Blood–brain barrier: Ageing and microvascular disease – systematic review and meta-analysis

• Published in: Neurobiology of aging Vol. 30; no. 3; pp. 337 - 352
• Main Authors: Farrall, Andrew J., Wardlaw, Joanna M.
• Format: Journal Article
• Language: English
• Published: London Elsevier Inc 01.03.2009; Elsevier
• Subjects: Ageing; Aging - physiology; Alzheimer Disease - metabolism; Alzheimer Disease - physiopathology; Alzheimer's disease; Animals; Biological and medical sciences; Blood-Brain Barrier - metabolism; Blood-Brain Barrier - physiopathology; Blood–brain barrier; Capillary Permeability - physiology; Cerebral circulation; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Cerebrovascular Circulation - physiology; Cerebrovascular disorders; Cerebrovascular Disorders - metabolism; Cerebrovascular Disorders - physiopathology; Dementia; Dementia, Vascular - metabolism; Dementia, Vascular - physiopathology; Development. Senescence. Regeneration. Transplantation; Fundamental and applied biological sciences. Psychology; Humans; Internal Medicine; Microcirculation; Microvessels - metabolism; Microvessels - physiopathology; Neurology; Stroke; Vascular disease; Vertebrates: nervous system and sense organs; White-matter disease; Vascular disease; Microcirculation; White-matter disease; Cerebrovascular disorders; Stroke; Ageing; Cerebral circulation; Alzheimer's disease; Blood–brain barrier; Dementia; Nervous system diseases; Senescence; Alzheimer disease; Central nervous system; Cardiovascular disease; Review; Blood brain barrier; White matter; Cerebral disorder; Encephalon; Blood-brain barrier; Central nervous system disease; Degenerative disease; Cerebrovascular disease
• ISSN: 0197-4580; 1558-1497; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2007.07.015

Cerebral “microvascular” disease occurs in lacunar stroke, leukoaraiosis, vascular dementia and Alzheimer's disease. It may arise from or contribute to insidious damage to the blood–brain barrier (BBB). We systematically reviewed the literature for evidence that BBB permeability is altered in patients with manifestations of cerebral microvascular disease. We found 31 BBB permeability studies (1953 individuals) of normal ageing or cerebral microvascular disease. In healthy humans, increasing age (10 comparisons, controls(C):subjects(S) = 357:336) was associated with increased BBB permeability (standardised mean difference (S.M.D.) 1.21, 95% confidence interval (CI) 0.60, 1.81, p < 0.01). BBB permeability was increased further in patients with either vascular or Alzheimer's dementia compared with age-matched controls (26 comparisons, C:S = 510:547, S.M.D. 0.81, 99% CI 0.37, 1.26, p < 0.01); in vascular compared with Alzheimer's dementia (10 comparisons, C:S = 291:165, S.M.D. 0.71, 99% CI 0.12, 1.29, p < 0.01); and with worsening leukoaraiosis (5 comparisons, C:S = 122:88, S.M.D. 0.60, 99% CI 0.30, 0.89, p < 0.01). BBB permeability increases with normal ageing and may be an important mechanism in the initiation or worsening of cerebral microvascular disease. Further studies on the role of BBB permeability are urgently needed.