Proteogenomic signature of risk of Alzheimer's disease and related dementia risk in individuals with a history of major depression disorder.

The mechanisms linking a history of major depressive disorder (MDD) to an increased risk of Alzheimer's disease and related dementia (ADRD) are not fully understood. Using the UK Biobank available proteomic and genomic data, we evaluated the biological mechanisms linking both conditions. In participants with a history of MDD at baseline (n=3,615), we found that plasma levels of NfL, GFAP, PSG1 were associated with higher risk (HR=1.38; 1.37; 1.34, respectively; all adjusted p-values<0.05), while VGF, GET3, and HPGDS were associated with lower risk of incident ADRD (n=150) (HR=0.73; 0.71; 0.66, respectively; all adjusted p-values<0.05) during a mean follow-up of 13.7 years (SD=2.2). Two-sample Mendelian randomization analysis using cis-pQTLs genetic instruments revealed that a lower protein expression of apolipoprotein E and higher IL-10 receptor subunit B were causally linked to incident ADRD. Finally, we developed a Proteomic Risk Score (PrRSMDD-ADRD), which showed strong discriminative power (C-statistic = 0.84) to identify participants with MDD that developed ADRD upon follow-up. In addition to demonstrating an association between plasma proteins associated with inflammation and future ADRD risk in individuals with MDD, our findings include an element of causality using Mendelian Randomization (MR) and PrRSMDD-ADRD can be useful to identify individuals with the highest risk to develop ADRD in a highly vulnerable population.

A proteomic signature of healthspan.

The focus of aging research has shifted from increasing lifespan to enhancing healthspan to reduce the time spent living with disability. Despite significant efforts to develop biomarkers of aging, few studies have focused on biomarkers of healthspan. We developed a proteomics-based signature of healthspan (healthspan proteomic score (HPS)) using data from the UK Biobank Pharma Proteomics Project (53,018 individuals and 2920 proteins). A lower HPS was associated with higher mortality risk and several age-related conditions, such as COPD, diabetes, heart failure, cancer, myocardial infarction, dementia, and stroke. HPS showed superior predictive accuracy for these outcomes compared to chronological age and biological age measures. Proteins associated with HPS were enriched in hallmark pathways such as immune response, inflammation, cellular signaling, and metabolic regulation. Our findings demonstrate the validity of HPS, making it a valuable tool for assessing healthspan and as a potential surrogate marker in geroscience-guided studies.

Pain Medication Frequency and Fall Risk Among Community-Dwelling Older Adults With Arthritis.

Pain medication is commonly used among older adults with arthritis, elevating the risk of falling. We examined fall risks related to the frequency of taking pain medication among community-dwelling older adults with arthritis by analyzing a nationally representative sample of community-dwelling Medicare beneficiaries aged >65 with self-reported arthritis (n = 4,225) in the 2015 National Health and Aging Trends Study. The survey-weighted logistic regression revealed that after controlling for confounding factors, recent falls were associated with taking pain medication daily compared to never (OR = 1.45, 95% CI: 1.06, 1.96). The other categories of medication frequency, compared to never, were not associated with fall risk. Findings suggest that more prudent use of pain medication should be stressed by health care providers for older adults with arthritis to help reduce the risk of falls and fall injuries. Nonpharmacological pain management is encouraged to support active living among older adults with arthritis.

Proteomic aging clock (PAC) predicts age-related outcomes in middle-aged and older adults.

Beyond mere prognostication, optimal biomarkers of aging provide insights into qualitative and quantitative features of biological aging and might, therefore, offer useful information for the testing and, ultimately, clinical use of gerotherapeutics. We aimed to develop a proteomic aging clock (PAC) for all-cause mortality risk as a proxy of biological age. Data were from the UK Biobank Pharma Proteomics Project, including 53,021 participants aged between 39 and 70 years and 2923 plasma proteins assessed using the Olink Explore 3072 assay®. 10.9% of the participants died during a mean follow-up of 13.3 years, with the mean age at death of 70.1 years. The Spearman correlation between PAC proteomic age and chronological age was 0.77. PAC showed robust age-adjusted associations and predictions for all-cause mortality and the onset of various diseases in general and disease-free participants. The proteins associated with PAC proteomic age deviation were enriched in several processes related to the hallmarks of biological aging. Our results expand previous findings by showing that biological age acceleration, based on PAC, strongly predicts all-cause mortality and several incident disease outcomes. Particularly, it facilitates the evaluation of risk for multiple conditions in a disease-free population, thereby, contributing to the prevention of initial diseases, which vary among individuals and may subsequently lead to additional comorbidities.

Proteomic aging clock (PAC) predicts age-related outcomes in middle-aged and older adults.

Beyond mere prognostication, optimal biomarkers of aging provide insights into qualitative and quantitative features of biological aging and might, therefore, offer useful information for the testing and, ultimately, clinical use of gerotherapeutics. We aimed to develop a proteomic aging clock (PAC) for all-cause mortality risk as a proxy of biological age. Data were from the UK Biobank Pharma Proteomics Project, including 53,021 participants aged between 39 and 70 years and 2,923 plasma proteins assessed using the Olink Explore 3072 assay®. The Spearman correlation between PAC proteomic age and chronological age was 0.77. A total of 10.9% of the participants died during a mean follow-up of 13.3 years, with the mean age at death 70.1 years. We developed a proteomic aging clock (PAC) for all-cause mortality risk as a surrogate of BA using a combination of least absolute shrinkage and selection operator (LASSO) penalized Cox regression and Gompertz proportional hazards models. PAC showed robust age-adjusted associations and predictions for all-cause mortality and the onset of various diseases in general and disease-free participants. The proteins associated with PAC were enriched in several processes related to the hallmarks of biological aging. Our results expand previous findings by showing that age acceleration, based on PAC, strongly predicts all-cause mortality and several incident disease outcomes. Particularly, it facilitates the evaluation of risk for multiple conditions in a disease-free population, thereby, contributing to the prevention of initial diseases, which vary among individuals and may subsequently lead to additional comorbidities.

Using Hybrid Effectiveness Studies to Facilitate Implementation in Community-Based Settings: Three Case Studies in Dementia Care Research.

The pipeline from discovery to testing and then implementing evidence-based innovations in real-world contexts may take 2 decades or more to achieve. Implementation science innovations, such as hybrid studies that combine effectiveness and implementation research questions, may help to bridge the chasm between intervention testing and implementation in dementia care. This paper describes hybrid effectiveness studies and presents 3 examples of dementia care interventions conducted in various community-based settings. Studies that focus on outcomes and implementation processes simultaneously may result in a truncated and more efficient implementation pipeline, thereby providing older persons, their families, health care providers, and communities with the best evidence to improve quality of life and care more rapidly. We offer post-acute and long-term care researchers considerations related to study design, sampling, data collection, and analysis that they can apply to their own dementia and other chronic disease care investigations.

Psychometric Properties of the Resilience Scale in Older Adults Post-Hip Fracture.

Objectives: The purpose of this study was to evaluate the psychometric properties of the modified 25-item Resilience Scale (RS-25) in older adults post-hip fracture using Rasch analysis. Methods: This was a descriptive study using baseline data from the Seventh Baltimore Hip Studies (BHS-7). There were 339 hip fracture patients included in this analysis. Results: Findings suggest there was support for reliability of the measure based on person and item separation index. The INFIT and OUTFIT statistics for testing validity were all in the acceptable range indicating that each item on the modified RS-25 fits the appropriate concept. There was no evidence of Differential Item Functioning (DIF) between genders. Conclusions: This study demonstrated evidence that the modified RS-25 is a reliable and valid measure to evaluate resilience among older adults post-hip fracture and therefore can be used in this population in clinical practice and research.

Exploring Factors Associated With Resilience and Physical Activity in Older Men and Women Post-Hip Fracture.

This study aimed to test a model of factors associated with resilience and physical activity post-hip fracture and compare model fit between men and women. We used data from the seventh Baltimore Hip Study that included 339 participants. Model testing indicated that health status (men: ß = .237, p = .002; women: ß = .265, p = <.001), depression (men: ß = -.245, p = .001; women: ß = -.241, p = <.001), and optimism (men: ß = .320, p = <.001; women: ß = .282, p = <.001) were associated with resilience in men and women, but resilience was only associated with physical activity in men (ß = .203, p = .038) and not in women. Social interaction was related to physical activity only among women (ß = .206, p = .044). This study provides support for the relationship between resilience and physical activity at least among men.

The Case for Conducting Pragmatic Dementia Care Trials in Medicaid Home and Community-Based Service Settings.

Medicaid-funded home and community-based services (HCBSs) reach large numbers of individuals living with dementia who would otherwise reside in nursing homes with Medicaid funding. Medicaid HCBSs also often augment care provided by family and other informal caregivers to individuals living with dementia. Although Medicaid-funded HCBSs are offered in most states in lieu of nursing home care, they have been largely overlooked as health care system partners for implementation and testing of evidence-based dementia care interventions using embedded pragmatic clinical trial (ePCT) designs. In this article, we make the case for the importance of Medicaid-funded HCBSs as dementia care ePCT partners because of the volume of vulnerable clients with dementia served and the potential positive impacts that evidence-based dementia care programs can have on clients and their informal caregivers. This article first characterizes the Medicaid HCBS setting in terms of populations served and organizational arrangements across states. We then characterize strengths and potential limitations presented by Medicaid HCBSs as settings within which to implement dementia care ePCTs, using as a conceptual framework the Pragmatic-Explanatory Continuum Indicator Summary (PRECIS-2) tool and its domains. We draw on our experiences implementing the Care of Persons with Dementia in their Environments (COPE) program in a statewide Medicaid HCBS setting to highlight how these potential ePCT partners can help optimize pragmatic approaches to several PRECIS-2 domains. We found that partners are especially effective in implementing pragmatic ways to determine eligibility for evidence-based dementia care programs; assist with recruitment of eligible individuals; incorporate dementia care interventions into the range of existing HCBSs; and track outcomes relevant to persons living with dementia, caregivers, HCBS providers, and Medicaid insurance stakeholders. We conclude with recommendations for researchers, potential ePCT partners, and policymakers to help facilitate the growth of dementia care ePCTs in Medicaid HCBS settings across the United States.

Association between Residential Exposure to Air Pollution and Incident Coronary Heart Disease Is Not Mediated by Leukocyte Telomere Length: A UK Biobank Study.

Higher air pollution exposure and shorter leukocyte telomere length (LTL) are both associated with increased risk of coronary heart disease (CHD), and share plausible mechanisms, including inflammation. LTL may serve as a biomarker of air pollution exposure and may be intervened with to reduce the risk of CHD. To the best of our knowledge, we are the first to test the mediation effect of LTL in the relationship between air pollution exposure and incident CHD. Using the UK Biobank (UKB) data (n = 317,601), we conducted a prospective study linking residential air pollution exposure (PM2.5, PM10, NO2, NOx) and LTL to incident CHD during a mean follow-up of 12.6 years. Cox proportional hazards models and generalized additive models with penalized spline functions were used to model the associations of pollutant concentrations and LTL with incident CHD. We found non-linear associations of air pollution exposure with LTL and CHD. Pollutant concentrations in the lower range were decreasingly associated with longer LTL and reduced risk of CHD. The associations between lower pollutant concentrations and reduced risk of CHD, however, were minimally mediated by LTL (<3%). Our findings suggest that air pollution influences CHD through pathways that do not involve LTL. Replication is needed with improved measurements of air pollution that more accurately assesses personal exposure.

Mid-life leukocyte telomere length and dementia risk: An observational and mendelian randomization study of 435,046 UK Biobank participants.

Telomere attrition is one of biological aging hallmarks and may be intervened to target multiple aging-related diseases, including Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD). The objective of this study was to assess associations of leukocyte telomere length (TL) with AD/ADRD and early markers of AD/ADRD, including cognitive performance and brain magnetic resonance imaging (MRI) phenotypes. Data from European-ancestry participants in the UK Biobank (n = 435,046) were used to evaluate whether mid-life leukocyte TL is associated with incident AD/ADRD over a mean follow-up of 12.2 years. In a subsample without AD/ADRD and with brain imaging data (n = 43,390), we associated TL with brain MRI phenotypes related to AD or vascular dementia pathology. Longer TL was associated with a lower risk of incident AD/ADRD (adjusted Hazard Ratio [aHR] per SD = 0.93, 95% CI 0.90-0.96, p = 3.37 × 10-7 ). Longer TL also was associated with better cognitive performance in specific cognitive domains, larger hippocampus volume, lower total volume of white matter hyperintensities, and higher fractional anisotropy and lower mean diffusivity in the fornix. In conclusion, longer TL is inversely associated with AD/ADRD, cognitive impairment, and brain structural lesions toward the development of AD/ADRD. However, the relationships between genetically determined TL and the outcomes above were not statistically significant based on the results from Mendelian randomization analysis results. Our findings add to the literature of prioritizing risk for AD/ADRD. The causality needs to be ascertained in mechanistic studies.

Pain Management in Older Adults Before and During the First Year of COVID-19 Pandemic: Prevalence, Trends, and Correlates.

BACKGROUND: There is limited knowledge on whether and how health care access restrictions imposed by the coronavirus disease of 2019 pandemic have affected utilization of both opioid and nonpharmacological treatments among US older adults living with chronic pain. METHODS: We compared prevalence of chronic pain and high impact chronic pain (ie, chronic pain limiting life or work activities on most days or every day in the past 6 months) between 2019 (pre-pandemic) and 2020 (first year of pandemic) and utilization of opioids and nonpharmacological pain treatments among adults aged ≥65 years enrolled in the National Health Interview Survey, a nationally representative sample of noninstitutionalized civilian U.S. adults. RESULTS: Of 12 027 survey participants aged ≥65 (representing 32.6 million noninstitutionalized older adults nationally), the prevalence of chronic pain was not significantly different from 2019 (30.8%; 95% confidence interval [CI], 29.7%-32.0%) to 2020 (32.1%; 95% CI, 31.0%-33.3%; p = .06). Among older adults with chronic pain, the prevalence of high impact chronic pain was also unchanged (38.3%; 95% CI, 36.1%-40.6% in 2019 versus 37.8%; 95% CI, 34.9%-40.8% in 2020; p = .79). Use of any nonpharmacological interventions for pain management decreased significantly from 61.2% (95 CI, 58.8%-63.5%) in 2019 to 42.1% (95% CI, 40.5%-43.8%) in 2020 (p < .001) among those with chronic pain, as did opioid use in the past 12 months from 20.2% (95% CI, 18.9%-21.6%) in 2019 to 17.9% (95% CI, 16.7%-19.1%) in 2020 (p = .006). Predictors of treatment utilization were similar in both chronic pain and high-impact chronic pain. CONCLUSION: Use of pain treatments among older adults with chronic pain declined in the first year of coronavirus disease of 2019 pandemic. Future research is needed to assess long-term effects of coronavirus disease of 2019 pandemic on pain management in older adults.

Feasibility of a Modified Otago Exercise Program for Older Adults With Cognitive Vulnerability.

Cognitive vulnerability, that is, clinically significant symptoms of dementia, depression, or delirium, puts older adults at high risk for physical inactivity and falls. Programs addressing activity and falls are needed. The purpose was to determine feasibility of an in-home, modified, Otago Exercise Program (OEP) for those with cognitive vulnerability, based on acceptability (retention and adherence), safety (pain intensity and falls), and potential positive effects (change in short physical performance battery (SPPB)). This secondary analysis of a randomized controlled trial included 80 participants who received the OEP; 64 completed it, 48% had depression, 22% had dementia, and 30% had a combination dementia/depression/delirium. Adherence to home exercise was low to moderate; pain was stable over 16 weeks; 31% of participants reported falls unrelated to OEP. SPPB increased from 6.95 to 7.74 (p < .01); age by time and diagnosis by time interactions were not significant. The modified OEP shows promising feasibility for older adults with cognitive vulnerability.

Exposure to ultrafine particles and cognitive decline among older people in the United States.

BACKGROUND: Some studies suggest that ambient particulate air pollution is associated with cognitive decline. However, the findings are mixed, and there is no relevant research examining the influences of ultrafine particles (UFP), which may have more toxicity than larger particles. We therefore conducted this study to investigate whether residential UFP exposure is associated with cognitive decline using data from the Alzheimer's Disease Research Centers in the United States. METHODS: This is a longitudinal study of participants who were aged 65 years and older and had normal cognitive status at baseline. Residential UFP exposure, expressed as particle number concentrations (PNC), was assessed in 2016-2017 using a nationwide land use regression model, and was assigned to each participant using their 3-digit residential ZIP codes. Cognitive functions including memory, attention, language, executive function, and global function were assessed annually using 15 neuropsychological tests from March 2015 to February 2022. Linear mixed-effects models were used to examine the associations after adjustment for covariates including baseline age, sex, APOE ε4 status, race, education, smoking status, history of diabetes, quartiles of neighborhood median household income, and interaction terms of follow-up time with each covariate. RESULTS: This study included 5646 participants (mean age 76 years, 65% female). On average, each participant had 4 annual visits. When PNC was treated as a continuous variable, there were no statistically or clinically significant changes in annual decline of each cognitive function in relation to an interquartile range elevation in PNC (4026 particles/cm3). Similarly, when PNC was treated as a categorical variable including five exposure groups, there were no linear exposure-response trends in annual decline of each cognitive function across the five exposure groups. CONCLUSIONS: This study found no meaningful associations between residential UFP exposure and cognitive decline in global and domain-specific functions. There is a need for further research that assigns UFP exposure at a finer geographic scale.

The Risk for Loneliness and Major Depression among Solo Agers.

Solo agers may be vulnerable to social isolation and mental health sequelae, particularly if they lack close family or friendship ties. This study examined associations among indicators of solo aging, frequency of loneliness, and Major Depressive Disorder among adults aged 60+. Depressed participants were diagnosed by a geriatric psychiatrist and control participants were not depressed. We hypothesized that older adults with more indicators of solo aging (i.e., living alone, being unmarried, not having family or friends nearby) would be more often lonely and more likely to be depressed. In multivariate analyses controlling for health comorbidities and financial difficulty, each additional solo aging indicator significantly increased the likelihood of frequent loneliness, 95% CI OR [1.50, 2.80], and having a depression diagnosis 95% CI OR [1.04, 2.07]. Solo agers may be vulnerable to loneliness and depression, reinforcing the need for assessment and intervention for social isolation among older adults.

Association of Race, Ethnicity, Education, and Neighborhood Context With Dementia Prevalence and Cognitive Impairment Severity Among Older Adults Receiving Medicaid-Funded Home and Community-Based Services.

OBJECTIVE: While racial, ethnic, and socioeconomic group disparities in cognitive impairment and dementia prevalence are well-documented among community-dwelling older adults, little is known about these disparity trends among older adults receiving Medicaid-funded home- and community-based services (HCBS) in lieu of nursing home admission. The authors determined how dementia prevalence and cognitive impairment severity compare by race, ethnicity, educational attainment, and neighborhood context in a Medicaid HCBS population. DESIGN/SETTING: A cross-sectional study in Connecticut. PARTICIPANTS: Adults age ≥65 in the HCBS program, January-March 2019 (N = 3,520). MEASUREMENTS: The data source was Connecticut's HCBS program Universal Assessment tool. The authors employed two outcomes: Cognitive Performance Scale (CPS2), a 9-point measure ranging from cognitively intact-very severe impairment; and presence or not of either diagnosed dementia or CPS2 score ≥4 (major impairment). Neighborhood context was measured using the Social Vulnerability Index (SVI). RESULTS: Cohort characteristics: 75.7% female; mean(SD) age = 79.1(8.2); Non-Hispanic White = 47.8%; Hispanic = 33.6%; Non-Hispanic Black = 15.9%. Covariate-adjusted multivariate analyses revealed no dementia/major impairment prevalence differences among White, Black, and Hispanic individuals, but impairment severity was greater among Hispanic participants (b = 0.22; p = 0.02). People with more than HS education had less severe impairment (b = -0.12; p <0.001) and lower likelihood of dementia/major impairment (AOR = 0.61; p <0.001). Dementia/major impairment likelihood and impairment severity were greater in less socially vulnerable neighborhoods. CONCLUSION: Racial and ethnic group differences in cognitive impairment are less pronounced in Medicaid-funded HCBS cohorts than in other community-dwelling older adult cohorts. SVI results suggest that, among other possible explanations, older adults with dementia may move to lower social vulnerability neighborhoods where supportive family members reside.

Implementing the Care of Persons With Dementia in Their Environments (COPE) Intervention in Community-Based Programs: Acceptability and Perceived Benefit From Care Managers' and Interventionists' Perspectives.

BACKGROUND AND OBJECTIVES: Nonpharmacologic interventions have demonstrated benefits for people living with dementia and their caregivers. Few studies have evaluated their implementation in real-world settings. Using normalization process theory (NPT), an implementation science framework, this study evaluated the acceptability of the care of persons with dementia in their environments (COPE) intervention by care managers and interventionists implemented in a Medicaid and state-revenue funded home and community-based services (HCBS) program. RESEARCH DESIGN AND METHODS: NPT and data from 9 care manager focus groups (n = 61) and 2 interventionist focus groups (n = 8) were utilized to understand COPE acceptability to program care managers and interventionists. NPT's 4 criteria, coherence, cognitive participation, collective action, and reflexive monitoring, framed the research questions used to evaluate the intervention's implementation. RESULTS: Care managers and interventionists demonstrated a shared understanding of COPE aims and the value of practices implemented (coherence). Training by national experts facilitated program buy-in to meet COPE goals and was demonstrated by care managers and interventionists as they used the training to broaden their program involvement (cognitive participation). Operational work done by care managers and interventionists to implement the intervention (collective action) and their shared perceptions of program benefits (reflexive monitoring) contributed to program implementation, families' positive responses to COPE and enhanced sustainability. DISCUSSION AND IMPLICATIONS: Introducing evidence-based dementia care interventions into HCBS programs strongly depends upon building shared understandings between care managers and interventionists and valuing the contributions of all stakeholders involved in delivering care innovations to people living with dementia and their caregivers.

Resilience in relation to older adults with multimorbidity: A scoping review.

The purpose of this scoping review is to identify conceptual and theoretical resilience models, types of resilience measures, and outcomes regarding resilience in relation to older adults with multimorbidity. PubMed, Embase, CINAHL, and PsycINFO were searched, and we identified 14 studies to July 2021. Most models operationalize resilience as dependent on the social and environmental context of older adults. Three of the five resilience measures in the included studies are used to evaluate general resilience. They are primarily psychological or psychosocial in nature, and measuring physical resilience therefore may help to better understand individuals' ability to cope with the physical challenges associated with various chronic diseases. Quality of life and physical activity were common outcomes in studies of resilience. Findings highlight the need for studies that incorporate physiological measures or physical properties of resilience and longitudinal studies that capture the dynamic process of resilience in older adults with multimorbidity.

Impact of psychological resilience on walking capacity in older adults following hip fracture.

BACKGROUND: Community-dwelling older adults experiencing hip fracture often fail to achieve adequate walking capacity following surgery and rehabilitation. Effects of psychological factors on post-fracture walking capacity are poorly understood. Accordingly, this paper investigates effects of psychological resilience on observed walking capacity measures in older adults following hip fracture, controlling for important covariates. METHODS: Data were drawn from the Community Ambulation Project, a clinical trial of 210 community-dwelling adults aged ≥60 years who experienced a minimal trauma hip fracture and were randomized to one of two 16-week home-based physical therapist-guided interventions. Psychological resilience was measured at study baseline using the 6-item Brief Resilience Scale (BRS); scores were classified into groups in order to distinguish levels of self-reported resilience. Walking capacity was assessed at study baseline and 16 weeks later using 4-Meter Gait Speed (4MGS), 50-Foot Walk Test (50FWT), and 6-Minute Walk Distance (SMWD). In multivariate analyses of covariance in which 16-week follow-up values of each walking measure were outcomes, covariates included clinical trial arm, gender, age, and baseline values of: walking measure corresponding to the outcome; body mass index; depressive symptom severity; degree of psychological optimism; cognitive status; informal caregiver need; and days from hospital admission to randomization. RESULTS: Increases between baseline and 16 weeks later in mean gait speed in meters/sec (m/s) and walking distance in meters (m) in 4MGS, 50FWT and SMWD were 0.06 m/s (p = 0.061), 0.11 m/s (p < 0.01), and 25.5 m (p = 0.056) greater, respectively, in the most resilient BRS group compared to the least resilient BRS group. CONCLUSION: Higher levels of psychological resilience were associated with greater walking speed and distance. Psychological resilience represents a potentially clinically important pathway and intervention target, toward the goal of improving walking capacity among older adults known to have substantial residual disability following hip fracture.

Cost-Benefit Analysis of the COPE Program for Persons Living With Dementia: Toward a Payment Model.

BACKGROUND AND OBJECTIVES: There is a critical need for effective interventions to support quality of life for persons living with dementia and their caregivers. Growing evidence supports nonpharmacologic programs that provide care management, disease education, skills training, and support. This cost-benefit analysis examined whether the Care of Persons with Dementia in their Environments (COPE) program achieves cost savings when incorporated into Connecticut's home- and community-based services (HCBS), which are state- and Medicaid-funded. RESEARCH DESIGN AND METHODS: Findings are based on a pragmatic trial where persons living with dementia and their caregiver dyads were randomly assigned to COPE with HCBS, or HCBS alone. Cost measures included those relevant to HCBS decision makers: intervention delivery, health care utilization, caregiver time, formal care, and social services. Data sources included care management records and caregiver report. RESULTS: Per-dyad mean cost savings at 12 months were $2 354 for those who received COPE with a mean difference-in-difference of -$6 667 versus HCBS alone (95% CI: -$15 473, $2 734; not statistically significant). COPE costs would consume 5.6%-11.3% of Connecticut's HCBS annual spending limit, and HCBS cost-sharing requirements align with participants' willingness to pay for COPE. DISCUSSION AND IMPLICATIONS: COPE represents a potentially cost-saving dementia care service that could be financed through existing Connecticut HCBS. HCBS programs represent an important, sustainable payment model for delivering nonpharmacological dementia interventions such as COPE.