Early Statin Use and the Progression of Alzheimer Disease

Lin, Feng; Chuang, Yun-Shiuan; Hsieh, Hui Min; Lee, Tzu Chi; Chiu, Kuei Fen; Liu, Ching Kuan; Wu, Ming Tsang

doi:10.1097/md.0000000000002143

Cited by 75 publications

(69 citation statements)

References 35 publications

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“…Moreover, cholesterol and plasma membrane lipid contents have been shown to control Aβ production by interfering with enzyme activity [116]. The use of cholesterol-lowering medication such as statins was able to reduce Aβ production in an AD mouse model [118] and AD progression in patients [119]. High doses of simvastatin reduced the cerebral levels of Aβ and Aβ in the cerebrospinal fluid and brain of guinea pig [120].…”

Section: Alzheimer's Diseasementioning

confidence: 99%

Cyclodextrins as Emerging Therapeutic Tools in the Treatment of Cholesterol-Associated Vascular and Neurodegenerative Diseases

et al. 2016

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Cardiovascular diseases, like atherosclerosis, and neurodegenerative diseases affecting the central nervous system (CNS) are closely linked to alterations of cholesterol metabolism. Therefore, innovative pharmacological approaches aiming at counteracting cholesterol imbalance display promising therapeutic potential. However, these approaches need to take into account the existence of biological barriers such as intestinal and blood-brain barriers which participate in the organ homeostasis and are major defense systems against xenobiotics. Interest in cyclodextrins (CDs) as medicinal agents has increased continuously based on their ability to actively extract lipids from cell membranes and to provide suitable carrier system for drug delivery. Many novel CD derivatives are constantly generated with the objective to improve CD bioavailability, biocompatibility and therapeutic outcomes. Newly designed drug formulation complexes incorporating CDs as drug carriers have demonstrated better efficiency in treating cardiovascular and neurodegenerative diseases. CD-based therapies as cholesterol-sequestrating agent have recently demonstrated promising advances with KLEPTOSE ® CRYSMEB in atherosclerosis as well as with the 2-hydroxypropyl-β-cyclodextrin (HPβCD) in clinical trials for Niemann-Pick type C disease. Based on this success, many investigations evaluating the therapeutical beneficial of CDs in Alzheimer's, Parkinson's and Huntington's diseases are currently on-going.

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Section: Alzheimer's Diseasementioning

confidence: 99%

Cyclodextrins as Emerging Therapeutic Tools in the Treatment of Cholesterol-Associated Vascular and Neurodegenerative Diseases

et al. 2016

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“…Table S2 shows the two RCTs 30,31 and three cohort-style studies. 4,32,33 Neither RCT ran for long enough to collect outcomes at 2 years (both were 72 wk) and are therefore only included for adverse events. All studies covered only dementia of the AD type.…”

Section: Resultsmentioning

confidence: 99%

Benefits and Harms of Statins in People with Dementia: A Systematic Review and Meta‐Analysis

Davis

Bishara

Perera

et al. 2020

J American Geriatrics Society

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OBJECTIVES More people with dementia also fall into the category of high vascular risk, for which a statin is usually prescribed. However, these recommendations are based on studies in people without dementia. We aimed to evaluate the evidence for the long‐term effectiveness and harm of statin therapy in patients with dementia. DESIGN Systematic review of randomized controlled trials and observational research. SETTING Publications from developed countries indexed in the PubMed, Web of Science, and Cochrane trial database between 2007 and 2019. PARTICIPANTS Trials including people with all types of dementia with a mean age older than 65 years. INTERVENTION Treatment with a statin for 6 months or longer. MEASUREMENTS Major adverse cardiovascular events, dementia progression, and general health at 2 years, or medication adverse events (AEs) at any time. Each article was assessed for bias using the Newcastle‐Ottawa or Cochrane Collaboration tools. A narrative synthesis and pooled analyses are reported. RESULTS Five articles met the inclusion criteria. They reported only on dementia of the Alzheimer's type. There was no evidence regarding cardiovascular events or general health. We made a very low confidence finding that statins reduce dementia progression based on three cohort studies of heterogeneous design. We made a very low confidence finding of no significant difference in AEs based on two randomized controlled trials of 18 months: odds ratios of any AE = 1.21 (95% confidence interval [CI] = .83‐1.77), serious AE = 1.03 (95% CI = .76‐1.87), and death = 1.69 (95% CI = .79‐3.62). CONCLUSION Evidence was insufficient to fully evaluate the efficacy of statins in people with dementia. We found that statins may have a small benefit delaying progression in Alzheimer's dementia, although this conflicted with previous findings from shorter randomized trials. For safety, the trial data lacked power to show clinically important differences between the groups. We recommend that clinical data be leveraged for further observational studies to inform prescribing decisions. J Am Geriatr Soc 68:650–658, 2020

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“…Seven cohort studies (Chen et al, ; Chuang, Lin, Lin, Sung, & Kao, ; Hendrie et al, ; Hippisley‐Cox & Coupland, ; Li et al, ; C.‐K. Wu et al, ; Yang et al, ) and five case control studies (Booker et al, ; Chen, Liu, Chen, & Wu, ; Corrao et al, ; Horsdal et al, ; Lin et al, ) found that statin use was associated with a reduced risk of dementia. According to these studies, beginning treatment with high doses of lipophilic statins before an early old age (<80 years old) and taking these statins for a long time might reduce the risk of dementia.…”

Section: Resultsmentioning

confidence: 99%

“…Drugs that act through different mechanisms mostly unrelated to their principal pharmacological properties could potentially modulate cognitive performance (Nevado-Holgado, Kim, Winchester, Gallacher, & Lovestone, 2016). On the one hand, many drugs known to decrease vascular risk factors, such as statins, antihypertensive medications (AHMs), and antidiabetics, could have a beneficial effect on cognition (Imfeld, Bodmer, Jick, & Meier, 2012;Lin et al, 2015;Yasar et al, 2016). On the other hand, many drugs are known to increase the risk of dementia (either degenerative dementia or vascular dementia) and cognitive decline.…”

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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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Early Statin Use and the Progression of Alzheimer Disease

Abstract: Supplemental Digital Content is available in the text

Cited by 75 publications

References 35 publications

Cyclodextrins as Emerging Therapeutic Tools in the Treatment of Cholesterol-Associated Vascular and Neurodegenerative Diseases

Cyclodextrins as Emerging Therapeutic Tools in the Treatment of Cholesterol-Associated Vascular and Neurodegenerative Diseases

Benefits and Harms of Statins in People with Dementia: A Systematic Review and Meta‐Analysis

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

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