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Alzheimers Dement. 2018 Dec;14(12):1640-1650. doi: 10.1016/j.jalz.2018.06.2857. Epub 2018 Aug 14.

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

Author information

1
Nestlé Institute of Health Sciences, EPFL Campus, Lausanne, Switzerland. Electronic address: genebowman@hsl.harvard.edu.
2
Nestlé Institute of Health Sciences, EPFL Campus, Lausanne, Switzerland.
3
Nestlé Health Science, Prometheus Laboratories, San Diego, CA, USA.
4
Precision for Medicine, Geneva, Switzerland.
5
Old Age Psychiatry, Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
6
CHUV Department of Laboratories, Lausanne, Switzerland.
7
Philipps University of Marburg, Institute of Immunology, Marburg, Germany.
8
Old Age Psychiatry, Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland; Geriatric Psychiatry, Department of Mental Health and Psychiatry, University Hospitals of Geneva, Geneva, Switzerland.

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.

DISCUSSION:

BBB breakdown is associated with more rapid cognitive decline. Inflammatory mechanisms, including cell adhesion, neutrophil migration, lipid metabolism, and angiogenesis may be implicated.

KEYWORDS:

Angiogenesis; Biomarkers; CSF; Chemokines; Cytokines; Elderly; HDL metabolism; IL-16; IL-8; MDC; Mild cognitive impairment; Neurovascular unit; Serum; Serum amyloid A; VEGF; sICAM-1

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