How Do Different Forms of Vascular Brain Injury Relate to Cognition in a Memory Clinic Population: The TRACE-VCI Study

J Alzheimers Dis. 2019;68(3):1273-1286. doi: 10.3233/JAD-180696.


Background: Memory clinic patients frequently present with different forms of vascular brain injury due to different etiologies, often co-occurring with Alzheimer's disease (AD) pathology.

Objective: We studied how cognition was affected by different forms of vascular brain injury, possibly in interplay with AD pathology.

Methods: We included 860 memory clinic patients with vascular brain injury on magnetic resonance imaging (MRI), receiving a standardized evaluation including cerebrospinal fluid (CSF) biomarker analyses (n = 541). The cognitive profile of patients with different forms of vascular brain injury on MRI (moderate/severe white matter hyperintensities (WMH) (n = 398), microbleeds (n = 368), lacunar (n = 188) and non-lacunar (n = 96) infarct(s), macrobleeds (n = 16)) was assessed by: 1) comparison of all these different forms of vascular brain injury with a reference group (patients with only mild WMH (n = 205) without other forms of vascular brain injury), using linear regression analyses also stratified for CSF biomarker AD profile and 2) multivariate linear regression analysis.

Results: The cognitive profile was remarkably similar across groups. Compared to the reference group effect sizes on all domains were <0.2 with narrow 95% confidence intervals, except for non-lacunar infarcts on information processing speed (age, sex, and education adjusted mean difference from reference group (β: - 0.26, p = 0.05). Results were similar in the presence (n = 300) or absence (n = 241) of biomarker co-occurring AD pathology. In multivariate linear regression analysis, higher WMH burden was related to a slightly worse performance on attention and executive functioning (β: - 0.08, p = 0.02) and working memory (β: - 0.08, p = 0.04).

Conclusion: Although different forms of vascular brain injury have different etiologies and different patterns of cerebral damage, they show a largely similar cognitive profile in memory clinic patients regardless of co-occurring AD pathology.

Keywords: Cerebral small vessel diseases; cerebrovascular disorders; cognitive disorders; neuropsychological test.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / etiology*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / psychology
  • Biomarkers / cerebrospinal fluid
  • Brain / diagnostic imaging
  • Brain / pathology
  • Cerebrovascular Trauma / cerebrospinal fluid
  • Cerebrovascular Trauma / complications*
  • Cerebrovascular Trauma / pathology
  • Cognition*
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mental Status and Dementia Tests
  • Neuroimaging


  • Biomarkers