Nighttime Blood Pressure Interacts with APOE Genotype to Increase the Risk of Incident Dementia of the Alzheimer’s Type in Hispanics

Article type: Research Article

Authors: Melgarejo, Jesus D.^{a; b} | Aguirre-Acevedo, Daniel C.^c | Gaona, Ciro^a | Chavez, Carlos A.^a | Calmón, Gustavo E.^d | Silva, Eglé R.^d | de Erausquin, Gabriel A.^{e; f} | Gil, Mario^{f; g} | Mena, Luis J.^h | Terwilliger, Joseph D.^{i; j; k; l} | Arboleda, Humberto^{m; n} | Scarmeas, Nikolaos^{o; p} | Lee, Joseph H.^{j; o; q} | Maestre, Gladys E.^{a; f; r; s; *}

Affiliations: [a] Laboratory of Neuroscience, University of Zulia, Maracaibo, Venezuela | [b] Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Sciences, KU University of Leuven, Leuven, Belgium | [c] Medical Research Institute, School of Medicine, University of Antioquia, Medellin, Colombia | [d] Instituto de Investigación de Enfermedades Cardiovasculares de la Universidad del Zulia, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela | [e] Department of Neurology, and Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, University of Texas Health Sciences Center at San Antonio, San Antonio, TX, USA | [f] Alzheimer’s Disease Resource Center for Minority Aging Research, University of Texas Rio Grande Valley, Brownsville, TX, USA | [g] Department of Psychological Science and Department of Neurosciences, University of Texas Rio Grande Valley, School of Medicine, Edinburg, TX, USA | [h] Department of Informatics, Universidad Politécnica de Sinaloa, Mazatlán, México | [i] Departments of Psychiatry and Genetics & Development, Columbia University Medical Center, New York, NY, USA | [j] Sergievsky Center & Department of Epidemiology, Columbia University Medical Center, New York, NY, USA | [k] Division of Medical Genetics, New York State Psychiatric Institute, New York, NY, USA | [l] Division of Public Health Genomics, National Institute for Health and Welfare, Helsinki, Finland | [m] Neurosciences Research Group, School of Medicine, Nacional University of Colombia, Bogotá, Colombia | [n] Genetic Institute, National University of Colombia, Bogotá, Colombia | [o] Taub Institute for Research on Alzheimer’s Disease and the Aging Brain and Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA | [p] 1st Department of Neurology, Medical School, National and Kapodistrian University of Athens, Athens, Greece | [q] Department of Epidemiology, School of Public Health, Columbia University, New York, NY, USA | [r] Department of Neurosciences, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA | [s] Department of Human Genetics University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA

Correspondence: [*] Correspondence to: Gladys E. Maestre, MD, PhD, One West University Blvd, BROBL Rm. 106, University of Texas Rio Grande Valley, Brownsville, TX 78520, USA. Tel.: +1 956 882 7495; E-mail: [email protected]., E-mail: [email protected].

Abstract: Background:Dementia of the Alzheimer’s type (DAT) impacts Hispanics disproportionately, with almost a twofold elevated risk of developing DAT, as well as earlier onset of the disease, than in non-Hispanic Whites. However, the role of main risk factors for DAT, such as APOE-ɛ4 and blood pressure (BP) levels, remains uncertain among Hispanics. Objective:To investigate the association of APOE-ɛ4 and BP levels, measures with 24-h ambulatory BP monitoring, with incidence of DAT in an elderly cohort of Hispanics. Methods:1,320 participants from the Maracaibo Aging Study, free of dementia at the baseline, and with ambulatory BP measurements and APOE genotype available were included. Adjusted Cox proportional models were performed to examine 1) the incidence of DAT and 2) the relationship between BP levels and DAT according to APOE genotypes. Models were adjusted by competing risk of death before the onset of DAT. Model performance was assessed by likelihood test. Results:The average follow-up time was 5.3 years. DAT incidence was 5.8 per 1000 person-year. APOE-ɛ4 carriers had a higher risk of DAT. In unadjusted analyses, conventional, 24-h, and nighttime systolic BP levels were significantly higher in participants who developed DAT and of APOE-ɛ4 carriers (p < 0.05). After adjustment for competing risks, only higher nighttime systolic BP was associated with DAT incidence, but only among subjects carrying APOE-ɛ4. Conclusion:In this Hispanic population, both APOE-ɛ4 genotype and assessment of nocturnal systolic BP (rather than diurnal or office BP) were necessary to estimate DAT risk.

Keywords: Alzheimer’s disease, ambulatory blood pressure monitoring, Apolipoprotein E, dementia of Alzheimer’s type, Hispanics, night-time blood pressure

DOI: 10.3233/JAD-200430

Journal: Journal of Alzheimer's Disease, vol. 77, no. 2, pp. 569-579, 2020