The Blood–Brain Barrier: Geriatric Relevance of a Critical Brain–Body Interface

Abstract

The blood-brain barrier (BBB) represents the interface between the brain and other body tissues. Its ability to protect the brain from harmful compounds has attracted the attention of both clinicians and investigators. However, far from being a simple physical barrier, the BBB is a complex, heterogeneous and dynamic tissue. The integrated function of the cerebral microvasculature, tight junction proteins, brain microvascular endothelial cells (BMEC), cellular transport pathways and enzymatic machinery jointly contribute to normal BBB integrity. Aging, systemic diseases and ischemic injury can disrupt these processes, resulting in a decline in overall BBB function and integrity. Based on the published literature, we propose that age- and disease-related BBB alterations play a key role in diminishing the ability of older patients to recover from acute ischemic stroke (AIS). Moreover, we also review evidence linking deficits in the cerebral microvasculature and BBB integrity to dementia, medication-related cognitive decline, white matter disease (leukoaraiosis), as well as related geriatric syndromes including delirium, gait disorders and urinary incontinence. Priority areas for a future research agenda include strategies to improve clinicians' ability to diagnose, prevent and manage BBB abnormalities. In future years, in vivo measures such as functional and contrast-enhanced neuroimaging will be used to evaluate BBB integrity in older adults while also assessing the effectiveness of interventions, some targeting inflammatory pathways known to disrupt the BBB, for their ability to prevent or slow the progression of these complex multifactorial geriatric syndromes.

Interventional Stroke Therapies in the Elderly: Are We Helping?

“…Previous studies have also reported similar recanalization rates in the old compared with the young groups. 31 Age-related changes such as increased incidence of amyloid angiopathy, 13,32 blood-brain barrier dysfunction, 15 reduced tPA clearance, 14 and impaired clotting mechanisms, 16 which have been previously described, could have predisposed the older patients to ICH.…”

“…Therapies including IA tPA, clot retrieval devices, and combination therapies with IV tPA have been shown to improve revascularization rates and stroke outcomes up to 6 hours after the onset of stroke in younger patients. [8][9][10][11][12] The higher incidence of amyloid angiopathy, 13 decreased tPA clearance, 14 difficult vascular access, polypharmacy, blood-brain barrier impairment, 15 and age-related alterations in coagulation 16,17 has raised concerns of increased complications, mainly SICH, which are associated with increased mortality and disability, 18,19 when applying these treatments to the elderly. The objective of this study was to assess the complication rates and functional outcomes in older patients treated with endovascular techniques.…”

Smoking and white matter hyperintensity progression

“…[1][2][3] Cross-sectional studies reporting on the association between smoking and WMH severity are mixed. [4][5][6][7][8][9][10][11] Prospective studies of smoking and WMH progression are likely more informative.…”

Do Anticholinergic Drugs Contribute to Functional and Cognitive Decline?

“…This is because of the greater permeability of the blood-brain barrier. As yet, translational research is needed to guide when this is necessary and which medications pose the greatest risk [13].…”

“…This can result in CNS effects that may not be expected or are more intense than usual. Systemic illness, particularly septicemia, may result in increased permeability of the blood-brain barrier and increased exposure to medications, their metabolites and any consequent side effects [13].…”