Aging is the leading risk factor for most chronic illnesses of old age, including Alzheimer disease (AD), a progressive neurodegenerative disease with currently no therapies that prevent, slow, or ...halt disease progression. Like other chronic diseases of old age, the progressive pathology of AD begins decades before the onset of symptoms. Many decades of research in biological gerontology have revealed common processes that are relevant to understanding why the aging brain is vulnerable to AD. In this review, we frame the development of novel therapeutics for AD in the context of biological gerontology. The many therapies currently in development based on biological gerontology principles provide promise for the development of a new generation of therapeutics to prevent and treat AD.
Objectives
To characterize Medicare expenditure and usage trends in individuals with a coded diagnosis of Alzheimer's disease and related dementia (ADRD) or mild cognitive impairment (MCI) during the ...periods leading up to and after diagnosis.
Design
Retrospective observational cohort study.
Setting
Five percent sample of the 2009 to 2013 Medicare claims files.
Participants
Individuals newly diagnosed with ADRD (n = 25,916) or MCI (n = 2,784), each with a propensity‐score matched control subject.
Measurements
Medicare expenditures and usage during the 24 months before and after a new diagnosis of ADRD or MCI.
Results
Medicare expenditures were 42% higher in participants with ADRD ($10,622 vs $15,091, P < .001) and 41% higher in those with MCI ($9,728 vs $13,691, P < .001) during the year before diagnosis than in matched controls. Medicare expenditures of participants with ADRD increased to $27,126 for the first 12 months immediately after diagnosis and decreased to $17,257 during the 12 months after that. For participants with MCI, average Medicare expenditures were $20,386 for the 12 months after diagnosis and $14,286 for the 12 months after that. Use of inpatient care, postacute skilled nursing facility care, and home health care increased substantially after diagnosis of ADRD or MCI.
Conclusion
Participants with ADRD and MCI incurred significantly higher Medicare expenditures than matched controls, even before they received a formal diagnosis. Medicare expenditures of individuals with ADRD and MCI may start to increase at least 12 months before their diagnosis, peak during the first few months immediately after diagnosis, and decrease afterward but remain at a higher level than before diagnosis. These findings highlight the importance of early diagnosis and indicate the need for complex case management to coordinate care transitions for individuals with ADRD and MCI.
Alzheimer's disease is the public health crisis of the 21st century. There is a clear need for a widely available, inexpensive and reliable method to diagnosis Alzheimer's disease in the earliest ...stages, track disease progression, and accelerate clinical development of new therapeutics. One avenue of research being explored is blood based biomarkers. In April 2012, the Alzheimer's Association and the Alzheimer's Drug Discovery Foundation convened top scientists from around the world to discuss the state of blood based biomarker development. This manuscript summarizes the meeting and the resultant discussion, including potential next steps to move this area of research forward.
Synapse damage and loss are fundamental to the pathophysiology of Alzheimer's disease (AD) and lead to reduced cognitive function. The goal of this review is to address the challenges of forging new ...clinical development approaches for AD therapeutics that can demonstrate reduction of synapse damage or loss. The key points of this review include the following: Synapse loss is a downstream effect of amyloidosis, tauopathy, inflammation, and other mechanisms occurring in AD.Synapse loss correlates most strongly with cognitive decline in AD because synaptic function underlies cognitive performance.Compounds that halt or reduce synapse damage or loss have a strong rationale as treatments of AD.Biomarkers that measure synapse degeneration or loss in patients will facilitate clinical development of such drugs.The ability of methods to sensitively measure synapse density in the brain of a living patient through synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) imaging, concentrations of synaptic proteins (e.g., neurogranin or synaptotagmin) in the cerebrospinal fluid (CSF), or functional imaging techniques such as quantitative electroencephalography (qEEG) provides a compelling case to use these types of measurements as biomarkers that quantify synapse damage or loss in clinical trials in AD.
A number of emerging biomarkers are able to measure synapse injury and loss in the brain and may correlate with cognitive function in AD. These biomarkers hold promise both for use in diagnostics and in the measurement of therapeutic successes.
The US National Institute of Neurological Disorders and Stroke convened major stakeholders in June 2012 to discuss how to improve the methodological reporting of animal studies in grant applications ...and publications. The main workshop recommendation is that at a minimum studies should report on sample-size estimation, whether and how animals were randomized, whether investigators were blind to the treatment, and the handling of data. We recognize that achieving a meaningful improvement in the quality of reporting will require a concerted effort by investigators, reviewers, funding agencies and journal editors. Requiring better reporting of animal studies will raise awareness of the importance of rigorous study design to accelerate scientific progress.
Individuals with Alzheimer's disease and related disorders (ADRD) have more frequent hospitalizations than individuals without ADRD, and some of these admissions may be preventable with proactive ...outpatient care.
This study was a cross-sectional analysis of Medicare claims data from 195,024 fee-for-service ADRD beneficiaries aged ≥65 years and an equal number of matched non-ADRD controls drawn from the 5% random sample of Medicare beneficiaries in 2007-2008. We analyzed the proportion of patients with potentially avoidable hospitalizations (PAHs, as defined by the Medicare Ambulatory Care Indicators for the Elderly) and used logistic regression to examine patient characteristics associated with PAHs. We used paired t tests to compare Medicare expenditures by ADRD status, stratified by whether there were PAHs related to a particular condition.
Compared with matched non-ADRD subjects, Medicare beneficiaries with ADRD were significantly more likely to have PAHs for diabetes short-term complications (OR = 1.43; 95% CI 1.31-1.57), diabetes long-term complications (OR = 1.08; 95% CI = 1.02-1.14), and hypertension (OR = 1.22; 95% CI 1.08-1.38), but less likely to have PAHs for chronic obstructive pulmonary disease (COPD)/asthma (OR = 0.85; 95% CI 0.82-0.87) and heart failure (OR = 0.89; 95% CI 0.86-0.92). Risks of PAHs increased significantly with comorbidity burden. Among beneficiaries with a PAH, total Medicare expenditures were significantly higher for those subjects who also had ADRD.
Medicare beneficiaries with ADRD were at a higher risk of PAHs for certain uncontrolled comorbidities and incurred higher Medicare expenditures compared with matched controls without dementia. ADRD appears to make the management of some comorbidities more difficult and expensive. Ideally, ADRD programs should involve care management targeting high-risk patients with multiple chronic conditions.
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