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.

Recommendations for clinical implementation of blood-based biomarkers for Alzheimer's disease.

Blood-based biomarkers (BBM) for Alzheimer's disease (AD) are being increasingly used in clinical practice to support an AD diagnosis. In contrast to traditional diagnostic modalities, such as amyloid positron emission tomography and cerebrospinal fluid biomarkers, BBMs offer a more accessible and lower cost alternative for AD biomarker testing. Their unique scalability addresses the anticipated surge in demand for biomarker testing with the emergence of disease-modifying treatments (DMTs) that require confirmation of amyloid pathology. To facilitate the uptake of BBMs in clinical practice, The Global CEO Initiative on Alzheimer's Disease convened a BBM Workgroup to provide recommendations for two clinical implementational pathways for BBMs: one for current use for triaging and another for future use to confirm amyloid pathology. These pathways provide a standardized diagnostic approach with guidance on interpreting BBM test results. Integrating BBMs into clinical practice will simplify the diagnostic process and facilitate timely access to DMTs for eligible patients.

Considerations for widespread implementation of blood-based biomarkers of Alzheimer's disease.

Diagnosing Alzheimer's disease (AD) poses significant challenges to health care, often resulting in delayed or inadequate patient care. The clinical integration of blood-based biomarkers (BBMs) for AD holds promise in enabling early detection of pathology and timely intervention. However, several critical considerations, such as the lack of consistent guidelines for assessing cognition, limited understanding of BBM test characteristics, insufficient evidence on BBM performance across diverse populations, and the ethical management of test results, must be addressed for widespread clinical implementation of BBMs in the United States. The Global CEO Initiative on Alzheimer's Disease BBM Workgroup convened to address these challenges and provide recommendations that underscore the importance of evidence-based guidelines, improved training for health-care professionals, patient empowerment through informed decision making, and the necessity of community-based studies to understand BBM performance in real-world populations. Multi-stakeholder engagement is essential to implement these recommendations and ensure credible guidance and education are accessible to all stakeholders.

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.

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.

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.

Expected wait times for access to a disease-modifying Alzheimer's treatment in the United States.

INTRODUCTION: A 2017 study had analyzed the preparedness of the U.S. health care system to deliver a disease-modifying Alzheimer's treatment and predicted substantial wait times. We update the prediction with an improved model and newer data. METHODS: The model tracks patients from initial evaluation, cognitive testing by a dementia specialist, confirmatory biomarker testing, and infusion delivery. All steps after initial evaluation are assumed to be capacity constrained. Model parameters and assumptions about care-seeking behavior were derived from the published literature and expert input. RESULTS: If patients were referred based on a brief cognitive test, wait times for specialist visits would reach around 50 months. If referral also required a positive blood-based biomarker test, wait times would be around 12 months. In both scenarios, wait times for confirmatory biomarker testing and infusion treatment would be limited. DISCUSSION: Better diagnostic tools at initial evaluation may reduce unnecessary delays in access to treatment.

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.

Association between state stay-at-home orders and risk reduction behaviors and mental distress amid the COVID-19 pandemic.

The 2019 Coronavirus Disease (COVID-19) pandemic has triggered stay-at-home orders in 43 states since March 19, 2020. Evidence is limited on how these orders affect peoples' behaviors and mental distress. We used a nationally representative survey of 1094 American adults collected between March 19 and March 31, 2020 to compare risk-reduction behaviors and mental distress in states with and without orders. Risk reduction behaviors included hand washing, wearing face mask and social distancing, and the mental distress was assessed by the four-item version of the Patient Health Questionnaire (PHQ-4). We predicted the probability of a person adopting risk reduction behaviors and the mental distress status using the number of days since their state issued the order relative to those in the non-order states, controlling for COVID-19 prevalence in the state, self-reported symptoms and demographic characteristics. The analysis was conducted in April 2020. Results show that the probability of adopting risk reduction behaviors increased between 8 (avoidance of people with high risk, 87% to 95%) and 27 (use of face mask, 18% to 45%) percentage points in the response period. Mental distress increased by 1.0 point on the PHQ-4 score (from 2.4 to 3.5 point) in the first week and started to drop afterwards. In summary, stay-at-home orders were associated with a differential increase in risk-reduction behaviors. People's mental distress rose in the first week under order and dropped afterwards. While in need for confirmation in longitudinal data, these results suggest that residents are responsive to orders.

The Predicted Long-Term Benefits of Ensuring Timely Treatment and Medication Adherence in Early Schizophrenia.

The impact of initiatives aimed at reducing time in untreated psychosis during early-stage schizophrenia will be unknown for many years. Thus, we simulate the effect of earlier treatment entry and better antipsychotic drug adherence on schizophrenia-related hospitalizations, receipt of disability benefits, competitive employment, and independent/family living over a ten-year horizon. We predict that earlier treatment entry reduces hospitalizations by 12.6-14.4% and benefit receipt by 7.0-8.5%, while increasing independent/family living by 41.5-46% and employment by 42-58%. We predict larger gains if a pro-adherence intervention is also used. Our findings suggest substantial benefits of timely and consistent early schizophrenia care.

Economic benefits of microprocessor controlled prosthetic knees: a modeling study.

BACKGROUND: Advanced prosthetic knees allow for more dynamic movements and improved quality of life, but payers have recently started questioning their value. To answer this question, the differential clinical outcomes and cost of microprocessor-controlled knees (MPK) compared to non-microprocessor controlled knees (NMPK) were assessed. METHODS: We conducted a literature review of the clinical and economic impacts of prosthetic knees, convened technical expert panel meetings, and implemented a simulation model over a 10-year time period for unilateral transfemoral Medicare amputees with a Medicare Functional Classification Level of 3 and 4 using estimates from the published literature and expert input. The results are summarized as an incremental cost effectiveness ratio (ICER) from a societal perspective, i.e., the incremental cost of MPK compared to NMPK for each quality-adjusted life-year gained. All costs were adjusted to 2016 U.S. dollars and discounted using a 3% rate to the present time. RESULTS: The results demonstrated that compared to NMPK over a 10-year time period: for every 100 persons, MPK results in 82 fewer major injurious falls, 62 fewer minor injurious falls, 16 fewer incidences of osteoarthritis, and 11 lives saved; on a per person per year basis, MPK reduces direct healthcare cost by $3676 and indirect cost by $909, but increases device acquisition and repair cost by $6287 and total cost by $1702; on a per person basis, MPK is associated with an incremental total cost of $10,604 and increases the number of life years by 0.11 and quality adjusted life years by 0.91. MPK has an ICER ratio of $11,606 per quality adjusted life year, and the economic benefits of MPK are robust in various sensitivity analyses. CONCLUSIONS: Advanced prosthetics for transfemoral amputees, specifically MPKs, are associated with improved clinical benefits compared to non-MPKs. The economic benefits of MPKs are similar to or even greater than those of other medical technologies currently reimbursed by U.S. payers.

Anesthesia Service Use During Outpatient Gastroenterology Procedures Continued to Increase From 2010 to 2013 and Potentially Discretionary Spending Remained High.

OBJECTIVES: Previous studies have identified an increasing number of gastroenterology (GI) procedures using anesthesia services to provide sedation, with a majority of these services delivered to low-risk patients. The aim of this study was to update these trends with the most recent years of data. METHODS: We used Medicare and commercial claims data from 2010 to 2013 to identify GI procedures and anesthesia services based on CPT codes, which were linked together using patient identifiers and dates of service. We defined low-risk patients as those who were classified as ASA (American Society of Anesthesiologists) physical status class I or II. For those patients without an ASA class listed on the claim, we used a prediction algorithm to impute an ASA physical status. RESULTS: Over 6.6 million patients in our sample had a GI procedure between 2010 and 2013. GI procedures involving anesthesia service accounted for 33.7% in 2010 and 47.6% in 2013 in Medicare patients, and 38.3% in 2010 and 53.0% in 2013 in commercially insured patients. Overall, as more patients used anesthesia services, total anesthesia service use in low-risk patients increased 14%, from 27,191 to 33,181 per million Medicare enrollees. Similarly, we observed a nearly identical uptick in commercially insured patients from 15,871 to 22,247 per million, an increase of almost 15%. During 2010-2013, spending associated with anesthesia services in low-risk patients increased from US$3.14 million to US$3.45 million per million Medicare enrollees and from US$7.69 million to US$10.66 million per million commercially insured patients. CONCLUSIONS: During 2010 to 2013, anesthesia service use in GI procedures continued to increase and the proportion of these services rendered for low-risk patients remained high.

Anesthesia Service Use and the Uptake of Screening Colonoscopies.

BACKGROUND: The Center for Medicare & Medicaid Services recently defined "screening colonoscopy" to include separately furnished anesthesia services. OBJECTIVE: To examine the relationship between anesthesia service use and the uptake of screening colonoscopies. STUDY DESIGN: We correlated metropolitan statistical area (MSA) level anesthesia service use rates, derived from the 2008, 2010, and 2012 Medicare and MarketScan claims data, with the presence of individual level guideline concordant screening colonoscopy using the Behavioral Risk Factor Surveillance System data for the same years. MEASURES: Proportion of colonoscopies with anesthesia service was calculated at the MSA level. A guideline concordant screening colonoscopy was defined as a colonoscopy received within the past 10 years. RESULTS: The average MSA level anesthesia service use rate in colonoscopy significantly increased from 25.34% in 2008 to 44.25% in 2012; but only a moderate increase in the rate of guideline concordant colonoscopies was observed, from 57.36% in 2008 to 65.32% in 2012. After adjusting for patient characteristics, we found a nonsignificant negative association between anesthesia service use rate and colonoscopy screening rate, with an odds ratio of 0.90 for receiving a guideline concordant colonoscopy for each percentage point increase in anesthesia service use rate (P=0.27). The relationship between anesthesia service use and the overall colorectal cancer screening rate followed the same pattern and was also not statistically significant. CONCLUSIONS: No significant association between anesthesia service use and colonoscopy screening or colorectal cancer screening rates was found, suggesting that more evidence is needed to support the Center for Medicare & Medicaid Services rule change.

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.

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.

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.

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.

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.