Examination of the FDA Warning for Statins and Cognitive Dysfunction

Sahebzamani, Frances M.

doi:10.4172/2329-6887.1000141

Cited by 22 publications

(26 citation statements)

References 60 publications

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“…It appears to be the reason why atorvastatin and simvastatin have higher association with non-hepatocytic adverse effects, such as cognitive impairment, compared to all other lipophilic statins [51,54]. Our findings of higher association of cognitive impairment with lipophilic atorvastatin were aligned with the other studies that have demonstrated higher association and severity of cognitive impairment with lipophilic statins compared with hydrophilic statins [11,21,46,[59][60][61][62].…”

Section: Discussionsupporting

confidence: 84%

“…As such the voluntary reporting to the AERS by the physicians varies between 1% and 10%, which is considered as extremely low [49]. Extrapolation of the underreported data estimates that annually about 3,000 -30,000 adverse effects of cognitive impairments due to statins, especially simvastatin and atorvastatin, were not reported to the AERS [21]. Hence, our finding of significantly higher association of cognitive impairment in patients who were on HIST compared to the general population highlights the importance of an inclusive approach in the adverse effect assessment in the form of periodic assessment of cognitive function of patients who are on statin therapy, especially in patients who are on HIST.…”

Section: Discussionmentioning

confidence: 99%

“…Low levels of cholesterol may have a negative influence on the composition and functioning of the neurons. Many studies have reported association between the use of statins to lower circulating cholesterol levels and decline in neurocognitive function [7][8][9][20][21][22][23]. On the contrary, there are many studies that have shown either no association between the use of statins and cognitive changes [24][25][26][27], or a beneficial neuroprotective role attributable to the statin use [28][29][30][31][32][33][34][35][36].…”

Section: Introductionmentioning

confidence: 99%

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Cognitive Function Assessment in Patients on Moderate- or High-Intensity Statin Therapy

et al. 2020

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Background: Cardiovascular diseases are the leading cause of death in the USA. Statin therapy reduces cardiovascular events significantly. Cognitive impairment has been reported with statin therapy but there is a lack of consensus. We analyzed the cognitive functions of adult patients who were on moderate-intensity statin therapy (MIST) or high-intensity statin therapy (HIST). Methods:A total of 213 patients underwent cognitive assessment testing. Cognitive function scores were correlated with the durations of statin therapy, age, and level of education by using Pearson correlation. Independent t-test was used to compare the mean cognitive function score to the gender, race, type of statin therapy, and comorbid conditions.Results: Mean age of all the patients was 55.4 years. Majority of the patients (66.2%) were on MIST while the rest (33.8%) were on HIST. Cognitive impairment was observed in 17.8% of the studied patients. A total of 41.7% of the patients in the HIST group and 5.7% in the MIST group had cognitive impairment (P < 0.001). There was no correlation between cognitive function score and age (r = -0.106), weakly positive correlation between the level of education and cognitive function score (r = 0.252), and weakly negative correlation between the duration of statin therapy and cognitive function score (r = -0.283). In the group of patients on HIST with cognitive impairment, the proportion of patients on atorvastatin 40 -80 mg was significantly higher than the proportion of patients on rosuvastatin 20 -40 mg (66.7% vs. 33.3%; P < 0.05). In the group of patients on MIST with cognitive impairment, atorvastatin 10 -20 mg was the most commonly used statin therapy (50%), followed by rosuvastatin 10 mg (25%), simvastatin 20 -40 mg (12.5%) and pravastatin 40 -80 mg (12.5%). Conclusions:We found a significantly higher association of cognitive impairment in patients who were on MIST or HIST compared to the general population. We found no correlation between cognitive function score and age, weakly positive correlation between the level of education and cognitive function score, and weakly negative correlation between the duration of statin therapy and cognitive function score. HIST was associated with a higher frequency of cognitive impairment compared to the MIST.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cognitive Function Assessment in Patients on Moderate- or High-Intensity Statin Therapy

et al. 2020

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“…47 However, another study also using FDA databases found that neurological disease was reported more often for lipophilic statins that more readily cross the blood-brain barrier, than for hydrophobic statins. 48 A meta-analysis of 23 randomised clinical intervention trials on statins reporting data on cognitive function in 29 012 participants failed to show adverse cognitive effects of statins and thus lower LDL .…”

Section: Other Studiesmentioning

confidence: 99%

Low LDL cholesterol,PCSK9andHMGCRgenetic variation, and risk of Alzheimer’s disease and Parkinson’s disease: Mendelian randomisation study

Benn

Nordestgaard

Frikke‐Schmidt

et al. 2017

BMJ

147

139

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Objective To test the hypothesis that low density lipoprotein (LDL) cholesterol due to genetic variation in the genes responsible for LDL cholesterol metabolism and biosynthesis(PCSK9 and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), respectively) is associated with a high risk of Alzheimer’s disease, vascular dementia, any dementia, and Parkinson’s disease in the general population. Design Mendelian randomisation study. Setting Copenhagen General Population Study and Copenhagen City Heart Study. Participants 111 194 individuals from the Danish general population. Main outcome measures Risk of Alzheimer’s disease, vascular dementia, all dementia, and Parkinson’s disease. Results In observational analyses, the multifactorially adjusted hazard ratio for Parkinson’s disease in participants with an LDL cholesterol level <1.8 mmol/L versus ≥4.0 mmol/L was 1.70 (95% confidence interval 1.03 to 2.79), whereas the corresponding hazard ratios for Alzheimer’s disease, vascular dementia, or any dementia did not differ from 1.0. PCSK9 and HMGCR variants combined were associated with a 9.3% lower LDL cholesterol level. In genetic, causal analyses adjusted for age, sex, and year of birth, the risk ratios for a lifelong 1 mmol/L lower LDL cholesterol level were 0.57 (0.27 to 1.17) for Alzheimer’s disease, 0.81 (0.34 to 1.89) for vascular dementia, 0.66 (0.34 to 1.26) for any dementia, and 1.02 (0.26 to 4.00) for Parkinson’s disease. Summary level data from the International Genomics of Alzheimer’s Project using Egger Mendelian randomisation analysis gave a risk ratio for Alzheimer’s disease of 0.24 (0.02 to 2.79) for 26 PCSK9 and HMGCR variants, and of 0.64 (0.52 to 0.79) for 380 variants of LDL cholesterol level lowering. Conclusion Low LDL cholesterol levels due to PCSK9 and HMGCR variants had no causal effect on high risk of Alzheimer’s disease, vascular dementia, any dementia, or Parkinson’s disease; however, low LDL cholesterol levels may have a causal effect in reducing the risk of Alzheimer’s disease.

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“…Some epidemiological studies and meta‐analyses found no difference in effects on cognition when comparing lipophilic and hydrophilic groups, but others reported a beneficial effect of the lipophilic group . Yet others suggested a beneficial role of lipophilic statins in noncarriers of ApoEe4 or a harmful effect of lipophilic statins . Another study showed that use of lipophilic statins was associated with more favourable white matter structural integrity in older adults with lower cognitive performance but no dementia diagnosis .…”

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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Examination of the FDA Warning for Statins and Cognitive Dysfunction

Cited by 22 publications

References 60 publications

Cognitive Function Assessment in Patients on Moderate- or High-Intensity Statin Therapy

Cognitive Function Assessment in Patients on Moderate- or High-Intensity Statin Therapy

Low LDL cholesterol,PCSK9andHMGCRgenetic variation, and risk of Alzheimer’s disease and Parkinson’s disease: Mendelian randomisation study

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

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