A call for comparative effectiveness research to learn whether routine clinical care decisions can protect from dementia and cognitive decline

Abstract

Common diseases like diabetes, hypertension, and atrial fibrillation are probable risk factors for dementia, suggesting that their treatments may influence the risk and rate of cognitive and functional decline. Moreover, specific therapies and medications may affect long-term brain health through mechanisms that are independent of their primary indication. While surgery, benzodiazepines, and anti-cholinergic drugs may accelerate decline or even raise the risk of dementia, other medications act directly on the brain to potentially slow the pathology that underlies Alzheimer’s and other dementia. In other words, the functional and cognitive decline in vulnerable patients may be influenced by the choice of treatments for other medical conditions. Despite the importance of these questions, very little research is available. The Alzheimer’s Drug Discovery Foundation convened an advisory panel to discuss the existing evidence and to recommend strategies to accelerate the development of comparative effectiveness research on how choices in the clinical care of common chronic diseases may protect from cognitive decline and dementia.

Association of metformin, sulfonylurea and insulin use with brain structure and function and risk of dementia and Alzheimer’s disease: Pooled analysis from 5 cohorts

“…Observational studies are essential in assessing the link between medical treatments and long-term cognitive health [14, 63]. While randomized controlled trials (RCTs) are considered the best levels of evidence and are the only study design which can establish causality, their role in understanding the relationships between diabetes medications and cognitive outcomes is limited.…”

“…Diabetes drugs’ mechanisms of action involve multiple pathologies common to diabetes and dementia and AD, including insulin resistance and impaired glucose metabolism [13]. Thus, there is an intense interest in whether type 2 diabetes drugs can be repurposed to slow cognitive aging and reduce the risk of cognitive impairment and dementia through direct effects in the brain that are independent of their approved indications for treating high blood glucose [14]. In contrast, type 2 diabetes medications may also have detrimental effects on the brain, possibly through their tendency to cause hypoglycemic episodes [15, 16].…”

The association between blood pressure variability (BPV) with dementia and cognitive function: a systematic review and meta-analysis protocol

“…Otherwise, only narrative reviews were reported for the potential role of BPV in dementia and cognitive dysfunction [ 39 – 42 ]. Given the reduction in treat-to-target blood pressure level in recent guidelines [ 43 ], and uncertainty around the optimal blood pressure for brain health [ 1 ], it is imperative to clarify the role of blood pressure and its variability in relation to dementia [ 44 ]. A systematic review and meta-analysis pertaining to BPVs’ association with dementia, cognitive impairment, and cognitive function might in turn assist in the design of subsequent epidemiological studies and inform clinicians.…”

The application of PRECIS-2 ratings in randomized controlled trials of Chinese herbal medicine

“…From a comparative effectiveness research (CER) perspective, the “effectiveness” of an intervention in pragmatic trials refers to the extent to which it benefits the targeted population in routine circumstances, with the goal of supporting informed decision-making and improving healthcare. [ 1 – 3 ] By contrast, the “efficacy” of an intervention is related to the degree to which the intervention does what is intended under ideal conditions by means of an explanatory randomized controlled trial (RCT). [ 4 , 5 ] Nowadays, many investigators do not value or distinguish between these two concepts when designing and performing clinical trials.…”