Effects of APOE ε4 on brain amyloid, lacunar infarcts, and white matter lesions: a study among patients with subcortical vascular cognitive impairment

Neurobiol Aging. 2013 Nov;34(11):2482-7. doi: 10.1016/j.neurobiolaging.2013.05.009. Epub 2013 Jun 12.

Abstract

The relationship between the apolipoprotein E ε4 allele (APOE4) and factors associated with vascular cognitive impairment (VCI) is unclear. We aimed to examine the effects of APOE4 on brain amyloid beta using Pittsburg compound B (PiB) and subcortical cerebrovascular disease, as assessed by lacunes and white matter hyperintensities (WMH) in subcortical VCI (SVCI) patients. We recruited 230 subjects with normal cognition, 111 subjects with cognitive impairment due to clinically defined Alzheimer's disease (ADCI), and 134 subjects with clinically defined SVCI. A PiB retention ratio greater than 1.5 was considered to be PiB positive. Logistic regression analysis was performed to investigate whether APOE4 increased the risk for each cognitive impairment group. Multiple linear regression analysis was performed to investigate whether APOE4 was associated with brain amyloid beta, lacunes, and WMH. APOE4 did not increase the risk of PiB(-) SVCI (odds ratio [OR], 1.50; 95% confidence interval [CI], 0.79-2.84), whereas APOE4 increased the risk of PiB(+) SVCI (OR, 4.52; 95% CI, 1.70-11.97) and PiB(+) ADCI (odds ratio, 4.84; 95% CI, 2.54-7.91). In SVCI patients, APOE4 was positively associated with PiB retention ratio, whereas APOE4 was not associated with the number of lacunes or with WMH volume. Our results suggest that amyloid beta burden can occur in patients with and without subcortical cerebrovascular disease, and that it is associated with APOE4. However APOE4 might be independent of subcortical cerebrovascular disease.

Keywords: APOE; Amyloid beta burden; Lacune; Subcortical vascular cognitive impairment; White matter hyperintensity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / complications
  • Amyloid beta-Peptides / metabolism*
  • Aniline Compounds
  • Apolipoprotein E4 / genetics
  • Apolipoprotein E4 / metabolism*
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Brain / pathology
  • Cognition Disorders / complications
  • Cognition Disorders / pathology*
  • Female
  • Genotype
  • Humans
  • Linear Models
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Nerve Fibers, Myelinated / pathology*
  • Neuropsychological Tests
  • Prospective Studies
  • Radionuclide Imaging
  • Thiazoles
  • Vascular Diseases / complications
  • Vascular Diseases / pathology*

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Apolipoprotein E4
  • Thiazoles