0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Clinical Trials |

Statin Use and the Risk of Incident Dementia:  The Cardiovascular Health Study FREE

Thomas D. Rea, MD, MPH; John C. Breitner, MD; Bruce M. Psaty, MD, PhD; Annette L. Fitzpatrick, PhD; Oscar L. Lopez, MD; Anne B. Newman, MD, MPH; William R. Hazzard, MD; Peter P. Zandi, PhD, MPH; Gregory L. Burke, MD, MS; Constantine G. Lyketsos, MD, MHS; Charles Bernick, MD; Lewis H. Kuller, MD, DrPH
[+] Author Affiliations

Author Affiliations: Departments of Medicine (Drs Rea, Breitner, Psaty, and Hazzard) and Epidemiology (Drs Psaty and Fitzpatrick), University of Washington, and Veterans Administration Puget Sound Healthcare System (Drs Breitner and Hazzard), Seattle; Departments of Neurology, Psychiatry, and Psychology (Dr Lopez), Medicine (Dr Newman), and Epidemiology (Drs Newman and Kuller), University of Pittsburgh School of Medicine, Pittsburgh, Pa; Department of Mental Health, Bloomberg School of Public Health (Dr Zandi), and Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, School of Medicine (Dr Lyketsos), The Johns Hopkins University, Baltimore, Md; Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (Dr Burke); and Division of Neurology, University of Nevada, Las Vegas (Dr Bernick).


Section Editor: Ira Shoulson, MD

More Author Information
Arch Neurol. 2005;62(7):1047-1051. doi:10.1001/archneur.62.7.1047.
Text Size: A A A
Published online

Background  Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) reduce cardiovascular risk through mechanisms that might affect the development of dementia.

Objective  To evaluate whether statin use is associated with a lower risk of dementia compared with never use of lipid-lowering agents (LLAs).

Design  Cohort study of community-dwelling adults 65 years and older. The analysis included 2798 participants free of dementia at baseline.

Main Outcome Measures  Using Cox proportional hazards regression analysis, we estimated the risk of incident all-cause and type-specific dementia associated with time-dependent statin therapy compared with never use of LLAs. The primary analyses incorporated a 1-year lag between exposure and outcome. Secondary analyses included the final year of exposure and modeled statin use as current use vs nonuse to simulate a case-control approach.

Results  Compared with never use of LLAs, ever use of statins was not associated with the risk of all-cause dementia (multivariable-adjusted hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.77-1.52), Alzheimer disease alone (HR, 1.21; 95% CI, 0.76-1.91), mixed Alzheimer disease and vascular dementia (HR, 0.87; 95% CI, 0.44-1.72), or vascular dementia alone (HR, 1.36; 95% CI, 0.61-3.06). In contrast, in secondary analyses, current use of statins compared with nonuse of LLAs was associated with HRs of 0.69 (95% CI, 0.46-1.02) for all-cause dementia and 0.56 (95% CI, 0.35-0.92) for any Alzheimer disease.

Conclusions  In this cohort study, statin therapy was not associated with a decreased risk of dementia. Methodological differences may explain why results of this cohort investigation differ from those of prior case-control studies. Additional investigation is needed to determine whether and for whom statin use may affect dementia risk.

Dementia is associated with excess morbidity and mortality.1 The most common causes of dementia are Alzheimer disease (AD) and cerebrovascular changes that produce vascular dementia (VaD). Although each type may evolve from distinct pathophysiologies, evidence suggests that the 2 may exist along a spectrum.2 For both causes, many demographic, socioeconomic, genetic, and clinical risk factors have been identified, perhaps reflecting different pathological processes.2,3 In particular, some evidence supports a role of lipid metabolism or inflammation in the development of dementia, specifically AD.4

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, prevent cardiovascular disease in at-risk populations. These agents may reduce cardiovascular risk by inhibiting cholesterol synthesis or through anti-inflammatory effects.5 Statin use could therefore affect the development of dementia. In vivo, in vitro, and epidemiological investigations have reported a possible protective association between statin use and the dementia process, specifically AD.612 In contrast, results from trials designed to assess the cardiovascular effects of statin use, in which a surrogate measure was used to assess dementia, have not shown a protective statin association.13 Using data from the Cardiovascular Health Cognition Study, an ancillary study of the Cardiovascular Health Study, we assessed the risk of incident all-cause and type-specific dementia associated with statin therapy. We hypothesized that statin therapy would be associated with a lower risk of dementia compared with never use of lipid-lowering therapy.

SETTING, SUBJECTS, AND DESIGN

The Cardiovascular Health Study14 is a prospective population-based cohort study of risk factors for cardiovascular disease among community-dwelling older adults. The Cardiovascular Health Cognition Study included the subset of Cardiovascular Health Study participants 65 years and older who underwent magnetic resonance imaging from 1991 to 1994 and a concurrent Mini-Mental State Examination. The present analyses include 2798 participants who were free of dementia at the time of the baseline magnetic resonance imaging. The study was approved by appropriate institutional review boards.

At baseline, the Cardiovascular Health Study collected data on demographics, clinical characteristics, medication use, diagnostic testing, laboratory assessments, and clinical outcomes. The clinical assessment included functional health status, cognitive function, smoking status, alcohol intake, blood pressure, diabetes mellitus status, and clinical and subclinical measures of cardiovascular disease. The laboratory assessment included baseline fasting lipid profile, APOE ε4 genotype, and C-reactive protein level. To assess medication use, participants brought all prescription medications used within the prior 2 weeks to each annual study visit.15 Participants were followed up annually with regard to functional health status, symptoms, physical examination, clinical characteristics, and medication use.

MAIN OUTCOME MEASURES

The criteria and process used to identify dementia in the Cardiovascular Health Cognition Study16 have been detailed previously. The main outcomes of the present analysis were incident all-cause dementia and dementia due solely to AD as defined by the criteria of the National Institute of Neurological and Communicative Diseases and Stroke.17 The State of California Alzheimer’s Disease Diagnostic and Treatment Centers criteria18 were used to identify VaD.

EXPOSURES

The main exposure was the use of lipid-lowering agents (LLAs), specifically statins, as assessed by the annual medication inventory. Lipid-lowering agents were grouped according to statin and nonstatin classifications. Statins were further classified as more lipophilic (lovastatin, simvastatin, and cervistatin) or less lipophilic (atorvastatin calcium, pravastatin sodium, and fluvastatin sodium).19 Nonstatin LLAs included fibrates, niacin, bile acid sequestrants, and probucol, with fibrate use constituting three quarters of nonstatin use. The baseline cognitive assessment was performed using the Modified Mini-Mental State Examination.20

STATISTICAL ANALYSIS

For the main analyses, the use of LLAs was modeled as a time-dependent covariate and categorized as never use, statin use, or nonstatin LLA use. The use of statins and nonstatin LLAs was modeled as ever use, current use, or former use. Time-dependent Cox proportional hazards regression analysis was used to compute multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of LLA use with dementia, using never users as the referent group.

For the primary analyses, follow-up started at the date of the baseline magnetic resonance imaging and extended to 1 year before the date of dementia diagnosis or censoring. The main models a priori incorporated this 1-year lag because dementia typically manifests in a gradual manner. Therefore, from a biological perspective, exposures that provide a protective effect would typically be present months or years before clinical dementia. A secondary set of models included the final year of exposure status and modeled LLA use as current use vs nonuse because this model best approximates the case-control approach.912

Additional analyses were restricted to persons with a diagnosis of coronary heart disease or a baseline total cholesterol level of 200 mg/dL or higher (≥5.18 mmol/L), which are indications for LLA therapy. Differences between subgroups defined by sex, age (≤75 vs >75 years), race, smoking status, hypertension, diabetes mellitus, clinical cerebrovascular disease, APOE ε4 genotype, or quartiles of C-reactive protein levels were assessed with the addition of a cross-product term between the covariate of interest and the categorical LLA variable. Analyses were done using Stata version 7.0 (StataCorp LP, College Station, Tex).

On average, person-years of LLA use were associated with alcohol abstinence, a higher score on the Mini-Mental State Examination, diabetes mellitus, clinical heart disease, and elevated total cholesterol and C-reactive protein levels (Table 1). In addition, person-years of statin use were associated with female sex and the presence of an APOE ε4 allele.

Table Graphic Jump LocationTable 1. Proportions of Person-years of Characteristics According to Use of Lipid-Lowering Agents*

During 15 030 person-years of follow-up, there were 480 incident cases of dementia, including 245 attributable to AD alone, 151 attributable to a combination of AD and VaD, 62 attributable to VaD alone, and 22 attributable to other causes. In the primary analyses with the 1-year lag in exposure classification (Table 2), ever use of statins was not associated with the risk of all-cause dementia (HR, 1.08; 95% CI, 0.77-1.52), AD alone (HR, 1.21; 95% CI, 0.76-1.91), mixed AD and VaD (HR, 0.87; 95% CI, 0.44-1.72), or VaD alone (HR, 1.36; 95% CI, 0.61-3.06) compared with never users. In analyses that recoded ever use of statin therapy into current or former use, current use was not associated with the risk of dementia. However, former use of statins was associated with an elevated risk of all-cause dementia (HR, 1.88; 95% CI, 1.05-3.36) and AD alone (HR, 2.54; 95% CI, 1.24-5.20) compared with never users. Ever use of nonstatin LLAs was not associated with the risk of all-cause dementia (HR, 0.86; 95% CI, 0.50-1.46) or AD alone (HR, 1.05; 95% CI, 0.51-2.13) compared with never use of LLAs. Further adjustment for race, smoking status, hypertension, diabetes mellitus, atrial fibrillation, low-density lipoprotein and total cholesterol levels, APOE ε4 genotype, C-reactive protein level, carotid intima-media thickness, aspirin use, benzodiazepine use, or total number of medications used did not appreciably change the estimates.

Table Graphic Jump LocationTable 2. Relative Risks of Incident All-Cause and Type-Specific Dementia According to Use of Lipid-Lowering Agents*

No dose response was detected with regard to risk and duration of statin use. Compared with never use of LLAs, the HRs of all-cause dementia were 0.98 (95% CI, 0.55-1.74) for ever use of statins for less than 1 year, 1.41 (95% CI, 0.89-2.25) for 1 to 3 years, and 0.74 (95% CI, 0.35-1.57) for greater than 3 years. For AD alone, the HRs were 1.52 (95% CI, 0.78-2.98) for ever use of statins for less than 1 year, 1.05 (95% CI, 0.49-2.24) for 1 to 3 years, and 1.04 (95% CI, 0.42-2.56) for greater than 3 years. Similarly, no difference was detected between use of statins that were more or less lipophilic. Compared with never use of LLAs, ever use of more lipophilic statins was associated with HRs of 0.94 (95% CI, 0.61-1.44) for all-cause dementia and 1.03 (95% CI, 0.57-1.86) for AD alone, and ever use of less lipophilic statins was associated with HRs of 1.38 (95% CI, 0.83-2.29) for all-cause dementia and 1.58 (95% CI, 0.80-3.11) for AD alone. When analyses were restricted to subjects with clinical coronary heart disease or a total cholesterol level of 200 mg/dL or higher (≥5.18 mmol/L), the HRs associated with ever use of statins were 0.97 (95% CI, 0.67-1.42) for all-cause dementia and 1.01 (95% CI, 0.61-1.69) for AD alone compared with never use. Similarly, no association differences were detected across the specific subgroups detailed in the “Methods” section.

In secondary analyses that included the final year of exposure, current use of statins compared with nonuse of LLAs was associated with HRs of 0.69 (95% CI, 0.46-1.02) for all-cause dementia and 0.59 (95% CI, 0.32-1.10) for AD alone. The HR for the association between current statin use and any AD, combining the AD alone and mixed AD and VaD events (n = 396), was 0.56 (95% CI, 0.35-0.92).

Given the prevalence of dementia and its associated morbidity and mortality, an effective preventive pharmacological treatment would have important public health implications. In this prospective cohort of older adults, antecedent statin use was not associated with a lower risk of all-cause dementia or AD compared with never use of LLAs after considering other known or suspected risk factors. In contrast, the results suggested a protective statin association in models that simulated the typical case-control design of a cross-sectional statin exposure and dementia outcome.

Several factors may explain why statin use was not associated with a lower risk of dementia. Participants were on average 75 years of age, and statin use was assessed for a median of 5 years. Statin exposure may need to occur earlier in adulthood or for longer periods to prevent dementia, although analyses that stratified the duration of statin use did not suggest a duration-dependent association. The potential benefit may depend on the particular type of statin used or the characteristics of the patient, although analyses that assessed the association by statin lipophilicity or by clinical subgroup did not detect differences.

Alternatively, statin use may not affect the development of dementia. Case-control studies912 have reported a protective association typically based on cross-sectional statin exposures and dementia outcomes and have not considered former use or incorporated a lag period into the analysis. A protective statin association was observed in the present investigation when analyses modeled the statin exposure as current use vs nonuse and did not incorporate a lag period, thereby simulating a case-control approach. In contrast, no association was evident in the primary analyses. Indeed, former use of statins was associated with an elevated risk of dementia. Although starting and stopping statin therapy may somehow trigger the dementia process, the most likely explanation is that former statin use (discontinuation of statin therapy) is a surrogate marker for declining health. Patients and physicians may be less inclined to maintain preventive treatments such as statin use as overall health deteriorates.21 Conversely, current statin use may be a surrogate marker for good health, which may be associated with a lower risk of dementia.

This study has limitations. Despite efforts to minimize confounding, we cannot exclude the possibility of uncontrolled confounding in this prospective cohort study. For example, the primary indication for statin therapy was elevated cholesterol in the setting of coronary heart disease or its risk factors. Some authors have reported that heart disease is a risk factor for dementia.3 However, analyses that adjusted for heart disease or restricted the assessment to persons with a clinical indication for statin therapy did not reveal an association. The primary analyses had greater than 80% power to detect a 50% decrease in risk of all-cause dementia or AD (a risk difference comparable to previous reports from epidemiological studies912); however, the study had modest power to detect associations among subgroups of interest.

In this investigation, statin therapy was not associated with a lower risk of dementia. Although statin use is an important treatment for cardiovascular disease, additional investigation is needed to determine whether and for whom statin use may affect dementia risk.

Correspondence: Thomas D. Rea, MD, MPH, Department of Medicine, University of Washington, Metropolitan Park, East Tower, 1730 Minor Ave, Suite 1360, Seattle, WA 98101 (rea123@u.washington.edu).

Accepted for Publication: March 1, 2005.

Author Contributions:Study concept and design: Rea, Breitner, Psaty, Hazzard, Burke, Lyketsos. Acquisition of data: Psaty, Lopez, Burke, Lyketsos, Kuller. Analysis and interpretation of data: Rea, Breitner, Psaty, Fitzpatrick, Newman, Zandi, Burke, Lyketsos, Bernick, Kuller. Drafting of the manuscript: Rea, Breitner, Kuller. Critical revision of the manuscript for important intellectual content: Breitner, Psaty, Fitzpatrick, Lopez, Newman, Hazzard, Zandi, Burke, Lyketsos, Bernick, Kuller. Statistical analysis: Rea, Fitzpatrick, Zandi. Obtained funding: Psaty, Lopez, Burke, Kuller. Administrative, technical, and material support: Lopez, Kuller. Study supervision: Breitner, Psaty. Geriatric expertise: Hazzard.

Funding/Support: This study was supported by grant R01 625566 and by contracts N01 HC85079, N01 HC85080, N01 HC85081, N01 HC85082, N01 HC85083, N01 HC85084, N01 HC85085, N01 HC85086, N01 HL35129, and N01 HL15103 from the National Heart, Lung, and Blood Institute, Bethesda, Md, and by grants R01 AG09556 and R01 AG15928 from the National Institute on Aging, Bethesda.

Barclay  LLZemcov  ABlass  JPSansone  J Survival in Alzheimer’s disease and vascular dementias. Neurology 1985;35834- 840
PubMed
Ritchie  KLovestone  S The dementias. Lancet 2002;3601759- 1766
PubMed
Kukull  WAGanguli  M Epidemiology of dementia. Neurol Clin 2000;18923- 949
PubMed
Crisby  MCarlson  LAWinblad  B Statins in the prevention and treatment of Alzheimer disease. Alzheimer Dis Assoc Disord 2002;16131- 136
Rosenson  RSTangney  CC Antiatherothrombotic properties of statins: implications for cardiovascular disease reduction. JAMA 1998;2791643- 1650
PubMed
Fassbender  KSimons  MBergmann  C  et al.  Simvastatin strongly reduces levels of Alzheimer’s disease β-amyloid peptides Aβ42 and Aβ40 in vitro and in vivo. Proc Natl Acad Sci U S A 2001;985856- 5861
Naidu  AXu  QCatalano  RCordell  B Secretion of apolipoprotein E by brain glia requires protein prenylation and is suppressed by statins. Brain Res 2002;958100- 111
PubMed
Refolo  LMPappolla  JLaFrancois  L  et al.  A cholesterol-lowering drug reduces β-amyloid pathology in a transgenic mouse model of Alzheimer disease. Neurobiol Dis 2001;8890- 899
PubMed
Jick  HZornberg  GLJick  SSSeshadri  SDrachman  DA Statins and the risk of dementia. Lancet 2000;3561627- 1631
PubMed
Wolozin  BKellman  WRuosseau  PCelesia  GGSiegel  G Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Arch Neurol 2000;571439- 1443
PubMed
Rockwood  KKirkland  SHogan  DB  et al.  Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people. Arch Neurol 2002;59223- 227
PubMed
Hajjar  ISchumpert  JHirth  VWieland  DEleazer  GP The impact of the use of statins on the prevalence of dementia and the progression of cognitive impairment. J Gerontol A Biol Sci Med Sci 2002;57M414- M418
Heart Protection Study Collaborative Group, MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;3607- 22
PubMed
Fried  LPBorhani  NOEnright  P  et al.  The Cardiovascular Health Study: design and rationale. Ann Epidemiol 1991;1263- 276
PubMed
Psaty  BMLee  MSavage  PJRutan  GHGerman  PSLyles  MCardiovascular Health Study Collaborative Research Group, Assessing the use of medications in the elderly: methods and initial experience in the Cardiovascular Health Study. J Clin Epidemiol 1992;45683- 692
PubMed
Lopez  OLKuller  LHFitzpatrick  AIves  DBecker  JBeauchamp  N Evaluation of dementia in the Cardiovascular Health Cognition Study. Neuroepidemiology 2003;221- 12
McKhann  GDrachman  DFolstein  MKatzman  RPrice  DStadlan  EM Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984;34939- 944
PubMed
Chui  HCVictoroff  JIMargolin  DJagust  WShankle  RKatzman  R Criteria for the diagnosis of ischemic vascular dementia proposed by the State of California Alzheimer’s Disease Diagnostic and Treatment Centers. Neurology 1992;42(3, pt 1)473- 480
PubMed
Corsini  ABellosta  SBaetta  R New insights into the pharmacodynamic and pharmacokinetic properties of statins. Pharmacol Ther 1999;84413- 428
PubMed
Teng  ELChui  HC The Modified Mini-Mental State (3MS) Examination. J Clin Psychiatry 1987;48314- 318
PubMed
Rodriguez  EGDodge  HHBirzescu  MAStoehr  GPGanguli  M Use of lipid-lowering drugs in older adults with and without dementia: a community-based epidemiological study. J Am Geriatr Soc 2002;501852- 1856
PubMed

Figures

Tables

Table Graphic Jump LocationTable 1. Proportions of Person-years of Characteristics According to Use of Lipid-Lowering Agents*
Table Graphic Jump LocationTable 2. Relative Risks of Incident All-Cause and Type-Specific Dementia According to Use of Lipid-Lowering Agents*

References

Barclay  LLZemcov  ABlass  JPSansone  J Survival in Alzheimer’s disease and vascular dementias. Neurology 1985;35834- 840
PubMed
Ritchie  KLovestone  S The dementias. Lancet 2002;3601759- 1766
PubMed
Kukull  WAGanguli  M Epidemiology of dementia. Neurol Clin 2000;18923- 949
PubMed
Crisby  MCarlson  LAWinblad  B Statins in the prevention and treatment of Alzheimer disease. Alzheimer Dis Assoc Disord 2002;16131- 136
Rosenson  RSTangney  CC Antiatherothrombotic properties of statins: implications for cardiovascular disease reduction. JAMA 1998;2791643- 1650
PubMed
Fassbender  KSimons  MBergmann  C  et al.  Simvastatin strongly reduces levels of Alzheimer’s disease β-amyloid peptides Aβ42 and Aβ40 in vitro and in vivo. Proc Natl Acad Sci U S A 2001;985856- 5861
Naidu  AXu  QCatalano  RCordell  B Secretion of apolipoprotein E by brain glia requires protein prenylation and is suppressed by statins. Brain Res 2002;958100- 111
PubMed
Refolo  LMPappolla  JLaFrancois  L  et al.  A cholesterol-lowering drug reduces β-amyloid pathology in a transgenic mouse model of Alzheimer disease. Neurobiol Dis 2001;8890- 899
PubMed
Jick  HZornberg  GLJick  SSSeshadri  SDrachman  DA Statins and the risk of dementia. Lancet 2000;3561627- 1631
PubMed
Wolozin  BKellman  WRuosseau  PCelesia  GGSiegel  G Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Arch Neurol 2000;571439- 1443
PubMed
Rockwood  KKirkland  SHogan  DB  et al.  Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people. Arch Neurol 2002;59223- 227
PubMed
Hajjar  ISchumpert  JHirth  VWieland  DEleazer  GP The impact of the use of statins on the prevalence of dementia and the progression of cognitive impairment. J Gerontol A Biol Sci Med Sci 2002;57M414- M418
Heart Protection Study Collaborative Group, MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;3607- 22
PubMed
Fried  LPBorhani  NOEnright  P  et al.  The Cardiovascular Health Study: design and rationale. Ann Epidemiol 1991;1263- 276
PubMed
Psaty  BMLee  MSavage  PJRutan  GHGerman  PSLyles  MCardiovascular Health Study Collaborative Research Group, Assessing the use of medications in the elderly: methods and initial experience in the Cardiovascular Health Study. J Clin Epidemiol 1992;45683- 692
PubMed
Lopez  OLKuller  LHFitzpatrick  AIves  DBecker  JBeauchamp  N Evaluation of dementia in the Cardiovascular Health Cognition Study. Neuroepidemiology 2003;221- 12
McKhann  GDrachman  DFolstein  MKatzman  RPrice  DStadlan  EM Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984;34939- 944
PubMed
Chui  HCVictoroff  JIMargolin  DJagust  WShankle  RKatzman  R Criteria for the diagnosis of ischemic vascular dementia proposed by the State of California Alzheimer’s Disease Diagnostic and Treatment Centers. Neurology 1992;42(3, pt 1)473- 480
PubMed
Corsini  ABellosta  SBaetta  R New insights into the pharmacodynamic and pharmacokinetic properties of statins. Pharmacol Ther 1999;84413- 428
PubMed
Teng  ELChui  HC The Modified Mini-Mental State (3MS) Examination. J Clin Psychiatry 1987;48314- 318
PubMed
Rodriguez  EGDodge  HHBirzescu  MAStoehr  GPGanguli  M Use of lipid-lowering drugs in older adults with and without dementia: a community-based epidemiological study. J Am Geriatr Soc 2002;501852- 1856
PubMed

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Topics
PubMed Articles
JAMAevidence.com

Users' Guides to the Medical Literature
Clinical Scenario

Users' Guides to the Medical Literature
Statin Dosing and LDL Levels