Abnormal sleep blood pressure patterns are associated with diffusion tensor imaging along perivascular spaces index in cognitively impaired individuals

Mariateresa Buongiorno^1,2,3*Gonzalo Sánchez-Benavides^4,5,6Giovanni Caruana⁷Andrea Elias⁷Cristina Artero²Natalia Cullell⁸Pilar Delgado³Darly Milena Giraldo^1,3Clara Marzal^2,9Oriol Grau-Rivera^10,4,5,6ALEJANDRO DE LA SIERRA¹¹Ariane Delgado-Sanchez¹²Niki Jane Ray¹³Jerzy Krupinski^13,2,8

• ¹Vall d'Hebron Research Institute (VHIR), Barcelona, Catalonia, Spain
• ²Department of Neurology, Mútua Terrassa University Hospital, Barcelona, Balearic Islands, Spain
• ³Department of Neurology ,Vall d'Hebron University Hospital, Barcelona, Balearic Islands, Spain
• ⁴BarcelonaBeta Brain Research Center, Barcelona, Spain
• ⁵Hospital del Mar Research Institute, Barcelona, Spain
• ⁶Network Biomedical Research Center on Frailty and Healthy Aging, Carlos III Health Institute (ISCIII), Madrid, Catalonia, Spain
• ⁷Department of Radiology, Mútua Terrassa University Hospital, Barcelona, Balearic Islands, Spain
• ⁸Teaching and Research Foundation, Mútua Terrassa University Hospital, Terrassa, Spain
• ⁹Department of Neurology, Bellvitge University Hospital, Barcelona, Balearic Islands, Spain
• ¹⁰Hospital del Mar, Parc de Salut Mar, Barcelona, Catalonia, Spain
• ¹¹Department of Internal Medicine, Mútua Terrassa University Hospital, Barcelona, Balearic Islands, Spain
• ¹²Faculty of Health and Education, Department of Psychology, Brooks Building, Manchester Metropolitan University, Manchester, United Kingdom
• ¹³Department of Life Sciences, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, North West England, United Kingdom

Blood pressure (BP) physiologically dips during sleep, and lack of dipping associates with adverse health outcomes and cognitive decline. Vascular pulsatility is the main driver of glymphatic cerebrospinal fluid transport, which removes metabolic waste products from the brain during sleep. We hypothesized that abnormal sleep BP patterns may affect glymphatic system health, and that this relationship may result in lower diffusion tensor imaging along perivascular spaces (DTI-ALPS) indices, a proposed neuroimaging index of glymphatic health. Twenty-one participants with mild-tomoderate cognitive impairment underwent 24-hour ambulatory BP monitoring, DTI-MRI and Alzheimer's disease (AD) biomarker studies. Eight participants were classified as dippers (≥10%) and 13 as non-dippers (<10%), using sleep/awake systolic BP percentage of change. We found that non-dippers had lower DTI-ALPS even when adjusted by age and clinical stage (p=0.013). Stiffness measures (pulse wave velocity) were negatively correlated to DTI-ALPS (r=-0.5), but the association disappeared when adjusted by age. Positive AD biomarkers were more frequent in individuals who were classified as nondippers of both systolic and diastolic BP, as compared to systolic and diastolic dippers (p=0.041). Our findings suggest that deviations of the physiological dipping sleep BP pattern may relate to poorer glymphatic function and increased AD pathology.