Effects of pioglitazone on the incidence of dementia in patients with diabetes

Chou, Ping-Song; Ho, Bo-Lin; Yang, Yuan-Han

doi:10.1016/j.jdiacomp.2017.01.006

Cited by 47 publications

(42 citation statements)

References 32 publications

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“…Two studies reported a protective association with pioglitazone on the risk of dementia with this benefit directly related to higher dosage and longer duration of exposure. 36 This observation warrants further study. There are two ongoing phase III trials examining the potential impact of pioglitazone on the course of AD.…”

Section: Discussionmentioning

confidence: 83%

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Impact of pharmacological treatment of diabetes mellitus on dementia risk: systematic review and meta-analysis

McMillan¹,

Mele

Hogan

et al. 2018

BMJ Open Diab Res Care

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BackgroundThe association between diabetes mellitus (DM) treatment and dementia is not well understood.ObjectiveTo investigate the association between treatment of diabetes, hypoglycemia, and dementia risk.Research design and methodsWe performed a systematic review and meta-analysis of pharmacological treatment of diabetes and incident or progressive cognitive impairment. We searched Ovid MEDLINE, Embase, Cochrane Central Registry of Controlled Trials, and PsychINFO from inception to 18 October 2017. We included cross-sectional, case–control, cohort, and randomized controlled studies. The study was registered with PROSPERO (ID CRD42017077953).ResultsWe included 37 studies into our systematic review and 13 into our meta-analysis. Ten studies investigated any antidiabetic treatment compared with no treatment or as add-on therapy to prior care. Treatment with an antidiabetic agent, in general, was not associated with incident dementia (risk ratio (RR) 1.01; 95% CI 0.93 to 1.10). However, we found differential effects across drug classes, with a signal of harm associated with insulin therapy (RR 1.21; 95% CI 1.06 to 1.39), but potentially protective effects with thiazolidinedione exposure (RR 0.71; 95% CI 0.55 to 0.93). Severe hypoglycemic episodes were associated with a nearly twofold increased likelihood of incident dementia (RR 1.77; 95% CI 1.35 to 2.33). Most studies did not account for DM duration or severity.Conclusions and limitationsThe association between treatment for diabetes and dementia is differential according to drug class, which is potentially mediated by hypoglycemic risk. Not accounting for DM duration and/or severity is a major limitation in the available evidence base.

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Section: Discussionmentioning

confidence: 83%

“…One study reported that, compared with non-exposed individuals, pioglitazone users had a 33% reduced risk of dementia (HR 0.77; 95% CI 0.62 to 0.96) with the greatest risk reduction at both the highest cumulative doses (HR 0.50; 95% CI 0.34 to 0.75) and longest durations of use (HR 0.53; 95% CI 0.36 to 0.77; for >536 days vs no use). 36 …”

Section: Resultsmentioning

confidence: 99%

Impact of pharmacological treatment of diabetes mellitus on dementia risk: systematic review and meta-analysis

McMillan¹,

Mele

Hogan

et al. 2018

BMJ Open Diab Res Care

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“…A phase II study of pioglitazone in AD showed that it is safe and well tolerated and two large phase III trials are ongoing [86]. In patients with diabetes, pioglitazone treatment is a time-and dose-dependent protective factor against dementia [87]. Cilostazol enhances LRP1 expression in liver by activating PPAR␥ through the peroxisome proliferator response element in the LRP1 promoter [88].…”

Section: Other Nuclear Receptor Agonistsmentioning

confidence: 99%

Is Alzheimer’s Disease a Liver Disease of the Brain?

Bassendine

Taylor-Robinson

Fertleman

et al. 2020

JAD

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Clinical specialization is not only a force for progress, but it has also led to the fragmentation of medical knowledge. The focus of research in the field of Alzheimer's disease (AD) is neurobiology, while hepatologists focus on liver diseases and lipid specialists on atherosclerosis. This article on AD focuses on the role of the liver and lipid homeostasis in the development of AD. Amyloid-␤ (A␤) deposits accumulate as plaques in the brain of an AD patient long before cognitive decline is evident. A␤ generation is a normal physiological process; the steady-state level of A␤ in the brain is determined by balance between A␤ production and its clearance. We present evidence suggesting that the liver is the origin of brain A␤ deposits and that it is involved in peripheral clearance of circulating A␤ in the blood. Hence the liver could be targeted to decrease A␤ production or increase peripheral clearance.

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“…Metformin alone and combined oral therapy (metformin and sulfonylureas) decreased the risk of dementia compared to that among patients without these medications (Hsu, Wahlqvist, Lee, & Tsai, 2011) and patients taking TZD (Cheng et al, 2014) and could be more effective than sulfonylureas (Orkaby, Cho, Cormack, Gagnon, & Driver, 2017). A cohort study (Heneka, Fink, & Doblhammer, 2015) and a case control study (Chou, Ho, & Yang, 2017) have also shown the efficacy of TZD in decreasing dementia risk. A meta-analysis performed by Ye, Luo, Xiao, Yu, and Yi (2016) found that metformin and TZD reduced the dementia risk.…”

Section: Antidiabeticsmentioning

confidence: 99%

Drug interactions with dementia‐related pathophysiological pathways worsen or prevent dementia

Barus

Béné

Deguil

et al. 2019

British J Pharmacology

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Many risk factors are known to induce or precipitate dementia. Drugs acting via different mechanisms can modulate cognitive performance and exert either beneficial or deleterious effects on cognition through functional or neuropathological mechanisms. This review discusses the association between several classes of drugs and cognitive impairment and dementia risk. These drugs can be divided into drugs targeting CNS disorders (e.g., anticholinergic drugs, antiepileptics, antipsychotics, benzodiazepines, and opioids) and drugs targeting non‐CNS disorders (e.g., antidiabetics, antihypertensives, proton pump inhibitors, and statins). Furthermore, we sought to highlight the pharmacological mechanisms underlying their possible detrimental or beneficial effects on cognition. Anticholinergic and antiepileptic drugs were excluded from this review because their effects on cognition are well known. Studies investigating benzodiazepines have revealed an increased risk of dementia. Conclusions on dementia risk or cognitive impairment regarding opioids and antipsychotic drugs are difficult to draw. These different classes appear to impair cognition not by a single clear mechanism of action specific to each class but by several relatively interdependent and interconnected mechanisms (e.g., impaired neurotransmission, neuroinflammation, neuronal death, oxidative stress, or interactions with dementia‐related pathways). The dementia risk initially associated with the use of proton pump inhibitors might have been overestimated. In contrast, statins, antihypertensive medications, and antidiabetics could potentially decrease the risk of dementia and cognitive impairment by acting in ways opposite to the mechanisms cited above. Linked Articles This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc

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Effects of pioglitazone on the incidence of dementia in patients with diabetes

Cited by 47 publications

References 32 publications

Impact of pharmacological treatment of diabetes mellitus on dementia risk: systematic review and meta-analysis

Impact of pharmacological treatment of diabetes mellitus on dementia risk: systematic review and meta-analysis

Is Alzheimer’s Disease a Liver Disease of the Brain?

Drug interactions with dementia‐related pathophysiological pathways worsen or prevent dementia

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