Our team of neuroscientists has authored dozens of scientific and opinion papers addressing a range of topics, from challenges in accelerating drug repurposing to evaluations of evidence surrounding dementia prevention strategies.
Repurposing Food and Drug Administration (FDA)-approved drugs for a new indication may offer an accelerated pathway for new treatments but is also fraught with significant commercial, regulatory and reimbursement challenges. The Alzheimer's Drug Discovery Foundation and the Michael J. Fox Foundation for Parkinson's Research convened an advisory panel in October 2013 to better understand stakeholder perspectives related to repurposing FDA-approved drugs for neurodegerative diseases. In the resulting paper, the foundations explore opportunities for philanthropy, industry and government to begin to address these challenges, promote policy changes and develop targeted funding strategies to accelerate drug repurposing.
Certain chronic conditions appear to be modifiable risk factors of Alzheimer's disease and related dementias. To understand the potential health and economic impacts of addressing those risk factors, we used data on a Medicare cohort to simulate four scenarios: a 10 percent reduction in the prevalence of diabetes, hypertension, cardiovascular diseases, respectively, and a 10 percent reduction in body mass index among beneficiaries who were overweight or obese. Our simulation demonstrated that reducing the prevalence of these conditions may yield "unintended benefits" by lowering the risk, delaying the onset, reducing the duration, and lowering the costs of dementia.
Though lacking conclusive proof, decades of research suggests that specific approaches, including the consumption of coffee, may be effective in preventing age-related cognitive decline and Alzheimer's disease. Coffee and caffeine are known to enhance short-term memory and cognition, and some limited research suggests that long-term use may protect against cognitive decline or dementia.
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.
Every medical decision should be based on the best available scientific evidence. This goal motivates evidence-based medicine, a movement with undisputable value that improves the rigor of research available for medical decisions. While not the original goal of evidence-based medicine, randomized clinical trials (RCTs) have not simply become the gold standard of confidence but have overshadowed and limited the use of other sources of useful information. As stated by Kaplan et al, “over-reliance on RCTs is similar to resting all of health care evidence on a one-legged stool.”
Increased knowledge about the biology of synaptic function has led to the development of novel cognitive-enhancing therapeutic strategies with the potential for increased efficacy and safety. This editorial highlights a diverse array of approaches currently being explored to target cognitive dysfunction due to aging and/or Alzheimer's disease.
This editorial provides recommendations to scientists on the process of selecting and managing a contract with an external vendor or contract research organization. Contract research organizations (CROs) are required by scientists to provide industry standard services for drug discovery and development programs. This editorial is the outcome of a one day advisory panel convened by the ADDF.
This meeting report from our 13th International Conference on Alzheimer's Drug Discovery provides an overview on a number of programs funded by the Alzheimer's Drug Discovery Foundation.
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.
Currently, the field is awaiting the results of several pivotal Phase III clinical Alzheimer's disease (AD) trials that target amyloid-β (Aβ). In light of the recent biomarker studies that indicate Aβ levels are at their most dynamic 5-10 years before the onset of clinical symptoms, it is becoming uncertain whether direct approaches to target Aβ will achieve desired clinical efficacy. AD is a complex neurodegenerative disease caused by dysregulation of numerous neurobiological networks and cellular functions, resulting in synaptic loss, neuronal loss, and ultimately impaired memory.
Human cognitive aging has been too long neglected and underappreciated for its critical importance to quality of life in old age. The articles in this session present novel approaches to improving cognitive function in normal aging persons with drugs and interventions that are based on findings in epidemiology, studies in aged animals, and in vitro research. In addition, since aging is the primary risk factor for Alzheimer's disease, these studies also have implications as interventions for prevention and treatment.
Although the molecular mechanisms underlying the pathogenesis of Alzheimer's disease and other related neurodegenerative diseases remain unclear, accumulation of misfolded proteins, neuroinflammation, mitochondrial dysfunction and perturbed calcium homeostasis have been identified as key events leading to neuronal loss during neurodegeneration.
Animal models have contributed significantly to our understanding of the underlying biological mechanisms of Alzheimer's disease (AD). As a result, over 300 interventions have been investigated and reported to mitigate pathological phenotypes or improve behavior in AD animal models or both. To date, however, very few of these findings have resulted in target validation in humans or successful translation to disease-modifying therapies.
To better understand the status of frontotemporal dementia (FTD) research, and identify opportunities to accelerate translational research, we analyzed international funding for FTD and related dementias between 1998 and 2008. Search terms were compiled to define the clinical spectrum of FTD and all known mechanisms. Funders were asked to return grants that contained these search terms in the title or abstract.
While Alzheimer's disease researchers continue to debate the underlying cause(s) of the disease, most agree that a diverse, multi-target approach to treatment will be necessary. To this end, the Alzheimer's Drug Discovery Foundation (ADDF) hosted its 11th International Conference on Alzheimer's Drug Discovery to highlight the array of exciting efforts from the ADDF's funded investigators.
This review summarizes the scientific talks presented at the conference "Therapeutics for Cognitive Aging," hosted by the New York Academy of Sciences and the Alzheimer's Drug Discovery Foundation on May 15, 2009. Attended by scientists from industry and academia and a number of lay people, the conference specifically tackled the many aspects of developing therapeutic interventions for cognitive impairment. Discussion also focused on how to define cognitive aging and whether it should be considered a treatable, tractable disease.
In order to significantly tackle the most catastrophic and devastating symptom of Alzheimer's disease (AD) we must be able to detect the disease prior to the onset of clinical symptoms, and be able to offer patients preventative treatments that block or significantly slow disease progression. This review summarizes a variety of the most promising early detection methods for Alzheimer's disease (AD) and mild cognitive impairment (MCI) that could be used to identify those at high risk of developing the disease.
These proceedings highlight new approaches to address and overcome the specific challenges of drug discovery for neurodegenerative diseases that were discussed at the 3rd Drug Discovery for Neurodegenerative Conference (held in Washington DC on 2–3 February 2009). This conference was hosted by the Alzheimer's Drug Discovery Foundation, in partnership with the National Institutes of Health, to advance drug discovery for neurodegenerative diseases by educating scientists on the process of translating basic research into novel therapies.
Early detection and diagnosis are critical to dementia care. However, many early cases remain undiagnosed as a result of the impracticality of neuropsychological testing, particularly in primary care. Mindstreams is an office-based computerized system for measuring cognitive function in multiple domains, with demonstrated validity, test-retest reliability, and sensitivity to treatment effects. This study evaluated its feasibility for assessment of the elderly.
This issue highlights advances in the field of drug discovery for Alzheimer’s disease (AD) that were discussed at the 7th International Conference on Alzheimer’s Disease Drug Discovery (held on October 12-13 2006 in New York) following previous conferences on similar theme. The conference involved around 150 attendees from academia, the pharmaceutical and biotechnology industries and focused solely on the development of new drugs for AD and related dementias.
This review condenses the available scientific evidence with practical information on the available sources of long-chain omega-3 fatty acids and the research steps needed to prove their efficacy in Alzheimer's disease and related dementias.
To better understand the status of frontotemporal dementia (FTD) research, and identify opportunities to accelerate translational research, we analyzed international funding for FTD and related dementias between 1998 and 2008. FTD received moderate funding over the past decade, which has decreased almost five-fold during this period. A sizable proportion of FTD funding supported mechanisms shared with Alzheimer’s disease.
Alzheimer’s disease (AD), as with other late life diseases, is undoubtedly caused by a multitude of factors that are influenced by stochastic events, an individual’s genetic makeup and environmental exposures. Combination therapy; including preventative treatments, disease modifying therapies, symptomatic agents and lifestyle changes may be our best hope at eradicating Alzheimer’s disease from our society.