Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1640-1650 |
| Number of pages | 11 |
| Journal | Alzheimer's and Dementia |
| Volume | 14 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 1 2018 |
| Externally published | Yes |
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Keywords
- Angiogenesis
- Biomarkers
- Chemokines
- CSF
- Cytokines
- Elderly
- HDL metabolism
- IL-16
- IL-8
- MDC
- Mild cognitive impairment
- Neurovascular unit
- Serum
- Serum amyloid A
- sICAM-1
- VEGF
ASJC Scopus subject areas
- Epidemiology
- Health Policy
- Developmental Neuroscience
- Clinical Neurology
- Geriatrics and Gerontology
- Cellular and Molecular Neuroscience
- Psychiatry and Mental health
Cite this
Blood-brain barrier breakdown, neuroinflammation, and cognitive decline in older adults. / Bowman, Gene; Dayon, Loïc; Kirkland, Richard; Wojcik, Jérôme; Peyratout, Gwendoline; Severin, India C.; Henry, Hugues; Oikonomidi, Aikaterini; Migliavacca, Eugenia; Bacher, Michael; Popp, Julius.
In: Alzheimer's and Dementia, Vol. 14, No. 12, 01.12.2018, p. 1640-1650.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Blood-brain barrier breakdown, neuroinflammation, and cognitive decline in older adults
AU - Bowman, Gene
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
PY - 2018/12/1
Y1 - 2018/12/1
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 - Chemokines
KW - CSF
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 - sICAM-1
KW - VEGF
UR - http://www.scopus.com/inward/record.url?scp=85059323429&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85059323429&partnerID=8YFLogxK
U2 - 10.1016/j.jalz.2018.06.2857
DO - 10.1016/j.jalz.2018.06.2857
M3 - Article
VL - 14
SP - 1640
EP - 1650
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
SN - 1552-5260
IS - 12
ER -