Does Statin Use for Cholesterol Control Cause Cognitive Decline, Dementia?

Senior Citizen Dementia

Statin therapy not associated with cognitive decline, dementia in older adults, study says.

Observational study adds to growing evidence that statin therapy is not associated with cognitive decline and dementia in older adults, but randomized trials are still needed.

The use of statin therapy in adults 65 years old or older is not associated with incident dementia, mild cognitive impairment (MCI), or decline in individual cognition domains, according to a study published in the Journal of the American College of Cardiology (JACC).

Cognitive decline and dementia are major health concerns in older individuals, affecting about 10% of people over 60 years old. Statins are used to reduce low-density lipoprotein cholesterol, or bad cholesterol, thus they are a fundamental treatment for prevention of primary and secondary cardiovascular disease (CVD) events. The Food and Drug Administration released a warning in 2012 about cases of apparent short-term cognitive impairment with statin use, while acknowledging that the cardiovascular benefits outweigh their risks.

However, systematic reviews have shown insufficient evidence on the impact of statins and research has shown mixed results, with some showing a neurocognitive benefit of statins and others reporting a null effect. According to the researchers of this study, since statins are widely used among older adults and expected to increase in use, determining the effects of statin therapy on cognition in older individuals is vital to help clinicians weigh their benefits against associated risks.

“With statins being increasingly prescribed to older adults, their potential long-term effects on cognitive decline and dementia risk have attracted growing interest,” said Zhen Zhou, PhD, Menzies Institute for Medical Research at the University of Tasmania in Australia and lead author of the study. “The present study adds to previous research by suggesting that statin use at baseline was not associated with subsequent dementia incidence and long-term cognitive decline in older adults.”

Researchers of this study analyzed data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial. ASPREE was a large prospective, randomized placebo-controlled trial of daily low-dose aspirin, which included 19,114 participants 65 years old or older with no prior CVD event, dementia or major physical disability, between 2010 and 2014 from Australia and the U.S. One of the key selection criteria of ASPREE was that participants had to have a score of <78 for the Modified Mini-Mental State Examination test, a screening test for cognitive abilities, at enrollment.

Researchers excluded participants with missing values for cognitive test scores and/or covariates at baseline, resulting in 18,846 participants. They were grouped by their baseline statin use versus non-statin use, with 5,898 (31.3%) of participants taking statins. The study aimed to measure outcomes including incident dementia and its subclassifications (probable Alzheimer’s disease [AD], mixed presentations); MCI and its subclassifications (MCI consistent with AD, MCI-other); changes in domain-specific cognition including global cognition, memory, language, and executive function, and psychomotor speed; and in the composite of these domains.

After a median of 4.7 years of follow-up, researchers found 566 incident cases of dementia (including probable AD and mixed presentations). Compared with no statin use, statin use was not associated with risk of all-cause dementia, probable AD, or mixed presentations of dementia. There were 380 incident cases of MCI found (including MCI consistent with AD and MCI-other).

Compared to no statin use, statin use was not associated with risk of MCI, MCI consistent with AD or other MCI. There was no statistically significant difference in the change of composite cognition and any individual cognitive domains between statin users versus non-statin users. Also, no significant differences were found in any of the outcomes of interest between users of hydrophilic and lipophilic statins. However, researchers did find interaction effects between baseline cognitive ability and statin therapy for all dementia outcomes.

According to the researchers, this study has several limitations, including observational study bias, lack of data on the length of prior use of statins, and the dose of statins was not recorded in the ASPREE trial, so their effects could not be fully explored. Researchers conclude the study must be interpreted with caution and will require confirmation by randomized clinical trials designed to explore the neurocognitive effects of statins in older populations.

In an accompanying editorial comment, Christie M. Ballantyne, MD, professor at Baylor College of Medicine in Houston, said the study does have limitations that the authors address, but agreed the findings suggest statins do not contribute to cognitive decline.

“Overall, the analysis was well done, and its main strengths are a large cohort with a battery of standardized tests that allowed the investigators to track both cognition and incidence of dementia and its subtypes over time,” Ballantyne said. “Lingering questions such as the one raised by this analysis regarding potential adverse effects of statins in individuals with mildly impaired cognition can only be answered in randomized controlled trials in the appropriate age group and population and with appropriate testing and adequate follow-up. In the meantime, practicing clinicians can have confidence and share with their patients that short-term lipid lowering therapy in older individuals, including with statins, is unlikely to have a major impact on cognition.”

Reference: “Effect of Statin Therapy on Cognitive Decline and Incident Dementia in Older Adults” by Zhen Zhou PhD, Joanne Ryan PhD, Michael E. Ernst PharmD, Sophia Zoungas MBBS, PhD, Andrew M. Tonkin PhD, Robyn L. Woods PhD, John J. McNeil MBBS, PhD, Christopher M. Reid PhD, Andrea J. Curtis PhD, Rory Wolfe PhD, Jo Wrigglesworth BSc(Hons), Raj C. Shah MDfElsdon Storey MBBS, DPhil, Anne Murray MD, MS, Suzanne G. Orchard PhD and Mark R. Nelson MBBS, PhD on behalf of theASPREE Investigator Group, 21 June 2021,  Journal of the American College of Cardiology.
DOI: 10.1016/j.jacc.2021.04.075

16 Comments on "Does Statin Use for Cholesterol Control Cause Cognitive Decline, Dementia?"

  1. From what I have learned, the pharma companies do not release study data because it is proprietary. But they do use a lead-in period in which people who have side effects drop out, so that the study is skewed from the beginning. Even with this advantage, they struggle to show any advantage for taking a statin, certainly not over raising HDL and lowering triglycerides through cutting out sugar, refined grains, and processed foods.

  2. John B. Egan | June 21, 2021 at 3:43 pm | Reply

    I can only speak of my own response to taking Statins.. I had been prescribed them for a period of time when I was in my late 50’s and took them for about 3 years. My mental processes began slowing down and I became easily angered, which is not like me normally.

    Over a period of time, I found that I felt weak, unmotivated, and just didn’t care much about anything.. I was late paying bills and twice had my water and electrics turned off for non-payment which required going to the various offices and paying the bills and fees to reconnect my services.. I would get angry at other drivers… Once, for example, I hard braked in front of a tailgater and then purposely drove 5 MPH until we parted directions.

    Eventually, I went to my pharmacy to get my Statins and was told that the cost was $50 or so, which was much higher than my normal copay.. I had the pharmacist call Blue Cross to see why that was and he told me that BC said I hadn’t paid my premium.. Instead of calling my doctor and getting a generic Statin from K-Mart for $4, I just went home and didn’t bother pursuing the matter.

    A week later I began feeling better… A month after that, without Statins I began feeling pretty good.. About 80% of my normal… It took about 3 years to get back to feeling like a human being again and I will never take Statins again.

  3. “Observational study adds to growing evidence that statin therapy is not associated with cognitive decline and dementia in older adults.” I call BALONEY on this. I took statins TWENTY YEARS AGO – – when I was in my mid-to-late FORTIES. After a few weeks, I was unable to find my way back home from the grocery store. The statins did lower my serum cholesterol numbers beautifully. But I was unable to perform the simplest tasks at work. When I complained to my primary physician, all he would do was to switch me to a different statin. I would be sobbing in the parking lot at work, unable to recall if I should be turning right or left in order to go home. I hate statins. I hate the arrogance of the medical community, who bow to the gods of Big Pharma. Your article is just a continuation of this GARBAGE attitude.

  4. Statins are big money for Big Pharma. And doctors love to prescribe them. I was on statins for a month and almost lost my job. I couldn’t concentrate and I lost the ability to edit copy and keep appointments straight. My urine grew dark and I was in lots of pain. It seems that I need fats in my brain!

  5. You need smart people to see if there is a loss. If you start with ppl smart as a box of rocks and try to measure cognitive decline the uncertainy in the measurement will overwhelm the signal.

  6. As stated above by @rassalas, you would need to test people who are not cognitively impaired to determine if statins cause cognitive impairment. According to the Modified Mini-Mental State exam, any score >= 78 is ‘normal’ and a score of < 78 indicates cognitive impairment. According to this article, the study it is based on, ASPREE, only accepted people with a 3MS score < 78. It would seem then that the study should in no way be used to determine if statins cause CI or dementia, as only people who already had CI were a part of the study.

  7. It has been well documented for over two decades that at least 2% of statin users suffer measurable cognitive decline. Memory loss was listed in the prescribing instructions, and there is sworn testimony from the recalled Baycol statin trial substantiating memory loss as an adverse effect. Dr. Graveline MD, a former NASA science astronaut, documented this in his book, Lipitor, Thief of Memory. There are documented cases of memory loss in statin users, which resolves (up to 85% of pre-statin capabilities) when statin use is halted. Sadly, patients who recovered, when re-challenged by another statin, not only suffer memory loss again, but when they halt that statin and recover, they only recover 85% of their capability – I.e., a permanent loss of 30% – and so on, if another statin is introduced. One well documented case showed a high functioning patient on Lipitor (at only 10 mg per day) suffered memory loss to the extent of being clinically tested at below the 1 percentile. It took over a decade after halting the Lipitor for that patient to recover 85% of former cognitive capabilities. This case was heavily covered in published studies, an article in major newspaper, and a multi-page article in a national money and investment magazine.

  8. A sampling of published studies on adverse effects of statin, to include cognitive & memory loss – from PubMed.gov:

    PubMed Results
    Items 1-28 of 28 (Display the 28 citations in PubMed)

    1.
    Statin adverse effects : a review of the literature and evidence for a mitochondrial mechanism.
    Golomb BA, Evans MA.
    Am J Cardiovasc Drugs. 2008;8(6):373-418. doi: 10.2165/0129784-200808060-00004.
    PMID: 19159124 Free PMC article. Review.
    2.
    Physicians’ Experiences as Patients with Statin Side Effects: A Case Series.
    Koslik HJ, Meskimen AH, Golomb BA.
    Drug Saf Case Rep. 2017 Dec;4(1):3. doi: 10.1007/s40800-017-0045-0.
    PMID: 28217821 Free PMC article.
    3.
    Statin Effects on Aggression: Results from the UCSD Statin Study, a Randomized Control Trial.
    Golomb BA, Dimsdale JE, Koslik HJ, Evans MA, Lu X, Rossi S, Mills PJ, White HL, Criqui MH.
    PLoS One. 2015 Jul 1;10(7):e0124451. doi: 10.1371/journal.pone.0124451. eCollection 2015.
    PMID: 26132393 Free PMC article. Clinical Trial.
    4.
    Statin-associated muscle-related adverse effects: a case series of 354 patients.
    Cham S, Evans MA, Denenberg JO, Golomb BA.
    Pharmacotherapy. 2010 Jun;30(6):541-53. doi: 10.1592/phco.30.6.541.
    PMID: 20500044 Free PMC article.
    5.
    Amyotrophic Lateral Sclerosis Associated with Statin Use: A Disproportionality Analysis of the FDA’s Adverse Event Reporting System.
    Golomb BA, Verden A, Messner AK, Koslik HJ, Hoffman KB.
    Drug Saf. 2018 Apr;41(4):403-413. doi: 10.1007/s40264-017-0620-4.
    PMID: 29427042
    6.
    Conceptual foundations of the UCSD Statin Study: a randomized controlled trial assessing the impact of statins on cognition, behavior, and biochemistry.
    Golomb BA, Criqui MH, White H, Dimsdale JE.
    Arch Intern Med. 2004 Jan 26;164(2):153-62. doi: 10.1001/archinte.164.2.153.
    PMID: 14744838 Free PMC article. Review.
    7.
    The UCSD Statin Study: a randomized controlled trial assessing the impact of statins on selected noncardiac outcomes.
    Golomb BA, Criqui MH, White HL, Dimsdale JE.
    Control Clin Trials. 2004 Apr;25(2):178-202. doi: 10.1016/j.cct.2003.08.014.
    PMID: 15020036 Free PMC article. Clinical Trial.
    8.
    Statin-associated adverse cognitive effects: survey results from 171 patients.
    Evans MA, Golomb BA.
    Pharmacotherapy. 2009 Jul;29(7):800-11. doi: 10.1592/phco.29.7.800.
    PMID: 19558254
    9.
    A survey of the FDA’s AERS database regarding muscle and tendon adverse events linked to the statin drug class.
    Hoffman KB, Kraus C, Dimbil M, Golomb BA.
    PLoS One. 2012;7(8):e42866. doi: 10.1371/journal.pone.0042866. Epub 2012 Aug 22.
    PMID: 22936996 Free PMC article.
    10.
    Association not causation.
    Golomb BA, Koperski S.
    Arch Intern Med. 2009 Jun 8;169(11):1079. doi: 10.1001/archinternmed.2009.156.
    PMID: 19506186 No abstract available.
    11.
    Do statins reduce the risk of infection?
    Golomb BA.
    BMJ. 2011 Nov 29;343:d7134. doi: 10.1136/bmj.d7134.
    PMID: 22127442 No abstract available.
    12.
    Reduction in blood pressure with statins: results from the UCSD Statin Study, a randomized trial.
    Golomb BA, Dimsdale JE, White HL, Ritchie JB, Criqui MH.
    Arch Intern Med. 2008 Apr 14;168(7):721-7. doi: 10.1001/archinte.168.7.721.
    PMID: 18413554 Free PMC article. Clinical Trial.
    13.
    Mood, Personality, and Behavior Changes During Treatment with Statins: A Case Series.
    Cham S, Koslik HJ, Golomb BA.
    Drug Saf Case Rep. 2016 Dec;3(1):1. doi: 10.1007/s40800-015-0024-2.
    PMID: 27747681 Free PMC article.
    14.
    Statins and activity: proceed with caution.
    Golomb BA.
    JAMA Intern Med. 2014 Aug;174(8):1270-2. doi: 10.1001/jamainternmed.2013.14543.
    PMID: 24912133 No abstract available.
    15.
    Physician response to patient reports of adverse drug effects: implications for patient-targeted adverse effect surveillance.
    Golomb BA, McGraw JJ, Evans MA, Dimsdale JE.
    Drug Saf. 2007;30(8):669-75. doi: 10.2165/00002018-200730080-00003.
    PMID: 17696579
    16.
    Amyotrophic lateral sclerosis-like conditions in possible association with cholesterol-lowering drugs: an analysis of patient reports to the University of California, San Diego (UCSD) Statin Effects Study.
    Golomb BA, Kwon EK, Koperski S, Evans MA.
    Drug Saf. 2009;32(8):649-61. doi: 10.2165/00002018-200932080-00004.
    PMID: 19591530
    17.
    A Fat to Forget: Trans Fat Consumption and Memory.
    Golomb BA, Bui AK.
    PLoS One. 2015 Jun 17;10(6):e0128129. doi: 10.1371/journal.pone.0128129. eCollection 2015.
    PMID: 26083739 Free PMC article.
    18.
    Implications of statin adverse effects in the elderly.
    Golomb BA.
    Expert Opin Drug Saf. 2005 May;4(3):389-97. doi: 10.1517/14740338.4.3.389.
    PMID: 15934847
    19.
    Misinterpretation of trial evidence on statin adverse effects may harm patients.
    Golomb BA.
    Eur J Prev Cardiol. 2015 Apr;22(4):492-3. doi: 10.1177/2047487314533085. Epub 2014 Apr 25.
    PMID: 24770566 No abstract available.
    20.
    Statins and muscle adverse effects: a complementary perspective.
    Golomb BA, Kopersk S, Evans MA.
    Drug Saf. 2010 Sep 1;33(9):803; author reply 803-4. doi: 10.2165/11538820-000000000-00000.
    PMID: 20731088 No abstract available.
    21.
    First-degree relatives with behavioural adverse effects on statins.
    Reilly D, Cham S, Golomb BA.
    BMJ Case Rep. 2011 Oct 28;2011:bcr0920114758. doi: 10.1136/bcr.09.2011.4758.
    PMID: 22675104 Free PMC article.
    22.
    New statins also produce fatigue: spontaneous reporting as a complementary system to increase safety knowledge–reply.
    Golomb BA, Koperski S.
    JAMA Intern Med. 2013 Feb 11;173(3):247-8. doi: 10.1001/jamainternmed.2013.2113.
    PMID: 23400663 No abstract available.
    23.
    The modern spectrum of rhabdomyolysis: drug toxicity revealed by creatine kinase screening.
    Linares LA, Golomb BA, Jaojoco JA, Sikand H, Phillips PS.
    Curr Drug Saf. 2009 Sep;4(3):181-7. doi: 10.2174/157488609789007010. Epub 2009 Sep 1.
    PMID: 19534642
    24.
    Improvement in sleep apnoea associated with switch from simvastatin to pravastatin.
    Cham S, Gill K, Koperski S, Golomb BA.
    BMJ Case Rep. 2009;2009:bcr05.2009.1875. doi: 10.1136/bcr.05.2009.1875. Epub 2009 Sep 1.
    PMID: 21886657 Free PMC article.
    25.
    Effects of statins on energy and fatigue with exertion: results from a randomized controlled trial.
    Golomb BA, Evans MA, Dimsdale JE, White HL.
    Arch Intern Med. 2012 Aug 13;172(15):1180-2. doi: 10.1001/archinternmed.2012.2171.
    PMID: 22688574 Free PMC article. Clinical Trial. No abstract available.
    26.
    Re: Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease.
    Golomb BA, Evans MA.
    Neurology. 2008 Jun 10;70(24):2349; author reply 2349-50. doi: 10.1212/01.wnl.0000317006.87071.b1.
    PMID: 18541892 No abstract available.
    27.
    Potential link between HMG-CoA reductase inhibitor (statin) use and interstitial lung disease.
    Golomb BA, Evans MA.
    Med J Aust. 2007 Aug 20;187(4):253. doi: 10.5694/j.1326-5377.2007.tb01223.x.
    PMID: 17708735 No abstract available.
    28.
    The older the better: are elderly study participants more non-representative? A cross-sectional analysis of clinical trial and observational study samples.
    Golomb BA, Chan VT, Evans MA, Koperski S, White HL, Criqui MH.
    BMJ Open. 2012 Dec 14;2(6):e000833. doi: 10.1136/bmjopen-2012-000833. Print 2012.
    PMID: 23242479 Free PMC article.

  9. Sure hope the 78. Evidence that statins harm cognition is still anecdotal, but they also have almost no benefit in reducing heart attack or stroke. That “50%” reduction in heart attacks? Means 3/100 on placebo had a HA and only 2/100 on the med had it. Any normal person recognizes that reduced your risk from 3% to 2%. That’s a 1% reduction, not 50. But since there are lies, damned lies, and statistics, the pharm companies use the ration of 3:2 to claim its 50%. Statins are useless and are not any risk level whatsoever imo.

  10. Mike McDermott | June 26, 2021 at 8:53 am | Reply

    I’d be concerned. Statins which were invented to prevent strokes and heart attacks suddenly were causing strokes and heart attacks. I believe because of their effect on kidneys. Now, like Alzheimer drugs, they’re being prescribed sooner to prevent. They might be only contributing to stroke and heart attack causes. I’ll guarantee you that p drug companies will only say, sorry.

  11. Raymond E Jeffrey | July 3, 2021 at 5:08 pm | Reply

    I have been on statins for 10+ years and have issues with short term memory. After reading this it makes me wonder if there is a relation to the statins.

  12. Totally buy this. The article couldn’t be more wrong. I’ve been on the drug for a while, what who again

  13. Mark Phillips | July 4, 2021 at 4:35 pm | Reply

    Since I have been on statin my short term memory is getting shorter!!! Also I’m a hell of a lot angrier!!! I think it’s time to do away with the statin!!

  14. Statins can absolutely cause memory and cognitive impairment. I’ve had several patients who are extremely intelligent and have highly skilled jobs that have reported serious inability to perform duties after beginning statin agents. Effects were noticed within two weeks and left within several days after cessation.

  15. Stewart Teaze | July 5, 2021 at 8:38 am | Reply

    I’m an (early) retired Aerospace Engineer… My right-hand man technician would always start to experience extreme impairment in his abilities to perform his work duties, whenever he would take these “statins”… I’d always tell him (it was obvious, because he couldn’t remember anything that happened the day before), and he would admit the Doctors had convinced him to “get back on the stuff”, and he would stop taking it again. He’s retired now, but I still know when he’s taking this crap, because he starts believing in all sorts of wild nonsense… but I hold my tongue now.

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