The effect of statin use on dementia risk remains unclear. This study aims to examine the association between long-term statin use and dementia risk.
Methods:
A nest case–control study within a nationwide representative population-based cohort. Individuals aged 50 years and older participating in Taiwan’s National Health Insurance program between 1998 and 2009 were enrolled. A total of 9257 patients with at least 3 outpatient or 1 inpatient claims records for dementia were identified. Comparison patients were selected at a 1:2 ratio from age- and sex-matched participants without dementia. The cumulative period and average daily dosages of statins, fibrates, and other lipid-lowering agents were measured.
Results:
The authors found a duration–response relationship, as dementia risk decreased by 9% per year of treatment of statins (adjusted odds ratio = 0.91; 95% confidence interval, 0.85-0.97). Use of high average dose statins for more than 1 year was associated with a lower risk of dementia than use of low average dose. However, there was no significant difference in dementia risks between lipophilic and hydrophilic statins. Fibrates or other lipid-lowering agents had no significant association with dementia risk.
Conclusion:
Our results suggest that long-term use of statin is associated with a reduced dementia risk.
MiddletonLEYaffeK. Promising strategies for the prevention of dementia. Arch Neurol. 2009;66(10):1210–1215.
2.
FillitHNashDTRundekTZuckermanA. Cardiovascular risk factors and dementia. Am J Geriatr Pharmacother. 2008;6(2):100–118.
3.
WongWBLinVWBoudreauDDevineEB. Statins in the prevention of dementia and Alzheimer's disease: a meta-analysis of observational studies and an assessment of confounding. Pharmacoepidemiol Drug Saf. 2013;22(4):345–358.
4.
McGuinnessBCraigDBullockRPassmoreP. Statins for the prevention of dementia. Cochrane Database Syst Rev. 2009;(2):CD003160.
5.
ZhouBTeramukaiSFukushimaM. Prevention and treatment of dementia or Alzheimer's disease by statins: a meta-analysis. Dement Geriatr Cogn Disord. 2007;23(3):194–201.
6.
MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):7–22.
7.
ShepherdJBlauwGJMurphyMB. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360(9346):1623–1630.
8.
BettermannKArnoldAMWilliamsonJ. Statins, risk of dementia, and cognitive function: secondary analysis of the ginkgo evaluation of memory study. J Stroke Cerebrovasc Dis. 2012;21(6):436–444.
9.
BeydounMABeason-HeldLLKitner-TrioloMH. Statins and serum cholesterol's associations with incident dementia and mild cognitive impairment. J Epidemiol Community Health. 2011;65(11):949–957.
10.
CramerCHaanMNGaleaSLangaKMKalbfleischJD. Use of statins and incidence of dementia and cognitive impairment without dementia in a cohort study. Neurology. 2008;71(5):344–350.
11.
HaagMDHofmanAKoudstaalPJStrickerBHBretelerMM. Statins are associated with a reduced risk of Alzheimer disease regardless of lipophilicity. the Rotterdam study. J Neurol Neurosurg Psychiatry. 2009;80(1):13–17.
12.
HorsdalHTOlesenAVGasseCSorensenHTGreenRCJohnsenSP. Use of statins and risk of hospitalization with dementia: a Danish population-based case–control study. Alzheimer Dis Assoc Disord. 2009;23(1):18–22.
13.
JickHZornbergGLJickSSSeshadriSDrachmanDA. Statins and the risk of dementia. Lancet. 2000;356(9242):1627–1631.
14.
LiGShoferJBRhewIC. Age-varying association between statin use and incident Alzheimer's disease. J Am Geriatr Soc. 2010;58(7):1311–1317.
15.
SparksDLKryscioRJSabbaghMNConnorDJSparksLMLiebsackC. Reduced risk of incident AD with elective statin use in a clinical trial cohort. Curr Alzheimer Res. 2008;5(4):416–421.
16.
ZamriniEMcGwinGRosemanJM. Association between statin use and Alzheimer's disease. Neuroepidemiology. 2004;23(1-2):94–98.
17.
RockwoodKKirklandSHoganDB. Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people. Arch Neurol. 2002;59(2):223–227.
18.
SmeethLDouglasIHallAJHubbardREvansS. Effect of statins on a wide range of health outcomes: a cohort study validated by comparison with randomized trials. Br J Clin Pharmacol. 2009;67(1):99–109.
19.
ArvanitakisZSchneiderJAWilsonRS. Statins, incident Alzheimer disease, change in cognitive function, and neuropathology. Neurology. 2008;70(19 pt 2):1795–1802.
20.
GlasserSPWadleyVJuddS. The association of statin use and statin type and cognitive performance: analysis of the reasons for geographic and racial differences in stroke (REGARDS) study. Clin Cardiol. 2010;33(5):280–288.
21.
Hippisley-CoxJCouplandC. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ. 2010;340:c2197.
22.
LiaoJK. Statin therapy for cardiac hypertrophy and heart failure. J Investig Med. 2004;52(4):248–253.
23.
ReaTDBreitnerJCPsatyBM. Statin use and the risk of incident dementia: the cardiovascular health study. Arch Neurol. 2005;62(7):1047–1051.
24.
ReitzCTangMXLuchsingerJMayeuxR. Relation of plasma lipids to Alzheimer disease and vascular dementia. Arch Neurol. 2004;61(5):705–714.
25.
ZandiPPSparksDLKhachaturianAS. Do statins reduce risk of incident dementia and Alzheimer disease?The Cache County Study. Arch Gen Psychiatry. 2005;62(2):217–224.
26.
GlynnRJSchneeweissSWangPSLevinRAvornJ. Selective prescribing led to overestimation of the benefits of lipid-lowering drugs. J Clin Epidemiol. 2006;59(8):819–828.
27.
BrookhartMAPatrickARDormuthC. Adherence to lipid-lowering therapy and the use of preventive health services: an investigation of the healthy user effect. Am J Epidemiol. 2007;166(3):348–354.
28.
CopelandKTCheckowayHMcMichaelAJHolbrookRH. Bias due to misclassification in the estimation of relative risk. Am J Epidemiol. 1977;105(5):488–495.
29.
TamimHMonfaredAALeLorierJ. Application of lag-time into exposure definitions to control for protopathic bias. Pharmacoepidemiol Drug Saf. 2007;16(3):250–258.
30.
BresciaFBalestraEIasellaMGDamatoAB. Effects of combined treatment with simvastatin and l-carnitine on triglyceride levels in diabetic patients with hyperlipidaemia. Clin Drug Investig. 2002;22(suppl 1):23–28.
31.
WuCSTingTTWangSCChangISLinKM. Effect of benzodiazepine discontinuation on dementia risk. Am J Geriatr Psychiatry. 2011;19(2):151–159.
32.
WHO Collaborating Centre for Drug Statistic Methodology. Guidelines for ATC Classification and DDD Assignment. Oslo: WHO; 2009.
33.
SchachterM. Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam Clin Pharmacol. 2004;19(1):117–125.
34.
ChongPHSeegerJDFranklinC. Clinically relevant differences between the statins: implications for therapeutic selection. Am J Med. 2001;111(5):390–400.
35.
FassbenderKSimonsMBergmannC. Simvastatin strongly reduces levels of Alzheimer's disease beta-amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo. Proc Natl Acad Sci USA. 2001;98(10):5856–5861.
36.
RosensonRSTangneyCCCaseyLC. Inhibition of proinflammatory cytokine production by pravastatin. Lancet. 1999;353(9157):983–984.
37.
EndresMLaufsUHuangZ. Stroke protection by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase. Proc Natl Acad Sci USA. 1998;95(15):8880–8885.
38.
SierraSRamosMCMolinaPEsteoCVazquezJABurgosJS. Statins as neuroprotectants: a comparative in vitro study of lipophilicity, blood–brain-barrier penetration, lowering of brain cholesterol, and decrease of neuron cell death. J Alzheimers Dis. 2011;23(2):307–318.
39.
WolozinBWangSWLiNCLeeALeeTAKazisLE. Simvastatin is associated with a reduced incidence of dementia and Parkinson's disease. BMC Med. 2007;5:20.
40.
YenYCYangMJShihCHLungFW. Cognitive impairment and associated risk factors among aged community members. Int J Geriatr Psychiatry. 2004;19(6):564–569.
41.
WuMSLanTHChenCMChiuHCLanTY. Socio-demographic and health-related factors associated with cognitive impairment in the elderly in Taiwan. BMC Public Health. 2011;11:22.
42.
ReidFDCookDGWhincupPH. Use of statins in the secondary prevention of coronary heart disease: is treatment equitable?Heart. 2002;88(1):15–19.
