The contribution of small vessel disease to subtypes of Alzheimer's disease: a study on cerebrospinal fluid and imaging biomarkers

Neurobiol Aging. 2018 Oct:70:18-29. doi: 10.1016/j.neurobiolaging.2018.05.028. Epub 2018 May 30.


We investigated whether subtypes of Alzheimer's disease (AD), that is, typical, limbic-predominant, hippocampal-sparing, and minimal atrophy AD, had a specific signature of small vessel disease and neurodegeneration. Four hundred twenty-three clinically diagnosed AD patients were included (161 typical, 121 limbic-predominant, 70 hippocampal-sparing, 71 minimal atrophy). One hundred fifty-six fulfilled a biomarkers-based AD diagnosis. White matter hyperintensities and cerebral microbleeds (CMB) had the highest prevalence in limbic-predominant AD, and the lowest prevalence in minimal atrophy AD. CMB existed evenly in lobar and deep brain areas in limbic-predominant, typical, and hippocampal-sparing AD. In minimal atrophy AD, CMB were mainly located in brain lobar areas. Perivascular spaces in the centrum semiovale were more prevalent in typical AD. Small vessel disease contributed to the prediction of Mini-Mental State Examination. Minimal atrophy AD showed highly pathological levels of cerebrospinal fluid Aß1-42, total tau, and phosphorylated tau, in the absence of overt brain atrophy. Cerebral amyloid angiopathy seems to have a stronger contribution to hippocampal-sparing and minimal atrophy AD, whereas hypertensive arteriopathy may have a stronger contribution to typical and limbic-predominant AD.

Keywords: Alzheimer's disease; Cerebrospinal fluid biomarkers; Magnetic resonance imaging; Neurodegeneration; Small vessel disease; Subtypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / complications
  • Alzheimer Disease / diagnostic imaging*
  • Biomarkers / cerebrospinal fluid
  • Brain / diagnostic imaging
  • Brain / pathology
  • Cerebral Small Vessel Diseases / cerebrospinal fluid*
  • Cerebral Small Vessel Diseases / complications
  • Cerebral Small Vessel Diseases / diagnostic imaging*
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Risk Factors
  • White Matter / diagnostic imaging
  • White Matter / pathology


  • Biomarkers