Care Ecosystem Collaborative Model and Health Care Costs in Medicare Beneficiaries With Dementia: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Collaborative dementia care programs are effective in addressing the needs of patients with dementia and their caregivers. However, attempts to consider effects on health care spending have been limited, leaving a critical gap in the conversation around value-based dementia care. Objective: To determine the effect of participation in collaborative dementia care on total Medicare reimbursement costs compared with usual care. Design, Setting, and Participants: This was a prespecified secondary analysis of the Care Ecosystem trial, a 12-month, single-blind, parallel-group randomized clinical trial conducted from March 2015 to March 2018 at 2 academic medical centers in California and Nebraska. Participants were patients with dementia who were living in the community, aged 45 years or older, and had a primary caregiver and Medicare fee-for-service coverage for the duration of the trial. Intervention: Telehealth dementia care program that entailed assignment to an unlicensed dementia care guide who provided caregiver support, standardized education, and connection to licensed dementia care specialists. Main Outcomes and Measures: Primary outcome was the sum of all Medicare claim payments during study enrollment, excluding Part D (drugs). Results: Of the 780 patients in the Care Ecosystem trial, 460 (59.0%) were eligible for and included in this analysis. Patients had a median (IQR) age of 78 (72-84) years, and 256 (55.7%) identified as female. Participation in collaborative dementia care reduced the total cost of care by $3290 from 1 to 6 months postenrollment (95% CI, -$6149 to -$431; P = .02) and by $3027 from 7 to 12 months postenrollment (95% CI, -$5899 to -$154; P = .04), corresponding overall to a mean monthly cost reduction of $526 across 12 months. An evaluation of baseline predictors of greater cost reduction identified trends for recent emergency department visit (-$5944; 95% CI, -$10 336 to -$1553; interaction P = .07) and caregiver depression (-$6556; 95% CI, -$11 059 to -$2052; interaction P = .05). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial among Medicare beneficiaries with dementia, the Care Ecosystem model was associated with lower total cost of care compared with usual care. Collaborative dementia care programs are a cost-effective, high-value model for dementia care. Trial Registration: ClinicalTrials.gov Identifier: NCT02213458.

Exploring behavioral phenotypes in a mouse model of fetal alcohol spectrum disorders.

Fetal alcohol spectrum disorders are one of the leading causes of developmental abnormalities worldwide. Maternal consumption of alcohol during pregnancy leads to a diverse range of cognitive and neurobehavioral deficits. Although moderate-to-heavy levels of prenatal alcohol exposure (PAE) have been associated with adverse offspring outcomes, there is limited data on the consequences of chronic low-level PAE. Here, we use a model of maternal voluntary alcohol consumption throughout gestation in a mouse model to investigate the effects of PAE on behavioral phenotypes during late adolescence and early adulthood in male and female offspring. Body composition was measured by dual-energy X-ray absorptiometry. Baseline behaviors, including feeding, drinking, and movement, were examined by performing home cage monitoring studies. The impact of PAE on motor function, motor skill learning, hyperactivity, acoustic reactivity, and sensorimotor gating was investigated by performing a battery of behavioral tests. PAE was found to be associated with altered body composition. No differences in overall movement, food, or water consumption were observed between control and PAE mice. Although PAE offspring of both sexes exhibited deficits in motor skill learning, no differences were observed in basic motor skills such as grip strength and motor coordination. PAE females exhibited a hyperactive phenotype in a novel environment. PAE mice exhibited increased reactivity to acoustic stimuli, and PAE females showed disrupted short-term habituation. Sensorimotor gating was not altered in PAE mice. Collectively, our data show that chronic low-level exposure to alcohol in utero results in behavioral impairments.

"Out of the clear blue sky she tells me she loves me": Connection experiences between caregivers and people with dementia.

BACKGROUND: Dementia can impede the relationship and connection between the person with dementia (PWD) and their caregiver. Yet, caregiving in dementia also offers opportunities for connection, which has implications for caregiver and PWD well-being. In this qualitative study, we describe and characterize ways caregivers felt connected to the person with dementia they care for. METHODS: We conducted a telephone-based survey with caregivers of people with dementia. For this paper, we analyzed responses to an open-ended question focused on when caregivers feel most connected to the person they are caring for. Responses were analyzed and coded and themes were identified through an iterative process involving a multidisciplinary team of researchers and clinicians. RESULTS: 437 caregivers participated in this study. We identified two domains of connection: activity-based and emotion-based connections. Within activity-based connections, the following themes emerged: everyday activities; reminiscing; activities of caregiving; novel experiences; and time with family and friends. Within emotional connections, the following themes emerged: expressions of love, appreciation, and gratitude; physical affection; sharing an emotion or emotional experience; and times when the PWD seems like "themself" again. CONCLUSIONS: Findings provide insights into ways caregivers experience a sense of connection with the person they care for. There is a call to shift away from focusing on reducing stress and toward optimizing positive experiences as a way to better support caregivers' health and well-being. Interventions that leverage these insights to foster caregiver - PWD connection could lead to better health and well-being for both members of the dyad. The amplification of a positive experience may be particularly important for caregivers who are struggling with limited support or respite. Clinicians may be interested in using a question about connection as a way to more fully understand a caregiver's current experience.

Loss of epigenetic information as a cause of mammalian aging.

All living things experience an increase in entropy, manifested as a loss of genetic and epigenetic information. In yeast, epigenetic information is lost over time due to the relocalization of chromatin-modifying proteins to DNA breaks, causing cells to lose their identity, a hallmark of yeast aging. Using a system called "ICE" (inducible changes to the epigenome), we find that the act of faithful DNA repair advances aging at physiological, cognitive, and molecular levels, including erosion of the epigenetic landscape, cellular exdifferentiation, senescence, and advancement of the DNA methylation clock, which can be reversed by OSK-mediated rejuvenation. These data are consistent with the information theory of aging, which states that a loss of epigenetic information is a reversible cause of aging.

Effect of collaborative dementia care on potentially inappropriate medication use: Outcomes from the Care Ecosystem randomized clinical trial.

INTRODUCTION: Potentially inappropriate medications (PIMs) cause adverse events and death. We evaluate the Care Ecosystem (CE) collaborative dementia care program on medication use among community-dwelling persons living with dementia (PLWD). METHODS: Secondary analysis of a randomized clinical trial (RCT) comparing CE to usual care (UC) on changes in PIMs, over 12 months between March 2015 and May 2020. Secondary outcomes included change in number of medications, clinically relevant PIMs, and anti-dementia medications. RESULTS: Of 804 PLWD, N = 490 had complete medication data. The CE resulted in significantly fewer PIMs compared to UC (-0.35; 95% CI, -0.49 to -0.20; P < 0.0001). Number needed to prevent an increase in 1 PIM was 3. Total medications, PIMs for dementia or cognitive impairment, CNS-active PIMs, anticholinergics, benzodiazepines, and opioids were also fewer. Anti-dementia medication regimens were modified more frequently. CONCLUSION: The CE medication review intervention embedded in collaborative dementia care optimized medication use among PLWD. HIGHLIGHTS: Compared to usual care (UC), the Care Ecosystem (CE) medication review intervention prevented increases in potentially inappropriate medications (PIMs). Use of anticholinergics, benzodiazepines, and opioids were significantly reduced, with a trend for antipsychotics. Anti-dementia medications were adjusted more frequently. The CE medication review intervention embedded in collaborative dementia care optimized medication use.

Complement Component C3 Loss leads to Locomotor Deficits and Altered Cerebellar Internal Granule Cell In Vitro Synaptic Protein Expression in C57BL/6 Mice.

Complement component 3 (C3) expression is increased in the cerebellum of aging mice that demonstrate locomotor impairments and increased excitatory synapse density. However, C3 regulation of locomotion, as well as C3 roles in excitatory synapse function, remains poorly understood. Here, we demonstrate that constitutive loss of C3 function in mice evokes a locomotor phenotype characterized by decreased speed, increased active state locomotor probability, and gait ataxia. C3 loss does not alter metabolism or body mass composition. No evidence of significant muscle weakness or degenerative arthritis was found in C3 knockout mice to explain decreased gait speeds. In an enriched primary cerebellar granule cell culture model, loss of C3 protein results in increased excitatory synaptic density and increased response to KCl depolarization. Our analysis of excitatory synaptic density in the cerebellar internal granule cell and molecular layers did not demonstrate increased synaptic density in vivo, suggesting the presence of compensatory mechanisms regulating synaptic development. Functional deficits in C3 knockout mice are therefore more likely to result from altered synaptic function and/or connectivity than gross synaptic deficits. Our data demonstrate a novel role for complement proteins in cerebellar regulation of locomotor output and control.

δ-Catenin engages the autophagy pathway to sculpt the developing dendritic arbor.

The development of the dendritic arbor in pyramidal neurons is critical for neural circuit function. Here, we uncovered a pathway in which δ-catenin, a component of the cadherin-catenin cell adhesion complex, promotes coordination of growth among individual dendrites and engages the autophagy mechanism to sculpt the developing dendritic arbor. Using a rat primary neuron model, time-lapse imaging, immunohistochemistry, and confocal microscopy, we found that apical and basolateral dendrites are coordinately sculpted during development. Loss or knockdown of δ-catenin uncoupled this coordination, leading to retraction of the apical dendrite without altering basolateral dendrite dynamics. Autophagy is a key cellular pathway that allows degradation of cellular components. We observed that the impairment of the dendritic arbor resulting from δ-catenin knockdown could be reversed by knockdown of autophagy-related 7 (ATG7), a component of the autophagy machinery. We propose that δ-catenin regulates the dendritic arbor by coordinating the dynamics of individual dendrites and that the autophagy mechanism may be leveraged by δ-catenin and other effectors to sculpt the developing dendritic arbor. Our findings have implications for the management of neurological disorders, such as autism and intellectual disability, that are characterized by dendritic aberrations.

Long-term digital device-enabled monitoring of functional status: Implications for management of persons with Alzheimer's disease.

INTRODUCTION: Informal caregiving is an essential element of health-care delivery. Little data describes how caregivers structure care recipients' lives and impact their functional status. METHODS: We performed observational studies of community dwelling persons with dementia (PWD) to measure functional status by simultaneous assessment of physical activity (PA) and lifespace (LS). We present data from two caregiver/care-recipient dyads representing higher and average degrees of caregiver involvement. RESULTS: We acquired >42,800 (subject 1); >41,300 (subject 2) PA data points and >154,500 (subject 1); >119,700 (subject 2) LS data points over 15 months of near continuous observation. PA and LS patterns provided insights into the caregiver's role in structuring the PWD's day-to-day function and change in function over time. DISCUSSION: We show that device-enabled functional monitoring (FM) can successfully gather and display data at resolutions required for dementia care studies. Objective quantification of individual caregiver/care-recipient dyads provides opportunities to implement patient-centered care.

Using care navigation to address caregiver burden in dementia: A qualitative case study analysis.

INTRODUCTION: Many caregivers of people with dementia experience burden and resulting health effects due to the intensive nature of caregiving. Phone- and web-based care navigation is an innovative model of care that may be useful in addressing caregiver burden in dementia. METHODS: Qualitative methods (interviews, focus groups, and case study analysis) were used to identify care navigator approaches used to address caregiver burden in dementia as part of a dementia care navigation program. RESULTS: Care navigators targeted caregiver burden by focusing on strategies to reduce caregiver guilt and frustration, manage patient-related behavior, address caregiver depression, and improve the relationship between the caregiver and person with dementia. The case studies presented demonstrate the ways that care navigators identified patient and caregiver needs and tailored their approaches to meet the specific social, cultural, economic, and geographic contexts of the dyads with which they worked. DISCUSSION: Findings provide insights into strategies used to address caregiver burden through care navigation. Care navigators who speak the same language as the caregivers with whom they work and who have an in-depth understanding of the symptoms of different dementia syndromes may be particularly effective.

The Care Ecosystem: Promoting self-efficacy among dementia family caregivers.

OBJECTIVES: To illustrate specific psychosocial interventions aimed at improving self-efficacy among family caregivers enrolled in the Care Ecosystem, a model of navigated care designed to support persons with dementia and their primary caregivers. Enrolled family caregivers work with unlicensed care team navigators who are trained in dementia care and provide information, linkages to community resources, and emotional support by phone and email. METHOD: We conducted focus groups and interviews with the care team navigators to identify the approaches they used to target caregiver self-efficacy. We assessed mean self-efficacy scores in a sample of 780 family caregivers and selected three exemplary cases in which the caregivers had low self-efficacy scores at baseline with significantly higher scores after six months of participation in the Care Ecosystem intervention. RESULTS: Multiple psychosocial strategies were utilized by care team navigators working with patients with dementia and their family caregivers. Using thematic coding we identified three categories of Care Team Navigator intervention: emotional, informational, and instrumental support. These are consistent with a psychosocial approach to building self-efficacy. DISCUSSION: Self-efficacy represents a family caregiver's knowledge and preparedness in managing the challenges of care. Psychosocial support shows benefit in improving caregiver self-efficacy that in turn, may positively influence caregiver health and well-being. The findings in this manuscript demonstrate how a model of navigated care can positively impact self-efficacy among dementia family caregivers.

Effect of Collaborative Dementia Care via Telephone and Internet on Quality of Life, Caregiver Well-being, and Health Care Use: The Care Ecosystem Randomized Clinical Trial.

Importance: Few health systems have adopted effective dementia care management programs. The Care Ecosystem is a model for delivering care from centralized hubs across broad geographic areas to caregivers and persons with dementia (PWDs) independently of their health system affiliations. Objective: To determine whether the Care Ecosystem is effective in improving outcomes important to PWDs, their caregivers, and payers beyond those achieved with usual care. Design, Setting, and Participants: A single-blind, randomized clinical trial with a pragmatic design was conducted among PWDs and their caregivers. Each PWD-caregiver dyad was enrolled for 12 months between March 20, 2015, and February 28, 2017. Data were collected until March 5, 2018. Study interventions and assessments were administered over the telephone and internet by clinical and research teams in San Francisco, California, and Omaha, Nebraska. Of 2585 referred or volunteer PWD-caregiver dyads in California, Iowa, or Nebraska, 780 met eligibility criteria and were enrolled. A total of 512 PWD-caregiver dyads were randomized to receive care through the Care Ecosystem and 268 dyads to receive usual care. All eligible PWDs had a dementia diagnosis; were enrolled or eligible for enrollment in Medicare or Medicaid; and spoke English, Spanish, or Cantonese. Analyses were intention-to-treat. Intervention: Telephone-based collaborative dementia care was delivered by a trained care team navigator, who provided education, support and care coordination with a team of dementia specialists (advanced practice nurse, social worker, and pharmacist). Main Outcomes and Measures: Primary outcome measure: Quality of Life in Alzheimer's Disease based on caregiver's rating of 13 aspects of PWD's well-being (including physical health, energy level, mood, living situation, memory, relationships, and finances) on a 4-point scale (poor to excellent). Secondary outcomes: frequencies of PWDs' use of emergency department, hospitalization, and ambulance services; caregiver depression (score on 9-Item Patient Health Questionnaire; higher scores indicate more severe depression); and caregiver burden (score on 12-Item Zarit Burden Interview; higher scores indicate more severe caregiver burden). Results: The 780 PWDs (56.3% female; mean [SD] age, 78.1 [9.9] years) and 780 caregivers (70.9% female; mean [SD] age, 64.7 [12.0] years) lived in California (n = 452), Nebraska (n = 284), or Iowa (n = 44). Of 780 dyads, 655 were still active at 12 months, and 571 completed the 12-month survey. Compared with usual care, the Care Ecosystem improved PWD quality of life (B, 0.53; 95% CI, 0.25-1.30; P = .04), reduced emergency department visits (B, -0.14; 95% CI, -0.29 to -0.01; P = .04), and decreased caregiver depression (B, -1.14; 95% CI, -2.15 to -0.13; P = .03) and caregiver burden (B, -1.90; 95% CI, -3.89 to -0.08; P = .046). Conclusions and Relevance: Effective care management for dementia can be delivered from centralized hubs to supplement usual care and mitigate the growing societal and economic burdens of dementia. Trial Registration: ClinicalTrials.gov identifier: NCT02213458.

Variations in Costs of a Collaborative Care Model for Dementia.

OBJECTIVES: Care coordination programs can improve patient outcomes and decrease healthcare expenditures; however, implementation costs are poorly understood. We evaluate the direct costs of implementing a collaborative dementia care program. DESIGN: We applied a micro-costing analysis to calculate operational costs per-participant-month between March 2015 and May 2017. SETTING: The University of California, San Francisco (UCSF) and the University of Nebraska Medical Center (UNMC). PARTICIPANTS: Participants diagnosed with dementia, enrolled in Medicare or Medicaid, 45 years of age or older, residents of California, Nebraska or Iowa, and having a caregiver. The sample was 272 (UCSF) and 192 (UNMC) participants. INTERVENTION: A collaborative dementia care program provided by care team navigators (CTNs), advanced practice nurses, a social worker, and a pharmacist, focusing on caregiver support and education, medications, advance care planning, and behavior symptom management. MEASUREMENTS: We measured costs (personnel, supplies, equipment, and training costs) during three program periods, Start-up, Early Operations, and Continuing Operations, and estimated the effects of caseload variation on costs. RESULTS: Start-up and Early Operations costs were, respectively, $581 and $328 (California), and $501 and $219 (Nebraska) per-participant-month. Average costs decreased across phases to $241 (California) and $142 (Nebraska) per-participant-month during Continuing Operations. We estimated that costs would range between $75 (UNMC) and $92 (UCSF) per-participant-month with the highest projected caseloads (90). CONCLUSION: We found that CTN caseload is an important driver of service cost. We provide strategies for maximizing caseload without sacrificing quality of care. We also discuss current barriers to broad implementation that can inform new reimbursement policies. J Am Geriatr Soc 67:2628-2633, 2019.

The Role of Care Navigators Working with People with Dementia and Their Caregivers.

BACKGROUND: Care navigation is an approach to personalized care management and care coordination that can help overcome barriers to care. Care navigation has not been extensively studied in dementia, where health care workforce innovations are needed as a result of increasing disease prevalence and resulting costs to the health care system. OBJECTIVE: To identify facilitators and barriers to care navigation in dementia and to assess dementia caregiver satisfaction with care navigation. METHODS: Methods include qualitative research (interviews, focus groups, observations) with "Care Team Navigators" (CTNs) who were part of a dementia care navigation program, the Care Ecosystem, and a quantitative survey with caregivers about their experiences with CTNs. Transcripts were analyzed to identify themes within the data. RESULTS: CTNs identified the following facilitators to care navigation in dementia: working closely with caregivers; providing emotional support; tailoring education and resources; and coordinating with a clinical team around issues ranging from clinical questions to financial and legal decision-making. The barriers CTNS identified included burn-out, the progressive nature of the disease; coordinating with primary care providers; and identifying resources for dyads who are low-income, do not speak English, or live in rural areas. Caregivers across both sites highly rated CTNs, though satisfaction was higher among those in Nebraska and Iowa. CONCLUSIONS: Innovative approaches to care delivery in dementia are crucial. Care navigation offers a feasible model to train unlicensed people to deliver care as a way to deliver larger-scale support for the growing population of adults living with dementia and their caregivers.

Association Between Caregiver Depression and Emergency Department Use Among Patients With Dementia.

IMPORTANCE: Current attempts to gauge the acute care needs of patients with dementia have not effectively addressed the role of caregivers, despite their extensive involvement in decisions about acute care management. OBJECTIVE: To determine whether caregiver depression is associated with increased use of the emergency department (ED) among patients with dementia. DESIGN, SETTING, AND PARTICIPANTS: This longitudinal cohort study used data from the Care Ecosystem study, a randomized clinical trial examining telephone-based supportive care for patients with dementia and their caregivers. Patients were 45 years or older with any type of dementia. A total of 780 caregiver-patient dyads were enrolled from March 20, 2015, until February 28, 2017, and 663 dyads contributed baseline and 6-month data and were included in the analysis. EXPOSURES: Caregiver depression (9-item Patient Health Questionnaire score of ≥10). Secondary analyses examined caregiver burden and self-efficacy. MAIN OUTCOMES AND MEASURES: The primary outcome was the number of ED visits in a 6-month period. RESULTS: Among the 663 caregivers (467 women and 196 men; mean [SD] age, 64.9 [11.8] years), 84 caregivers (12.7%) had depression at baseline. The mean incidence rate of ED visits was 0.9 per person-year. Rates of ED presentation were higher among dyads whose caregiver did vs did not have depression (1.5 vs 0.8 ED visits per person-year). In a Poisson regression model adjusting for patient age, sex, severity of dementia, number of comorbidities, and baseline ED use, as well as caregiver age and sex, caregiver depression continued to be associated with ED use, with a 73% increase in rates of ED use among dyads with caregivers with depression (adjusted incident rate ratio, 1.73; 95% CI, 1.30-2.30). Caregiver burden was associated with higher ED use in the unadjusted model, but this association did not reach statistical significance after adjustment (incident rate ratio, 1.19; 95% CI, 0.93-1.52). Caregiver self-efficacy was inversely proportional to the number of ED visits in the unadjusted and adjusted models (adjusted incident rate ratio, 0.96; 95% CI, 0.92-0.99). CONCLUSIONS AND RELEVANCE: Among patients with dementia, caregiver depression appears to be significantly associated with increased ED use, revealing a key caregiver vulnerability, which, if addressed with patient- and caregiver-centered dementia care, could improve health outcomes and lower costs for this high-risk population.

The costs of dementia subtypes to California Medicare fee-for-service, 2015.

INTRODUCTION: Dementia is among the costliest of medical conditions, but it is not known how these costs vary by dementia subtype. METHODS: The effect of dementia diagnosis subtype on direct health care costs and utilization was estimated using 2015 California Medicare fee-for-service data. Potential drivers of increased costs in Lewy body dementia (LBD), in comparison to Alzheimer's disease, were tested. RESULTS: 3,001,987 Medicare beneficiaries were identified, of which 8.2% had a dementia diagnosis. Unspecified dementia was the most common diagnostic category (59.6%), followed by Alzheimer's disease (23.2%). LBD was the costliest subtype to Medicare, on average, followed by vascular dementia. The higher costs in LBD were explained in part by falls, urinary incontinence or infection, depression, anxiety, dehydration, and delirium. DISCUSSION: Dementia subtype is an important predictor of health care costs. Earlier identification and targeted treatment might mitigate the costs associated with co-occurring conditions in LBD.

Mice lacking galectin-3 (Lgals3) function have decreased home cage movement.

BACKGROUND: Galectins are a large family of proteins evolved to recognize specific carbohydrate moieties. Given the importance of pattern recognition processes for multiple biological tasks, including CNS development and immune recognition, we examined the home cage behavioral phenotype of mice lacking galectin-3 (Lgals3) function. Using a sophisticated monitoring apparatus capable of examining feeding, drinking, and movement at millisecond temporal and 0.5 cm spatial resolutions, we observed daily behavioral patterns from 10 wildtype male C57BL/6J and 10 Lgals3 constitutive knockout (Lgals3-/-; both cohorts aged 2-3 months) mice over 17 consecutive days. We performed a second behavioral assessment of this cohort at age 6-7 months. RESULTS: At both ages, Lgals3-/- mice demonstrated less movement compared to wildtype controls. Both forward locomotion and movement-in-place behaviors were decreased in Lgals3-/- mice, due to decreased bout numbers, initiation rates, and durations. We additionally noted perturbation of behavioral circadian rhythms in Lgals3-/- mice, with mice at both ages demonstrating greater variability in day-to-day performance of feeding, drinking, and movement (as assessed by Lomb-Scargle analysis) compared to wildtype. CONCLUSION: Carbohydrate recognition tasks performed by Lgals3 may be required for appropriate development of CNS structures involved in the generation and control of locomotor behavior.

Extended, continuous measures of functional status in community dwelling persons with Alzheimer's and related dementia: Infrastructure, performance, tradeoffs, preliminary data, and promise.

BACKGROUND: The past decades have seen phenomenal growth in the availability of inexpensive and powerful personal computing devices. Efforts to leverage these devices to improve health care outcomes promise to remake many aspects of healthcare delivery, but remain in their infancy. NEW METHOD: We describe the development of a mobile health platform designed for daily measures of functional status in ambulatory, community dwelling subjects, including those who have Alzheimer's disease or related neurodegenerative disorders. Using Smartwatches and Smartphones we measure subject overall activity and outdoor location (to derive their lifespace). These clinically-relevant measures allow us to track a subject's functional status in their natural environment over prolonged periods of time without repeated visits to healthcare providers. Functional status metrics are integrated with medical information and caregiver reports, which are used by a caregiving team to guide referrals for physician/APRN/NP care. COMPARISON: with Existing Methods We describe the design tradeoffs involved in all aspects of our current system architecture, focusing on decisions with significant impact on system cost, performance, scalability, and user-adherence. RESULTS: We provide real-world data from current subject enrollees demonstrating system accuracy and reliability. CONCLUSIONS: We document real-world feasibility in a group of men and women with dementia that Smartwatches/Smartphones can provide long-term, relevant clinical data regarding individual functional status. We describe the underlying considerations of this system so that interested organizations can adapt and scale our approach to their needs. Finally, we provide a potential agenda to guide development of future systems.

Mobile Phone-Based Measures of Activity, Step Count, and Gait Speed: Results From a Study of Older Ambulatory Adults in a Naturalistic Setting.

BACKGROUND: Cellular mobile telephone technology shows much promise for delivering and evaluating healthcare interventions in cost-effective manners with minimal barriers to access. There is little data demonstrating that these devices can accurately measure clinically important aspects of individual functional status in naturalistic environments outside of the laboratory. OBJECTIVE: The objective of this study was to demonstrate that data derived from ubiquitous mobile phone technology, using algorithms developed and previously validated by our lab in a controlled setting, can be employed to continuously and noninvasively measure aspects of participant (subject) health status including step counts, gait speed, and activity level, in a naturalistic community setting. A second objective was to compare our mobile phone-based data against current standard survey-based gait instruments and clinical physical performance measures in order to determine whether they measured similar or independent constructs. METHODS: A total of 43 ambulatory, independently dwelling older adults were recruited from Nebraska Medicine, including 25 (58%, 25/43) healthy control individuals from our Engage Wellness Center and 18 (42%, 18/43) functionally impaired, cognitively intact individuals (who met at least 3 of 5 criteria for frailty) from our ambulatory Geriatrics Clinic. The following previously-validated surveys were obtained on study day 1: (1) Late Life Function and Disability Instrument (LLFDI); (2) Survey of Activities and Fear of Falling in the Elderly (SAFFE); (3) Patient Reported Outcomes Measurement Information System (PROMIS), short form version 1.0 Physical Function 10a (PROMIS-PF); and (4) PROMIS Global Health, short form version 1.1 (PROMIS-GH). In addition, clinical physical performance measurements of frailty (10 foot Get up and Go, 4 Meter walk, and Figure-of-8 Walk [F8W]) were also obtained. These metrics were compared to our mobile phone-based metrics collected from the participants in the community over a 24-hour period occurring within 1 week of the initial assessment. RESULTS: We identified statistically significant differences between functionally intact and frail participants in mobile phone-derived measures of percent activity (P=.002, t test), active versus inactive status (P=.02, t test), average step counts (P<.001, repeated measures analysis of variance [ANOVA]) and gait speed (P<.001, t test). In functionally intact individuals, the above mobile phone metrics assessed aspects of functional status independent (Bland-Altman and correlation analysis) of both survey- and/or performance battery-based functional measures. In contrast, in frail individuals, the above mobile phone metrics correlated with submeasures of both SAFFE and PROMIS-GH. CONCLUSIONS: Continuous mobile phone-based measures of participant community activity and mobility strongly differentiate between persons with intact functional status and persons with a frailty phenotype. These measures assess dimensions of functional status independent of those measured using current validated questionnaires and physical performance assessments to identify functional compromise. Mobile phone-based gait measures may provide a more readily accessible and less-time consuming measure of gait, while further providing clinicians with longitudinal gait measures that are currently difficult to obtain.

Increased whole cerebellar serotonin in aged C57BL/6 mice.

Mobility and locomotor impairments have high prevalence, morbidity, and significant mortality in older adult populations. Cerebellar functional changes have been implicated in the pathogenesis of these age-related mobility and gait deficits unrelated to stroke, Parkinson's disease, or degenerative joint disease. We thus examined total cerebellar glutamate, glutamine, GABA, glycine, dopamine, norepinephrine, tryptophan, serotonin, alanine, threonine, and asparagine content from male 2-3-month (young, n = 6) and 21-24-month-old (aged, n = 6) C57BL/6 mice. Neurotransmitter and amino acid concentrations were determined by high-performance liquid chromatography followed with mass spectroscopy. We found a significant increase in cerebellar serotonin in aged versus young mice, but otherwise no significant phenotypic differences in measured neurotransmitter concentrations. Applying current thought about cerebellar aging and cerebellar serotonergic systems, we consider how this age-related increase in cerebellar serotonin may contribute to gait ataxia.