Implications of treatment duration and frequency for value and cost-effective price of Alzheimer treatments.

BACKGROUND: Disease-modifying Alzheimer treatments are becoming available. The value of the treatments will be attenuated by their complexity of delivery and monitoring, creating additional medical cost and caregiver burden. OBJECTIVE: To estimate net treatment value using different assumptions for treatment duration and intensity. METHODS: We estimated the lifetime value of hypothetical treatments that reduce disease progression by 30% from a payer perspective, which considers cost offsets, i.e., reduced medical and formal social care costs, and quality-adjusted life-year gains, and a societal perspective, which adds reduction in caregiver burden. Estimates for gross value of the treatment were based on a prior publication, medical cost on Medicare payment rates, and caregiver time use on a survey of 21 clinics. We analyzed 5 hypothetical treatment scenarios: treatment until progression to moderate dementia with (1) biweekly and (2) 4-weekly infusions, and time-limited infusions every 4 weeks for (3) 72, (4) 52, and (5) 24 weeks. RESULTS: Treatment until progression to moderate dementia would take 5.7 years and generate gross value of $20,734 in direct cost offsets, $83,761 from a payer and $87,749 from a societal perspective, respectively. Added medical cost and caregiver burden for the 5 scenarios would be $44,179, $24,875, $21,632, $20,416, and $14,350, respectively. The maximum value-based price per year would be $7,687, $11,088, $47,708, $67,273, and $158,954. CONCLUSIONS: Assuming identical efficacy and safety, the net value generation of time-limited treatment is projected to be larger than that of chronic treatment. Such determination of net lifetime value can be useful to determine value-based prices for different treatment types.

Acceptable performance of blood biomarker tests of amyloid pathology - recommendations from the Global CEO Initiative on Alzheimer's Disease.

Anti-amyloid treatments for early symptomatic Alzheimer disease have recently become clinically available in some countries, which has greatly increased the need for biomarker confirmation of amyloid pathology. Blood biomarker (BBM) tests for amyloid pathology are more acceptable, accessible and scalable than amyloid PET or cerebrospinal fluid (CSF) tests, but have highly variable levels of performance. The Global CEO Initiative on Alzheimer's Disease convened a BBM Workgroup to consider the minimum acceptable performance of BBM tests for clinical use. Amyloid PET status was identified as the reference standard. For use as a triaging test before subsequent confirmatory tests such as amyloid PET or CSF tests, the BBM Workgroup recommends that a BBM test has a sensitivity of ≥90% with a specificity of ≥85% in primary care and ≥75-85% in secondary care depending on the availability of follow-up testing. For use as a confirmatory test without follow-up tests, a BBM test should have performance equivalent to that of CSF tests - a sensitivity and specificity of ~90%. Importantly, the predictive values of all biomarker tests vary according to the pre-test probability of amyloid pathology and must be interpreted in the complete clinical context. Use of BBM tests that meet these performance standards could enable more people to receive an accurate and timely Alzheimer disease diagnosis and potentially benefit from new treatments.

State Department of Motor Vehicles Reporting Mandates of Dementia Diagnoses and Dementia Underdiagnosis.

Importance: With older drivers representing the fastest growing segment of the driver population and dementia prevalence increasing with age, policymakers face the challenge of balancing road safety and mobility of older adults. In states that require reporting a dementia diagnosis to the Department of Motor Vehicles (DMV), individuals with dementia may be reluctant to disclose symptoms of cognitive decline, and clinicians may be reluctant to probe for those symptoms, which may be associated with missed or delayed diagnoses. Objective: To assess whether DMV reporting policies for drivers with dementia are associated with primary care clinicians' underdiagnosing dementia. Design, Setting, and Participants: This cross-sectional study used data from the 100% Medicare fee-for-service program and the Medicare Advantage plans from 2017 to 2019 on 223 036 primary care clinicians with at least 25 Medicare patients. Statistical analysis was performed from July to October 2023. Exposures: State DMV reporting policies for drivers with dementia. Main Outcomes and Measures: The main outcome was a binary variable indicating whether the clinician underdiagnosed dementia or not. Each clinician's expected number of dementia cases was estimated using a predictive model based on patient characteristics. Comparing the estimation with observed dementia diagnoses identified clinicians who underdiagnosed dementia vs those who did not, after accounting for sampling errors. Results: Four states have clinician reporting mandates, 14 have mandates requiring drivers to self-report dementia diagnoses, and 32 states and the District of Columbia do not have explicit requirements. Among primary care clinicians in states with clinician reporting mandates (n = 35 620), 51.4% were female, 91.9% worked in a metropolitan area, and 19.9% of the patient panel were beneficiaries dually eligible for Medicare and Medicaid. Among primary care clinicians in states with patient self-reporting mandates (n = 57 548), 55.7% were female, 83.1% worked in a metropolitan area, and 15.4% of the patient panel were dually eligible for Medicare and Medicaid. Among clinicians in states without mandates, 55.7% were female, 83.0% worked in a metropolitan area, and 14.6% of the patient panel were dually eligible for Medicare and Medicaid. Clinicians in states with clinician reporting mandates had an adjusted 12.4% (95% CI, 10.5%-14.2%) probability of underdiagnosing dementia compared with 7.8% (95% CI, 6.9%-8.7%) in states with self-reporting and 7.7% (95% CI, 6.9%-8.4%) in states with no mandates, an approximately 4-percentage point difference (P < .001). Conclusions and Relevance: Results of this cross-sectional study of primary care clinicians suggest that mandatory DMV policies for clinicians to report patients with dementia may be associated with a higher risk of missed or delayed dementia diagnoses. Future research is needed to better understand the unintended consequences and the risk-benefit tradeoffs of these policies.

Disparities in Access to Diagnostic Evaluation for Alzheimer's Disease in Individuals Dually Eligible for Medicare and Medicaid: A Modeling Study.

Background: Individuals dually eligible for Medicare and Medicaid (duals) may face greater obstacles to access to disease-modifying Alzheimer's treatments in spite of their higher disease burden, because of clinicians' reluctance to accept Medicaid and the so-called "lesser of" policy, under which Medicaid may pay providers lower rates. Objective: To project differential wait times for duals compared to Medicare-only beneficiaries by state. Methods: We used State Medicaid payment policy and Medicare enrollment data and a Markov model to predict differential wait times for duals and non-duals from 2023 to 2050. We estimated available diagnostic appointments by state for both groups based on reluctance of clinicians to accept Medicaid and the "lesser of" policy for each year. Results: We estimate overall average wait times of almost two years (22.9 months) but almost three times as long for duals (59.8 months) than non-duals (20.7 months) because of higher disease burden. The effects of Medicaid payment policy would increase average wait times for duals to 89 months with 20 states having wait times of 99 months or more, which would effectively deprive duals of access. Conclusions: The added average wait times in many states would effectively deprive duals from access to treatment and translate into avoidable disease progression and mortality. Policy interventions to reduce financial and nonfinancial obstacles are dearly needed to avoid deepening disparities. Examples are coverage arrangements that integrate Medicare and Medicaid coverage, covering the co-payment for physician services in full, and stricter network adequacy requirements for Medicaid Managed Care plans.

Focusing on Earlier Management of Alzheimer Disease: Expert Opinion Based on a Modified Nominal Group Technique.

BACKGROUND: Despite the number of people living with Alzheimer disease (AD), awareness of the early stages of this condition, including mild cognitive impairment due to AD-which poses management challenges-continues to be low. To identify areas for improvement in early AD management, dementia specialists convened in a virtual roundtable meeting. METHODOLOGY: A modified version of the nominal group technique was followed to prioritize specific topics and allow experts to provide their opinions. The overarching topics prioritized and discussed were (1) education and support for primary care physicians on cognitive assessment, detection of mild cognitive impairment, and patient monitoring; (2) nonpharmacological interventions; (3) and the introduction of disease-modifying therapies. CONCLUSIONS: Consensus was achieved regarding the need for educating primary care physicians on identifying people with cognitive impairment and for better diagnostic tools for its detection and early management. Management of mild cognitive impairment due to AD should encompass an adequate follow-up schedule aiming to maintain function for as long as possible, and primary care physicians and patients should be aware of the benefits of nonpharmacological interventions.

The Value of Medicare Coverage on Depressive Symptoms Among Older Immigrants.

BACKGROUND AND OBJECTIVES: The immigrant population, the primary driver of U.S. population growth, is aging and many immigrants remain uninsured. Lack of health insurance limits access to care, aggravating the already high level of depression for older immigrants. However, there is scarce evidence on how health insurance, particularly Medicare, affects their mental health. Using the Health and Retirement Study, this study examines the effect of Medicare coverage on depressive symptoms of older immigrants in the United States. RESEARCH DESIGN AND METHODS: Exploiting the fact that many immigrants are not covered by Medicare after passing age 65, we use a difference-in-difference model with propensity score weighting to compare differences in depressive symptoms pre- and post-age-65. We further stratify the sample by socioeconomic status and by race/ethnicity. RESULTS: Medicare coverage was significantly associated with a reduction in the probability of reporting depressive symptoms for immigrants with low socioeconomic status, especially for those below median wealth levels. The beneficial effect of Medicare coverage was also statistically significant for non-White immigrants-Black, Hispanic, and Asian/Pacific Islander-even when holding socioeconomic status constant. DISCUSSION AND IMPLICATIONS: Our findings imply that immigration policies that expand health care protection to older immigrants can lead to further health benefits and reduce existing disparities for the aging population. Policy reforms such as providing limited Medicare access to immigrants who paid sufficient taxes but are still awaiting permanent residency status could increase coverage for the uninsured and improve participation of immigrants in the payroll system.

Expected wait times for access to a disease-modifying Alzheimer's treatment in England: A modelling study.

OBJECTIVES: We previously analysed the preparedness to deliver a disease-modifying Alzheimer's treatment in the United Kingdom and predicted substantial wait times. This study updates the prediction for the National Health Service (NHS) in England, using an improved model and newer data. METHODS: We reviewed published data on capacity for diagnosis of cognitive impairment combined with expert input and constructed a model for wait times to access from 2023 to 2043. The model tracks patients from initial evaluation in primary care, cognitive testing by a dementia specialist, confirmatory biomarker testing with positron emission tomography (PET) scans or examination of cerebrospinal fluid and infusion delivery. Capacity for specialist visits and PET scans are assumed to be capacity constrained, and cerebrospinal fluid testing and infusion delivery to be scalable. RESULTS: Capacity constraints were projected to result in substantial wait times: patients referred to specialists based on a brief cognitive test, which is the current standard of care, would expect an overall initial wait times of 56 months in 2023, increasing to 129 months in 2029 and then falling slowly to around 100 months. Use of a blood test for the confirmation of Alzheimer's pathology as an additional triage step, would reduce wait times to around 17 to 25 months. DISCUSSION: The NHS England lacks capacity to provide timely access to a disease-modifying treatment, which is estimated to result in significant wait times and potentially avoidable disease progression. Better diagnostic tools at initial evaluation may reduce delays.

The age-specific comorbidity burden of mild cognitive impairment: a US claims database study.

BACKGROUND: Identifying individuals with mild cognitive impairment (MCI) who are likely to progress to Alzheimer's disease and related dementia disorders (ADRD) would facilitate the development of individualized prevention plans. We investigated the association between MCI and comorbidities of ADRD. We examined the predictive potential of these comorbidities for MCI risk determination using a machine learning algorithm. METHODS: Using a retrospective matched case-control design, 5185 MCI and 15,555 non-MCI individuals aged ≥50 years were identified from MarketScan databases. Predictive models included ADRD comorbidities, age, and sex. RESULTS: Associations between 25 ADRD comorbidities and MCI were significant but weakened with increasing age groups. The odds ratios (MCI vs non-MCI) in 50-64, 65-79, and ≥ 80 years, respectively, for depression (4.4, 3.1, 2.9) and stroke/transient ischemic attack (6.4, 3.0, 2.1). The predictive potential decreased with older age groups, with ROC-AUCs 0.75, 0.70, and 0.66 respectively. Certain comorbidities were age-specific predictors. CONCLUSIONS: The comorbidity burden of MCI relative to non-MCI is age-dependent. A model based on comorbidities alone predicted an MCI diagnosis with reasonable accuracy.

A Literature Review on the Burden of Alzheimer's Disease on Care Partners.

BACKGROUND: Many individuals with Alzheimer's disease (AD) are dependent on nonprofessional care partners. Providing informal care can result in emotional, physical, and financial burdens; however, there is a need for a better understanding of the impact of AD on care partners to support the clinical and economic assessment of potential new treatments. OBJECTIVE: We conducted a literature review to evaluate the burden experienced by care partners of individuals with AD. METHODS: Electronic screening and supplementary searches identified studies published from 2011 to 2022 describing the association between AD and the quality of life (QoL) and physical health of care partners, and the economic or financial burden of AD. RESULTS: Following electronic screening, 62, 25, and 39 studies were included on care partner burden, cost, and healthcare resource use in AD, respectively. Supplementary searches identified an additional 32 studies, resulting in 149 unique studies. These studies showed that care partners of individuals with AD report moderate to severe burden. Higher burden and lower QoL were observed in those caring for individuals with more severe AD. Care partners of individuals with AD experience higher burden, lower QoL, and higher levels of stress, depression, and anxiety than those without caring responsibilities. Informal care costs increased with AD severity and accounted for the greatest proportion of overall societal cost. CONCLUSIONS: Care partners of individuals with AD experience emotional and economic burden, which increases with AD severity. These impacts should be quantified comprehensively in future studies and captured in economic evaluations of AD interventions.

Expected and diagnosed rates of mild cognitive impairment and dementia in the U.S. Medicare population: observational analysis.

BACKGROUND: With the emergence of disease-modifying Alzheimer's treatments, timely detection of early-stage disease is more important than ever, as the treatment will not be indicated for later stages. Contemporary population-level data for detection rates of mild cognitive impairment (MCI), the stage at which treatment would ideally start, are lacking, and detection rates for dementia are only available for subsets of the Medicare population. We sought to compare documented diagnosis rates of MCI and dementia in the full Medicare population with expected rates based on a predictive model. METHODS: We performed an observational analysis of Medicare beneficiaries aged 65 and older with a near-continuous enrollment over a 3-year observation window or until death using 100% of the Medicare fee-for-service or Medicare Advantage Plans beneficiaries from 2015 to 2019. Actual diagnoses for MCI and dementia were derived from ICD-10 codes documented in those data. We used the 2000-2016 data of the Health and Retirement Study to develop a prediction model for expected diagnoses for the included population. The ratios between actually diagnosed cases of MCI and dementia over number of cases expected, the observed over expected ratio, reflects the detection rate. RESULTS: Although detection rates for MCI cases increased from 2015 to 2019 (0.062 to 0.079), the results mean that 7.4 of 8 million (92%) expected MCI cases remained undiagnosed. The detection rate for MCI was 0.039 and 0.048 in Black and Hispanic beneficiaries, respectively, compared with 0.098 in non-Hispanic White beneficiaries. Individuals dually eligible for Medicare and Medicaid had lower estimated detection rates than their Medicare-only counterparts for MCI (0.056 vs 0.085). Dementia was diagnosed more frequently than expected (1.086 to 1.104) from 2015 to 2019, mostly in non-Hispanic White beneficiaries (1.367) compared with 0.696 in Black beneficiaries and 0.758 in Hispanic beneficiaries. CONCLUSIONS: These results highlight the need to increase the overall detection rates of MCI and of dementia particularly in socioeconomically disadvantaged groups.

Preparedness of China's health care system to provide access to a disease-modifying Alzheimer's treatment.

INTRODUCTION: Although the majority of patients with Alzheimer's disease (AD) reside in low-and middle-income countries, little is known of the infrastructure in these countries for delivering emerging disease-modifying treatments. METHODS: We analyze the preparedness of China, the world's most populous middle-income country, using desk research, expert interviews and a simulation model. RESULTS: Our findings suggest that China's health care system is ill-prepared to provide timely access to Alzheimer's treatment. The current pathway, in which patients seek evaluation in hospital-based memory clinics without a prior assessment in primary care, would overwhelm existing capacity. Even with triage using a brief cognitive assessment and a blood test for the AD pathology, predicted wait times would remain over 2 years for decades, largely due to limited capacity for confirmatory biomarker testing despite adequate specialist capacity. DISCUSSION: Closing this gap will require the introduction of high-performing blood tests, greater reliance on cerebrospinal fluid (CSF) testing, and expansion of positron emission tomography (PET) capacity.

Blood-based biomarkers for Alzheimer's disease: Current state and future use in a transformed global healthcare landscape.

Timely detection of the pathophysiological changes and cognitive impairment caused by Alzheimer's disease (AD) is increasingly pressing because of the advent of biomarker-guided targeted therapies that may be most effective when provided early in the disease. Currently, diagnosis and management of early AD are largely guided by clinical symptoms. FDA-approved neuroimaging and cerebrospinal fluid biomarkers can aid detection and diagnosis, but the clinical implementation of these testing modalities is limited because of availability, cost, and perceived invasiveness. Blood-based biomarkers (BBBMs) may enable earlier and faster diagnoses as well as aid in risk assessment, early detection, prognosis, and management. Herein, we review data on BBBMs that are closest to clinical implementation, particularly those based on measures of amyloid-ß peptides and phosphorylated tau species. We discuss key parameters and considerations for the development and potential deployment of these BBBMs under different contexts of use and highlight challenges at the methodological, clinical, and regulatory levels.

Expanding the use of brief cognitive assessments to detect suspected early-stage cognitive impairment in primary care.

INTRODUCTION: Mild cognitive impairment remains substantially underdiagnosed, especially in disadvantaged populations. Failure to diagnose deprives patients and families of the opportunity to treat reversible causes, make necessary life and lifestyle changes and receive disease-modifying treatments if caused by Alzheimer's disease. Primary care, as the entry point for most, plays a critical role in improving detection rates. METHODS: We convened a Work Group of national experts to develop consensus recommendations for policymakers and third-party payers on ways to increase the use of brief cognitive assessments (BCAs) in primary care. RESULTS: The group recommended three strategies to promote routine use of BCAs: providing primary care clinicians with suitable assessment tools; integrating BCAs into routine workflows; and crafting payment policies to encourage adoption of BCAs. DISSCUSSION: Sweeping changes and actions of multiple stakeholders are necessary to improve detection rates of mild cognitive impairment so that patients and families may benefit from timely interventions.

A framework for addressing Alzheimer's disease: Without a frame, the work has no aim.

Confronting Alzheimer's disease (AD) involves patients, healthcare professionals, supportive services, caregivers, and government agencies interacting along a continuum from initial awareness to diagnosis, treatment, support, and care. This complex scope presents a challenge for health system transformation supporting individuals at risk for, or diagnosed with, AD. The AD systems preparedness framework was developed to help health systems identify specific opportunities to implement and evaluate focused improvement programs. The framework is purposely flexible to permit local adaptation across different health systems and countries. Health systems can develop solutions tailored to system-specific priorities considered within the context of the overall framework. Example metric concepts and initiatives are provided for each of ten areas of focus. Examples of funded projects focusing on screening and early detection are provided. It is our hope that stakeholders utilize the common framework to generate and share additional implementation evidence to benefit individuals with AD.

Preparedness of the Brazilian health-care system to provide access to a disease-modifying Alzheimer's disease treatment.

BACKGROUND: While the majority of patients with Alzheimer's disease resides in low and middle-income countries, little is known of their preparedness for emerging disease-modifying treatments. We analyze the preparedness of Brazil, one of the most populous middle-income countries, from a capacity and institutional preparedness perspective. METHODS: Desk research and 12 interviews for background and capacity data. Markov model to estimate wait times for access to treatment. FINDINGS: Brazil has no national dementia strategy or established pathway for evaluation of cognitive concerns, and dementia is typically diagnosed late if at all. While members of private health plans have ready access to elective specialty care, wait times in the public sector are long. Assuming potentially treatment-eligible patients are referred from primary to specialty care based on a brief cognitive exam and a blood test for the Alzheimer's pathology, available capacity will not be sufficient to match the projected demand. The biggest obstacle is availability of dementia specialist visits, and the effect of population growth and ageing means that the wait list for specialist appointment will continue to grow from around 400,000 in 2022 to over 2.2 million in 2040. We do not project substantial wait times for confirmatory biomarker testing and treatment delivery but note that this is a consequence of patients waiting for their specialist appointments. These queues will result in estimated persistent wait times for treatment of around two years on average with substantial differences between the public and private sectors, as capacity growth is insufficient to keep up with increasing demand. DISCUSSION: Our findings suggest that Brazil is ill-prepared to provide timely access to an Alzheimer's treatment with predicted wait times of about two years, largely because of a limited number of dementia specialists.

Association of wound healing with quality and continuity of care and sociodemographic characteristics.

OBJECTIVES: To evaluate the association between clinics' wound healing performance and clinic-level measures of care continuity, clinical quality, and sociodemographic characteristics of the population in their catchment areas. STUDY DESIGN: In this cross-sectional analysis, we analyzed electronic health records for 180,336 chronic wounds from 480 wound care clinics during the 2018 calendar year. METHODS: We measured healing performance using a clinic's observed to expected (O/E) ratio, which is based on the rate at which chronic wounds were predicted to heal within 12 weeks given its case mix and the actual healing rate. We compared the top and bottom quintiles, in terms of the O/E ratio, of clinics. Multivariable regression was used to estimate the effect of the clinic-level measures on the O/E ratio. RESULTS: Clinics in the top quintile had higher rates of care continuity and quality measures, as well as a lower proportion of disadvantaged populations in their catchment areas. In the regression model, 10% increases in a clinic's rate of weekly provider visits, nurse visits, and debridement were associated with 2.5%, 3.0% and 0.7% increases, respectively, in the O/E ratio. The weekly provider visit rate had a greater marginal effect when the proportion of African American residents in the clinic's catchment area was larger. CONCLUSIONS: Clinic-level measures of care continuity, clinical quality, and sociodemographic composition of their catchment areas' population explain a meaningful part of differences in clinics' wound healing performance. Better care continuity appears to have a greater beneficial effect in disadvantaged populations.

Projecting the long-term societal value of a disease-modifying treatment for Alzheimer's disease in the United States.

INTRODUCTION: We estimate societal value of a disease-modifying Alzheimer's disease (AD) treatment that reduces progression by 30% in early stages. METHODS: Using the International Society for Pharmacoeconomics and Outcomes Research value flower as framework, we estimate gross societal value, that is, not including treatment cost, from avoided medical and social care costs, productivity and quality-adjusted life-years (QALY) gains for patients and caregivers, adjusting for severity of disease, value of financial insurance, and value of insurance for currently unafflicted adults with a Markov model. RESULTS: Predicted societal value from 2021 until 2041 is $2.62 trillion for the overall afflicted US population and $986 billion for the 2021 prevalent cohort or $134,418 per person, with valuation of patients' QALY gains (63%) and avoided nursing-home costs (20%) as largest components. Delays in access because of health system capacity constraints could reduce realized value between 52% and 69%. The value of insurance for the unafflicted is $4.52 trillion or $18,399 on average per person. DISCUSSION: With a total of $5.5 trillion, the projected gross societal value of a hypothetical AD treatment is substantial, which may help to put the cost of treatment into perspective.