CSF biomarkers and neuropsychological profiles in patients with cerebral small-vessel disease

PLoS One. 2014 Aug 22;9(8):e105000. doi: 10.1371/journal.pone.0105000. eCollection 2014.

Abstract

Despite existing criteria, differential diagnosis of Vascular Dementia (VD) and Alzheimer's disease (AD) remains difficult. The aim of this study is to figure out cognitive and biomarker profiles that may help to distinguish between VD, AD and AD + Cerebral Small Vessel Disease (CSVD). We examined a cohort of patients with CSVD (n = 92). After stratification of cognitive impaired patients (n = 59) using the standard CSF beta-amyloid 42/40 ratio cut-off point of 0.975, we obtained two groups which differed with respect to several features: 32 patients with normal beta-amyloid 42/40 ratio (>0.975) showed markedly impaired blood-brain-barrier function as indicated by an elevated albumin ratio (median 8.35). They also differed in cognitive profiles when compared to 27 patients with AD typical beta-amyloid ratio and normal albumin ratio. We also enrolled an additional group of patients with AD (no significant CSVD on MRI, n = 27) which showed no impairment of the blood-brain-barrier. We showed a negative correlation between the albumin ratio and executive cognitive function (p = 0.016) and a negative correlation between memory function and typical AD markers like Tau (p = 0.004) and p181-Tau (p = 0.023) in our cohort. We suppose that the group of patients with normal beta-amyloid ratio represents VD while patients in the other groups represent AD+CSVD and pure AD. Our results support the idea that a dysfunction of the blood-brain-barrier might be contributing factor in the development of cognitive decline in CSVD as it seems to be of more importance than the severity of white matter lesions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / cerebrospinal fluid
  • Case-Control Studies
  • Cerebral Small Vessel Diseases / cerebrospinal fluid*
  • Cerebral Small Vessel Diseases / diagnosis
  • Cerebral Small Vessel Diseases / psychology*
  • Dementia, Vascular / diagnosis
  • Diagnosis, Differential
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests

Substances

  • Biomarkers

Grants and funding

Part of the study was supported by the mobility exchange program BMBF ARG 07/008. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.