Peroxisome Proliferator-Activated Receptor-Gamma Agonists for Alzheimer’s Disease and Amnestic Mild Cognitive Impairment: A Systematic Review and Meta-Analysis

Liu, Jia; Wang, Luning; Jia, Jianping

doi:10.1007/s40266-014-0228-7

Cited by 46 publications

(36 citation statements)

References 33 publications

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“…Two recent meta-analyses of primarily small trials reported that pioglitazone may be beneficial for patients with mild-to-moderate AD, particularly in patients with comorbid diabetes [82,83].…”

Section: Ppar Agonistsmentioning

confidence: 99%

Targeting neuroinflammation in Alzheimer’s disease: evidence for NSAIDs and novel therapeutics

Deardorff

Grossberg

2016

Expert Review of Neurotherapeutics

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There is an increasing recognition of the immune system as an important mediator in the pathogenesis of Alzheimer's disease (AD). As immune system modulators, non-steroidal anti-inflammatory drugs (NSAIDs) garnered initial enthusiasm from pre-clinical and epidemiologic studies as agents to reduce the risk of AD. Areas covered: This article will examine the evidence for the use of NSAIDs in AD by discussing the proposed mechanism of action, results from epidemiologic studies, and data from randomized controlled trials. In addition, a survey of several novel approaches to targeting inflammatory pathways currently in pre-clinical and clinical phases of development is presented. These agents primarily act to modulate microglial functioning, enhance amyloid-β phagocytosis, suppress potentially harmful pro-inflammatory responses, or enhance systemic immunity. Expert commentary: While long-term use of NSAIDs is associated with a reduced incidence of AD in epidemiologic studies, randomized controlled trials have not replicated these findings. Thus, NSAID use cannot currently be recommended either for primary prevention or treatment of AD. However, the available evidence does suggest that cognitively normal patients taking long-term courses of NSAIDs for other indications likely have a decreased risk of AD, which represents an important finding given the high prevalence of NSAID use among older adults.

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Section: Ppar Agonistsmentioning

confidence: 99%

Targeting neuroinflammation in Alzheimer’s disease: evidence for NSAIDs and novel therapeutics

Deardorff

Grossberg

2016

Expert Review of Neurotherapeutics

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“…These observations logically led to the idea of repurposing T2D drugs in AD (Yarchoan and Arnold, 2014). Insulin, thiazolidinediones and glucagon-like peptide-1 (GLP-1) analog are still the subject of clinical trials in dementia, albeit with mitigated results (Craft et al, 2012;Gejl et al, 2016;J. Liu et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Repurposing beta3-adrenergic receptor agonists for Alzheimer’s disease: Beneficial effects on recognition memory and amyloid pathology in a mouse model

Tournissac

Vrabic

et al. 2020

Preprint

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Old age, the most important risk factor for Alzheimer's disease (AD), is associated with thermoregulatory deficits. Brown adipose tissue (BAT) is the main thermogenic driver in mammals and its stimulation, through β3-adrenergic receptor (β3AR) agonists or cold acclimation, counteracts metabolic deficits in rodents and humans. Studies in animal models show that AD neuropathology leads to thermoregulatory deficits and cold-induced tau hyperphosphorylation is prevented by BAT stimulation through cold acclimation. Since metabolic disorders and AD share strong pathogenic links, we hypothesized that BAT stimulation through a β3AR agonist could exert benefits in AD as well.Here, we show that β3AR agonist administration (CL-316,243, 1 mg/kg/day i.p., from 15 to 16 months of age) decreased body weight and improved peripheral glucose metabolism and BAT thermogenesis in both non-transgenic and 3xTg-AD mice. One-month treatment with a β3AR agonist increased recognition index by 19% in 16-month-old 3xTg-AD mice compared to pre-treatment (14-month-old).Locomotion, anxiety and tau pathology were not modified. Finally, insoluble Aβ42/Aβ40 ratio was decreased by 27% in the hippocampus of CL-316,243-injected 3xTg-AD mice.Overall, our results indicate that β3AR stimulation reverses memory deficits and shifts downward the insoluble Aβ42/Aβ40 ratio in 16-month-old 3xTg-AD mice. As β3AR agonists are being clinically developed for metabolic disorders, repurposing them in AD could be a valuable therapeutic strategy.

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“…1 Numerous studies have demonstrated shared pathophysiological mechanisms between AD and diabetes mellitus (DM) such as oxidative stress, mitochondrial dysfunction, inflammation, and insulin resistance. 1 Numerous studies have demonstrated shared pathophysiological mechanisms between AD and diabetes mellitus (DM) such as oxidative stress, mitochondrial dysfunction, inflammation, and insulin resistance.…”

Section: Introductionmentioning

confidence: 99%

“…Alzheimer's disease (AD) is characterized by progressive cognitive and functional impairments due to the accumulation of neurofibrillary tangles and plaques. 1 Numerous studies have demonstrated shared pathophysiological mechanisms between AD and diabetes mellitus (DM) such as oxidative stress, mitochondrial dysfunction, inflammation, and insulin resistance. 2 Mild cognitive impairment (MCI) is characterized by cognitive impairment in the absence of significant functional decline; it is often prodromal to the development of AD and other forms of dementia.…”

Section: Introductionmentioning

confidence: 99%

Comparative efficacy and acceptability of antidiabetic agents for Alzheimer's disease and mild cognitive impairment: A systematic review and network meta‐analysis

Cao

Rosenblat

Brietzke

et al. 2018

Diabetes Obesity Metabolism

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This study (registered with PROSPERO, CRD42018085967) compares the efficacy (i.e. pro-cognitive effects) and acceptability of antidiabetic agents for Alzheimer's disease (AD) and mild cognitive impairment (MCI). Cochrane Library (CENTRAL), PubMed/MEDLINE, EMBASE and PsycINFO were searched from inception to January 15, 2018 for randomized controlled trials comparing antidiabetic agents with placebo and/or another active antidiabetic agent for the treatment of AD or MCI. Nineteen eligible studies (n = 4855) evaluating the effects of 6 different antidiabetic drugs (i.e. intranasal insulin, pioglitazone, rosiglitazone, metformin, sitagliptin and liraglutide) were included. The results of 29 pairwise comparisons indicated that cognition was significantly improved in subjects treated with antidiabetic agents compared with placebo. Pioglitazone 15 to 30 mg demonstrated the greatest efficacy compared to placebo in network meta-analysis. No significant differences in acceptability were identified when comparing agents with each other and with placebo. The current findings indicate a pro-cognitive class effect of antidiabetic agents in AD/MCI. Other antidiabetic agents should also be investigated in future studies.

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Peroxisome Proliferator-Activated Receptor-Gamma Agonists for Alzheimer’s Disease and Amnestic Mild Cognitive Impairment: A Systematic Review and Meta-Analysis

Cited by 46 publications

References 33 publications

Targeting neuroinflammation in Alzheimer’s disease: evidence for NSAIDs and novel therapeutics

Targeting neuroinflammation in Alzheimer’s disease: evidence for NSAIDs and novel therapeutics

Repurposing beta3-adrenergic receptor agonists for Alzheimer’s disease: Beneficial effects on recognition memory and amyloid pathology in a mouse model

Comparative efficacy and acceptability of antidiabetic agents for Alzheimer's disease and mild cognitive impairment: A systematic review and network meta‐analysis

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