TY - JOUR
T1 - Blood-brain barrier breakdown, neuroinflammation, and cognitive decline in older adults
AU - Bowman, Gene L.
AU - Dayon, Loïc
AU - Kirkland, Richard
AU - Wojcik, Jérôme
AU - Peyratout, Gwendoline
AU - Severin, India C.
AU - Henry, Hugues
AU - Oikonomidi, Aikaterini
AU - Migliavacca, Eugenia
AU - Bacher, Michael
AU - Popp, Julius
N1 - Funding Information:
G.L.B. conceptualized and designed the study, analyzed and interpreted the data, drafted and revised the manuscript. L.D. interpreted the data and revised the manuscript. R.K. conducted the inflammatory biomarker assays and revised the manuscript. J.W. conducted the statistical analysis, generated the figures and tables, and interpreted the data. G.P. conducted study visits and data collection and revised the manuscript. I.C.S. conducted literature search and revised the manuscript. H.H. conducted study visits and data collection, and manuscript revision. A.O. conducted study visits and data collection and revised the manuscript. E.M. analyzed and interpreted the data and revised the manuscript. M.B. interpreted the data and revised the manuscript. J.P. contributed to concept and design, analyzed and interpreted the data, and revised the manuscript., The authors thank Barbara Moullet, Domicile Tatvydaite, and Mehdi Gholamrezaee for their assistance in the conduct of this study., The Swiss National Research Foundation (SNF 320030_141179) supported the enrollment and clinical evaluation of the study participants. Nestle supported the blood- and CSF-based biomarker and statistical analysis.
PY - 2018/12
Y1 - 2018/12
N2 - Introduction: 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. Serum interleukin-16, vascular endothelial growth factor-D, interleukin-15, and other variables generated an area under the curve of 0.92. Discussion: BBB breakdown is associated with more rapid cognitive decline. Inflammatory mechanisms, including cell adhesion, neutrophil migration, lipid metabolism, and angiogenesis may be implicated. Cell adhesion, neutrophil migration, high-density lipoprotein metabolism, and angiogenesis are implicated.
AB - Introduction: 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. Serum interleukin-16, vascular endothelial growth factor-D, interleukin-15, and other variables generated an area under the curve of 0.92. Discussion: BBB breakdown is associated with more rapid cognitive decline. Inflammatory mechanisms, including cell adhesion, neutrophil migration, lipid metabolism, and angiogenesis may be implicated. Cell adhesion, neutrophil migration, high-density lipoprotein metabolism, and angiogenesis are implicated.
KW - Angiogenesis
KW - Biomarkers
KW - CSF
KW - Chemokines
KW - Cytokines
KW - Elderly
KW - HDL metabolism
KW - IL-16
KW - IL-8
KW - MDC
KW - Mild cognitive impairment
KW - Neurovascular unit
KW - Serum
KW - Serum amyloid A
KW - VEGF
KW - sICAM-1
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U2 - 10.1016/j.jalz.2018.06.2857
DO - 10.1016/j.jalz.2018.06.2857
M3 - Article
C2 - 30120040
AN - SCOPUS:85059323429
VL - 14
SP - 1640
EP - 1650
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
SN - 1552-5260
IS - 12
ER -