a recent study, we reported alterations in the serum levels of hepcidin and other iron-related proteins in Alzheimer’s disease (AD) patients (Sternberg et al., 2017). Based on these findings, this pilot study compared serum levels of one of the polyamin...

Exploring individual hallmarks of brain ageing is important. Here, we propose the age-related glucose metabolism pattern (ARGMP) as a potential index to characterize brain ageing in cognitively normal (CN) elderly people. We collected 18F-fluorodeoxyglucose (18F-FDG) PET brain images from two independent cohorts: the Alzheimer’s Disease Neuroimagin...

Introduction: The Alzheimer's Disease Composite Score (ADCOMS) is a tool developed to detect clinical progression and measure treatment effect in patients in early stages of Alzheimer's disease (AD). The psychometric properties of the ADCOMS have been established; however, the threshold for clinical meaningfulness has yet to be identified. Method...

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we ai...

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 ris...

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...

Alzheimer’s disease (AD) is defined by amyloid (A) and tau (T) pathologies, with T better correlated to neurodegeneration (N). However, T and N have complex regional relationships in part related to non-AD factors that influence N. With machine learning, we assessed heterogeneity in 18F-flortaucipir vs. 18F-fluorodeoxyglucose positron emission tomo...

Introduction: Impairment in financial capacity places older adults at risk of fraud or abuse and can be a harbinger of loss of independence. Online automated monitoring of financial transactions offers an objective, unobtrusive, and continuous data collection strategy to minimize risk and to detect early changes in an important complex activity of...

Objective To determine the sensitivity and specificity of α-synuclein seed amplification assay (αSyn-SAA) in antemortem and postmortem CSF and brain homogenate samples of autopsy-confirmed patients with a spectrum of Lewy-related pathology (LRP). Methods Antemortem CSF samples were examined from 119 subjects with standardized neuropathological exa...

Seasonal variation in rest-activity patterns has been observed in healthy adult populations. This study examined seasonal variation in total time spent overnight in the bedroom by cognitively intact older adults and older adults with mild cognitive impairment (MCI). We hypothesize that seasonal variation in rest-activity patterns is observed in the...

Background: α-klotho might play a role in neurodegenerative diseases. Objective: To determine levels of α-klotho and apoE in serum and cerebrospinal fluid (CSF) samples and their relationship with the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR). Methods: All subjects were between age 39 to 83+ (n = 94). CDR and MMSE...

Background and Objectives The Remote Assessment and Dynamic Response (READyR) Program was developed in order to address the current lack of early-stage dementia care planning programs that assess the care needs of persons with dementia. The goal was to create a program informed by care values and ongoing ecologically-valid data. The objectives of t...

Genome-wide association studies have demonstrated that polygenic risks shape Alzheimer’s disease (AD). To elucidate the polygenic architecture of AD phenotypes at a cellular level, we established induced pluripotent stem cells from 102 patients with AD, differentiated them into cortical neurons and conducted a genome-wide analysis of the neuronal p...

Introduction: Reproducibility and replicability of results are rarely achieved for digital biomarkers analyses. We reproduced and replicated previously reported sample size estimates based on digital biomarker and neuropsychological test outcomes in a hypothetical 4-year early-phase Alzheimer's disease trial. Methods: Original data and newly col...

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...

Socially isolated older adults with MCI are at greater risk of developing ADRD. This study compares the emotional status of older adults with MCI to their cognitively normal counterparts within a socially isolated sample. We used baseline data from the Internet-based Conversational Engagement Clinical Trial (NCT02871921). MCI status was determined...

The COVID-19 pandemic has greatly impacted the economic security of millions of older adults. Job loss and reductions in personal income were significant in 2020 stemming from pandemic-induced shutdowns that temporarily closed large swaths of the U.S. economy. Yet, the specific financial impacts of the pandemic on older adults, including family car...

Results from a June 2020 survey on comfort with two forms of artificial companion (AC) robots in normal compared with pandemic times will be presented. 1,082 adults age 21-92 (mean 64) completed the online survey for a response rate of 45%. Significantly greater comfort is reported with small AC robots relative to larger human-shaped robots in both...

Online cognitive tests offer a cost-effective, accessible means of cognitive screening and may prove especially important for individuals with memory complaints, a risk factor for cognitive impairment (Kaup et al., 2015). Although older adults’ perceptions of everyday technologies impact their uptake and adoption, there is limited understanding abo...

This study aimed to simultaneously examine the associations between social activity and connectedness and depressive symptoms in older adult couples. Using SEM and data from 116 community-dwelling couples (age 76.18 ± 8.49), we found that engagement in social activities was associated with lower depressive symptoms in men (p = 0.014), whereas more...

Actigraphy has been used to detect agitation in persons with dementia, although this technology must be worn by participants. Another promising sensing methodology is passive infrared (PIR) motion, which provides continuous, low-cost, and unobtrusive data, and may also improve the detection of agitated periods. Using data from the MODERATE (Monitor...

Background In a progressively technology-infused world, older adults are becoming accustomed to the digitization of research participation. During the COVID-19 pandemic, it became necessary to conduct remote study visits typically carried out over the telephone or using video calling programs (e.g. Zoom). Methods The National Alzheimer’s Coordinat...

Indoor room transition is an underexplored real-world activity outcome. We estimated the stability and variability of indoor room transitions and their associations with mild cognitive impairment (MCI) in older adults. Older adults living-alone (n=159, age=78.3±8.8 years, 14% MCI) from the Oregon Center for Aging & Technology (ORCATECH) and the Min...

Subjective assessments of dementia caregiver burden are vulnerable to recall and recency biases. Objective continuous home assessment using passive technologies (e.g., bed mats, actigraphy watches) can provide ecologically valid detail on caregiver stress and family function. We tested the utility of objective assessment of activity before, during...

Heterogeneity of brain diseases is a challenge for precision diagnosis/prognosis. We describe and validate Smile-GAN (SeMI-supervised cLustEring-Generative Adversarial Network), a semi-supervised deep-clustering method, which examines neuroanatomical heterogeneity contrasted against normal brain structure, to identify disease subtypes through neuro...

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...

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...

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...

Background 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...

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...

Background 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 absen...

Background Shifting and diminished circadian and activity rhythms characterize older adults with cognitive impairment, but studies rarely consider both temporal and spatial aspects of life activity patterns. We examined hourly in‐home and out‐of‐home activity patterns using latent group trajectory models to characterize older adults with and withou...

Background 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...

Background 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 info...

Background 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 usa...

Plasma phosphorylated-tau181 (p-tau181) showed the potential for Alzheimer’s diagnosis and prognosis, but its role in detecting cerebral pathologies is unclear. We aimed to evaluate whether it could serve as a marker for Alzheimer’s pathology in the brain. A total of 1189 participants with plasma p-tau181 and PET data of amyloid, tau or FDG PET wer...

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...