Capillary dysfunction is associated with symptom severity and neurodegeneration in Alzheimer's disease

Alzheimer's & Dementia - Tập 13 - Trang 1143-1153 - 2017
Rune B. Nielsen1, Lærke Egefjord2, Hugo Angleys1, Kim Mouridsen1, Michael Gejl2,3, Arne Møller4, Birgitte Brock2,3, Hans Brændgaard5, Hanne Gottrup5, Jørgen Rungby6, Simon F. Eskildsen1, Leif Østergaard1,7
1Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark
2Department of Biomedicine, Aarhus University, Aarhus, Denmark
3Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
4PET-Center, Department of Nuclear Medicine, Aarhus University Hospital, Aarhus, Denmark
5Dementia Clinic, Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
6Department of Endocrinology, Bispebjerg University Hospital, Copenhagen, Denmark
7Department of Neuroradiology, Aarhus University Hospital, Aarhus, Denmark

Tóm tắt

AbstractIntroductionWe examined whether cortical microvascular blood volume and hemodynamics in Alzheimer's disease (AD) are consistent with tissue hypoxia and whether they correlate with cognitive performance and the degree of cortical thinning.MethodsThirty‐two AD patients underwent cognitive testing, structural magnetic resonance imaging (MRI), and perfusion MRI at baseline and after 6 months. We measured cortical thickness, microvascular cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and capillary transit time heterogeneity (CTH) and estimated tissue oxygen tension (PtO2).ResultsAt baseline, poor cognitive performance and regional cortical thinning correlated with lower CBF and CBV, with higher MTT and CTH and with low PtO2 across the cortex. Cognitive decline over time was associated with increasing whole brain relative transit time heterogeneity (RTH = CTH/MTT).DiscussionOur results confirm the importance of microvascular pathology in AD. Deteriorating microvascular hemodynamics may cause hypoxia, which is known to precipitate amyloid retention.

Tài liệu tham khảo

10.1126/science.1072994 10.1016/S1474-4422(12)70291-0 10.1016/S1474-4422(15)00153-2 10.1007/s00401-010-0718-6 10.1038/nrn3114 10.1016/j.neurobiolaging.2012.09.011 10.1016/j.expneurol.2009.07.033 10.1073/pnas.0606298103 10.1002/ana.20493 10.1016/j.neuroimage.2005.06.066 Moustafa RR, 2007, The Ischemic Penumbra, 31 10.1016/j.neurobiolaging.2008.01.012 10.1001/jama.290.12.1581 10.1001/archneurol.2009.913 10.1038/jcbfm.2011.153 10.1038/jcbfm.2013.18 10.1152/ajpheart.2001.281.6.H2417 10.1002/mrm.1910360511 10.1038/jcbfm.2014.111 Egefjord L, 2012, Effects of liraglutide on neurodegeneration, blood flow and cognition in Alzheimer's disease—protocol for a controlled, randomized double‐blinded trial, Dan Med J, 59, A4519 Gejl M, 2016, In Alzheimer's disease, 6‐month treatment with GLP‐1 analog prevents decline of brain glucose metabolism: randomized, placebo‐controlled, double‐blind clinical trial, Front Aging Neurosci, 8, 97, 10.3389/fnagi.2016.00108 10.1093/arclin/acv037 10.1016/j.neuroimage.2012.09.058 10.1016/j.neuroimage.2013.05.065 10.1016/j.neurobiolaging.2014.04.034 Eskildsen SF, 2006, Active surface approach for extraction of the human cerebral cortex from MRI, Med Image Comput Comput Assist Interv, 9, 823 Eskildsen SF, 2008, SIBGRAPI Proceedings of the XXI Brazilian Symposium on Computer Graphics and Image Processing. Campo Grande, Brazil, 137 CollignonA MaesF DelaereD VandermeulenD SuetensP MarchalGAutomated multi‐modality image registration based on information theory.Proc IPMI 1995. 10.1002/mrm.20759 10.1002/mrm.1910340412 10.1002/1522-2586(200009)12:3<381::AID-JMRI2>3.0.CO;2-Y 10.1097/00004647-199804000-00011 10.1038/jcbfm.2014.213 10.1111/j.1365-2990.2010.01139.x 10.1016/j.nic.2005.09.008 10.1016/j.neuroimage.2010.12.032 10.1002/1531-8249(200001)47:1<93::AID-ANA15>3.0.CO;2-8 10.3233/JAD-2010-091699 10.1148/radiol.2503080751 10.1016/j.acra.2013.01.020 10.1212/WNL.0b013e3181f11e35 10.1148/radiol.2343040197 10.3174/ajnr.A1562 10.1038/jcbfm.2013.241 10.1038/jcbfm.2012.58 10.1007/s00062-011-0124-z Klein B, 1986, Interdependency of local capillary density, blood flow, and metabolism in rat brains, Am J Physiol, 251, H1333 10.1016/S0301-0082(00)00068-X 10.1097/00001756-199502000-00018 10.1016/j.neuron.2014.12.032