@article{cbeda6111226484fa01a9b273ca7e393,
title = "Vascular and metabolic risk factor differences prior to dementia diagnosis: a multidatabase case-control study using European electronic health records",
abstract = "Objective The objective of the study is to compare body mass index (BMI), systolic/diastolic blood pressure (SBP/DBP) and serum total cholesterol levels between dementia cases and controls at multiple time intervals prior to dementia onset, and to test time interval as a modifying factor for these associations. Design Case-control study. Setting Six European electronic health records databases. Participants 291 780 cases at the date of first-recorded dementia diagnosis, compared with 29 170 549 controls randomly selected from the same databases, age matched and sex matched at this index date. Exposure The following measures were extracted whenever recorded within each dataset: BMI (kg/m(2)), SBP and DBP (mm Hg) and serum total cholesterol (mmol/L). Levels for each of these variables were defined within six 2-year time intervals over the 12 years prior to the index date. Main outcomes Case-control differences in exposures of interest were modelled for each time period and adjusted for demographic and clinical factors (ischaemic/unspecified stroke, type 2 diabetes mellitus, acute myocardial infarction, hypertension diagnosis, antihypertensive medication, cholesterol-lowering medication). Coefficients and interactions with time period were meta-analysed across the six databases. Results Mean BMI (coefficient -1.16 kg/m(2); 95% CI -1.38 to 0.93) and SBP (-2.83 mm Hg; 95% CI -4.49 to -1.16) were lower in cases at diagnosis, and case-control differences were greater in more recent time periods, as indicated by significant case-x-time interaction and case-x-time-squared interaction terms. Time variations in coefficients for cholesterol levels were less consistent between databases and those for DBP were largely not significant. Conclusion Routine clinical data show emerging divergence in levels of BMI and SBP prior to the diagnosis of dementia but less evidence for DBP or total cholesterol levels. These divergences should receive at least some consideration in routine dementia risk screening, although underlying mechanisms still require further investigation.",
keywords = "ALZHEIMERS-DISEASE, ASSOCIATION, BODY-MASS INDEX, INCIDENT DEMENTIA, LATE-LIFE, LOW BLOOD-PRESSURE, MIDLIFE, TOTAL CHOLESTEROL, WEIGHT-LOSS, WOMEN, dementia, epidemiology, health informatics, hypertension, mental health, physiology",
author = "Gayan Perera and Rijnbeek, {P. R.} and Myriam Alexander and David Ansell and Paul Avillach and Talita Duarte-Salles and Gordon, {Mark Forrest} and Francesco Lapi and Mayer, {Miguel Angel} and Alessandro Pasqua and Lars Pedersen and {van der Lei}, Johan and Visser, {Pieter Jelle} and Robert Stewart",
note = "Funding Information: Acknowledgements MAA received funding from Roche and GSK as a contracted employee; GP received funding from Roche as contracted employee during this project; MFG has prior employment at Boehringer Ingelheim Pharmaceuticals, and is a current employee of Teva Pharmaceuticals; RS has received research funding from Roche, Janssen, GSK and Takeda. Funding Information: Contributors The analysis was conceived and designed by RS, PRR, PJV, MA, MFG, FL and JvDL. Data extractions and advice on analysis design were provided by the data controllers (DA, TD-S, MAM, AP, LP, JvDL) in liaison with PRR and PA. Analyses were carried out by LP and GP. The manuscript was written by GP and RS. Further comments and significant input were obtained from all coauthors who also oversaw the planning and development of the project. Funding The research leading to these results has received support from the Innovative Medicines Initiative (IMI) Joint Undertaking under EMIF grant agreement n° 115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies{\textquoteright} in kind contribution. RS and GP are part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre and Dementia Biomedical Research Unit at South London and Maudsley NHS Foundation Trust and King's College London. Funding Information: The EMIF project, funded through the IMI programme (Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115372), had designed and implemented a federated platform to connect health data from a variety of sources across Europe, to facilitate large scale clinical and life sciences research. It enabled approved users to analyse securely multiple, diverse, data via a single portal, thereby mediating research opportunities across a large quantity of research data. EMIF developed a code of practice (ECoP) to ensure the privacy protection of data subjects, protect the interests of data sharing parties, comply with legislation and various organisational policies on data protection, uphold best practices in the protection of personal privacy and information governance, and eventually promote these best practices more widely. EMIF convened an Ethics Advisory Board, to provide feedback on its approach, platform, and the EcoP19 and all use of the data resources described was carried out with full approval of the data owners and thus complied with pre-existing governance specifications for secondary analysis. Publisher Copyright: {\textcopyright} 2020 Author(s). Published by BMJ.",
year = "2020",
doi = "10.1136/bmjopen-2020-038753",
language = "English",
volume = "10",
journal = "BMJ Open",
issn = "2044-6055",
publisher = "BMJ Publishing Group",
number = "11",
}