Introduction: Cardiovascular disease increases the risk of developing Alzheimer's disease (AD), and growing evidence suggests an involvement of cerebrovascular pathology in AD. Capillary dysfunction, a condition in which capillary flow disturbances rather than arterial blood supply limit brain oxygen extraction, could represent an overlooked vascular contributor to neurodegeneration. We examined whether cortical capillary transit-time heterogeneity (CTH), an index of capillary dysfunction, is elevated in amyloid-positive patients with mild cognitive impairment (prodromal AD [pAD]). Methods: We performed structural and perfusion weighted MRI in 22 pAD patients and 21 healthy controls. Results: We found hypoperfusion, reduced blood volume, and elevated CTH in the parietal and frontal cortices of pAD-patients compared to controls, while only the precuneus showed focal cortical atrophy. Discussion: We propose that microvascular flow disturbances antedate cortical atrophy and may limit local tissue oxygenation in pAD. We speculate that capillary dysfunction contributes to the development of neurodegeneration in AD.
|Tidsskrift||Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring|
|Status||Udgivet - 2020|
Bibliografisk noteFunding Information:
This study was supported by a research grant from The Danish Council for Independent Research, [grant number DFF‐4004‐00305]. LØ received funding from the VELUX Foundation (ARCADIA—Aarhus Research Center for Aging and Dementia) and from the EU Joint Programming initiative within Neurodegenerative Diseases, funded by the Danish Strategic Research Council (APGeM—Pre‐clinical genotype‐phenotype predictors of Alzheimer's disease and other dementias [grant number 3056‐00001]).
This study was supported by a research grant from The Danish Council for Independent Research, [grant number DFF-4004-00305]. L? received funding from the VELUX Foundation (ARCADIA?Aarhus Research Center for Aging and Dementia) and from the EU Joint Programming initiative within Neurodegenerative Diseases, funded by the Danish Strategic Research Council (APGeM?Pre-clinical genotype-phenotype predictors of Alzheimer's disease and other dementias [grant number 3056-00001]). We thank radiographers Dora Grauballe and Michael Geneser for help with acquiring MRI, and Irene Kl?rke Mikkelsen for providing technical support during data processing.
© 2020 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, Inc. on behalf of the Alzheimer's Association.