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A. Mimenza-Alvarado

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Review Open access Aug 2026

Biomarkers of the blood-brain barrier and the neurovascular unit and their relationship with cognitive decline and cognitive frailty.

Aging is accompanied by an increasing prevalence of frailty and age-related cognitive decline (CD). Cognitive frailty (CF), characterized by physical frailty and cognitive impairment, has been associated with oxidative stress, neuroinflammation, mitochondrial dysfunction, and cardiovascular impairment. However, its biological foundations remain only partially understood. This review synthesizes evidence on biomarkers associated with the blood-brain barrier (BBB) and neurovascular unit (NVU) in CD and CF. These biomarkers are associated with endothelial injury, pericyte damage, BBB permeability, tight junction disruption, glial activation, and extracellular vesicles (EVs). They are assessed by analyzing cerebrospinal fluid (CSF), blood, neuroimaging (including DCE-MRI), and histology. The most frequently evaluated markers were CSF sPDGFRβ, the CSF/serum albumin ratio (QAlb), DCE-MRI permeability, and the adhesion molecules ICAM-1 and VCAM-1. Key convergent findings suggest that BBB breakdown (particularly pericyte injury, as indicated by elevated CSF sPDGFRβ) can precede or occur independently of classical amyloid-β and tau pathology, predict CD in APOE4 carriers over up to 4.5 years, and be associated with disrupted default mode network connectivity. Elevated QAlb demonstrated dose-response prognostic value for clinical deterioration, while DCE-MRI permeability was associated with poorer episodic memory and predicted white-matter injury, which mediated cognitive impairment. Endothelial activation markers were elevated early and predicted progression, whereas vWF exhibited a stage-dependent, potentially biphasic association. Overall, BBB/NVU biomarkers support vascular and neuroinflammatory mechanisms as early, partially Alzheimer's disease-independent contributors to CD and CF, with significant modification by APOE4 and metabolic comorbidities, and with distinct signatures across Alzheimer's disease and vascular cognitive impairment.

Juan de Dios Rodríguez-Callejas, A. Mimenza-Alvarado, C. Lomas-Soria et al. · 0 citations
Review Open access Aug 2026

Social vulnerability and health determinants of Intrinsic Capacity in Mexican older adults: Evidence from the Mexican Health and Aging Study round 2021

Background Population aging has increased interest in Intrinsic Capacity (IC), defined as the composite of physical and mental abilities that support healthy aging. Because declines in IC precede disability, IC is a useful framework for characterizing individuals with greater vulnerability in later life. Methods We conducted a cross-sectional analysis of the 2021 Mexican Health and Aging Study, a nationally representative survey of adults aged 50 years and older. IC was assessed across five domains using domain-specific impairment, number of impaired domains, and a continuous latent IC score derived from factor analysis. Ordinal logistic regression models were used to examine associations with sociodemographic characteristics, health conditions, and a Social Vulnerability Index (SVI) constructed using a cumulative deficit approach. Findings The sample included 13,403 adults (mean age 65.9 years [SD 9.8]; 57.3% women). IC impairment was highly prevalent: 67.1% had impairment in two or more domains, whereas only 12.5% had no impaired domains. Lower IC was associated with increasing age (≥80 years: OR 3.31; 95% CI 1.10–10.02) and poorer health, including multimorbidity (OR 2.29; 95% CI 1.44–3.64) and poor self-rated health (OR 1.69; 95% CI 1.24–2.28). Lower IC was further associated with social disadvantage, including lower educational attainment (OR 2.33; 95% CI 1.69–3.22) and food insecurity (OR 1.51; 95% CI 1.06–2.16), with higher social vulnerability associated with lower IC (β −0.46; 95% CI −0.51 to −0.41). Interpretation IC impairment is highly prevalent among Mexican adults aged 50 years and older and is strongly associated with social vulnerability and modifiable health factors, supporting IC as an integrative framework to identify vulnerable individuals and inform intervention strategies.

M. T. López-Teros, Fabiola Yocupicio Medrano, Karla Animas Mijangos et al. · 0 citations