Shelby Bachman

Digital health technologies offer valuable advantages to dementia researchers and clinicians as screening tools, diagnostic aids, and monitoring instruments. To support the use and advancement of these resources, a comprehensive overview of the current technological landscape is essential. A multi-stakeholder working group, convened by the Digital Medicine Society (DiMe), conducted a landscape review to identify digital health technologies for Alzheimers disease and related dementia populations. We searched studies indexed in PubMed, Embase, and APA PsycInfo to identify manuscripts published between May 2003 to May 2023 reporting analytical validation, clinical validation, or usability/feasibility results for relevant digital health technologies. Additional technologies were identified through community outreach. We collated 172 peer-reviewed manuscripts, poster presentations, or regulatory documents for 106 different technologies for Alzheimers disease and related dementia assessment covering diverse populations such as Lewy Body, vascular dementias, frontotemporal dementias, and all severities of Alzheimers disease. Wearable sensors represent 32% of included technologies, non-wearables 61%, and technologies with components of both account for the remaining 7%. Neurocognition is the most prevalent concept of interest, followed by physical activity and sleep. Clinical validation is reported in 69% of evidence, analytical validation in 34%, and usability/feasibility in 20% (not mutually exclusive). These findings provide a landscape overview for clinicians and researchers to appraise the clinical utility and relative maturity of …

We present data from the Heart Rate Variability and Emotion Regulation (HRV-ER) randomized clinical trial testing effects of HRV biofeedback. Younger (N = 121) and older (N = 72) participants completed baseline magnetic resonance imaging (MRI) including T1-weighted, resting and emotion regulation task functional MRI (fMRI), pulsed continuous arterial spin labeling (PCASL), and proton magnetic resonance spectroscopy (1H MRS). During fMRI scans, physiological measures (blood pressure, pulse, respiration, and end-tidal CO2) were continuously acquired. Participants were randomized to either increase heart rate oscillations or decrease heart rate oscillations during daily sessions. After 5 weeks of HRV biofeedback, they repeated the baseline measurements in addition to new measures (ultimatum game fMRI, training mimicking during blood oxygen level dependent (BOLD) and PCASL fMRI …

Physiological arousal affects attention and memory, sometimes enhancing and other times impairing what we attend to and remember. In the present study, we investigated how changes in physiological arousal—induced through short bursts of isometric handgrip exercise—affected subsequent working memory performance. A sample of 57 younger (ages 18–29) and 56 older (ages 65–85) participants performed blocks of isometric handgrip exercise in which they periodically squeezed a therapy ball, alternating with blocks of an auditory working memory task. We found that, compared with those in a control group, participants who performed isometric handgrip had faster reaction times on the working memory task. Handgrip-speeded responses were observed for both younger and older participants, across working memory loads. Analysis of multimodal physiological responses indicated that physiological arousal …

Background Abnormally phosphorylated tau, an indicator of Alzheimer’s disease, starts accumulating in the locus coeruleus (LC), the brain’s major noradrenaline supply, during the first decades of life. Facilitated by technical advances, recent evidence shows that age‐related deficits in noradrenergic neuromodulation impinge on late‐life memory. However, investigations assessing longitudinal locus coeruleus changes and their association with senescent memory are scarce. Moreover, comparisons to other neuromodulatory systems that decline with age are lacking, questioning the specificity of noradrenergic effects. Method We collected high‐resolution magnetic resonance imaging (MRI) data of the dopaminergic substantia nigra–ventral tegmental area (SN–VTA) and the noradrenergic locus coeruleus (LC) of 320 younger and older participants of the Berlin Aging Study‐II at two time points (TP1, TP2; ∼1.9 …

Methods: We collected high-resolution magnetic resonance imaging (MRI) data of the dopaminergic substantia nigra–ventral tegmental area (SN–VTA) and the noradrenergic locus coeruleus (LC) of 320 younger and older adults at two time points (TP1, TP2;∼ 1.9 years delay). The imaging protocol included three scans sensitive to the SN–VTA and LC—a Fast-Spin-Echo [FSE] sequence, and a Magnetization-Transfer sequence, acquired once with a dedicated magnetic saturation pulse [MT+] and once without, resulting in a proton-density image [MT−]. We aggregated the information shared across imaging modalities by estimating multimodal latent factors expressing dopaminergic and noradrenergic integrity.Participants also completed a comprehensive cognitive battery at three time points (TP1, TP2, TP3), including tests of fluid intelligence, episodic and working memory. We used structural equation modeling to …

Background The locus coeruleus (LC) innervates the cerebrovasculature and plays a critical role in optimally regulating cerebral blood flow. However, few studies have examined potential relationships between these systems in humans with widely available neuroimaging methods, and none have explored how relationships may change in the presence of growing Alzheimer’s disease (AD) pathology. Method Participants were 66 community‐dwelling older adults free of dementia (ages 55‐87) recruited at the University of Southern California. Pseudocontinuous arterial spin labeling (pCASL) MRI measured regional perfusion, and T1‐fast spin echo (T1‐FSE) MRI quantified rostral LC contrast, a well‐established measure of LC structural integrity. Subsets of participants underwent neuropsychological testing (n = 36) as well as fasting venipuncture to measure plasma AD biomarker concentrations of Aβ42/40 ratio …

ObjectiveThe locus coeruleus (LC) innervates the cerebrovasculature and plays a crucial role in optimal regulation of cerebral blood flow. However, no human studies to date have examined links between these systems with widely available neuroimaging methods. We quantified associations between LC structural integrity and regional cortical perfusion and probed whether varying levels of plasma Alzheimer’s disease (AD) biomarkers (Aß42/40 ratio and ptau181) moderated these relationships.Participants and Methods64 dementia-free community-dwelling older adults (ages 55-87) recruited across two studies underwent structural and functional neuroimaging on the same MRI scanner. 3D-pCASL MRI measured regional cerebral blood flow in limbic and frontal cortical regions, while T1-FSE MRI quantified rostral LC-MRI contrast, a well-established proxy measure of LC structural integrity. A subset of participants …

Previous research suggests that higher heart rate variability (HRV) is associated with better cognitive function. However, since most previous findings on the relationship between HRV and cognitive function were correlational in nature, it is unclear whether individual differences in HRV play a causal role in cognitive performance. To investigate whether there are causal relationships, we used a simple breathing manipulation that increases HRV through a 5-week HRV biofeedback intervention and examined whether this manipulation improves cognitive performance in younger and older adults (N = 165). The 5-week HRV biofeedback intervention did not significantly improve inhibitory control, working memory and processing speed across age groups. However, improvement in the Flanker score (a measure of inhibition) was associated with the amplitude of heart rate oscillations during practice sessions in the …

As an arousal hub region in the brain, the locus coeruleus (LC) has bidirectional connections with the autonomic nervous system. Magnetic resonance imaging (MRI)-based measures of LC structural integrity have been linked to cognition and arousal, but less is known about factors that influence LC structure and function across time. Here, we tested the effects of heart rate variability (HRV) biofeedback, an intervention targeting the autonomic nervous system, on LC MRI contrast and sympathetic activity. Younger and older participants completed daily HRV biofeedback training for five weeks. Those assigned to an experimental condition performed biofeedback involving slow, paced breathing designed to increase heart rate oscillations, whereas those assigned to a control condition performed biofeedback to decrease heart rate oscillations. At the pre- and post-training timepoints, LC contrast was assessed using …

Heart rate variability is a robust biomarker of emotional well-being, consistent with the shared brain networks regulating emotion regulation and heart rate. While high heart rate oscillatory activity clearly indicates healthy regulatory brain systems, can increasing this oscillatory activity also enhance brain function? To test this possibility, we randomly assigned 106 young adult participants to one of two 5-week interventions involving daily biofeedback that either increased heart rate oscillations (Osc+ condition) or had little effect on heart rate oscillations (Osc− condition) and examined effects on brain activity during rest and during regulating emotion. While there were no significant changes in the right amygdala-medial prefrontal cortex (MPFC) functional connectivity (our primary outcome), the Osc+ intervention increased left amygdala-MPFC functional connectivity and functional connectivity in emotion-related resting …

PURPOSEThe burden of cancer cachexia on patients' health-related quality of life, specifically their physical functioning, is well documented, but clinical trials thus far have failed to show meaningful improvement in physical functioning. The purpose of this review is to summarize existing methods of assessing physical function in cancer cachexia, outline a path forward for measuring what is meaningful to patients using digital measures derived from digital health technologies (DHTs), and discuss the current landscape of digital measures from the clinical and regulatory standpoint.DESIGNFor this narrative review, peer-reviewed articles were searched on PubMed, clinical trials records were searched on clinicaltrials.gov, and records of digital measures submitted for regulatory qualification were searched on the US Food and Drug Administration's Drug Development Tool Qualification Program database.RESULTS …

Correction: Effects of a Randomised Trial of 5-Week Heart Rate Variability Biofeedback Intervention on Cognitive Function: Possible Benefits for Inhibitory Control - PMC Back to Top Skip to main content NIH NLM Logo Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation Search PMC Full-Text Archive Search in PMC Advanced Search User Guide Journal List Springer Open Choice PMC10074510 Other Formats PDF (292K) Actions Cite Collections Share Permalink Copy RESOURCES Similar articles Cited by other articles Links to NCBI Databases Journal List Springer Open Choice PMC10074510 As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice Logo of springeropen Applied …

Changes in dopaminergic neuromodulation play a key role in adult memory decline. Recent research has also implicated noradrenaline in shaping late-life memory. However, it is unclear whether these two neuromodulators have distinct roles in age-related cognitive changes. Here, combining longitudinal MRI of the dopaminergic substantia nigra–ventral tegmental area (SN-VTA) and noradrenergic locus coeruleus (LC) in younger (n = 69) and older (n = 251) adults, we found that dopaminergic and noradrenergic integrity are differentially associated with memory performance. While LC integrity was related to better episodic memory across several tasks, SN-VTA integrity was linked to working memory. Longitudinally, we found that older age was associated with more negative change in SN-VTA and LC integrity. Notably, changes in LC integrity reliably predicted future episodic memory. These differential …

Alzheimer’s disease (AD) is a devastating neurodegenerative disease and the primary cause of dementia worldwide. Despite the magnitude of AD’s impact on patients, caregivers, and society, nearly all AD clinical trials fail. A potential contributor to this high rate of failure is that established clinical outcome assessments fail to capture subtle clinical changes, entail high burden for patients and their caregivers, and ineffectively address the aspects of health deemed important by patients and their caregivers. AD progression is associated with widespread changes in physical behavior that have impacts on the ability to function independently, which is a meaningful aspect of health for patients with AD and important for diagnosis. However, established assessments of functional independence remain underutilized in AD clinical trials and are limited by subjective biases and ceiling effects. Digital measures of real-world …

Acute stress activates the brain’s locus coeruleus (LC)-noradrenaline system. Recent studies indicate that a magnetic resonance imaging (MRI)-based measure of LC structure is associated with better cognitive outcomes in later life. Yet despite the LC’s documented role in promoting physiological arousal during acute stress, no studies have examined whether MRI-assessed LC structure is related to arousal responses to acute stress. In this study, 102 younger and 51 older adults completed an acute stress induction task while we assessed multiple measures of physiological arousal (heart rate, breathing rate, systolic and diastolic blood pressure, sympathetic tone, and heart rate variability, HRV). We used turbo spin echo MRI scans to quantify LC MRI contrast as a measure of LC structure. We applied univariate and multivariate approaches to assess how LC MRI contrast was associated with arousal at rest and …

Previous studies indicate that the structure and function of medial prefrontal cortex (PFC) and lateral orbitofrontal cortex (OFC) are associated with heart rate variability (HRV). Typically, this association is assumed to reflect the PFC's role in controlling HRV and emotion regulation, with better prefrontal structural integrity supporting greater HRV and better emotion regulation. However, as a control system, the PFC must monitor and respond to heart rate oscillatory activity. Thus, engaging in regulatory feedback during heart rate oscillatory activity may over time help shape PFC structure, as relevant circuits and connections are modified. In the current study with younger and older adults, we tested whether 5 weeks of daily sessions of biofeedback to increase heart rate oscillations (Osc+ condition) vs. to decrease heart rate oscillations (Osc− condition) affected cortical volume in left OFC and right OFC, two regions …

Researchers generally agree that when upregulating and downregulating emotion, control regions in the prefrontal cortex turn up or down activity in affect-generating brain areas. However, the “affective dial hypothesis” that turning up and down emotions produces opposite effects in the same affect-generating regions is untested. We tested this hypothesis by examining the overlap between the regions activated during upregulation and those deactivated during downregulation in 54 male and 51 female humans. We found that upregulation and downregulation both recruit regulatory regions, such as the inferior frontal gyrus and dorsal anterior cingulate gyrus, but act on distinct affect-generating regions. Upregulation increased activity in regions associated with emotional experience, such as the amygdala, anterior insula, striatum, and anterior cingulate gyrus as well as in regions associated with sympathetic …

The effects of aversive events on memory are complex and go beyond the simple enhancement of threatening information. Negative experiences can also rescue related but otherwise forgettable details encoded close in time. Here, we used functional magnetic resonance imaging (fMRI) in healthy young adults to examine the brain mechanisms that support this retrograde memory effect. In a two-phase incidental encoding paradigm, participants viewed different pictures of tools and animals before and during Pavlovian fear conditioning. During Phase 1, these images were intermixed with neutral scenes, which provided a unique ‘context tag’ for this specific phase of encoding. A few minutes later, during Phase 2, new pictures from one category were paired with a mild shock (threat-conditioned stimulus; CS+), while pictures from the other category were not shocked. FMRI analyses revealed that, across-participants …

Background Age‐related deficits in dopaminergic neuromodulation play a key role in determining memory decline. Facilitated by technical advancements, recent research has also implicated noradrenergic neuromodulation in shaping late‐life memory development. However, investigations disentangling the contribution of the two neuromodulators to the neurobiological basis of human cognitive aging are scarce. Method We collected high‐resolution magnetic resonance imaging (MRI) data of the dopaminergic substantia nigra–ventral tegmental area and the noradrenergic locus coeruleus of 320 younger and older adults at two time points (T1, T2; ∼1.9 years delay). The imaging protocol included three scans sensitive for the substantia nigra–ventral tegmental area and locus coeruleus—a Fast‐Spin‐Echo [FSE] sequence, and a Magnetization‐Transfer sequence, acquired once with a dedicated magnetic …

The locus coeruleus-noradrenergic system integrates signals about arousal states throughout the brain and helps coordinate cognitive selectivity. However, age-related changes in this system may impact how arousal coordinates selectivity in older adults. To examine this, we compared how increases in emotional arousal modulates cognitive selectivity for images differing in perceptual salience in young and older adults. Using functional magnetic resonance imaging, we found that relative to older adults, hearing an arousing sound enhanced young adults’ bottom-up processing and incidental memory for high versus low salience category-selective body images. We also examined how arousing sounds impacted a top-down goal to detect dot-probes that appeared immediately after high or low salience images. We found that young adults were slower to detect probes appearing after high salience body images on …