Clinical studies
Effects of lovastatin on cognitive function and psychological well-being,

https://doi.org/10.1016/S0002-9343(00)00353-3Get rights and content

Abstract

PURPOSE: Animal research and cross-sectional studies suggest that serum lipid concentrations may influence cognitive function, mood, and behavior, but few clinical trials have studied these effects.

SUBJECTS AND METHODS: In this double-blind investigation, 209 generally healthy adults with a serum low-density-lipoprotein (LDL) cholesterol level of 160 mg/dL or higher were randomly assigned to 6-month treatment with lovastatin (20 mg) or placebo. Assessments of neuropsychological performance, depression, hostility, and quality of life were conducted at baseline and at the end of the treatment period. Summary effect sizes were estimated as z scores on a standard deviation (SD) scale.

RESULTS: Placebo-treated subjects improved between baseline and posttreatment periods on neuropsychological tests in all five performance domains, consistent with the effects of practice on test performance (all P <0.04), whereas those treated with lovastatin improved only on tests of memory recall (P = 0.03). Comparisons of the changes in performance between placebo- and lovastatin-treated subjects revealed small, but statistically significant, differences for tests of attention (z score = 0.18; 95% confidence interval (CI), 0.06 to 0.31; P = 0.005) and psychomotor speed (z score = 0.17; 95% CI, 0.05 to 0.28; P = 0.004) that were consistent with greater improvement in the placebo group. Psychological well-being, as measured several ways, was not affected by lovastatin.

CONCLUSION: Treatment of hypercholesterolemia with lovastatin did not cause psychological distress or substantially alter cognitive function. Treatment did result in small performance decrements on neuropsychological tests of attention and psychomotor speed, the clinical importance of which is uncertain.

Section snippets

Material and methods

Subjects were generally healthy men and women with hypercholesterolemia, defined as a serum low-density-lipoprotein (LDL) cholesterol level 160 mg/dL or higher, between the ages of 24 and 60 years. After stratification by sex and age (45 years and younger, older than 45 years), each participant was randomly assigned to daily treatment with lovastatin (Mevacor, Merck and Co., Rahway, New Jersey, 20 mg) or matching placebo for 6 months. Exclusion criteria included secondary hyperlipidemia

Results

Overall, subjects were young to middle aged, mostly employed with some college education and moderate hypercholesterolemia (Table 1). Five of the 192 participants who completed the study had a history of ischemic heart disease. Baseline measures from a sample of neuropsychological tests and quality-of-life scales are provided in Table 1; additional pretreatment data appear in Table 2, Table 3. Mean systolic blood pressure was somewhat greater in the subjects assigned to lovastatin, but it was

Discussion

We studied the effects of pharmacologic cholesterol lowering on a broad range of cognitive skills and indexes of psychological well-being among nonelderly subjects with moderate hypercholesterolemia. We found significant effects of lovastatin treatment on measures of psychomotor and attentional processes, as compared with placebo. Performance in three other domains—mental flexibility, working memory, and memory recall—also tended to decrease compared with placebo, but the differences were not

References (67)

  • M.F Muldoon et al.

    Effects of cholesterol lowering on mortalitya quantitative review of primary prevention trials

    Br Med J

    (1990)
  • M.F Muldoon

    Injury, death, and cholesterol

    Ann Intern Med

    (1994)
  • Randomised trial of cholesterol lowering in 4444 patients with coronary heart diseasethe Scandinavian Simvastatin Survival Study (4S)

    Lancet

    (1994)
  • F.M Sacks et al.

    The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels

    NEJM

    (1996)
  • A Ryman

    Cholesterol, violent death, and mental disorder

    Br Med J

    (1994)
  • S Yehuda et al.

    Effects of dietary fat on pain threshold, thermoregulation and motor activity in rats

    Pharmacol Biochem Behav

    (1986)
  • J.R Kaplan et al.

    Influence of dietary lipids on agonistic and affiliative behavior in Macaca fascicularis

    Am J Primatol

    (1996)
  • B.A Golomb

    Cholesterol and violenceis there a connection?

    Ann Intern Med

    (1998)
  • D Jacobs et al.

    Report of the conference on low blood cholesterolmortality associations

    Circulation

    (1992)
  • M Hillbrand et al.

    Serum cholesterol and aggression in hospitalized male forensic patients

    J Behav Med

    (1995)
  • D.S Freedman et al.

    Plasma lipid levels and psychologic characteristics in men

    Am J Epid

    (1995)
  • J.R Kaplan et al.

    Assessing the observed relationship between low cholesterol and violence-related mortalityimplications for suicide risk

    Ann New York Acad Sci

    (1997)
  • Muldoon MF, Flory JD, Ryan CM. Serum cholesterol, the brain, and cognitive functioning. In: Waldstein SR, Elias MF,...
  • D Benton

    Do low cholesterol levels slow mental processing?

    Psychosom Med

    (1995)
  • M.F Muldoon et al.

    Serum cholesterol and intellectual performance

    Psychosom Med

    (1997)
  • G.E Swan et al.

    Decline in cognitive performance in aging twins. Heritability and biobehavioral predictors from the National Heart, Lung, and Blood Institute Twin Study

    Arch Neurol

    (1992)
  • L Cattin et al.

    Factors associated with cognitive impairment among older Italian inpatients

    J Am Geriat Soc

    (1997)
  • J Kuusisto et al.

    Association between features of the insulin resistance syndrome and Alzheimer’s disease independently of apolipoprotein E4 phenotypecross sectional population based study

    BMJ

    (1997)
  • W.T Friedewald et al.

    Estimation of the concentration of low density lipoprotein cholesterol in plasma without the use of the preparative ultracentrifuge

    Clin Chem

    (1972)
  • S.R Waldstein et al.

    Hypertension and neuropsychological performance in meninteractive effects of age

    Health Psych

    (1996)
  • J.B Kostis et al.

    Central nervous system effects of HMG CoA reductase inhibitorslovastatin and pravastatin on sleep and cognitive performance in patients with hypercholesterolemia

    Clin Pharm

    (1994)
  • R.W.S Harrison et al.

    Do cholesterol-lowering agents affect brain activity? A comparison of simvastatin, pravastatin, and placebo in healthy volunteers

    Br J Clin Pharm

    (1994)
  • F Gengo et al.

    Effects of treatment with lovastatin and pravastatin on daytime cognitive performance

    Clin Cardiol

    (1995)
  • Cited by (261)

    • The effects of statin monotherapy on depressive symptoms: A systematic review and meta-analysis

      2022, Journal of Affective Disorders
      Citation Excerpt :

      Fifty-nine potentially eligible articles were assessed full-text, of which 14 were finally included in this systematic review. The characteristics of the 14 retrieved trials (Carlsson et al., 2002; Chan et al., 2017; Gengo et al., 1995; Harrison and Ashton, 1994; Hyyppä et al., 2003; Morales et al., 2006; Muldoon et al., 2000; Robertson et al., 2017; Santanello et al., 1997; Sheridan et al., 2014; Sparks et al., 2005; Stewart et al., 2000; Visseren et al., 2001; Wardle et al., 1996) were reported in Table 1. The study samples included: nine trials in people with hyperlipidaemia (Carlsson et al., 2002; Gengo et al., 1995; Hyyppä et al., 2003; Morales et al., 2006; Muldoon et al., 2000; Santanello et al., 1997) of which two involving patients with comorbid coronary artery disease (Stewart et al., 2000; Wardle et al., 1996) while one trial included comorbid type-2 diabetes mellitus (Visseren et al., 2001); one trial in healthy volunteers (Harrison and Ashton, 1994); one trial on patients with secondary progressive multiple sclerosis (Chan et al., 2017); one trial in adults with traumatic brain injury (Robertson et al., 2017); one trial in patients diagnosed with mild-to-moderate Alzheimer disease (Sparks et al., 2005); one trial in individuals affected by chronic hepatitis C (Sheridan et al., 2014).

    View all citing articles on Scopus

    Supported by the Public Health Service (HL46328). The placebo and lovastatin tablets were donated by Merck and Co.

    Access the “Journal Club” discussion of this paper at http://www.elsevier.com/locate/ajmselect/

    View full text