Multi‐center study of regulation of cerebral perfusion using spontaneous time‐series data shows impairment of CO2 vasoreactivity in MCI & AD patients

Abstract Background Three AD Centers have joined together to study the regulation of cerebral perfusion at resting conditions using spontaneous time‐series data with a modeling methodology that previously yielded indications reduced dynamic vasomotor CO2 reactivity in amnestic MCI patients [ Marmarelis et al., J. Alzh. Dis. 56:89–105, 2017 ] and significant correlation this reduction functional impairment chemoreflex these 75:1‐16, 2020 ]. The goal multi‐center is confirm preliminary findings larger cohorts patients, age‐matched cognitively normal controls (NC), examine time‐course impairments longitudinal over 5 years. Method Quantitative results were obtained through effects changes arterial blood pressure (ABP) end‐tidal (etCO2) upon flow velocity (CBFV) middle arteries measured via transcranial Doppler. subject‐specific input‐output predictive models used compute indices (physio‐markers) quantify Dynamic Vasomotor Reactivity (DVR) each subject/patient compare differences between NC, MCI/AD patients. Result DVR significantly different for (9 4 taken due small numbers) vs. 32 (p=0.026). Notably, delineation improved (p=0.009) after session slow paced‐breathing (8 breaths/minute) led average inter‐subject variability indices. This illustrated Figure 1, where model‐predicted responses (representing CBFV response unit‐step change etCO2) are shown 13 (red line) (blue before session. Further improvement delineating from achieved (p=9x10 ‐5 ) when two sessions averaged subject/patient. Conclusion Significantly lower index under was observed relative NC (p= 0.026) Averaging substantially ).