Racial and ethnic differences in disease course Medicare expenditures for beneficiaries with dementia.

BACKGROUND: Research on racial and ethnic disparities in costs of care during the course of dementia is sparse. We analyzed Medicare expenditures for beneficiaries with dementia to identify when during the course of care costs are the highest and whether they differ by race and ethnicity. METHODS: We analyzed data from the 2000-2016 Health and Retirement Study (HRS) linked with corresponding Medicare claims to estimate total Medicare expenditures for four phases: (1) the year before a dementia diagnosis, (2) the first year following a dementia diagnosis, (3) ongoing care for dementia after the first year, and (4) the last year of life. We estimated each patient's phase-specific and disease course Medicare expenditures by using a race-specific survival model and monthly expenditures adjusted for patient characteristics. We investigated healthcare utilization by service type across races/ethnicities and phases of care. RESULTS: Adjusted mean total Medicare expenditures for non-Hispanic (NH) Black ($165,730) and Hispanic beneficiaries with dementia ($160,442) exceeded corresponding expenditures for NH Whites ($136,326). In the year preceding and immediately following initial dementia diagnosis, mean Medicare expenditures for NH Blacks ($26,337 and $20,429) exceeded expenditures for Hispanics and NH Whites ($21,399-23,176 and 17,182-18,244). The last year of life was responsible for the greatest cost contribution: $51,294 (NH Blacks), $47,469 (Hispanics), and $39,499 (NH Whites). These differences were driven by greater use of high-cost services (e.g., emergency department, inpatient and intensive care), especially during the last year of life. CONCLUSIONS: NH Black and Hispanic beneficiaries with dementia had higher disease course Medicare expenditures than NH Whites. Expenditures were highest for NH Black beneficiaries in every phase of care. Further research should address mechanisms of such disparities and identify methods to improve communication, shared decision-making, and access to appropriate services for all populations.

Life-Sustaining Treatments Among Medicare Beneficiaries with and without Dementia at the End of Life.

BACKGROUND: Older adults with dementia including Alzheimer's disease may have difficulty communicating their treatment preferences and thus may receive intensive end-of-life (EOL) care that confers limited benefits. OBJECTIVE: This study compared the use of life-sustaining interventions during the last 90 days of life among Medicare beneficiaries with and without dementia. METHODS: This cohort study utilized population-based national survey data from the 2000-2016 Health and Retirement Study linked with Medicare and Medicaid claims. Our sample included Medicare fee-for-service beneficiaries aged 65 years or older deceased between 2000 and 2016. The main outcome was receipt of any life-sustaining interventions during the last 90 days of life, including mechanical ventilation, tracheostomy, tube feeding, and cardiopulmonary resuscitation. We used logistic regression, stratified by nursing home use, to examine dementia status (no dementia, non-advanced dementia, advanced dementia) and patient characteristics associated with receiving those interventions. RESULTS: Community dwellers with dementia were more likely than those without dementia to receive life-sustaining treatments in their last 90 days of life (advanced dementia: OR = 1.83 [1.42-2.35]; non-advanced dementia: OR = 1.16 [1.01-1.32]). Advance care planning was associated with lower odds of receiving life-sustaining treatments in the community (OR = 0.84 [0.74-0.96]) and in nursing homes (OR = 0.68 [0.53-0.86]). More beneficiaries with advanced dementia received interventions discordant with their EOL treatment preferences. CONCLUSIONS: Community dwellers with advanced dementia were more likely to receive life-sustaining treatments at the end of life and such treatments may be discordant with their EOL wishes. Enhancing advance care planning and patient-physician communication may improve EOL care quality for persons with dementia.

Disease progression and costs at the 3-year follow-up of the GERAS-US study.

Introduction: GERAS-US prospectively characterized clinical and economic outcomes of early symptomatic Alzheimer's disease (AD). Societal cost changes were examined in amyloid-positive patients with mild cognitive impairment due to AD (MCI) and mild dementia due to AD (MILD). Methods: Cognition, function, and caregiver burden were assessed using Mini-Mental State Examination (MMSE), Cognitive Function Index (CFI), and Zarit Burden Interview, respectively. Costs are presented as least square mean for the overall population and for MCI versus MILD using mixed model repeated measures. Results: MMSE score and CFI worsened. Total societal costs (dollars/month) for MCI and MILD, respectively, were higher at baseline ($2430 and $4063) but steady from 6 ($1977 and $3032) to 36 months ($2007 and $3392). Direct non-medical costs rose significantly for MILD. Caregiver burden was higher for MILD versus MCI at 12, 18, and 24 months. Discussion: Function and cognition declined in MILD. Non-medical costs reflect the increasing impact of AD even in its early stages. HIGHLIGHTS: In the GERAS-US study, total societal costs for patients with mild cognitive impairment due to Alzheimer's disease (MCI) and mild dementia due to Alzheimer's disease (MILD) were higher at baseline but steady from 6 to 36 months.Mini-Mental State Examination (MMSE) and Cognitive Function Index (CFI) worsened; the rate of decline was significant for patients with MILD but not for those with MCI.There was a rise in direct non-medical costs at 36 months for patients with MILD.Caregiver burden was higher for MILD versus MCI at 12, 18, and 24 months.Slowing the rate of disease progression in this early symptomatic population may allow patients to maintain their ability to carry out everyday activities longer.

Toward comprehensive value assessment for Alzheimer's disease innovations.

INTRODUCTION: Assessing medical technologies for Alzheimer's disease (AD) creates challenges for current methods of value assessment. New value assessment approaches for AD are also needed. METHODS: We adapted concepts from health economics to help guide decision makers to more informed decisions about AD therapies and diagnostics. RESULTS: We propose a value framework based on five categories: perspective, value elements, analysis, reporting, and decision making. AD value assessments should include the perspective of the patient-caregiver dyad. We propose a broader array of value elements than currently used. Analytics and decision methods can synthesize evidence for all elements of value. Decisions should use a "deliberative appraisal" approach informed by the composite evidence and be transparently reported. DISCUSSION: Using the proposed framework, the value of forthcoming innovations for AD may be more thoroughly assessed for and by all stakeholders. It can guide decision makers to carefully consider all relevant elements of value contributing to more holistic and transparent decision making. RESEARCH HIGHLIGHTS: Alzheimer's disease challenges common methods of evaluating medical technology. Using current methods, new AD innovations might not be appropriately valued. Poor value assessments will adversely affect patient access to AD innovations. A full AD value framework expands perspective, elements, analysis, decision-making, reporting.

Recommendations to address key recruitment challenges of Alzheimer's disease clinical trials.

Clinical trials for Alzheimer's disease (AD) are slower to enroll study participants, take longer to complete, and are more expensive than trials in most other therapeutic areas. The recruitment and retention of a large number of qualified, diverse volunteers to participate in clinical research studies remain among the key barriers to the successful completion of AD clinical trials. An advisory panel of experts from academia, patient-advocacy organizations, philanthropy, non-profit, government, and industry convened in 2020 to assess the critical challenges facing recruitment in Alzheimer's clinical trials and develop a set of recommendations to overcome them. This paper briefly reviews existing challenges in AD clinical research and discusses the feasibility and implications of the panel's recommendations for actionable and inclusive solutions to accelerate the development of novel therapies for AD.

Alzheimer's disease medication use and adherence patterns by race and ethnicity.

BACKGROUND: We examined racial and ethnic differences in medication use for a representative US population of patients with Alzheimer's disease and related dementias (ADRD). METHODS: We examined cholinesterase inhibitors and memantine initiation, non-adherence, and discontinuation by race and ethnicity, using data from the 2000-2016 Health and Retirement Study linked with Medicare and Medicaid claims. RESULTS: Among newly diagnosed ADRD patients (n = 1299), 26% filled an ADRD prescription ≤90 days and 36% ≤365 days after diagnosis. Among individuals initiating ADRD-targeted treatment (n = 1343), 44% were non-adherent and 24% discontinued the medication during the year after treatment initiation. Non-Hispanic Blacks were more likely than Whites to not adhere to ADRD medication therapy (odds ratio: 1.50 [95% confidence interval: 1.07-2.09]). DISCUSSION: Initiation of ADRD-targeted medications did not vary by ethnoracial group, but non-Hispanic Blacks had lower adherence than Whites. ADRD medication non-adherence and discontinuation were substantial and may relate to cost and access to care. HIGHLIGHTS: Initiation of anti-dementia medications among newly diagnosed Alzheimer's disease and related dementias (ADRD) patients was low in all ethnoracial groups. ADRD medication non-adherence and discontinuation were substantial and may relate to cost and access to care. Compared to Whites, Blacks and Hispanics had lower use, poorer treatment adherence, and more frequent discontinuation of ADRD medication, but when controlling for disease severity and socioeconomic factors, racial disparities diminish. Our findings demonstrate the importance of adjusting for socioeconomic characteristics and disease severity when studying medication use and adherence in ADRD patients.

Racial and Ethnic Differences in Hospice Use and Hospitalizations at End-of-Life Among Medicare Beneficiaries With Dementia.

Importance: The pool of studies examining ethnic and racial differences in hospice use and end-of-life hospitalizations among patients with dementia is limited and results are conflicting, making it difficult to assess health care needs of underresourced racial and ethnic groups. Objective: To explore differences in end-of-life utilization of hospice and hospital services among patients with dementia by race and ethnicity. Design, Setting, and Participants: This cohort study used national survey data from the Health and Retirement Study linked with Medicare and Medicaid claims that reflected a range of socioeconomic, health, and psychosocial characteristics. Eligible participants were Medicare fee-for-service beneficiaries aged 65 years or older diagnosed with dementia who died between 2000 and 2016. Analyses were performed from June to December 2021. Exposures: Race and ethnicity. Main Outcomes and Measures: We examined the frequency and costs of hospice care, emergency department (ED) visits, and hospitalizations during the last 180 days of life among Medicare decedents with dementia. We analyzed the proportion of dementia decedents with advance care planning and their end-of-life care preferences. Results: The cohort sample included 5058 beneficiaries with dementia (mean [SD] age, 85.5 [8.0] years; 3038 women [60.1%]; 809 [16.0%] non-Hispanic Black, 357 [7.1%] Hispanic, and 3892 non-Hispanic White respondents [76.9%]). In adjusted analysis, non-Hispanic Black decedents (odds ratio [OR], 0.65; 95% CI, 0.55-0.78), nursing home residents (OR, 0.81; 95% CI, 0.71-0.93), and survey respondents represented by a proxy (OR, 0.84; 95% CI, 0.71-0.99) were less likely to use hospice, whereas older decedents (age 75-84 vs 65-74 years: OR, 1.39; 95% CI, 1.12-1.72; age ≥85 vs 65-74 years: OR, 1.39; 95% CI, 1.13-1.71), women (OR, 1.19; 95% CI, 1.05-1.35), and decedents with higher education (high school vs less than high school: OR, 1.17; 95% CI, 1.01-1.36; more than high school vs less than high school: OR, 1.32; 95% CI, 1.13-1.54), more severe cognitive impairment (OR, 1.51; 95% CI, 1.02-2.23), and more instrumental activities of daily living limitations (OR, 1.07; 95% CI, 1.01-1.12) were associated with higher hospice enrollment. A higher proportion of Black and Hispanic decedents with dementia used ED (645 of 809 [79.7%] and 274 of 357 [76.8%] vs 2753 of 3892 [70.7%]; P < .001) and inpatient services (625 of 809 [77.3%] and 275 of 357 [77.0%] vs 2630 of 3892 [67.5%]; P < .001) and incurred roughly 60% higher inpatient expenditures at the end of life compared with White decedents (estimated mean: Black, $23 279; 95% CI, $20 690-$25 868; Hispanic, $23 471; 95% CI, $19 532-$27 410 vs White, $14 609; 95% CI, $13 800-$15 418). A higher proportion of Black and Hispanic than White beneficiaries with dementia who were enrolled in hospice were subsequently admitted to the ED (56 of 309 [18.1%] and 22 of 153 [14.4%] vs 191 of 1967 [9.7%]; P < .001) or hospital (48 of 309 [15.5%] and 17 of 153 [11.1%] vs 119 of 1967 [6.0%]; P < .001) before death. The proportion of dementia beneficiaries completing advance care planning was lower among Black (146 of 704 [20.7%]) and Hispanic (66 of 308 [21.4%]) beneficiaries compared with White beneficiaries (1871 of 3274 [57.1%]). A higher proportion of Black and Hispanic decedents with dementia had written instructions choosing all care possible to prolong life (30 of 144 [20.8%] and 12 of 65 [18.4%] vs 72 of 1852 [3.9%]), whereas a higher proportion of White decedents preferred to limit care in certain situations (1708 of 1840 [92.8%] vs 114 of 141 [80.9%] and 51 of 64 [79.7%]), withhold treatments (1448 of 1799 [80.5%] vs 87 of 140 [62.1%] and 41 of 62 [66.1%]), and forgo extensive life-prolonging measures (1712 of 1838 [93.1%] vs 120 of 138 [87.0%] and 54 of 65 [83.1%]). Conclusions and Relevance: The results of this cohort study highlight unique end-of-life care utilization and treatment preferences across racial and ethnic groups among patients with dementia. Medicare should consider alternative payment models to promote culturally competent end-of-life care and reduce low-value interventions and costs among the population with dementia.

Investing in Late-Life Brain Capital.

Within many societies and cultures around the world, older adults are too often undervalued and underappreciated. This exacerbates many key challenges that older adults may face. It also undermines the many positive aspects of late life that are of tremendous value at both an individual and societal level. We propose a new approach to elevate health and well-being in late life by optimizing late-life Brain Capital. This form of capital prioritizes brain skills and brain health in a brain economy, which the challenges and opportunities of the 21st-century demands. This approach incorporates investing in late-life Brain Capital, developing initiatives focused on building late-life Brain Capital.

Commentary: Global Alzheimer's disease and Alzheimer's disease related dementia research funding organizations support and engage the research community throughout the COVID-19 pandemic.

The COVID-19 pandemic has disproportionately affected more vulnerable populations, including those living with dementia. Over 50 million individuals worldwide are living with Alzheimer's disease (AD) or other dementia, and it is crucial to continue the fight against the condition during the global pandemic. Since the start of mandated lockdowns in March 2020, charity and non-profit organizations that fund AD and related dementia research continue to respond to the needs of the AD research community, ensuring the momentum continues and accelerates. Members of the International Alzheimer's and Related Dementia Research Funder Consortium, a group of nearly 40 funding organizations that informally convene throughout the year to share updates and information, have taken a number of steps to ensure the continued support of the research community. Even during times of uncertainty, it is essential that the field moves forward to uncover preventions, diagnoses, and treatments for these diseases that affect many millions globally.

Predicted Lifetime Health Outcomes for Aducanumab in Patients with Early Alzheimer's Disease.

INTRODUCTION: Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease that places a substantial burden on patients and caregivers. Aducanumab is the first AD therapy approved by the US Food and Drug Administration to reduce a defining pathophysiological feature of the disease, brain amyloid plaques. In the phase 3 clinical trial EMERGE (NCT02484547), aducanumab reduced clinical decline in patients with mild cognitive impairment (MCI) due to AD and mild AD dementia and confirmed amyloid pathology. METHODS: We used a Markov modeling approach to predict the long-term clinical benefits of aducanumab for patients with early AD based on EMERGE efficacy data. In the model, patients could transition between AD severity levels (MCI due to AD; mild, moderate, and severe AD dementia) and care settings (community vs. institution) or transition to death. The intervention was aducanumab added to standard of care (SOC), and the comparator was SOC alone. Data sources for base-case and scenario analyses included EMERGE, published National Alzheimer's Coordinating Center analyses, and other published literature. RESULTS: Per patient over a lifetime horizon, aducanumab treatment corresponded to 0.65 incremental patient quality-adjusted life-years (QALYs) and 0.09 fewer caregiver QALYs lost compared with patients treated with SOC. Aducanumab treatment translated to a lower lifetime probability of transitioning to AD dementia, a lower lifetime probability of transitioning to institutionalization (25.2% vs. 29.4%), delays in the median time to transition to AD dementia (7.50 vs. 4.92 years from MCI to moderate AD dementia or worse), and an incremental median time in the community of 1.32 years compared with SOC. CONCLUSION: The model predicted long-term benefits of aducanumab treatment in patients with MCI due to AD and mild AD dementia and their caregivers. The predicted outcomes provide a foundation for healthcare decision-makers and policymakers to understand the potential clinical and socioeconomic value of aducanumab.

Impact of agitation in long-term care residents with dementia in the United States.

OBJECTIVES: To describe characteristics and compare clinical outcomes including falls, fractures, infections, and neuropsychiatric symptoms (NPS) among long-term care residents with dementia with and without agitation. METHODS: A cross-sectional secondary analysis of administrative healthcare data was conducted whereby residents with dementia residing in a long-term care facility for ≥12 months were identified from the AnalytiCare LLC database (10/2010-06/2014) and were classified into mutually exclusive cohorts (Agitation Cohort or No-Agitation Cohort) based on available agitation-related symptoms. Entropy balancing was used to balance demographic and clinical characteristics between the two cohorts. The impact of agitation on clinical outcomes was compared between balanced cohorts using weighted logistic regression models. RESULTS: The study included 6,265 long-term care residents with dementia among whom, 3,313 were included in the Agitation Cohort and 2,952 in the No-Agitation Cohort. Prior to balancing, residents in the Agitation Cohort had greater dementia-related cognitive impairment and clinical manifestations compared to the No-Agitation Cohort. After balancing, residents with and without agitation, respectively, received a median of five and four distinct types of medications (including antipsychotics). Further, compared to residents without agitation, those with agitation were significantly more likely to have a recorded fall (OR = 1.58), fracture (OR = 1.29), infection (OR = 1.18), and other NPS (OR = 2.11). CONCLUSIONS: Agitation in long-term care residents with dementia was associated with numerically higher medication use and an increased likelihood of experiencing falls, fractures, infections, and additional NPS compared to residents without agitation, highlighting the unmet need for effective management of agitation symptoms in this population.

Riluzole, a glutamate modulator, slows cerebral glucose metabolism decline in patients with Alzheimer's disease.

Dysregulation of glutamatergic neural circuits has been implicated in a cycle of toxicity, believed among the neurobiological underpinning of Alzheimer's disease. Previously, we reported preclinical evidence that the glutamate modulator riluzole, which is FDA approved for the treatment of amyotrophic lateral sclerosis, has potential benefits on cognition, structural and molecular markers of ageing and Alzheimer's disease. The objective of this study was to evaluate in a pilot clinical trial, using neuroimaging biomarkers, the potential efficacy and safety of riluzole in patients with Alzheimer's disease as compared to placebo. A 6-month phase 2 double-blind, randomized, placebo-controlled study was conducted at two sites. Participants consisted of males and females, 50 to 95 years of age, with a clinical diagnosis of probable Alzheimer's disease, and Mini-Mental State Examination between 19 and 27. Ninety-four participants were screened, 50 participants who met inclusion criteria were randomly assigned to receive 50 mg riluzole (n = 26) or placebo (n = 24) twice a day. Twenty-two riluzole-treated and 20 placebo participants completed the study. Primary end points were baseline to 6 months changes in (i) cerebral glucose metabolism as measured with fluorodeoxyglucose-PET in prespecified regions of interest (hippocampus, posterior cingulate, precuneus, lateral temporal, inferior parietal, frontal); and (ii) changes in posterior cingulate levels of the neuronal viability marker N-acetylaspartate as measured with in vivo proton magnetic resonance spectroscopy. Secondary outcome measures were neuropsychological testing for correlation with neuroimaging biomarkers and in vivo measures of glutamate in posterior cingulate measured with magnetic resonance spectroscopy as a potential marker of target engagement. Measures of cerebral glucose metabolism, a well-established Alzheimer's disease biomarker and predictor of disease progression, declined significantly less in several prespecified regions of interest with the most robust effect in posterior cingulate, and effects in precuneus, lateral temporal, right hippocampus and frontal cortex in riluzole-treated participants in comparison to the placebo group. No group effect was found in measures of N-acetylaspartate levels. A positive correlation was observed between cognitive measures and regional cerebral glucose metabolism. A group × visit interaction was observed in glutamate levels in posterior cingulate, potentially suggesting engagement of glutamatergic system by riluzole. In vivo glutamate levels positively correlated with cognitive performance. These findings support our main primary hypothesis that cerebral glucose metabolism would be better preserved in the riluzole-treated group than in the placebo group and provide a rationale for more powered, longer duration studies of riluzole as a potential intervention for Alzheimer's disease.

Dementia Diagnosis Disparities by Race and Ethnicity.

BACKGROUND: Dementia is often underdiagnosed and this problem is more common among some ethnoracial groups. OBJECTIVE: The objective of this study was to examine racial and ethnic disparities in the timeliness of receiving a clinical diagnosis of dementia. RESEARCH DESIGN: This was a prospective cohort study. SUBJECTS: A total of 3966 participants age 70 years and above with probable dementia in the Health and Retirement Study, linked with their Medicare and Medicaid claims. MEASURES: We performed logistic regression to compare the likelihood of having a missed or delayed dementia diagnosis in claims by race/ethnicity. We analyzed dementia severity, measured by cognition and daily function, at the time of a dementia diagnosis documented in claims, and estimated average dementia diagnosis delay, by race/ethnicity. RESULTS: A higher proportion of non-Hispanic Blacks and Hispanics had a missed/delayed clinical dementia diagnosis compared with non-Hispanic Whites (46% and 54% vs. 41%, P<0.001). Fully adjusted logistic regression results suggested more frequent missed/delayed dementia diagnoses among non-Hispanic Blacks (odds ratio=1.12; 95% confidence interval: 0.91-1.38) and Hispanics (odds ratio=1.58; 95% confidence interval: 1.20-2.07). Non-Hispanic Blacks and Hispanics had a poorer cognitive function and more functional limitations than non-Hispanic Whites around the time of receiving a claims-based dementia diagnosis. The estimated mean diagnosis delay was 34.6 months for non-Hispanic Blacks and 43.8 months for Hispanics, compared with 31.2 months for non-Hispanic Whites. CONCLUSIONS: Non-Hispanic Blacks and Hispanics may experience a missed or delayed diagnosis of dementia more often and have longer diagnosis delays. When diagnosed, non-Hispanic Blacks and Hispanics may have more advanced dementia. Public health efforts should prioritize racial and ethnic underrepresented communities when promoting early diagnosis of dementia.

Value-Generating Exploratory Trials in Neurodegenerative Dementias.

Drug development for Alzheimer disease and other neurodegenerative dementias, including frontotemporal dementia, has experienced a long history of phase 2 and phase 3 clinical trials that failed to show efficacy of investigational drugs. Despite differences in clinical and behavioral characteristics, these disorders have shared pathologies and face common challenges in designing early-phase trials that are predictive of late-stage success. Here, we discuss exploratory clinical trials in neurodegenerative dementias. These are generally phase 1b or phase 2a trials that are designed to assess pharmacologic effects and rely on biomarker outcomes, with shorter treatment durations and fewer patients than traditional phase 2 studies. Exploratory trials can establish go/no-go decision points, support proof of concept and dose selection, and terminate drugs that fail to show target engagement with suitable exposure and acceptable safety profiles. Early failure saves valuable resources including opportunity costs. This is especially important for programs in academia and small biotechnology companies but may be applied to high-risk projects in large pharmaceutical companies to achieve proof of concept more rapidly at lower costs than traditional approaches. Exploratory studies in a staged clinical development program may provide promising data to warrant the substantial resources needed to advance compounds through late-stage development. To optimize the design and application of exploratory trials, the Alzheimer's Drug Discovery Foundation and the Association for Frontotemporal Degeneration convened an advisory panel to provide recommendations on outcome measures and statistical considerations for these types of studies and study designs that can improve efficiency in clinical development.

Rasagiline effects on glucose metabolism, cognition, and tau in Alzheimer's dementia.

BACKGROUND: A Phase II proof of concept (POC) randomized clinical trial was conducted to evaluate the effects of rasagiline, a monoamine oxidase B (MAO-B) inhibitor approved for Parkinson disease, in mild to moderate Alzheimer's disease (AD). The primary objective was to determine if 1 mg of rasagiline daily for 24 weeks is associated with improved regional brain metabolism (fluorodeoxyglucose-positron emission tomography [FDG-PET]) compared to placebo. Secondary objectives included measurement of effects on tau PET and evaluation of directional consistency of clinical end points. METHODS: This was a double-blind, parallel group, placebo-controlled, community-based, three-site trial of 50 participants randomized 1:1 to receive oral rasagiline or placebo (NCT02359552). FDG-PET was analyzed for the presence of an AD-like pattern as an inclusion criterion and as a longitudinal outcome using prespecified regions of interest and voxel-based analyses. Tau PET was evaluated at baseline and longitudinally. Clinical outcomes were analyzed using an intention-to-treat (ITT) model. RESULTS: Fifty patients were randomized and 43 completed treatment. The study met its primary end point, demonstrating favorable change in FDG-PET differences in rasagiline versus placebo in middle frontal (P < 0.025), anterior cingulate (P < 0.041), and striatal (P < 0.023) regions. Clinical measures showed benefit in quality of life (P < 0.04). Digit Span, verbal fluency, and Neuropsychiatric Inventory (NPI) showed non-significant directional favoring of rasagiline; no effects were observed in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) or activities of daily living. Rasagiline was generally well tolerated with low rates of adverse events and notably fewer neuropsychiatric symptoms in the active treatment group. DISCUSSION: These outcomes illustrate the potential benefits of rasagiline on clinical and neuroimaging measures in patients with mild to moderate AD. Rasagiline appears to affect neuronal activity in frontostriatal pathways, with associated clinical benefit potential warranting a more fully powered trial. This study illustrated the potential benefit of therapeutic repurposing and an experimental medicine proof-of-concept design with biomarkers to characterize patient and detect treatment response.

Real-World Treatment Patterns and Characteristics Among Patients with Agitation and Dementia in the United States: Findings from a Large, Observational, Retrospective Chart Review.

BACKGROUND: Few studies have examined patient characteristics and treatment patterns among patients with dementia and agitation in the United States (US). OBJECTIVE: To examine real-world treatment patterns and characteristics of patients with agitation related to dementia who were treated with antipsychotics in US residential care and community-based settings. METHODS: This retrospective chart review collected US physician-level data from patients 55 to 90 years old initiated on an antipsychotic medication for the treatment of agitation related to dementia from January 2018 to May 2018. Clinical characteristics and treatment patterns were assessed overall and stratified by residential care and community-based settings. RESULTS: A total of 313 participating physicians, 59.5% of whom were primary care physicians, abstracted 801 patient charts (residential care: n = 312; community-based: n = 489). Of patients with agitation who were initiated on an antipsychotic, most patients (74.5%) were initiated within 3 months of the onset of their studied agitation episode, and 62.8% experienced multiple agitation episodes before initiation. While non-pharmacological therapies are recommended first-line approach for agitation in dementia, use of non-pharmacological therapy before initiation of antipsychotics was reported for only 37.8% of patients in residential care and 21.3% in community-based settings. CONCLUSION: Most patients were initiated on an antipsychotic treatment after multiple episodes of agitation and largely without initial non-pharmacological therapy, suggesting that current treatment guideline recommendations for first-line non-pharmacological intervention may not be adequately followed in clinical practice. Understanding the clinical burden and treatment patterns among dementia patients with agitation is imperative for effective disease management.

Real-Time Digital Contact Tracing: Development of a System to Control COVID-19 Outbreaks in Nursing Homes and Long-Term Care Facilities.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can spread rapidly in nursing homes and long-term care (LTC) facilities. Symptoms-based screening and manual contact tracing have limitations that render them ineffective for containing the viral spread in LTC facilities. Symptoms-based screening alone cannot identify asymptomatic people who are infected, and the viral spread is too fast in confined living quarters to be contained by slow manual contact tracing processes. OBJECTIVE: We describe the development of a digital contact tracing system that LTC facilities can use to rapidly identify and contain asymptomatic and symptomatic SARS-CoV-2 infected contacts. A compartmental model was also developed to simulate disease transmission dynamics and to assess system performance versus conventional methods. METHODS: We developed a compartmental model parameterized specifically to assess the coronavirus disease (COVID-19) transmission in LTC facilities. The model was used to quantify the impact of asymptomatic transmission and to assess the performance of several intervention groups to control outbreaks: no intervention, symptom mapping, polymerase chain reaction testing, and manual and digital contact tracing. RESULTS: Our digital contact tracing system allows users to rapidly identify and then isolate close contacts, store and track infection data in a respiratory line listing tool, and identify contaminated rooms. Our simulation results indicate that the speed and efficiency of digital contact tracing contributed to superior control performance, yielding up to 52% fewer cases than conventional methods. CONCLUSIONS: Digital contact tracing systems show promise as an effective tool to control COVID-19 outbreaks in LTC facilities. As facilities prepare to relax restrictions and reopen to outside visitors, such tools will allow them to do so in a surgical, cost-effective manner that controls outbreaks while safely giving residents back the life they once had before this pandemic hit.

Artificial Intelligence-Powered Digital Health Platform and Wearable Devices Improve Outcomes for Older Adults in Assisted Living Communities: Pilot Intervention Study.

BACKGROUND: Wearables and artificial intelligence (AI)-powered digital health platforms that utilize machine learning algorithms can autonomously measure a senior's change in activity and behavior and may be useful tools for proactive interventions that target modifiable risk factors. OBJECTIVE: The goal of this study was to analyze how a wearable device and AI-powered digital health platform could provide improved health outcomes for older adults in assisted living communities. METHODS: Data from 490 residents from six assisted living communities were analyzed retrospectively over 24 months. The intervention group (+CP) consisted of 3 communities that utilized CarePredict (n=256), and the control group (-CP) consisted of 3 communities (n=234) that did not utilize CarePredict. The following outcomes were measured and compared to baseline: hospitalization rate, fall rate, length of stay (LOS), and staff response time. RESULTS: The residents of the +CP and -CP communities exhibit no statistical difference in age (P=.64), sex (P=.63), and staff service hours per resident (P=.94). The data show that the +CP communities exhibited a 39% lower hospitalization rate (P=.02), a 69% lower fall rate (P=.01), and a 67% greater length of stay (P=.03) than the -CP communities. The staff alert acknowledgment and reach resident times also improved in the +CP communities by 37% (P=.02) and 40% (P=.02), respectively. CONCLUSIONS: The AI-powered digital health platform provides the community staff with actionable information regarding each resident's activities and behavior, which can be used to identify older adults that are at an increased risk for a health decline. Staff can use this data to intervene much earlier, protecting seniors from conditions that left untreated could result in hospitalization. In summary, the use of wearables and AI-powered digital health platform can contribute to improved health outcomes for seniors in assisted living communities. The accuracy of the system will be further validated in a larger trial.