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Cerebrovascular disease
Endothelial and inflammatory markers in relation to progression of ischaemic cerebral small-vessel disease and cognitive impairment: a 6-year longitudinal study in patients with type 2 diabetes mellitus
  1. T Umemura1,
  2. T Kawamura2,
  3. H Umegaki3,
  4. S Mashita4,
  5. A Kanai2,
  6. T Sakakibara1,
  7. N Hotta2,
  8. G Sobue5
  1. 1Department of Neurology, Chubu Rosai Hospital, Nagoya, Japan
  2. 2Department of Diabetes and Endocrine Internal Medicine, Chubu Rosai Hospital, Nagoya, Japan
  3. 3Department of Geriatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan
  4. 4Department of Radiology, Chubu Rosai Hospital, Nagoya, Japan
  5. 5Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan
  1. Correspondence to Dr Toshitaka Umemura, Department of Neurology, Chubu Rosai Hospital, 1-10-6 Komei, Minato-ku, Nagoya City, Aichi 455-8530, Japan; t.umemura{at}


Background Progression of silent brain infarctions (SBIs) and white-matter lesions (WMLs) seen on brain MRI is associated with an increased risk of cognitive impairment, but their relation to endothelial and inflammatory markers is unknown in type 2 diabetes mellitus.

Methods In 190 type 2 diabetic outpatients (mean age 62.7 years), the authors related baseline levels of soluble intercellular adhesion molecule-1 (sICAM-1) and high-sensitivity C-reactive protein (hs-CRP) to subsequent brain MRI findings and cognitive function. The authors assessed incident SBIs and changes in periventricular and subcortical WMLs (PVWMLs and SCWMLs) on MRI performed at baseline and 3 and 6 years. Neuropsychological tests were administered to 83 patients older than 65 years at 6 years. This present study represents an extension of the authors' previously published study.

Results SBIs were observed in 46 patients (24.2%), PVWMLs in 93 (48.9%) and SCWMLs in 87 (45.8%) on baseline MRI. After adjustment for age, gender, hypertension, duration of diabetes, baseline MRI findings and medication use, the relative odds associated with a 1SD increase in sICAM-1 levels at baseline were 1.67 (95% CI 1.02 to 3.05) for SBI progression and 2.17 (95% CI 1.29 to 3.62) for PVWML progression at 6 years. In contrast, baseline hs-CRP levels were significantly associated with SBI progression only at 3 years. Significant trends were observed between quartiles of sICAM-1 at baseline and scores in Digit Symbol substitution (p for trend=0.01).

Conclusions The findings suggest that higher sICAM-1 levels are associated with SBI and PVWML progression, and may predict impairment in psychomotor function in type 2 diabetes.

  • Small-vessel disease
  • soluble intercellular adhesion molecule-1
  • high sensitivity C reactive protein
  • diabetes mellitus
  • cognitive impairment
  • cerebrovascular disease
  • MRI
  • vascular dementia

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  • Funding This study was supported by research funds provided to promote the hospital functions of the Japan Labor Health and Welfare Organization.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics approval was provided by the Ethics Committee of Chubu Rosai Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.