Statin use reduces the risk of dementia in elderly patients: a nationwide data survey and propensity analysis

Wu, Cho Kai; Lin, Tsung-Kun; Tsai, Chia Ti; Hwang, Juey‐Jen; Lin, Jiunn Lee; Chen, Pau‐Chung; Chiang, Fu-Tien; Lin, Lian‐Yu

doi:10.1111/joim.12262

Cited by 32 publications

(26 citation statements)

References 25 publications

(27 reference statements)

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“…10 In a nationwide data survey in Taiwan, Wu et al reported a significant protective effect for individuals who took statins for more than 830 days. 36 In our study, for the continuous statin users, the average time from baseline until diagnosis was 5.8 years.…”

Section: Discussionmentioning

confidence: 70%

Statin Use, Incident Dementia and Alzheimer Disease in Elderly African Americans

et al. 2015

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Objective: To investigate the association between statin use, incident dementia, and Alzheimer disease (AD) in a prospective elderly African American cohort. Design:Two stage design with a screening interview followed by a comprehensive in-home assessment conducted over an eight-year period. Diagnoses of incident AD and dementia were made by consensus. Statin use was collected at each evaluation. Measurements of low-density lipoprotein cholesterol (LDL), C-reactive protein (CRP) and APOE genotype were obtained from baseline blood samples. Logistic regression models were used to test the association of statin use on incident dementia and AD and its possible association with lipid and CRP levels. Setting: Indianapolis, IndianaParticipants: From an original cohort of 2629 participants, a subsample of 974 African Americans aged >70 years with normal cognition, at least one follow up evaluation, complete statin information, and biomarker availability were included. Main Outcome Measures: Incident dementia and incident AD.Results: After controlling for age at diagnosis, sex, education level, presence of the APOE ε4 allele and history of stroke for the incident dementia model, baseline use of statins was associated with a significantly decreased risk of incident dementia (OR=.44, P=.029) and incident AD (OR=.40, P=.029). The significant effect of statin use on reduced AD risk and trend for dementia risk was found only for those participants who reported consistent use over the observational period (incident AD: P=.034; incident dementia: P=.061). Additional models found no significant interaction between baseline statin use, baseline LDL, or CRP level and incident dementia/AD.Conclusions: Consistent use of statin medications during eight years of followup resulted in significantly reduced risk for incident AD and a trend toward reduced risk for incident dementia. Ethn Dis.2015;25(3):345-354.

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Section: Discussionmentioning

confidence: 70%

Statin Use, Incident Dementia and Alzheimer Disease in Elderly African Americans

et al. 2015

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“…The interaction between ApoE4 and statin treatment appears to be mixed , but a recent study suggested a beneficial role of simvastatin in slowing the cognitive decline and improving cognitive function in a 10‐year follow‐up of AD patients homozygous for ApoE ε4 . The outcomes and inclusion criteria of enrolled patients differed amongst studies making them hard to compare . A comparison of the effects shown in different study designs identified that the protective effect of statins was reported usually in cross‐sectional but not in longitudinal studies .…”

Section: Medications With Potential Effects On the Brain Cholesterol mentioning

confidence: 99%

Connecting the brain cholesterol and renin–angiotensin systems: potential role of statins and RAS‐modifying medications in dementia

et al. 2018

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Petek B, Sweden; S€ odersjukhuset, Stockholm, Sweden). Connecting the brain cholesterol and reninangiotensin systems: potential role of statins and RAS-modifying medications in dementia (Review). J Intern Med 2018;284: 620-642.Millions of people worldwide receive agents targeting the renin-angiotensin system (RAS) to treat hypertension or statins to lower cholesterol. The RAS and cholesterol metabolic pathways in the brain are autonomous from their systemic counterparts and are interrelated through the cholesterol metabolite 27-hydroxycholesterol (27-OHC). These systems contribute to memory and dementia pathogenesis through interference in the amyloid-beta cascade, vascular mechanisms, glucose metabolism, apoptosis, neuroinflammation and oxidative stress. Previous studies examining the relationship between these treatments and cognition and dementia risk have produced inconsistent results. Defining the blood-brain barrier penetration of these medications has been challenging, and the mechanisms of action on cognition are not clearly established. Potential biases are apparent in epidemiological and clinical studies, such as reverse epidemiology, indication bias, problems defining medication exposure, uncertain and changing doses, and inappropriate grouping of outcomes and medications. This review summarizes current knowledge of the brain cholesterol and RAS metabolism and the mechanisms by which these pathways affect neurodegeneration. The putative mechanisms of action of statins and medications inhibiting the RAS will be examined, together with prior clinical and animal studies on their effects on cognition. We review prior epidemiological studies, analysing their strengths and biases, and identify areas for future research. Understanding the pathophysiology of the brain cholesterol system and RAS and their links to neurodegeneration has enormous potential. In future, well-designed epidemiological studies could identify potential treatments for Alzheimer's disease (AD) amongst medications that are already in use for other indications.2 Promotion of oxidative stress by acting on LRX in astroglia [90,91].Brain cholesterol and RAS in dementia / B. Petek et al.

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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%

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

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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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Statin use reduces the risk of dementia in elderly patients: a nationwide data survey and propensity analysis

Cited by 32 publications

References 25 publications

Statin Use, Incident Dementia and Alzheimer Disease in Elderly African Americans

Statin Use, Incident Dementia and Alzheimer Disease in Elderly African Americans

Connecting the brain cholesterol and renin–angiotensin systems: potential role of statins and RAS‐modifying medications in dementia

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

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