title: Higher incidence of mild cognitive impairment in familial hypercholesterolemia.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institut d'Investigacions Biomédiques August Pi Sunyer, Hospital Clinic, Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zambón
authors.forename: Melibea
authors.initials: M
authors.lastname: Quintana
authors.forename: Pedro
authors.initials: P
authors.lastname: Mata
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Alonso
authors.forename: Jaume
authors.initials: J
authors.lastname: Benavent
authors.forename: Felix
authors.initials: F
authors.lastname: Cruz-Sánchez
authors.forename: Jordi
authors.initials: J
authors.lastname: Gich
authors.forename: Miguel
authors.initials: M
authors.lastname: Pocoví
authors.forename: Fernando
authors.initials: F
authors.lastname: Civeira
authors.forename: Sebastian
authors.initials: S
authors.lastname: Capurro
authors.forename: David
authors.initials: D
authors.lastname: Bachman
authors.forename: Kumar
authors.initials: K
authors.lastname: Sambamurti
authors.forename: Joyce
authors.initials: J
authors.lastname: Nicholas
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Pappolla
mesh_terms: D008078:Cholesterol, LDL / Q000097:blood; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000150:complications* / Q000453:epidemiology; D015994:Incidence; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018110:Receptors, Lipoprotein / Q000097:blood; D012189:Retrospective Studies; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology
chemical_list: D008078:Cholesterol, LDL; D018110:Receptors, Lipoprotein