Leif Østergaard

Disruption of microvascular flow-patterns in Alzheimer's disease correlates with neurodegeneration and cognitive decline

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BACKGROUND: The capillary dysfunction hypothesis of Alzheimer’s disease (AD) proposes that changes in capillary morphology and function disrupts microvascular flow-patterns, consequently, limiting oxygen delivery, causing tissue-hypoxia and neurodegeneration. Capillary dysfunction is characterized by elevated capillary transit time heterogeneity (CTH) and accompanying raised maximum oxygen extraction fraction (OEFmax), which theoretically reflects weakened tissue oxygen-tension. AIM: We tested whether the severity of CTH and the level of OEFmax correlated with the severity of cognitive symptoms and neurodegeneration in AD. METHOD: 24 patients diagnosed with AD were assessed at inclusion and after six months. Using perfusion magnetic resonance imaging (MRI), we estimated CTH, flow-normalized CTH termed relative transit time heterogeneity (RTH), OEFmax and relative cerebral blood flow (rCBF). Neurodegeneration was quantified as cortical thickness utilizing structural MRI, while cognitive abilities were tested with brief cognitive status exam (BCSE). Low BCSE-score indicates worse symptoms. Regional means were extracted from atrophic cortical grey matter (A-CGM), defined using MRIs from the ADNI-database. Correlation was assessed with linear regression, adjusting for age in the baseline models. Longitudinally, we applied the correlation models across the entire cortex. RESULTS: At baseline, BCSE correlated negatively with CTH and with OEFmax and positively with rCBF. CGM-thickness correlated negatively with CTH and with OEFmax and positively with rCBF. Longitudinally, declining BCSE correlated with increasing RTH within posterior cingulum, prefrontal cortex and cuneus. CONCLUSION: The results associate capillary dysfunction in AD with cognitive symptoms and neurodegeneration within AD-vulnerable cortical regions. Studies should investigate causal relations between microvascular pathology, hypoxia and neurodegeneration in AD.
Original languageDanish
Publication year2016
Number of pages1
Publication statusPublished - 2016
Event10th FENS Forum of Neuroscience 2016 -
Duration: 2 Jul 20165 Jul 2016


Conference10th FENS Forum of Neuroscience 2016

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