DOI: 10.1002/alz.077089 ISSN: 1552-5260

Blood‐brain barrier permeability and risk of conversion to dementia in patients with mild cognitive impairment

Albert Puig‐Pijoan, Aida Fernández‐Lebrero, Greta Garcia‐Escobar, Irene Navalpotro‐Gómez, Rosa Maria Manero‐Borr, José Contador, Antoni Suárez‐Pérez, Víctor Puente‐Periz, Oriol Grau‐Rivera, Marc Suarez‐Calvet, Joan Jimenez‐Balado, Jaume Roquer, Angel Ois,
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



Cardiovascular risk factors (CVRF) have been associated with an increased risk of cognitive decline and dementia. Increase of blood‐brain barrier permeability (BBBp) measured by CSF/serum albumin ratio (Qalb) have been associated with CVRF. The aim of this study was to analyze the possible role of Qalb as a predictor of conversion to dementia in patients with mild cognitive impairment (MCI).


A total of 144 individuals with MCI were recruited from the BIODEGMAR cohort at Hospital del Mar (Barcelona) from 2017 to 2021. Study protocol included neuropsychological assessment, blood sampling, lumbar puncture and brain MRI. Follow‐up visits were performed yearly (12 +‐2 months) until January 2023. The endpoint of the study was a diagnosis of dementia (Global Deterioration Scale –GDS‐ > 3 and/or Clinical Dementia Rating ‐CDR‐ score > 0.5). BBBp was measured by CSF/serum albumin ratio (Qalb). Azheimer’s Disease (AD) was biologically‐defined according to CSF Aβ42/p‐tau ratio (AD+/‐). A composite vascular score (CVS) was calculated by assigning one point for the presence of each of the following CVRF (hypertension, hyperlipidemia and diabetes mellitus) plus another point if Fazekas scale higher than 1 or presence of brain infarcts on MRI. We performed a multivariate Cox regression analysis including the following variables: age, sex, AD and CVS.


Sixty‐two cases (39.2%) developed dementia in a median follow‐up of 25.89 +/‐ 13.98 months. Univariate analysis showed that Qalb (p < 0.01), AD+ (p < 0.01) and CVS (p = 0.016) were associated with dementia. The regression model results showed an independent relationship between conversion to dementia and Qalb, HR = 1.333 (95% CI 1.185‐1.499) and AD+, HR = 4.118 (2.202‐7.699).


An increase in BBBp was independently associated with a higher risk of conversion to dementia in MCI patients. This result points to a potential role of Qalb as a useful biomarker of clinical prognosis of MCI patients.

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