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Blood‐brain barrier breakdown, neuroinflammation, and cognitive decline in older adults
Author(s) -
Bowman Gene L.,
Dayon Loïc,
Kirkland Richard,
Wojcik Jérôme,
Peyratout Gwendoline,
Severin India C.,
Henry Hugues,
Oikonomidi Aikaterini,
Migliavacca Eugenia,
Bacher Michael,
Popp Julius
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.2857
Subject(s) - cerebrospinal fluid , cognitive decline , blood–brain barrier , dementia , medicine , neuroinflammation , inflammation , immunology , pathology , central nervous system , disease
Blood‐brain barrier (BBB) breakdown is observed in older versus younger adults and in late‐onset Alzheimer's disease versus age‐matched controls, but its causes and consequences in aging are unclear. We tested the hypothesis that BBB breakdown is associated with cognitive decline and inflammation in nondemented elders. Methods Cerebrospinal fluid and serum inflammatory markers were measured using sandwich immunoassays in 120 subjects. Least Absolute Shrinkage and Selection Operator‐logistic regression selected cerebrospinal fluid and serum signatures that best classified BBB impairment defined by the cerebrospinal fluid albumin index ≥9. Linear regression examined changes in Clinical Dementia Rating sum of boxes as a function of BBB integrity at baseline. Results Mean age was 70 years, mean Mini–Mental State Examination was 27, and BBB impairment was recorded in 13.5%. BBB breakdown was associated with cognitive decline ( P = .015). Cerebrospinal fluid intercellular adhesion molecule‐1, vascular endothelial growth factor, interleukin‐8, serum amyloid A, macrophage derived chemokine, and gender generated an area under the curve of 0.95 for BBB impairment, and serum IL‐16, VEGF‐D, IL‐15, and other variables generated an AUC of 0.92 for BBB impairment. Discussion BBB breakdown is associated with more rapid cognitive decline. Inflammatory mechanisms, including cell adhesion, neutrophil migration, lipid metabolism, and angiogenesis may be implicated.