White Matter Hyperintensities Potentiate Hippocampal Volume Reduction in Non-Demented Older Individuals with Abnormal Amyloid-beta

Whitney M. Freeze*, Heidi I. L. Jacobs, Ed H. Gronenschild, Jacobus F. A. Jansen, Saartje Burgmans, Pauline Aalten, Lies Clerx, Stephanie J. Vos, Mark A. van Buchem, Frederik Barkhof, Wiesje M. van der Flier, Marcel M. Verbeek, Marcel Olde Rikkert, Walter H. Backes, Frans R. Verhey, LeARN Project

*Corresponding author for this work

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Abstract

Cerebral small vessel disease (cSVD) and amyloid-beta (A beta) deposition often co-exist in (prodromal) dementia, and both types of pathology have been associated with neurodegeneration. We examined whether cSVD and A beta have independent or interactive effects on hippocampal volume (HV) in a memory clinic population. We included 87 individuals with clinical diagnoses of Alzheimer's disease (AD) (n = 24), mild cognitive impairment (MCI) (n = 26), and subjective cognitive complaints (SCC) (n = 37). cSVD magnetic resonance imaging markers included white matter hyperintensity (WMH) volume, lacunar infarct presence, and microbleed presence. A beta pathologywas assessed as cerebrospinal fluid-derived A beta(1-42) levels and dichotomized into normal or abnormal, and HV was determined by manual volumetric measurements. A linear hierarchical regression approach was applied for the detection of additive or interaction effects between cSVD and A beta on HV in the total participant group (n = 87) and in the non-demented group (including SCC and MCI individuals only, n = 63). The results revealed that abnormal A beta and lacunar infarct presence were independently associated with lower HV in the non-demented individuals. Interestingly, A beta and WMH pathology interacted in the non-demented individuals, such that WMH had a negative effect on HV in individuals with abnormal CSF A beta(42) levels, but not in individuals with normal CSF A beta(42) levels. These associations were not present when individuals with AD were included in the analyses. Our observations suggest that relatively early on in the disease process older individuals with abnormal A beta levels are at an increased risk of accelerated disease progression when concomitant cSVD is present.

Original languageEnglish
Pages (from-to)333-342
Number of pages10
JournalJournal of Alzheimer's Disease
Volume55
Issue number1
DOIs
Publication statusPublished - 1 Nov 2017

Keywords

  • Amyloid-beta
  • cerebral small vessel disease
  • dementia
  • neurodegeneration
  • MILD COGNITIVE IMPAIRMENT
  • SMALL-VESSEL DISEASE
  • CEREBROSPINAL-FLUID BIOMARKERS
  • SUBCORTICAL VASCULAR DEMENTIA
  • ALZHEIMERS-DISEASE
  • A-BETA
  • CEREBRAL MICROBLEEDS
  • NORMATIVE DATA
  • CEREBROVASCULAR-DISEASE
  • CORTICAL THICKNESS

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