Use of Statins and Risk of Dementia in Heart Failure: A Retrospective Cohort Study

Chitnis, A.S.; Aparasu, Rajender R.; Chen, Hua; Kunik, Mark E.; Schulz, Paul E.; Johnson, Michael L.

doi:10.1007/s40266-015-0295-4

Cited by 11 publications

(10 citation statements)

References 81 publications

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“…This is important because CAD patients are at high risk of cognitive dysfunction21–24 and many CAD patients, particularly statin users, frequently have low LDL concentrations. The findings of this study are consistent with several well-designed and well-powered studies that also did not find an association between LDL and cognition15–17 in general, though those studies had not been performed specifically in patients with CAD. At least from this initial study, it appears that CAD patients can be safely treated with statins to relatively low LDL levels (<1.5 mmol/L) without concern about cognition, although future longitudinal studies will be helpful to confirm this.…”

Section: Discussionsupporting

confidence: 91%

“…Recent human studies suggest that statin users are more likely to suffer from cognitive impairment than non-statin users,12 with impairments in executive functioning, episodic memory, and other cognitive domains associated with low LDL levels 13,14. This remains controversial, as well-designed prospective longitudinal studies and randomized controlled trials have not necessarily found an association between LDL and cognition 15–17…”

Section: Introductionmentioning

confidence: 99%

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Serum low-density lipoprotein levels, statin use, and cognition in patients with coronary artery disease

Rej¹,

Saleem

Herrmann

et al. 2016

NDT

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AimStatins have been associated with decreased cognition due to the effects of low concentrations of low-density lipoprotein (LDL) on brain function. This has remained controversial and is particularly relevant to patients with coronary artery disease (CAD), who have an increased risk of cognitive decline and are frequently prescribed statins. This study hypothesized that low concentration of LDL is associated with poor cognition in CAD patients using statins. It also explored the association between high-dose versus low-dose statins on cognition in this population.Patients and methodsBaseline cross-sectional data from a longitudinal study of 120 statin-using CAD patients were examined (mean statin duration 25±43 months). The main outcomes were measures of global cognition and cognitive domains, with poor cognition defined as cognitive performance ≤1 standard deviation below the population age and education adjusted means. A battery of cognitive tests was used to assess verbal memory, executive function, speed of processing, visuospatial memory, and global cognition. Adjusting for age, sex, education, and other covariates, multivariable logistic regression analyses assessed associations between low LDL levels (<1.5 mmol/L), statin use, and poor cognition.ResultsLDL levels were not associated with global cognition or individual cognitive domains. High-dose statin use was associated with higher visuospatial memory (odds ratio, OR [95% confidence interval, CI] =0.12 [0.02–0.66], P=0.01) and executive functioning (OR =0.25 [0.06–0.99], P=0.05). This effect was independent of covariates such as LDL levels.ConclusionLow LDL levels do not appear to be associated with poor cognition in CAD patients using statins. Whether high-dose statin use may have positive effects on cognition in CAD patients could be investigated in future studies.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Serum low-density lipoprotein levels, statin use, and cognition in patients with coronary artery disease

Rej¹,

Saleem

Herrmann

et al. 2016

NDT

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“…In total, twenty-five articles met the inclusion criteria and were included in the current systematic review and meta-analysis (Table 1 ) 8 – 10 , 13 , 16 , 18 , 19 , 21 – 23 , 25 , 36 , 38 , 40 – 51 . Table 1 provides characteristics of included studies.…”

Section: Resultsmentioning

confidence: 99%

Use of statins and the risk of dementia and mild cognitive impairment: A systematic review and meta-analysis

Chu

Tseng²,

Stubbs

et al. 2018

Sci Rep

128

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We conducted a systematic review and meta-analysis to investigate whether the use of statins could be associated with the risk of all-caused dementia, Alzheimer’s disease (AD), vascular dementia (VaD), and mild cognitive impairment (MCI). Major electronic databases were searched until December 27th, 2017 for studies investigating use of statins and incident cognitive decline in adults. Random-effects meta-analyses calculating relative risks (RRs) were conducted to synthesize effect sizes of individual studies. Twenty-five studies met eligibility criteria. Use of statins was significantly associated with a reduced risk of all-caused dementia (k = 16 studies, adjusted RR (aRR) = 0.849, 95% CI = 0.787–0.916, p = 0.000), AD (k = 14, aRR = 0.719, 95% CI = 0.576–0.899, p = 0.004), and MCI (k = 6, aRR = 0.737, 95% CI = 0.556–0.976, p = 0.033), but no meaningful effects on incident VaD (k = 3, aRR = 1.012, 95% CI = 0.620–1.652, p = 0.961). Subgroup analysis suggested that hydrophilic statins were associated with reduced risk of all-caused dementia (aRR = 0.877; CI = 0.818–0.940; p = 0.000) and possibly lower AD risk (aRR = 0.619; CI = 0.383–1.000; p = 0.050). Lipophilic statins were associated with reduced risk of AD (aRR = 0.639; CI = 0.449–0.908; p = 0.013) but not all-caused dementia (aRR = 0.738; CI = 0.475–1.146; p = 0.176). In conclusion, our meta-analysis suggests that the use of statins may reduce the risk of all-type dementia, AD, and MCI, but not of incident VaD.

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“…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. However, two cohort studies (Chitnis et al, ; Gnjidic et al, ) did not find any differences in the risk of dementia among statin users and non‐users. All meta‐analyses involving observational studies (Macedo et al, ; Song, Nie, Xu, Zhang, & Wu, ; Swiger, Manalac, Blumenthal, Blaha, & Martin, ; Wong, Lin, Boudreau, & Devine, ; X. Zhang, Wen, & Zhang, ) found a decreased risk of dementia and AD.…”

Section: Resultsmentioning

confidence: 95%

“…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. However, two cohort studies (Chitnis et al, 2015;Gnjidic et al, 2016) The precognitive effect of statins could be due to pleiotropic effects (Mendoza-Oliva et al, 2014). By decreasing the prenylation of Rho GTPases, statins could up-regulate the production of endothelial NOS (Hamel, Royea, Ongali, & Tong, 2016) and thus restore neurovascular coupling and cerebral blood flow, which are impaired in AD patients.…”

Section: Statinsmentioning

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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Use of Statins and Risk of Dementia in Heart Failure: A Retrospective Cohort Study

Abstract: This study found no difference in the risk of dementia among current and former users of statins as compared with nonusers in an already at-risk HF population.

Cited by 11 publications

References 81 publications

Serum low-density lipoprotein levels, statin use, and cognition in patients with coronary artery disease

Serum low-density lipoprotein levels, statin use, and cognition in patients with coronary artery disease

Use of statins and the risk of dementia and mild cognitive impairment: A systematic review and meta-analysis

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

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