Higher incidence of mild cognitive impairment in familial hypercholesterolemia

Daniel Zambón, Melibea Quintana, Pedro Mata, Rodrigo Alonso, Jaume Benavent, Felix Cruz-Sánchez, Jordi Gich, Miguel Pocoví, Fernando Civeira, Sebastian Capurro, David Bachman, Kumar Sambamurti, Joyce Nicholas, Miguel Pappolla

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)267-274
Number of pages8
JournalAmerican Journal of Medicine
Volume123
Issue number3
DOIs
StatePublished - Mar 2010
Externally publishedYes

Fingerprint

Hyperlipoproteinemia Type II
Incidence
Hypercholesterolemia
LDL Receptors
Apolipoprotein E2
Cognitive Dysfunction
Apolipoprotein E4
Leukoencephalopathies
Neuropsychological Tests
Transient Ischemic Attack
Neuroimaging
Cognition
Primary Health Care
Alzheimer Disease
Cohort Studies
Stroke
Pathology

Keywords

  • Alzheimer's disease
  • Hypercholesterolemia
  • Lipoprotein receptors
  • Mild cognitive impairment

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Higher incidence of mild cognitive impairment in familial hypercholesterolemia. / Zambón, Daniel; Quintana, Melibea; Mata, Pedro; Alonso, Rodrigo; Benavent, Jaume; Cruz-Sánchez, Felix; Gich, Jordi; Pocoví, Miguel; Civeira, Fernando; Capurro, Sebastian; Bachman, David; Sambamurti, Kumar; Nicholas, Joyce; Pappolla, Miguel.

In: American Journal of Medicine, Vol. 123, No. 3, 03.2010, p. 267-274.

Research output: Contribution to journalArticle

Zambón, D, Quintana, M, Mata, P, Alonso, R, Benavent, J, Cruz-Sánchez, F, Gich, J, Pocoví, M, Civeira, F, Capurro, S, Bachman, D, Sambamurti, K, Nicholas, J & Pappolla, M 2010, 'Higher incidence of mild cognitive impairment in familial hypercholesterolemia', American Journal of Medicine, vol. 123, no. 3, pp. 267-274. https://doi.org/10.1016/j.amjmed.2009.08.015
Zambón D, Quintana M, Mata P, Alonso R, Benavent J, Cruz-Sánchez F et al. Higher incidence of mild cognitive impairment in familial hypercholesterolemia. American Journal of Medicine. 2010 Mar;123(3):267-274. https://doi.org/10.1016/j.amjmed.2009.08.015
Zambón, Daniel ; Quintana, Melibea ; Mata, Pedro ; Alonso, Rodrigo ; Benavent, Jaume ; Cruz-Sánchez, Felix ; Gich, Jordi ; Pocoví, Miguel ; Civeira, Fernando ; Capurro, Sebastian ; Bachman, David ; Sambamurti, Kumar ; Nicholas, Joyce ; Pappolla, Miguel. / Higher incidence of mild cognitive impairment in familial hypercholesterolemia. In: American Journal of Medicine. 2010 ; Vol. 123, No. 3. pp. 267-274.
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AU - Zambón, Daniel

AU - Quintana, Melibea

AU - Mata, Pedro

AU - Alonso, Rodrigo

AU - Benavent, Jaume

AU - Cruz-Sánchez, Felix

AU - Gich, Jordi

AU - Pocoví, Miguel

AU - Civeira, Fernando

AU - Capurro, Sebastian

AU - Bachman, David

AU - Sambamurti, Kumar

AU - Nicholas, Joyce

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N2 - 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.

AB - 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.

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KW - Lipoprotein receptors

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