Cerebrospinal fluid/plasma albumin quotient in dementia: a systematic review of biomarker potential and clinical associations.

The blood-cerebrospinal fluid barrier (BCB) maintains central nervous system homeostasis. Its dysfunction, reflected by an increased cerebrospinal fluid/plasma albumin ratio (Q-Alb), has been reported in several neurodegenerative diseases. However, the diagnostic utility of Q-Alb in dementia remains uncertain. This review aimed to systematically evaluate Q-Alb as a biomarker in dementia by examining inter-group differences, diagnostic performance, and associations with other biomarkers. To address this questions, PubMed was searched for observational and longitudinal studies reporting Q-Alb in patients with dementia and healthy controls (HC). Data on Q-Alb levels, diagnostic accuracy, and biomarker associations were extracted. Meta-analyses were performed for Alzheimer's disease (AD) and vascular dementia (VaD). The search identified forty-three studies, spanning AD, VaD, Parkinson's disease (PD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). Q-Alb was significantly higher in VaD compared with HC (pooled standardized mean difference 0.69, 95% CI: 0.53-0.86) and moderately increased in AD compared with HC (0.25, 95% CI: 0.14-0.36). Only two studies directly investigated the diagnostic accuracy. Q-Alb correlated positively with IgG index, neurofilament light chain, and vascular and inflammatory markers. Taken together, these findings suggest that Q-Alb is not a reliable standalone diagnostic biomarker, particularly for AD, but is consistently elevated in VaD and disorders with subcortical or vascular pathology. Findings support its role as a supportive marker of blood-cerebrospinal fluid barrier dysfunction. Further large, multimodal studies integrating vascular imaging are warranted to clarify its diagnostic and prognostic utility.