Novel tracers and emerging targets for positron emission tomography in Alzheimer's disease and related dementias.

One-year health-care costs associated with delirium in older hospitalized patients with and without Alzheimer's disease and related dementias (ADRD) have not been examined previously. Medicare costs were determined prospectively at discharge, and at 30, 90, and 365 days in a cohort (n = 311) of older adults after hospital admission. Seventy-six (24%) patients had ADRD and were more likely to develop delirium (51% vs. 24%, P < 0.001) and die within 1 year (38% vs. 21%, P = 0.002). In ADRD patients with versus without delirium, adjusted mean difference in costs associated with delirium were $34,828; most of the excess costs were incurred between 90 and 365 days (P = 0.03). In non-ADRD patients, delirium was associated with increased costs at all timepoints. Excess costs associated with delirium in ADRD patients increased progressively over 1 year, whereas in non-ADRD patients the increase was consistent across time periods. Our findings highlight the complexity of health-care costs for ADRD patients who develop delirium, a potentially preventable source of expenditures. Novel examination of health-care costs of delirium in persons with and without Alzheimer's disease and related dementias (ADRD). Increased 1-year costs of $34,828 in ADRD patients with delirium (vs. without). Increased costs for delirium in ADRD occur later during the 365-day study period. For ADRD patients, cost differences between those with and without delirium increased over 1 year. For non-ADRD patients, the parallel cost differences were consistent over time.

Increasing engagement of Hispanics/Latinos in clinical trials on Alzheimer's disease and related dementias

AI approaches for phenotyping Alzheimer's disease and related dementias using electronic health records.

We evaluated the independent associations between high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels with Alzheimer's disease and related dementias (ADRD). Among 177,680 members of Kaiser Permanente Northern California who completed a survey on health risks, we residualized TGs and HDL-C conditional on age, sex, and body mass index. We included these residuals individually and concurrently in Cox models predicting ADRD incidence. Low (hazard ratio [HR]1.06, 95% confidence interval [CI] 1.02-1.10) and high quintiles (HR 1.07, 95% CI 1.03-1.12) of HDL-C residuals were associated with an increased risk of ADRD compared to the middle quintile. Additional adjustment for TGs attenuated the association with high HDL-C (HR 1.03, 95% CI 0.99-1.08). Low TG residuals were associated with an increased ADRD risk (HR 1.10, 95% CI 1.06-1.15); high TG residuals were protective (HR 0.92, 95% CI 0.88-0.96). These estimates were unaffected by HDL-C adjustment. Low HDL-C and TG levels are independently associated with increased ADRD risk. The correlation with low TG level explains the association of high HDL-C with ADRD. Strong correlations between lipid levels are important considerations when investigating lipids as late-life risk factors for Alzheimer's disease and related dementias (ADRD). Low levels of high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) were independently associated with an increased risk of ADRD. We found no evidence for an association between high HDL-C and increased ADRD risk after adjustment for TGs. High levels of TGs were consistently associated with a decreased risk of ADRD. There may be interaction between TG and HDL-C levels, where both low HDL-C and TG levels increase the risk of ADRD compared to average levels of both.

Injuries are a leading cause of emergency department (ED) visits among older adults, and individuals with Alzheimer's disease and related dementias (ADRD) may be at particular risk. We compared injury-related ED use among assisted living (AL) residents with and without ADRD and assessed differences in the risk of injury-related ED visits among individuals with ADRD residing in ALs with memory care designation versus general AL. Using Medicare claims, we identified a cohort of fee-for-service beneficiaries who lived in AL in 2018 and resided in one of 20 states with site-specific information on memory care designation (n=116,754). Outcomes included all injury-related ED visits and injury-related ED visits resulting in hospitalization in the calendar year 2018. We fit multilevel models of the association between ADRD and outcomes, adjusting for resident demographic characteristics and chronic conditions, license type characteristics, and AL characteristics, with random intercepts at the AL and license type levels. Among residents with ADRD, we examined whether memory care licensure was associated with injury-related ED visits. The adjusted risk of injury-related ED use during the year was 20.1% (95% CI: 19.6%, 20.6%) for residents with ADRD compared to 16.1% for residents without ADRD (95% CI: 15.7%, 16.5%; p < 0.001). The adjusted risk of injury-related ED use ending in hospitalization was 4.9% (95% CI: 4.6%, 5.1%) for AL residents with ADRD and 3.9% for residents without ADRD (95% CI: 3.8%, 4.1%; p < 0.001). There were no significant differences in injury-related ED visits between residents with ADRD in ALs with memory care designation and residents in general AL. Injury-related ED visits are common among AL residents with ADRD and residents in memory care, but residents in memory care AL experienced similar risks of injury as those in general AL. Further research should identify modifiable factors that can prevent injury among AL residents with ADRD.

Longstanding gaps in the detection of Alzheimer's disease and related dementias (ADRD) and biopsychosocial care call for public health action to improve population health. We aim to broaden the understanding of the iterative role state plans have played over the last 20 years in prioritizing improvements in the detection of ADRD, primary care capacity, and equity for disproportionately affected populations. Informed by national ADRD priorities, state plans convene stakeholders to identify local needs, gaps, and barriers and set the stage for development of a national public health infrastructure that can align clinical practice reform with population health goals. We propose policy and practice actions that would accelerate the collaboration between public health, community organizations, and health systems to improve ADRD detection-the point of entry into care pathways that could ultimately improve outcomes on a national scale. HIGHLIGHTS: We systematically reviewed the evolution of state/territory plans for Alzheimer's disease and related dementias (ADRD). Plan goals improved over time but lacked implementation capacity. Landmark federal legislation (2018) enabled funding for action and accountability. The Centers for Disease Control and Prevention (CDC) funds three Public Health Centers of Excellence and many local initiatives. Four new policy steps would promote sustainable ADRD population health improvement.

The increasing prevalence of Alzheimer's disease and related dementias (ADRD) presents both a burden and an opportunity for intervention. This study aims to estimate the impacts of health insurance and resources on the burden attributed to ADRD. Data were mainly collected from global databases for ADRD. Analysis of variance, Pearson correlation, random-effects, and fixed-effects model analyses were used in this study. Although the current medical expenditures were increasing and out of pocket (OOP) expenditures were declining generally in various countries, the collected global data showed an increased burden of ADRD on patients both physically and economically. Furthermore, health resources were negatively associated with disability-adjusted life years (DALY), death, and years of life lost (YLL), but were otherwise positively associated with years of life lived with disability (YLD). Effective measures should be considered to cope with the rising burden. Meanwhile, there is an urgent call for constructive and sustainable rational plans and global collaboration. We explored how health insurance and resources affect Alzheimer's disease and related dementias (ADRD)-related burden. Health insurance and resources were imbalanced among four income level groups. Health insurance and resources may decrease the total ADRD burden primarily from a reduction in death-related burden. Health insurance and resources may increase disability-related burden.

The objectives of this study were to review the diagnostic, International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM), diagnosis related groups (DRGs), and common procedural terminology (CPT) coding and reimbursement issues (including Medicare Part B reimbursement for physicians) encountered in caring for patients with Alzheimer's disease and related dementias (ADRD); to review the implications of these policies for the long-term clinical management of the patient with ADRD; and to provide recommendations for promoting appropriate recognition and reimbursement for clinical services provided to ADRD patients. Relevant English-language articles identified from MEDLINE about ADRD prevalence estimates; disease morbidity and mortality; diagnostic coding practices for ADRD; and Medicare, Medicaid, and managed care organization data on diagnostic coding and reimbursement were reviewed. Alzheimer's disease (AD) is grossly undercoded. Few AD cases are recognized at an early stage. Only 13% of a group of patients receiving the AD therapy donepezil had AD as the primary diagnosis, and AD is rarely included as a primary or secondary DRG diagnosis when the condition precipitating admission to the hospital is caused by AD. In addition, AD is often not mentioned on death certificates, although it may be the proximate cause of death. There is only one ICD-9-CM code for AD-331.0-and no clinical modification codes, despite numerous complications that can be directly attributed to AD. Medicare carriers consider ICD-9 codes for senile dementia (290 series) to be mental health codes and pay them at a lower rate than medical codes. DRG coding is biased against recognition of ADRD as an acute, admitting diagnosis. The CPT code system is an impediment to quality of care for ADRD patients because the complex, time-intensive services ADRD patients require are not adequately, if at all, reimbursed. Also, physicians treating significant numbers of AD patients are at greater risk of audit if they submit a high frequency of complex codes. AD is grossly undercoded in acute hospital and outpatient care settings because of failure to diagnose, limitations of the coding system, and reimbursement issues. Such undercoding leads to a lack of recognition of the effect of AD and its complications on clinical care and impedes the development of better care management. We recommend continuing physician education on the importance of early diagnosis and care management of AD and its documentation through appropriate coding, expansion of the current ICD-9-CM codes for AD, more appropriate use of DRG coding for ADRD, recognition of the need for time-intensive services by ADRD patients that result in a higher frequency of use of complex CPT codes, and reimbursement for CPT codes that cover ADRD care management services.

The Role of Neighborhood Socioeconomic Status in Institutionalization of Home Health Care Patients With and Without Alzheimer's Disease and Related Dementias

Individuals living in rural communities are at heightened risk for Alzheimer's disease and related dementias (ADRD), which parallels other persistent place-based health disparities. Identifying multiple potentially modifiable risk factors specific to rural areas that contribute to ADRD is an essential first step in understanding the complex interplay between various barriers and facilitators. An interdisciplinary, international group of ADRD researchers convened to address the overarching question of: "What can be done to begin minimizing the rural health disparities that contribute uniquely to ADRD?" In this state of the science appraisal, we explore what is known about the biological, behavioral, sociocultural, and environmental influences on ADRD disparities in rural settings. A range ofindividual, interpersonal, and community factors were identified, including strengths of rural residents in facilitating healthy aging lifestyle interventions. Alocation dynamics model and ADRD-focused future directions are offered for guiding rural practitioners, researchers, and policymakers in mitigating rural disparities. Rural residents face heightened Alzheimer's disease and related dementia (ADRD) risks and burdens due to health disparities. Defining the unique rural barriers and facilitators to cognitive health yields insight. The strengths and resilience of rural residents can mitigate ADRD-related challenges. A novel "location dynamics" model guides assessment of rural-specific ADRD issues.

Contemporary patients with heart failure with reduced ejection fraction (HFrEF) are older and have a higher prevalence of cognitive impairment than those studied in trials. The risk/benefit trade-off of routine beta-blocker (BB) use in patients with HFrEF and Alzheimer's disease and related dementias (ADRD) has not been explored. This study aimed to determine the association between BB use and outcomes among patients with HFrEF and ADRD. Using a random 40% sample of Medicare Parts A, B, and D data we identified patients with ≥1 hospitalization for HFrEF between 2008 and 2018. Each patient was classified based on BB use prior to admission and after discharge. Outcomes include 90-day and 1-year mortality and readmission. Between 2008 and 2018, we identified 357,030 patients hospitalized with HFrEF; 12.7% had ADRD. Patients with HFrEF and ADRD had higher 90-day and 1-year mortality compared to patients with HFrEF-only. Among patients admitted on a BB, 60.5% of patients with HFrEF-only were continued on therapy after discharge, compared to 56.8% of patients with HFrEF and ADRD. Discontinuing BB was associated with a 2.2-fold higher risk of 90-day mortality (p< 0.001) among patients with HF-only and a 2.- fold higher risk of 90-day mortality (p< 0.001) among patients with HFrEF+ ADRD. Not starting a BB was associated with a 1.8-fold higher risk of 90-day mortality (p< 0.001) among patients with HFrEF-only and a 1.7-fold higher risk of 90-day mortality (p< 0.001) among patients with HFrEF+ ADRD. Similar risks were seen at 1year. BB therapy is associated with significantly lower short and long-term mortality rates among all patients with HFrEF; the magnitude of these associated benefits appear at least as large in patients with HFrEF and ADRD compared to patients with HFrEF-only.

Effect of apolipoprotein E (APOE) on Alzheimer's disease and related dementias (ADRD) risk is heterogeneous across populations, with scarce data on Hispanics/Latinos. APOE genotype was studied in 12,221 Hispanics/Latinos (per cohort and via metanalysis): Caribbean-Hispanics, Mexicans, Mexican-Americans, and Peruvians/Bolivians. A subsample had longitudinal assessment and plasma p-tau. We tested the modifying effects of global and local ancestries. Results were replicated in an independent Peruvian cohort and brain samples. APOE ε4 effect was strongest in Peruvians/Bolivians (odds ratio [OR]=6.13, 95% confidence interval [CI]=2.71-13.83), followed by Mexicans (OR=4.31, 95% CI=1.58-11.74), Mexican-Americans (OR=3.06, 95% CI=2.04-4.59), and Caribbean-Hispanics (OR=2.22, 95% CI=1.99-2.48). Meta-analyses showed OR=2.32 (95% CI=2.09-2.57) and OR=0.81 (95% CI=0.68-0.97) for the ε4 and ε2 allele, respectively. The APOE ε4 effect was replicated independently in Peruvians (OR=5.06, 95% CI=2.48-10.70). ε4 carriers displayed higher ADRD conversions and p-tau levels. Global and local ancestries did not modify ADRD risk, and they were associated with Braak stage. APOE shows a heterogeneous effect on ADRD risk in our Hispanics/Latinos sample, the largest to date. The apolipoprotein E (APOE) ε4 effect is stronger in Peruvians/Bolivians than in other Hispanic/Latino groups. The strong APOE effect size in Peruvians and Bolivians was replicated in a second independent Peruvian cohort. Meta-analysis for ε4 and ε2 confirmed a significant association with Alzheimer's disease and related dementias (ADRD). Global and local ancestry do not modify the association between APOE genotype and ADRD.

INTRODUCTIONWhether reductions in glycated hemoglobin (HbA1c) levels and body mass index (BMI) mediate the association between glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) and Alzheimer's disease and related dementias (ADRD) risk is unknown.METHODSThis cohort study included 22,908 patients aged ≥ 50 years with type 2 diabetes (T2D) newly prescribed GLP‐1RA or other second‐line glucose‐lowering drugs (GLDs). Causal mediation analysis was used to estimate to what extent the effect of GLP‐1RAs on ADRD risk was attributable to lowering HbA1c or BMI.RESULTSCompared to other GLD users, GLP‐1RA users had significant reductions in HbA1c levels by 0.16% and BMI by 0.23 kg/m2, along with a 26% lower ADRD risk. The direct protective effect of GLP‐1RAs on ADRD risk persisted even after accounting for HbA1c and BMI reductions, with minimal mediation effects observed through these factors.DISCUSSIONGLP‐1RAs reduce ADRD risk, largely independent of their effects on HbA1c and BMI.HighlightsGlucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) were associated with reductions in glycated hemoglobin (HbA1c) and body mass index (BMI) compared to other second‐line glucose‐lowering drugs(GLDs).GLP‐1RA users were associated with a 26% lower risk of Alzheimer's disease and related dementias (ADRD) than other GLD users.The protective effect of GLP‐1RAs against ADRD in adults with type 2 diabetes (T2D) is largely independent of their effects on HbA1c and BMI.

How Long-Term Care Quality Measures Address Alzheimer's Disease and Related Dementias in European Countries.

This review covers recent advances (2023–2024) in neuroimaging research into the pathophysiology, progression, and treatment of Alzheimer's disease (AD) and related dementias (ADRD). Despite the rapid emergence of blood‐based biomarkers, neuroimaging continues to be a vital area of research in ADRD. Here, we discuss neuroimaging as a powerful tool to topographically visualize and quantify amyloid, tau, neurodegeneration, inflammation, and vascular disease in the brain. We examine the utility of neuroimaging for (1) tracking the spatiotemporal progression of pathology, (2) serving as the reference standard for validating novel fluid biomarkers, (3) characterizing disease heterogeneity, (4) exploring the role of brain networks in ADRD progression, and (5) evaluating biomarkers for better individualized estimates of treatment benefit. Finally, we discuss advances in radiotracer development and AD risk factors. By reviewing the most promising breakthroughs in the neuroimaging field, we hope to spark new ideas for future discoveries that will deepen our understanding of ADRD.HighlightsThe diagnostic and staging criteria for Alzheimer's disease (AD) were updated in 2024.Despite robust harmonization methods for amyloid beta positron emission tomography (PET), parallel efforts for tau PET remain challenging.Larger anti‐amyloid drug effects were seen at lower levels of amyloid and tau PET.Phosphorylated tau217 (p‐tau217) is currently the most promising plasma biomarker to detect AD pathology.There are new tracer developments for alpha‐synuclein, primary tauopathies, and inflammation.