With your extra risk of dementia your competent? doctor needs to find prevention solutions! Is your doctor even working on that? NO? So, your doctor is in the process of being fired?
1. A documented 33% dementia chance post-stroke from an Australian study? May 2012.
2. Then this study came out and seems to have a range from 17-66%. December 2013.`
3. A 20% chance in this research. July 2013.
4. Dementia Risk Doubled in Patients Following Stroke September 2018
The latest here:
Data-driven discovery of associations between prescribed drugs and dementia risk: A systematic review
Benjamin R. Underwood and Ilianna Lourida contributed equally and are joint first authors
Abstract
Recent clinical trials on slowing dementia progression have led to renewed focus on finding safer, more effective treatments. One approach to identify plausible candidates is to assess whether existing medications for other conditions may affect dementia risk. We conducted a systematic review to identify studies adopting a data-driven approach to investigate the association between a wide range of prescribed medications and dementia risk. We included 14 studies using administrative or medical records data for more than 130 million individuals and 1 million dementia cases. Despite inconsistencies in identifying specific drugs that may modify Alzheimer's or dementia risk, some themes emerged for drug classes with biological plausibility. Antimicrobials, vaccinations, and anti-inflammatories were associated with reduced risk, while diabetes drugs, vitamins and supplements, and antipsychotics were associated with increased risk. We found conflicting evidence for antihypertensives and antidepressants. Drug repurposing for use in dementia is an urgent priority. Our findings offer a basis for prioritizing candidates and exploring underlying mechanisms.
Highlights
- · We present a systematic review of studies reporting association between drugs prescribed for other conditions and risk of dementia including 139 million people and 1 million cases of dementia.
- · Our work supports some previously reported associations, for example, showing decreased risk of dementia with drugs to treat inflammatory disease and increased risk with antipsychotic treatment.
- · Antimicrobial treatment was perhaps more surprisingly associated with decreased risk, supportive of recent increased interest in this potential therapeutic avenue.
- · Our work should help prioritize drugs for entry into adaptive platform trials in Alzheimer's disease and will serve as a useful resource for those investigating drugs or classes of drugs and risk of dementia.
1 INTRODUCTION
Dementia is a leading cause of morbidity and mortality and has an estimated worldwide economic cost in excess of 1 trillion dollars.1 It can lead to profound distress in the individual and in those caring for them. As such, dementia represents one of the most important challenges in medicine and public health. Current medical treatments for dementia are symptomatic and have a modest effect. Despite intensive efforts, trial results of disease-modifying drugs have historically been largely disappointing. Any disease-modifying drug would need only a relatively modest effect to have a significant impact; delaying the onset of Alzheimer's disease (AD) by 5 years would translate into lower prevalence and its associated costs by 40%.2 The recent findings that two new drugs, lecanemab and donanemab, reduce amyloid plaque levels in early symptomatic AD and result in statistically significant clinical benefits are a momentous step in the field.3, 4 However, these drugs target a single pathway in a complex condition, carry a significant risk of severe side effects, and there is wide consensus that multiple approaches are likely to be needed to provide maximally effective treatment.5, 6 An increasing number of pathological mechanisms have been identified and these have been targeted by both novel and repurposed drugs. Importantly, many of these mechanisms, for example, protein misfolding, production, and degradation, are common to many of the underlying causes of dementia7 and therefore any treatment targeting a common mechanism may have benefit in several different conditions.
Once a pathogenic pathway is identified, generic drugs can be screened to find those that act on the pathway and be tested in animal models of disease. Associations can then be sought from large clinical databases to examine if these prespecified drugs are associated with altered incidence of dementia or individual diseases leading to dementia. Examples of this approach include assessing medications which may act on specific pathways such as inflammation or the unfolded protein response as well as drugs with pleiotropic proposed mechanisms.8-10
Examining risk reduction associated with already prescribed medications can complement the traditional drug discovery approach. Currently prescribed drugs may interact with dementia-related pathophysiological pathways by way of mechanisms unrelated to their original therapeutic indication.8 For example, some but not all, drug treatments for diabetes have been associated with reduced dementia risk suggesting that any effect may be separate to the ability to lower blood glucose.11 Other drug classes, for example benzodiazepines, have been associated with increased risk of dementia12 although more recent studies suggest that the role of benzodiazepines in dementia risk is questionable.13
Available evidence is primarily based on large prospective cohort studies (eg, UK Biobank) or retrospective studies studying associations between specific drugs or classes and dementia incidence. An alternative approach is to utilize large clinical datasets and examine all drugs in current use for associations with dementia risk. The increasing availability of routinely collected data such as electronic health records (EHRs) and administrative health claims data, along with the application of more sophisticated methodological approaches, allow the study of associations between hundreds of drugs with multiple outcomes in millions of patients. This approach has been adopted to identify individual drugs which have then been investigated in the lab to understand their potential mechanism, a reversal of the usual approach.14 Other studies have used routinely collected data to generate drug repurposing hypotheses or develop dementia risk prediction models. Some of these have identified specific medications or drug classes as important predictors of dementia risk, sometimes with conflicting results (eg, statins, antibiotics, antipsychotics).15-17
We conducted a systematic review to identify and summarize studies adopting a data-driven approach to investigate the association between prescribed medications and dementia risk. Though this methodology excludes some high-quality papers examining specific drugs or groups of drugs, it has the advantage of minimizing publication bias (only positive associations with hypothesized drugs being reported), serves as a complementary approach to attempt to replicate previously reported findings using alternative designs and, crucially, includes all currently prescribed drugs, which allows the potential for identifying drugs which might alter risk but which have not previously been the focus of research. Studies investigating many medications are liable to false positive findings. Each paper allowed for this in their original publication. However, one of our motivations for completing this review was to see if findings replicated in different databases using different techniques. If associations were true positives one would expect them to be identified in more than one paper taking this approach. Our aim was to identify consistent patterns of individual or classes of drugs which alter risk of a dementia diagnosis to support potential candidates for drug repurposing and inform risk reduction and prevention strategies.
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