Population Dementia Incidence and Direct Oral Anticoagulant Use in a Representative Population With Atrial Fibrillation.

BACKGROUND AND OBJECTIVES: Incidence and prevalence of atrial fibrillation (AF), a risk factor of dementia, have been increasing over time. Oral anticoagulation reduces risk of stroke and other negative outcomes of AF and may reduce dementia health inequities. The objective of this study was to estimate dementia incidence in patients with newly-diagnosed AF and taking an anticoagulant as use of direct oral anticoagulants (DOACs) increased. METHODS: We used a retrospective cohort design with annual incident AF cohorts of community-dwelling Medicare Fee-for-Service beneficiaries, enrolled in Parts A, B, and D from 2007 to 2017. The sample was limited to beneficiaries aged 67 years and older with incident AF; no prior dementia; and use of anticoagulants warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban in year t. RESULTS: A total of 1,083,338 beneficiaries were included in the study, 58.5% female, with mean (SD) age 77.2 (6.75) years. Among anticoagulated, incident AF cohorts, use of DOACs increased from 10.6% in their first year of availability (2011) to 41.4% in 2017. Among incident AF cohorts taking any oral anticoagulant, 3-year dementia incidence did not change significantly over the cohorts after adjusting for confounders. For example, incidence was 9.1% (95% CI 8.9-9.4) among White persons diagnosed with AF in 2007 and 2008 and 8.9% (95% CI 8.7-9.1) in 2017. Across cohorts, dementia incidence was consistently highest for Black persons, followed by American Indian/Alaska Native and White persons, and lowest for Asian persons. In 2017, 10.9% (95% CI 10.4-11.3) of Black persons in the cohort developed dementia within 3 years, 9.4% (95% CI 8.0-10.9) of American Indian/Alaska Native, 8.9% (95% CI 8.7-9.1) of White, 8.7% (95% CI 8.2-9.1) of Hispanic, and 6.9% (95% CI 6.4-7.4) of Asian persons. Across race/ethnicity, 3-year stroke risk decreased consistently over time; however, the increasing availability of DOACs did not alter the trend. DISCUSSION: Increased use of DOACs among incident AF cohorts from 2007 to 2017 was not associated with significant declines in dementia or stroke risk. Consideration of similar stroke and dementia risk, as well as differences in cost, is warranted when weighing the risks and benefits of available oral anticoagulants.

Diagnoses and Treatment of Behavioral and Psychological Symptoms of Dementia Among Racially and Ethnically Diverse Persons Living with Dementia.

Background: Behavioral and psychological symptoms of dementia (BPSD) and prescribed central nervous system (CNS) active drugs to treat them are prevalent among persons living with Alzheimer's disease and related dementias (PLWD) and lead to negative outcomes for PLWD and their caregivers. Yet, little is known about racial/ethnic disparities in diagnosis and use of drugs to treat BPSD. Objective: Quantify racial/ethnic disparities in BPSD diagnoses and CNS-active drug use among community-dwelling PLWD. Methods: We used a retrospective cohort of community-dwelling Medicare Fee-for-Service beneficiaries with dementia, continuously enrolled in Parts A, B and D, 2017-2019. Multivariate logistic models estimated rates of BPSD diagnosis and, conditional on diagnosis, CNS-active drug use. Results: Among PLWD, 67.1% had diagnoses of an affective, psychosis or hyperactivity symptom. White (68.3%) and Hispanic (63.9%) PLWD were most likely, Blacks (56.6%) and Asians (52.7%) least likely, to have diagnoses. Among PLWD with BPSD diagnoses, 78.6% took a CNS-active drug. Use was highest among whites (79.3%) and Hispanics (76.2%) and lowest among Blacks (70.8%) and Asians (69.3%). Racial/ethnic differences in affective disorders were pronounced, 56.8% of white PLWD diagnosed; Asians had the lowest rates (37.8%). Similar differences were found in use of antidepressants. Conclusions: BPSD diagnoses and CNS-active drug use were common in our study. Lower rates of BPSD diagnoses in non-white compared to white populations may indicate underdiagnosis in clinical settings of treatable conditions. Clinicians' review of prescriptions in this population to reduce poor outcomes is important as is informing care partners on the risks/benefits of using CNS-active drugs.

Medicare Part D Plans Greatly Increased Utilization Restrictions On Prescription Drugs, 2011-20.

Drug utilization management tools can be employed to ensure that medicines are prescribed cost-effectively, but they can also be implemented in ways that reduce adherence and harm patient health. We examined trends in the prevalence of utilization restrictions on non-protected-class compounds in Medicare Part D plans during the period 2011-20, including prior authorization and step therapy requirements as well as formulary exclusions. Part D plans became significantly more restrictive over time, rising from an average of 31.9 percent of compounds restricted in 2011 to 44.4 percent restricted in 2020. The prevalence of formulary exclusions grew particularly fast: By 2020, plan formularies excluded an average of 44.7 percent of brand-name-only compounds. Formulary restrictions were more common among brand-name-only compared with generic-available compounds, among more expensive compounds, and in stand-alone compared with Medicare Advantage prescription drug plans.

Why higher copayments for opioids did not reduce use among Medicare beneficiaries.

To examine whether higher cost-sharing deterred prescription opioid use. Medicare Part D claims from 2007 to 2016 for a 20% random sample of Medicare enrollees. We obtain estimates of the effect of cost-sharing on prescription opioid use using ordinary least squares and instrumental variables methods. In both, we exploit the variation (change) in cost-sharing within plans over time for a sample of beneficiaries who remain in the same plan. Focusing on changes in cost-sharing within a plan for a constant sample of beneficiaries mitigates potential bias from plan selection and using a constant set of weights derived from use in year (t) eliminates changes in the cost-sharing indexes due to (endogenous) consumer choice in year (t+1). Part D plans adopted benefit changes designed to reduce opioid use, including moving opioids to higher cost-sharing tiers. Increasing plan copayments for hydrocodone or oxycodone was associated with reductions in plan-paid claims and offsetting increases in cash claims. Widespread availability of low-cost generics combined with the anti-clawback provision in Part D mediated the effect of higher cost sharing to curb opioid use. As plans moved generic opioids to higher cost-sharing tiers, beneficiaries simply paid cash prices and aggregate use remained largely unchanged. The anti-clawback provision in Part D, intended to protect beneficiaries from price gouging, limited plans' ability to constrain opioid use through typical demand-side measures such as increased cost-sharing.

Trends in Incident Dementia Diagnosis Before and After Medicare Risk Adjustment.

This cohort study examines rates of new diagnosis of Alzheimer disease and related dementias among beneficiaries of Medicare Advantage plans vs traditional Medicare from 2016 through 2020.

Estimates of diagnosed dementia prevalence and incidence among diverse beneficiaries in traditional Medicare and Medicare Advantage.

Approximately half of Medicare beneficiaries are enrolled in Medicare Advantage (MA), a private plan alternative to traditional Medicare (TM). Yet little is known about diagnosed dementia rates among MA enrollees, limiting population estimates. All (100%) claims of Medicare beneficiaries using encounter data for MA and claims for TM for the years 2015 to 2018 were used to quantify diagnosed dementia prevalence and incidence rates in MA, compare rates to TM, and provide estimates for the entire Medicare population and for different racial/ethnic populations. In 2017, dementia incidence and prevalence among MA beneficiaries were 2.54% (95% confidence interval [CI]: 2.53 to 2.55) and 7.04% (95% CI: 7.03 to 7.06). Comparison to TM adjusted for sociodemographic and health differences among beneficiaries in MA and TM; the prevalence of diagnosed dementia among beneficiaries in MA was lower (7.1%; 95% CI: 7.12 to 7.13) than in TM (8.7%; 95% CI: 8.71 to 8.72). The diagnosed dementia incidence rate was also lower in MA (2.50%; 95% CI: 2.50 to 2.50) compared to TM (2.99%; 95% CI: 2.99 to 2.99). There were lower rates in MA compared to TM for men and women and White, Black, Hispanic, Asian, American Indian/Alaska Native persons. Diagnosed dementia prevalence and incidence for the entire Medicare population was 7.9% (95% CI: 7.91 to 7.93) and 2.8% (95% CI: 2.77 to 2.78). Lower diagnosed dementia rates in MA compared to TM may exacerbate racial/ethnic disparities in diagnosed dementia. Rates tracked over time will provide understanding of the impact on dementia diagnosis of 2020 MA risk adjustment for dementia.

Potentially Inappropriate Medication Use in Community-Dwelling Older Adults Living with Dementia.

BACKGROUND: The Beers Criteria identifies potentially inappropriate medications (PIMs) that should be avoided in older adults living with dementia. OBJECTIVE: The aim of this study was to provide estimates of the prevalence and persistence of PIM use among community-dwelling older adults living with dementia in 2011-2017. METHODS: Medicare claims data were used to create an analytic dataset spanning from 2011 to 2017. The analysis included community-dwelling Medicare fee-for-service beneficiaries aged 65 and older who were enrolled in Medicare Part D plans, had diagnosis for dementia, and were alive for at least one calendar year. Dementia status was determined using Medicare Chronic Conditions Date Warehouse (CCW) Chronic Condition categories and Charlson Comorbidity Index. PIM use was defined as 2 or more prescription fills with at least 90 days of total days-supply in a calendar year. Descriptive statistics were used to report the prevalence and persistence of PIM use. RESULTS: Of 1.6 million person-year observations included in the sample, 32.7% used one or more PIMs during a calendar year in 2011-2017. Breakdown by drug classes showed that 14.9% of the sample used anticholinergics, 14.0% used benzodiazepines, and 11.0% used antipsychotics. Conditional on any use, mean annual days-supply for all PIMs was 270.6 days (SD = 102.7). The mean annual days-supply for antipsychotic use was 302.7 days (SD = 131.2). CONCLUSION: Significant proportion of community-dwelling older adults with dementia used one or more PIMs, often for extended periods of time. The antipsychotic use in the community-dwelling older adults with dementia remains as a significant problem.

Part D beneficiaries' incentives and responses under preferred pharmacy networks.

OBJECTIVES: The share of Medicare stand-alone prescription drug plans with a preferred pharmacy network has grown from less than 9% in 2011 to 98% in 2021. This article assesses the financial incentives that such networks created for unsubsidized and subsidized beneficiaries and their pharmacy switching. STUDY DESIGN: We analyzed prescription drug claims data for a nationally representative 20% sample of Medicare beneficiaries from 2010 through 2016. METHODS: We evaluated the financial incentives for using preferred pharmacies by simulating unsubsidized and subsidized beneficiaries' annual out-of-pocket spending differentials between using nonpreferred and preferred pharmacies for all their prescriptions. We then compared beneficiaries' use of pharmacies before and after their plans adopted preferred networks. We also examined the amount of money that beneficiaries left on the table under such networks, based on their pharmacy use. RESULTS: Unsubsidized beneficiaries faced substantial incentives-on average, $147 annually in out-of-pocket spending-and moderately switched toward preferred pharmacies, whereas subsidized beneficiaries were insulated from the incentives and demonstrated little switching. Among those who continued to mainly use nonpreferred pharmacies (half of the unsubsidized and about two-thirds of the subsidized), on average, the unsubsidized paid more out of pocket ($94) relative to if they had used preferred pharmacies, whereas Medicare bore the extra spending ($170) for the subsidized through cost-sharing subsidies. CONCLUSIONS: Preferred networks have important implications for beneficiaries' out-of-pocket spending and the low-income subsidy program. Further research is needed about the impact on the quality of beneficiaries' decision-making and cost savings to fully evaluate preferred networks.

Formulary restrictions and stroke risk in patients with atrial fibrillation.

OBJECTIVES: To determine the use of formulary restrictions (prior authorization and step therapy) on the use of non-vitamin K antagonist oral anticoagulants (NOACs) and their effect on health outcomes. STUDY DESIGN: Longitudinal cohort study. We identified a sample of Medicare beneficiaries with an incident diagnosis of atrial fibrillation (AF) in 2011 to 2015 and followed them until the end of 2016 or death. We compared anticoagulant use and health outcomes associated with Medicare Part D plan coverage of NOACs. METHODS: The primary outcomes were composite rates of death, stroke, transient ischemic attack, and systemic embolism. We used Cox proportional hazards models to estimate the association between formulary restrictions and adverse health outcomes. RESULTS: Beneficiaries enrolled in Part D plans that restricted access to NOACs had a lower probability of NOAC use (30.2% vs 32.2%), worse adherence conditional on NOAC use (32.1% vs 34.3% adherent), and longer delays in filling an initial prescription (46% vs 55% filled within 30 days of AF diagnosis). Beneficiaries in restricted plans had higher aggregate risk of mortality/stroke/transient ischemic attack (adjusted HR, 1.098; 95% CI, 1.079-1.118). CONCLUSIONS: Limiting access to NOACs may exacerbate current underuse of anticoagulants and increase the risk of stroke among patients with newly diagnosed AF. Pharmacy benefit managers and Part D plans need to continuously review the appropriateness of formulary policies to ensure patient access to effective medications.

Benzodiazepine use and the risk of dementia.

Introduction: Benzodiazepines (BZDs) are commonly prescribed for anxiety and agitations, which are early symptoms of Alzheimer's disease and related dementias (ADRD). It is unclear whether BZDs causally affect ADRD risk or are prescribed in response to early symptoms of dementia. Methods: We replicate prior case-control studies using longitudinal Medicare claims. To mitigate bias from prodromal use, we compare rates of ADRD diagnosis for beneficiaries exposed and unexposed to BZDs for cervical/lumbar pain, stenosis, and sciatica, none of which are associated with dementia. Results: Approximately 8% of Medicare beneficiaries used a BZD in 2007, increasing to nearly 13% by 2013. Estimates from case-control designs are sensitive to duration of look-back period, health histories, medication use, and exclusion of decedents. Incident BZD use is not associated with an increased risk of dementia in an "uncontaminated" sample of beneficiaries prescribed a BZD for pain (odds ratios (ORs) of 1.007 [95% confidence interval [CI] = 0.885, 1.146] and 0.986 [95% CI = 0.877, 1.108], respectively, in the 2013 and 2013 to 2015 pooled samples). Higher levels of BZD exposure (>365 days over a 2-year period) are associated with increased odds of a dementia diagnosis, but the results are not statistically significant at the 5% or 10% levels (1.190 [95% CI = 0.925, 1.531] and 1.167 [95% CI = 0.919, 1.483]). Discussion: We find little evidence of a causal relation between BZD use and dementia risk. Nonetheless, providers should limit the extended use in elderly populations.

Reforming the Medicare Part D Benefit Design: Financial Implications for Beneficiaries, Private Plans, Drug Manufacturers, and the Federal Government.

CONTEXT: Reforming the Medicare Part D program-which provides prescription drug coverage to 49 million beneficiaries-has emerged as a key policy priority. METHODS: The authors evaluate prescription drug claims from a 100% sample of Medicare Part D beneficiaries to evaluate the current spending distribution across different payers for different types of beneficiaries across different benefit phases. They then model how these estimates would change under a proposal to redesign the Medicare Part D standard benefit. FINDINGS: Spending patterns differ for beneficiaries who do and do not qualify for low-income subsidies. Part D plans face limited liability for total spending under the current standard benefit design, amounting to 36% of total spending for beneficiaries who do not receive low-income subsidies and 28% of total spending for those who do. Proposed reforms would increase plan liability and significantly change the distribution of liability across plans, drug manufacturers, and the federal government. CONCLUSIONS: Though the original goal of the Part D program was to create a market of competing private plans that provide prescription drug coverage to Medicare beneficiaries, the standard benefit design that was included in the original legislation reflected significant political compromises. Reforming the standard benefit design to give plans more skin in the game could significantly affect competition in the market, with differential impact across drug classes and types of beneficiaries.

Pharmacy switching in response to preferred pharmacy networks in Medicare Part D.

OBJECTIVE: To evaluate the effects of preferred pharmacy networks-a tool that Medicare Part D plans have recently adopted to steer patients to lower cost pharmacies-on the use of preferred pharmacies and factors underlying beneficiaries' decisions on whether to switch to preferred pharmacies. DATA SOURCES: Medicare claims data were collected for a nationally representative 20% sample of beneficiaries during 2010-2016 and merged with annual Part D pharmacy network files. STUDY DESIGN: We examined preferred networks' impact on pharmacy choice by estimating a difference-in-differences model comparing preferred pharmacies' claim share before and after implementation among unsubsidized and subsidized beneficiaries. Additionally, we evaluated the factors affecting whether a beneficiary switched from mainly using nonpreferred to preferred pharmacies. DATA COLLECTION/EXTRACTION METHODS: We examined stand-alone drug plans that adopted a preferred network during 2011-2016. Our main sample included beneficiaries 65 years and older who stayed in their plan in both the first year of implementation and the year before and whose cost-sharing subsidy status and ZIP code remained unchanged during the 2-year period. PRINCIPAL FINDINGS: Unsubsidized Part D beneficiaries faced an average difference of $129 per year in out-of-pocket spending between using nonpreferred and preferred pharmacies, while subsidized beneficiaries were insulated from these cost differences. The implementation of preferred networks resulted in a 3.7-percentage point (95% CI: 3.3, 4.2) increase in preferred pharmacies' claim share in the first year among the unsubsidized. Existing relationships with preferred pharmacies, the size of financial incentives, proximity to preferred pharmacies, and urban residence were positively associated with beneficiaries' decisions to switch to these pharmacies. CONCLUSIONS: Preferred pharmacy networks caused a moderate shift on average towards preferred pharmacies among unsubsidized beneficiaries, although stronger financial incentives correlated with more switching. Researchers and policymakers should better understand plans' cost-sharing strategies and assess whether communities have equitable access to preferred pharmacies.

Acute Bacterial Infections and Longitudinal Risk of Readmissions and Mortality in Patients Hospitalized with Heart Failure.

AIMS: Infections are associated with worse short-term outcomes in patients with heart failure (HF). However, acute infections may have lasting pathophysiologic effects that adversely influence HF outcomes after discharge. Our objective was to describe the impact of acute bacterial infections on longitudinal outcomes of patients hospitalized with a primary diagnosis of HF. METHODS AND RESULTS: This paper is based on a retrospective cohort study of patients hospitalized with a primary diagnosis of HF with or without a secondary diagnosis of acute bacterial infection in Optum Clinformatics DataMart from 2010-2015. Primary outcomes were 30 and 180-day hospital readmissions and mortality, intensive care unit admission, length of hospital stay, and total hospital charge, compared between those with or without an acute infection. Cohorts were compared after inverse probability of treatment weighting. Multivariable logistic regression was used to examine relationship to outcomes. Of 121,783 patients hospitalized with a primary diagnosis of HF, 27,947 (23%) had a diagnosis of acute infection. After weighting, 30-day hospital readmissions [17.1% vs. 15.7%, OR 1.11 (1.07-1.15), p < 0.001] and 180-day hospital readmissions [39.6% vs. 38.7%, OR 1.04 (1.01-1.07), p = 0.006] were modestly greater in those with an acute infection versus those without. Thirty-day [5.5% vs. 4.3%, OR 1.29 (1.21-1.38), p < 0.001] and 180-day mortality [10.7% vs. 9.4%, OR 1.16 (1.11-1.22), p < 0.001], length of stay (7.1 ± 7.0 days vs. 5.7 ± 5.8 days, p < 0.001), and total hospital charges (USD 62,200 ± 770 vs. USD 51,100 ± 436, p < 0.001) were higher in patients with an infection. CONCLUSIONS: The development of an acute bacterial infection in patients hospitalized for HF was associated with an increase in morbidity and mortality after discharge.

Incorporating Prescription Drug Utilization Information Into the Marketplace Risk Adjustment Model Improves Payment Accuracy and Reduces Adverse Selection Incentives.

Beginning with the 2018 benefit year, the Centers for Medicare and Medicaid Services started incorporating select prescription drug utilization information into the Marketplace risk adjustment model. There has been little evidence about the impact of this change on payment accuracy and the mechanisms through which it may occur. Using commercial claims in 2017 from a large national health insurer, we find that the policy change improves payment accuracy in our sample and would help mitigate insurers' selection incentives for some enrollees through two channels: imputing missing diagnoses and varying risk scores to better capture the heterogeneity in expenditures among patients with certain health conditions. However, while improving payment accuracy overall, there are potential perverse incentives that could distort treatment choice for marginal patients. Additionally, overcompensation and undercompensation persists for certain patient subgroups, suggesting an opportunity to further refine and improve the model.

Drug therapies for chronic conditions and risk of Alzheimer's disease and related dementias: A scoping review.

INTRODUCTION: Most older Americans use drug therapies for chronic conditions. Several are associated with risk of Alzheimer's disease and related dementias (ADRD). METHODS: A scoping review was used to identify drug classes associated with increasing or decreasing ADRD risk. We analyzed size, type, and findings of the evidence. RESULTS: We identified 29 drug classes across 11 therapeutic areas, and 404 human studies. Most common were studies on drugs for hypertension (93) or hyperlipidemia (81). Fewer than five studies were identified for several anti-diabetic and anti-inflammatory drugs. Evidence was observational only for beta blockers, proton pump inhibitors, benzodiazepines, and disease-modifying anti-rheumatic drugs. For 13 drug classes, 50% or more of the studies reported consistent direction of effect on risk of ADRD. DISCUSSION: Future research targeting drug classes with limited/non-robust evidence, examining sex, racial heterogeneity, and separating classes by molecule, will facilitate understanding of associated risk, and inform clinical and policy efforts to alleviate the growing impact of ADRD.

Variation in generic dispensing rates in Medicare Part D.

OBJECTIVES: The use of generics in Medicare Part D generates cost savings for plan sponsors, beneficiaries, and the federal government. However, there is considerable variation in generic use across plans, even within a therapeutic class. Our objective is to understand the extent of variation in generic use in Part D and to understand factors associated with generic use. STUDY DESIGN: We used an observational study design using Medicare Part D claims from 2006 to 2016. METHODS: We used descriptive statistics and regression analysis to examine the variation in generic and brand use across plans and the extent to which patient, plan, and area characteristics are associated with the choice of medication within a therapeutic class. RESULTS: Although generic use has increased markedly over time in Part D, substantial variation across plans persists in a number of common therapeutic classes. Beneficiary characteristics such as gender and health status are associated with higher/lower generic use, as are plan characteristics such as plan type (stand-alone prescription drug plan or Medicare Advantage), premium, and parent company. CONCLUSIONS: Because we cannot study the impact of brand-name drug rebates on generic use, we can study the variation in generic use across Part D plans as an indirect way to assess pharmacy benefit manager and plan incentives. We find circumstantial evidence that, in certain classes, rebates may play a role in influencing brand over generic use, although the exact relationship is unknowable given the proprietary nature of rebates.

Pharmaceutical Treatment for Alzheimer's Disease and Related Dementias: Utilization and Disparities.

BACKGROUND: Four prescription drugs (donepezil, galantamine, memantine, and rivastigmine) are approved by the US FDA to treat symptoms of Alzheimer's disease (AD). Even modest effectiveness could potentially reduce the population-level burden of AD and related dementias (ADRD), especially for women and racial/ethnic minorities who have higher incidence of ADRD. OBJECTIVE: Describe the prevalence of antidementia drug use and timing of initiation relative to ADRD diagnosis among a nationally representative group of older Americans, and if there are disparities in prevalence and timing by sex and race/ethnicity. METHODS: Descriptive analyses and logistic regressions of Medicare claims (2008-2016) for beneficiaries who had an ADRD or dementia-related symptom diagnosis, or use of an FDA approved drug for AD. We investigate prevalence of use and timing of treatment initiation relative to ADRD diagnosis across time and beneficiary characteristics (age, sex, race/ethnicity, socioeconomic status, comorbidities). RESULTS: Among persons diagnosed with ADRD or related symptoms, 33.3% used an approved drug over the study period. Odds of use was higher among Whites than non-Whites. Among ADRD drug users, 40% initiated use within 6 months of the initial ADRD or related symptoms diagnosis, and 16% initiated prior to a diagnosis. We observed disparities by race/ethnicity: 28% of Asians, 24% of Hispanics, 16% of Blacks, and 15% of Whites initiated prior to diagnosis. CONCLUSIONS: The use of antidementia drugs is relatively low and varies widely by race/ethnicity. Heterogeneity in timing of initiation and use may affect health and cost outcomes, but these effects merit further study.

Association of combination statin and antihypertensive therapy with reduced Alzheimer's disease and related dementia risk.

BACKGROUND: Hyperlipidemia and hypertension are modifiable risk factors for Alzheimer's disease and related dementias (ADRD). Approximately 25% of adults over age 65 use both antihypertensives (AHTs) and statins for these conditions. While a growing body of evidence found statins and AHTs are independently associated with lower ADRD risk, no evidence exists on simultaneous use for different drug class combinations and ADRD risk. Our primary objective was to compare ADRD risk associated with concurrent use of different combinations of statins and antihypertensives. METHODS: In a retrospective cohort study (2007-2014), we analyzed 694,672 Medicare beneficiaries in the United States (2,017,786 person-years) who concurrently used both statins and AHTs. Using logistic regression adjusting for age, socioeconomic status and comorbidities, we quantified incident ADRD diagnosis associated with concurrent use of different statin molecules (atorvastatin, pravastatin, rosuvastatin, and simvastatin) and AHT drug classes (two renin-angiotensin system (RAS)-acting AHTs, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin-II receptor blockers (ARBs), vs non-RAS-acting AHTs). FINDINGS: Pravastatin or rosuvastatin combined with RAS-acting AHTs reduce risk of ADRD relative to any statin combined with non-RAS-acting AHTs: ACEI+pravastatin odds ratio (OR) = 0.942 (CI: 0.899-0.986, p = 0.011), ACEI+rosuvastatin OR = 0.841 (CI: 0.794-0.892, p<0.001), ARB+pravastatin OR = 0.794 (CI: 0.748-0.843, p<0.001), ARB+rosuvastatin OR = 0.818 (CI: 0.765-0.874, p<0.001). ARBs combined with atorvastatin and simvastatin are associated with smaller reductions in risk, and ACEI with no risk reduction, compared to when combined with pravastatin or rosuvastatin. Among Hispanics, no combination of statins and RAS-acting AHTs reduces risk relative to combinations of statins and non-RAS-acting AHTs. Among blacks using ACEI+rosuvastatin, ADRD odds were 33% lower compared to blacks using other statins combined with non-RAS-acting AHTs (OR = 0.672 (CI: 0.548-0.825, p<0.001)). CONCLUSION: Among older Americans, use of pravastatin and rosuvastatin to treat hyperlipidemia is less common than use of simvastatin and atorvastatin, however, in combination with RAS-acting AHTs, particularly ARBs, they may be more effective at reducing risk of ADRD. The number of Americans with ADRD may be reduced with drug treatments for vascular health that also confer effects on ADRD.