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     <jats:p>AD patients from two teaching hospitals in Taiwan with 3\u2010year follow\u2010ups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PARTICIPANTS<\/jats:title>\n                    <jats:p>A total of 330\u2009AD patients with a mean age of 80.7\u2009years, a mean Mini\u2010Mental State Examination (MMSE) score 18.7, and a mean Clinical Dementia Rating Sum of Boxes (CDRSB) score of 6.9.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MEASUREMENTS<\/jats:title>\n                    <jats:p>All patients completed a clinically functional assessment and a neuropsychological test battery at baseline and yearly follow\u2010ups. The VRF burden was combined into a summative VRF index at baseline (ie, having one, two, or more VRFs); VRFs included coronary heart disease, cardiac arrhythmia, hypertension, cerebrovascular disease, diabetes mellitus, obesity, smoking, and physical inactivity. The generalized estimating equation (GEE) method was used to analyze the correlations between the VRFs and longitudinal MMSE and CDRSB changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      The results of the GEE adjusted for age, years of education, sex, disease duration, baseline MMSE score, time, apolipoprotein E (APOE) \u03b54 carrier status, use of medications (acetylcholinesterase inhibitors or N\u2010methyl\u2010D\u2010aspartate receptor antagonists), and hospitalization rates and showed that patients with more than three VRFs had more rapid cognitive decline than patients without VRFs (MMSE,\n                      <jats:italic>P<\/jats:italic>\n                      = .02; CDRSB,\n                      <jats:italic>P<\/jats:italic>\n                      = .001) as well as patients with three or fewer VRFs (MMSE,\n                      <jats:italic>P<\/jats:italic>\n                      = .009; CDRSB,\n                      <jats:italic>P<\/jats:italic>\n                      = .02). Subsequent analyses of APOE \u03b54 carriers with more than three VRFs also showed their more rapid cognitive decline compared with patients without VRFs (MMSE,\n                      <jats:italic>P<\/jats:italic>\n                      = .02; CDRSB,\n                      <jats:italic>P<\/jats:italic>\n                      = .001) and patients with three or fewer VRFs (MMSE,\n                      <jats:italic>P<\/jats:italic>\n                      = .009; CDRSB,\n                      <jats:italic>P<\/jats:italic>\n                      = .02), but no significant difference was found in APOE \u03b54 noncarriers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Multiple VRFs have summative effects on the progression of AD, especially in APOE \u03b54 carriers.\n                      <jats:bold>J Am Geriatr Soc 68:129\u2013136, 2019<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jgs.16181","type":"journal-article","created":{"date-parts":[[2019,10,6]],"date-time":"2019-10-06T05:06:47Z","timestamp":1570338407000},"page":"129-136","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Summative Effects of Vascular Risk Factors on the Progression of Alzheimer Disease"],"prefix":"10.1111","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3720-4539","authenticated-orcid":false,"given":"Wei\u2010Ju","family":"Lee","sequence":"first","affiliation":[{"name":"Neurological Institute Taichung Veterans General Hospital  Taichung Taiwan"},{"name":"Faculty of Medicine National Yang\u2010Ming University Schools of Medicine  Taipei Taiwan"},{"name":"Dementia and Parkinson's Disease Integrated Center Taichung Veterans General Hospital  Taichung Taiwan"},{"name":"Center for Geriatrics and Gerontology 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