The American Journal of Medicine
Volume 123, Issue 3 , Pages 267-274, March 2010

Higher Incidence of Mild Cognitive Impairment in Familial Hypercholesterolemia

  • Daniel Zambón, MD, PhD

      Affiliations

    • Unitat de Lípids, Institut d'Investigacions Biomédiques August Pi Sunyer, Hospital Clinic, Barcelona, Spain
    • ,
  • Melibea Quintana, MS

      Affiliations

    • Unitat de Lípids, Institut d'Investigacions Biomédiques August Pi Sunyer, Hospital Clinic, Barcelona, Spain
    • ,
  • Pedro Mata, MD, PhD

      Affiliations

    • Servei d'Endocrinologia i Nutrició, Institut d'Investigacions Biomédiques August Pi Sunyer, Hospital Clinic, Barcelona, Spain
    • ,
  • Rodrigo Alonso, MD, PhD

      Affiliations

    • Servei d'Endocrinologia i Nutrició, Institut d'Investigacions Biomédiques August Pi Sunyer, Hospital Clinic, Barcelona, Spain
    • ,
  • Jaume Benavent, MD

      Affiliations

    • Consorci d'Atenció Primària de Salut de l'Eixample, Barcelona, Spain
    • ,
  • Felix Cruz-Sánchez, MD, PhD

      Affiliations

    • Universitat Internacional de Catalunya, Barcelona, Spain
    • ,
  • Jordi Gich, MS

      Affiliations

    • Unitat de Lípids, Institut d'Investigacions Biomédiques August Pi Sunyer, Hospital Clinic, Barcelona, Spain
    • ,
  • Miguel Pocoví, MD, PhD

      Affiliations

    • Servet University Hospital and Department of Biochemistry, Universidad de Zaragoza, Zaragoza, Spain
    • ,
  • Fernando Civeira, MD, PhD

      Affiliations

    • Servet University Hospital and Department of Biochemistry, Universidad de Zaragoza, Zaragoza, Spain
    • ,
  • Sebastian Capurro, MD

      Affiliations

    • Centre de Diagnòstic per l'Imatge, Hospital Clinic, Barcelona, Spain
    • ,
  • David Bachman, MD

      Affiliations

    • Department of Neurosciences, Medical University of South Carolina, Charleston
    • ,
  • Kumar Sambamurti, PhD

      Affiliations

    • Department of Neurosciences, Medical University of South Carolina, Charleston
    • ,
  • Joyce Nicholas, PhD

      Affiliations

    • Department of Neurosciences, Medical University of South Carolina, Charleston
    • ,
  • Miguel A. Pappolla, MD, PhD

      Affiliations

    • Department of Neurosciences, Medical University of South Carolina, Charleston
    • Corresponding Author InformationReprint requests should be addressed to Miguel A. Pappolla, MD, PhD, Josephine T. Morse, Professor of Neurology, Medical University of South Carolina-Neurosciences, 173 Ashley Ave 403 BSB, Charleston, SC 29425

Abstract 

Objective

Hypercholesterolemia is an early risk factor for Alzheimer's disease. Low-density lipoprotein (LDL) receptors might be involved in this disorder. Our objective was to determine the risk of mild cognitive impairment in a population of patients with heterozygous familial hypercholesterolemia, a condition involving LDL receptor dysfunction and lifelong hypercholesterolemia.

Methods

By using a cohort study design, patients with familial hypercholesterolemia (N=47) meeting inclusion criteria and comparison patients without familial hypercholesterolemia (N=70) were consecutively selected from academic specialty and primary care clinics, respectively. All patients were older than 50 years. Those with disorders that could affect cognition, including history of stroke or transient ischemic attacks, were excluded from both groups. Thirteen standardized neuropsychologic tests were performed in all subjects. Mutational analysis was performed in patients with familial hypercholesterolemia, and brain imaging was obtained in those with familial hypercholesterolemia and mild cognitive impairment.

Results

Patients with familial hypercholesterolemia showed a high incidence of mild cognitive impairment compared with those without familial hypercholesterolemia (21.3% vs 2.9%; P=.00). This diagnosis was unrelated to structural pathology or white matter disease. There were significant differences, independent of apolipoprotein E4 or E2 status, between those with familial hypercholesterolemia and those with no familial hypercholesterolemia in several cognitive measures, all in the direction of worse performance for those with familial hypercholesterolemia.

Conclusion

Because prior studies have shown that older patients with sporadic hypercholesterolemia do not show a higher incidence of mild cognitive impairment, the findings presented suggest that early exposure to elevated cholesterol or LDL receptor dysfunction may be risk factors for mild cognitive impairment.

Keywords: Alzheimer's disease, Hypercholesterolemia, Lipoprotein receptors, Mild cognitive impairment

 

 Funding: National Institute on Aging (US) AG-022103, AG-10483; Alzheimer's Association Zenith award; the Spanish Ministry of Health (RT/C03-01 and RT/G03-181); the Familial Hypercolesterolemia Foundation of Spain and the Fundació Privada Catalana de Nutrició i Lípids, Barcelona, Spain.

 Conflict of Interest: None of the authors have any conflicts of interest associated with the work presented in this manuscript.

 Authorship: All authors had access to the data and played a role in writing this manuscript.

PII: S0002-9343(09)00817-1

doi:10.1016/j.amjmed.2009.08.015

The American Journal of Medicine
Volume 123, Issue 3 , Pages 267-274, March 2010

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