Decreased Vascular Pulsatility in Alzheimer's Disease Dementia Measured by Transcranial Color-Coded Duplex Sonography.

Impaired paravascular drainage of β-Amyloid (Aβ) has been proposed as a contributing cause for sporadic Alzheimer's disease (AD), as decreased cerebral blood vessel pulsatility and subsequently reduced propulsion in this pathway could lead to the accumulation and deposition of Aβ in the brain. Therefore, we hypothesized that there is an increased impairment in pulsatility across AD spectrum. Using transcranial color-coded duplex sonography (TCCS) the resistance and pulsatility index (RI; PI) of the middle cerebral artery (MCA) in healthy controls (HC, n=14) and patients with AD dementia (ADD, n=12) were measured. In a second step, we extended the sample by adding patients with mild cognitive impairment (MCI) stratified by the presence (MCI-AD, n=8) or absence of biomarkers (MCI-nonAD, n=8) indicative for underlying AD pathology, and compared RI and PI across the groups. To control for atherosclerosis as a confounder, we measured the arteriolar-venular-ratio of retinal vessels. Left and right RI (p=0.020; p=0.027) and left PI (p=0.034) differed between HC and ADD controlled for atherosclerosis with AUCs of 0.776, 0.763, and 0.718, respectively. The RI and PI of MCI-AD tended towards ADD, of MCI-nonAD towards HC, respectively. RIs and PIs were associated with disease severity (p=0.010, p=0.023). Our results strengthen the hypothesis that impaired pulsatility could cause impaired amyloid clearance from the brain and thereby might contribute to the development of AD. However, further studies considering other factors possibly influencing amyloid clearance as well as larger sample sizes are needed.

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© 2019 Ortner et al.

Déclaration de conflit d'intérêts

None of the authors declared any conflicts of interest with regard to this paper. Outside the submitted work Dr. Grimmer reported having received consulting fees from Actelion, Biogen, Eli Lilly, Iqvia/Quintiles; MSD; Novartis, Quintiles, Roche Pharma, lecture fees from Biogen, Lilly, Parexel, Roche Pharma, and grants to his institution from Actelion and PreDemTech. Outside the submitted work Dr. Diehl-Schmid reported having received lecture fees from Novartis. Outside the submitted work Professor Holger Poppert reports serving on a scientific advisory board, fees paid to his institution from Bristol-Myers Squibb, personal fees from Daiichi Sankyo, serving on a scientific advisory board, fees paid to his institution from Bayer Healthcare, personal fees from Pfizer, personal fees from Bayer Healthcare. Part of the research presented in this paper was presented at the AAIC 2016 in Toronto, at the DGPPN congress 2016 in Berlin and at the ADPD convention 2017 in Vienna.