Blood-brain barrier breakdown, neuroinflammation, and cognitive decline in older adults

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 inflammati...

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Bibliographic Details
Published in:Alzheimer's & dementia 2018-12, Vol.14 (12), p.1640-1650
Main Authors: Bowman, Gene L., Dayon, Loïc, Kirkland, Richard, Wojcik, Jérôme, Peyratout, Gwendoline, Severin, India C., Henry, Hugues, Oikonomidi, Aikaterini, Migliavacca, Eugenia, Bacher, Michael, Popp, Julius
Format: Article
Language:English
Subjects:
Aged
Angiogenesis
Apolipoprotein E4 - genetics
Biomarkers
Biomarkers - blood
Biomarkers - cerebrospinal fluid
Blood-Brain Barrier - metabolism
Cerebrovascular Disorders - blood
Cerebrovascular Disorders - cerebrospinal fluid
Cerebrovascular Disorders - immunology
Chemokines
Cognitive Dysfunction - blood
Cognitive Dysfunction - cerebrospinal fluid
Cognitive Dysfunction - immunology
Cohort Studies
CSF
Cytokines
Disease Progression
Elderly
Female
HDL metabolism
Humans
IL-16
IL-8
Inflammation - blood
Inflammation - cerebrospinal fluid
Inflammation - immunology
Male
MDC
Mild cognitive impairment
Neuropsychological Tests
Neurovascular unit
Serum
Serum amyloid A
sICAM-1
VEGF
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Summary: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. 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. 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. BBB breakdown is associated with more rapid cognitive decline. Inflammatory mechanisms, including cell adhesion, neutrophil migration, lipid metabolism, and angiogenesis may be implicated.
ISSN:1552-5260
1552-5279
DOI:10.1016/j.jalz.2018.06.2857