Impaired perfusion and capillary dysfunction in prodromal Alzheimer's disease

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.