AbstractBackgroundA multi‐center study in Los Angeles (USC), Kansas City (KUMC) and Dallas (UT‐SWMC) has been quantifying the dynamics of CO2 vasoreactivity in MCI/AD patients and cognitively normal controls under spontaneous resting conditions. The goal is to develop effective vasoreactivity physio‐markers for early diagnosis of MCI and pre‐clinical AD, based on previous findings of significantly reduced vasoreactivity in MCI patients [Marmarelis et al., J. Alzh. Dis. 56:89‐105, 2017]. Here, we report on the effects of slow‐paced breathing upon these physio‐markers.MethodSpontaneous changes in arterial blood pressure (ABP), end‐tidal CO2 (etCO2), and cerebral blood flow velocity (CBFV) in middle cerebral arteries were recorded under resting conditions over two 6‐8 min sessions, separated by session of slow‐paced breathing (6 breaths/minute), in 47 MCI and 25 AD patients and 58 age‐matched cognitively normal controls. Using our novel methodology, we obtained predictive models of the dynamic effects of ABP and etCO2 upon CBFV using the universal convolutional form of linear dynamic models, which are defined by the respective “kernels” estimated from time‐series data. The etCO2‐to‐CBFV kernel is used to compute indices (physio‐markers) that quantify the vasoreactivity in each participant.ResultThe vasoreactivity index for each participant is computed from the integrated etCO2‐to‐CBFV kernel as the time‐average over the first 30 sec. The average kernels for patients and controls are shown in Figures 1‐2 for the two sessions respectively. Note the smaller kernel values for patients – while the difference is reduced after slow‐paced breathing. The obtained vasoreactivity indices are significantly smaller for 72 patients (MCI and AD taken together) vs 58 controls for the first session [p = 0.018; mean (SD): 0.057 (0.539) vs 0.424 (1.076)] but NOT for the session after slow‐paced breathing [p = 0.237; mean (SD): 0.193 (0.731) vs 0.361 (0.863)]. Average etCO2 was lower after paced‐breathing [p = 10−6; mean (SD): 36.23 (6.18) vs 33.44 (6.36)].ConclusionQuantitative analysis of cerebral CO2 vasoreactivity under resting spontaneous conditions in 72 MCI/AD patients vs 58 age‐matched controls, before and after slow‐paced breathing, revealed that the significant vasoreactivity deficit in MCI/AD patients is mitigated (at least temporarily) after slow‐paced breathing. This effect may be due to observed hypocapnia induced by slow‐paced breathing.