Rosiglitazone Does Not Improve Cognition or Global Function when Used as Adjunctive Therapy to AChE Inhibitors in Mild-to-Moderate Alzheimers Disease: Two Phase 3 Studies

Harrington, Conn M; Sawchak, Sharon; Chiang, Carl; Davies, J.; Donovan, Carly; Saunders, Ann M.; Irizarry, Michael C.; Jeter, Barbara; Zvartau-Hind, Marina; Dyck, C H van; Gold, Maike

doi:10.2174/156720511796391935

Cited by 166 publications

(120 citation statements)

References 37 publications

(54 reference statements)

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“…150 Similarly, Rosiglitazone did not improve cognition or global function at 48 weeks when used as adjunctive therapy to AChEI in two other phase 3 RCTs in mild-to-moderate Alzheimer's disease. 151 There was no evidence of an interaction between treatment and APOE status in all three studies. Oedema was the most common side effect with rosiglitazone treatment; anaemia and heart failure were also common in the rosiglitazone group compared with placebo.…”

Section: Grade a Level 1 ++mentioning

confidence: 77%

Systematic review of recent dementia practice guidelines

2014

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Level Type of Evidence + +High quality meta-analyses, systematic reviews of randomised controlled trials (RCTs), or RCTs with a very low risk of bias. +Well conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias. -Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias + +High quality systematic reviews of case control or cohort studies. High quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal 2 + Well conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal -Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal 3Non-analytic studies, e.g. case reports, case series 4 Expert opinion Levels of evidence and grades of recommendation Statement of IntentThese guidelines are not intended to serve as a standard of medical care. Standards of medical care are determined on the basis of all clinical data available for an individual case and are subject to change as scientific knowledge advances and patterns of care evolve.The contents of this publication are guidelines to clinical practice, based on the best available evidence at the time of development. Adherence to these guidelines may not ensure a successful outcome in every case. These guidelines should neither be construed as including all proper methods of care, nor exclude other acceptable methods of care. Each physician is ultimately responsible for the management of his/her unique patient, in the light of the clinical data presented by the patient and the diagnostic and treatment options available. ForewordDementia represents a major public health concern in Singapore and worldwide. Being the most prevalent neurodegenerative disease, dementia is expected to affect 55,000 patients in Singapore by the year 2020. The commonest cause of dementia is Alzheimer's disease with vascular dementia being the next most important cause. Right from the stage of mild dementia up to the stages of severe dementia, this condition poses a significant health and socio-economic burden to patients, caregivers and the nation as a whole. Early diagnosis will allow appropriate use of pharmacological and non-pharmacological management. Along with disease stabilization, efforts to address caregiver burden, patient safety and medico legal concerns should form the principles of management. Clear practise guidelines will allow holistic and optimal care in dementia.I am pleased to present the revised clinical practise guidelines for dementia. In this regard the workgroup has performed a thorough review of the existing literature to recommend both pharmacological and nonpharmacological aspects of management for patients ranging from mild cognitive impairment to severe dementia. This revised guidelines also highlights issues related to the management of mild cognitive impairment, young onset dementia and e...

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Section: Grade a Level 1 ++mentioning

confidence: 77%

Systematic review of recent dementia practice guidelines

2014

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“…However another small study failed to observe improvements in cognitive symptoms in patients with Alzheimer's [90]. While a randomized clinical trial failed to demonstrate efficacy of rosiglitazone to improve symptoms in Alzheimer's disease [91], larger trials are necessary to clarify the efficacy of pioglitazone to improve cognitive symptoms in Alzheimer's disease [92].…”

Section: Neuroprotective Effects Of Ppargamma Agonistsmentioning

confidence: 99%

Neuroprotection by dietary restriction and the PPAR transcription complex

Mobbs

Moreno

Kim

et al. 2012

Translational Neuroscience

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Although the pathophysiology of neurodegenerative diseases is distinct for each disease, considerable evidence suggests that a single manipulation, dietary restriction, is strikingly protective against a wide range of such diseases. Thus pharmacological mimetics of dietary restrictions could prove widely protective across a range of neurodegenerative diseases. The PPAR transcription complex functions to re-program gene expression in response to nutritional deprivation as well as in response to a wide variety of lipophilic compounds. In mammals there are three PPAR homologs, which dimerize with RXR homologs and recruit coactivators Pgc1-alpha and Creb-binding protein (Cbp). PPARs are currently of clinical interest mainly because PPAR activators are approved for use in humans to reduce lipidemia and to improve glucose control in Type 2 diabetic patients. However, pharmacological enhancement of the activity of the PPAR complex is neuroprotective across a wide variety of models for neuropathological processes, including stroke, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Conversely activity of the PPAR transcriptional complex is reduced in a variety of neuropathological processes. The main mechanisms mediating the neuroprotective effects of the PPAR transcription complex appear to be re-routing metabolism away from glucose metabolism and toward alternative subtrates, and reduction in inflammatory processes. Recent evidence suggests that the PPAR transcriptional complex may also mediate protective effects of dietary restriction on neuropathological processes. Thus this complex represents one of the most promising for the development of pharmacological treatment of neurodegenerative diseases.

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“…However, there is also contrast report that the long-term use of TZDs is not associated with the risk of developing AD [47] . In some clinical trials, TZDs failed to show any improvements on cognitive performance in the patients with mild-to-moderate AD [48,49] . In addition, the use of TZDs is limited by the increased risk of hepatic impairment.…”

Section: Thiazolidinedionesmentioning

confidence: 99%

Fight against Glucose Rescues Age-Related Cognitive Decline

Tong

Chen

2016

Neurosci Commun

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Aging is commonly associated with dysfunctions of various systems, especially the cognitive decline that seriously diminishes the independence and life quality of old individuals. Exploring the approaches for maintaining a healthy brain is now a critical public health concern. Calorie restriction (CR) has been known to extend longevity, promote metabolic health, and delay the progress of aging and the risk of age-related diseases, such as type 2 diabetes and Alzheimer's disease (AD). Studies have shown that CR improves the insulin sensitivity. Moreover, defected insulin signaling in individuals with or without diabetes is related to a higher risk of age-related cognitive deficits or AD. Evidences suggest that treatment of diabetes mimics the activity of CR, modulating the metabolism of glucose and lipid and the function of insulin system, thus may has the anti-aging potential. In this paper, we reviewed the laboratory experiment and clinical data that focused on the protective role of CR, and that investigated the effect of several types of common agents for diabetes treatment on aging or cognitive ability. The progress in recent years inspires researchers to explore the mechanisms of age-related cognitive decline, and search for safe and effective therapeutic strategies. In the future, more high-quality studies are required to optimize the application of CR or diabetes therapies on the prevention or treatment of brain aging.

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Rosiglitazone Does Not Improve Cognition or Global Function when Used as Adjunctive Therapy to AChE Inhibitors in Mild-to-Moderate Alzheimers Disease: Two Phase 3 Studies

Cited by 166 publications

References 37 publications

Systematic review of recent dementia practice guidelines

Systematic review of recent dementia practice guidelines

Neuroprotection by dietary restriction and the PPAR transcription complex

Fight against Glucose Rescues Age-Related Cognitive Decline

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