{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T02:55:58Z","timestamp":1793933758510,"version":"4.8.0"},"reference-count":71,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T00:00:00Z","timestamp":1668384000000},"content-version":"vor","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Life Molecular Imaging GmbH"},{"DOI":"10.13039\/501100003061","name":"Erasmus Medical Center","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003061","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006190","name":"Research and Development","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006190","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005992","name":"Ministry of Education, Culture and Science","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005992","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Higher vascular disease burden increases the likelihood of developing dementia, including Alzheimer\u2019s disease. Better understanding the association between vascular risk factors and Alzheimer\u2019s disease pathology at the predementia stage is critical for developing effective strategies to delay cognitive decline. In this work, we estimated the impact of six vascular risk factors on the presence and severity of in vivo measured brain amyloid-beta (A\u03b2) plaques in participants from the population-based Rotterdam Study. Vascular risk factors (hypertension, hypercholesterolaemia, diabetes, obesity, physical inactivity and smoking) were assessed 13 (2004\u20132008) and 7 years (2009\u20132014) prior to 18F-florbetaben PET (2018\u20132021) in 635 dementia-free participants. Vascular risk factors were associated with binary amyloid PET status or continuous PET readouts (standard uptake value ratios, SUVrs) using logistic and linear regression models, respectively, adjusted for age, sex, education, APOE4 risk allele count and time between vascular risk and PET assessment. Participants\u2019 mean age at time of amyloid PET was 69 years (range: 60\u201390), 325 (51.2%) were women and 190 (29.9%) carried at least one APOE4 risk allele. The adjusted prevalence estimates of an amyloid-positive PET status markedly increased with age [12.8% (95% CI 11.6; 14) in 60\u201369 years versus 35% (36; 40.8) in 80\u201389 years age groups] and APOE4 allele count [9.7% (8.8; 10.6) in non-carriers versus 38.4% (36; 40.8) to 60.4% (54; 66.8) in carriers of one or two risk allele(s)]. Diabetes 7 years prior to PET assessment was associated with a higher risk of a positive amyloid status [odds ratio (95% CI) = 3.68 (1.76; 7.61), P &amp;lt; 0.001] and higher standard uptake value ratios, indicating more severe A\u03b2 pathology [standardized beta = 0.40 (0.17; 0.64), P = 0.001]. Hypertension was associated with higher SUVr values in APOE4 carriers (mean SUVr difference of 0.09), but not in non-carriers (mean SUVr difference 0.02; P = 0.005). In contrast, hypercholesterolaemia was related to lower SUVr values in APOE4 carriers (mean SUVr difference \u22120.06), but not in non-carriers (mean SUVr difference 0.02). Obesity, physical inactivity and smoking were not related to amyloid PET measures. The current findings suggest a contribution of diabetes, hypertension and hypercholesterolaemia to the pathophysiology of Alzheimer\u2019s disease in a general population of older non-demented adults. As these conditions respond well to lifestyle modification and drug treatment, further research should focus on the preventative effect of early risk management on the development of Alzheimer\u2019s disease neuropathology.<\/jats:p>","DOI":"10.1093\/brain\/awac354","type":"journal-article","created":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T16:04:21Z","timestamp":1664208261000},"page":"337-348","source":"Crossref","is-referenced-by-count":84,"title":["Diabetes and hypertension are related to amyloid-beta burden in the population-based Rotterdam Study"],"prefix":"10.1093","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7294-1633","authenticated-orcid":false,"given":"Joyce","family":"van Arendonk","sequence":"first","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Centre , Rotterdam , The Netherlands"},{"name":"Department of Epidemiology, Erasmus MC, University Medical Centre , Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5739-466X","authenticated-orcid":false,"given":"Julia","family":"Neitzel","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Centre , Rotterdam , The Netherlands"},{"name":"Department of Epidemiology, Erasmus MC, University Medical Centre , Rotterdam , The Netherlands"},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2689-5490","authenticated-orcid":false,"given":"Rebecca M E","family":"Steketee","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Centre , Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani\u00eblle M E","family":"van Assema","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Centre , Rotterdam , The Netherlands"},{"name":"Department of Medical Imaging, Nuclear Medicine, Northwest Clinics , Alkmaar , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6586-3750","authenticated-orcid":false,"given":"Henri A","family":"Vrooman","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Centre , Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Segbers","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Centre , Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0372-8585","authenticated-orcid":false,"given":"M Arfan","family":"Ikram","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Erasmus MC, University Medical Centre , Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4658-2176","authenticated-orcid":false,"given":"Meike W","family":"Vernooij","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Centre , Rotterdam , The Netherlands"},{"name":"Department of Epidemiology, Erasmus MC, University Medical Centre , Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,11,12]]},"reference":[{"key":"2023070317480987300_awac354-B1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0140-6736(20)30367-6","article-title":"Dementia prevention, intervention, and care: 2020 report of the Lancet Commission","volume":"396","author":"Livingston","year":"2020","journal-title":"Lancet"},{"key":"2023070317480987300_awac354-B2","author":"Gauthier"},{"key":"2023070317480987300_awac354-B3","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.biopsych.2020.06.029","article-title":"Longitudinal cognitive and biomarker measurements support a unidirectional pathway in Alzheimer\u2019s disease pathophysiology","volume":"89","author":"Guo","year":"2021","journal-title":"Biol Psychiatry"},{"key":"2023070317480987300_awac354-B4","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S1474-4422(12)70291-0","article-title":"Tracking pathophysiological processes in Alzheimer's disease: An updated hypothetical model of dynamic biomarkers","volume":"12","author":"Jack CR","year":"2013","journal-title":"Lancet Neurol"},{"key":"2023070317480987300_awac354-B5","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s13195-021-00807-6","article-title":"Early detection of amyloid load using (18)F-florbetaben PET","volume":"13","author":"Bullich","year":"2021","journal-title":"Alzheimers Res Ther"},{"key":"2023070317480987300_awac354-B6","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.jalz.2015.02.004","article-title":"Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer's disease: Phase 3 study","volume":"11","author":"Sabri","year":"2015","journal-title":"Alzheimers Dement"},{"key":"2023070317480987300_awac354-B7","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1212\/WNL.43.8.1467","article-title":"Association of apolipoprotein E allele \u025b4 with late-onset familial and sporadic Alzheimer\u2019s disease","volume":"43","author":"Saunders","year":"1993","journal-title":"Neurology"},{"key":"2023070317480987300_awac354-B8","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3002156","article-title":"Human apoE isoforms differentially regulate brain amyloid-beta peptide clearance","volume":"3","author":"Castellano","year":"2011","journal-title":"Sci Transl Med"},{"key":"2023070317480987300_awac354-B9","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1006\/nbdi.2000.0304","article-title":"Hypercholesterolemia accelerates the Alzheimer\u2019s amyloid pathology in a transgenic mouse model","volume":"7","author":"Refolo","year":"2000","journal-title":"Neurobiol Dis"},{"key":"2023070317480987300_awac354-B10","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/nrneurol.2017.185","article-title":"Brain insulin resistance in type 2 diabetes and Alzheimer disease: Concepts and conundrums","volume":"14","author":"Arnold","year":"2018","journal-title":"Nat Rev Neurol"},{"key":"2023070317480987300_awac354-B11","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1161\/HYPERTENSIONAHA.112.195511","article-title":"Hypertension induces brain \u03b2-amyloid accumulation, cognitive impairment, and memory deterioration through activation of receptor for advanced glycation end products in brain vasculature","volume":"60","author":"Carnevale","year":"2012","journal-title":"Hypertension"},{"key":"2023070317480987300_awac354-B12","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/nrn3012","article-title":"Linking lipids to Alzheimer\u2019s disease: Cholesterol and beyond","volume":"12","author":"Di Paolo","year":"2011","journal-title":"Nat Rev Neurosci"},{"key":"2023070317480987300_awac354-B13","article-title":"Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol","volume":"118","author":"Wang","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2023070317480987300_awac354-B14","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1096\/fj.03-0978fje","article-title":"Diet-induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer\u2019s disease","volume":"18","author":"Ho","year":"2004","journal-title":"FASEB J"},{"key":"2023070317480987300_awac354-B15","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/s41581-021-00430-6","article-title":"Hypertension-induced cognitive impairment: From pathophysiology to public health","volume":"17","author":"Ungvari","year":"2021","journal-title":"Nat Rev Nephrol"},{"key":"2023070317480987300_awac354-B16","doi-asserted-by":"crossref","first-page":"100068","DOI":"10.1016\/j.ynirp.2021.100068","article-title":"Vascular risk is not associated with Alzheimer\u2019s disease neuropathology among cognitively normal older adults","volume":"1","author":"Bilgel","year":"2021","journal-title":"Neuroimage Rep"},{"key":"2023070317480987300_awac354-B17","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/j.jalz.2019.04.015","article-title":"Vascular risk factors are associated with longitudinal changes in cerebrospinal fluid tau markers and cognition in preclinical Alzheimer\u2019s disease","volume":"15","author":"Bos","year":"2019","journal-title":"Alzheimers Dement"},{"key":"2023070317480987300_awac354-B18","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1001\/jamaneurol.2018.1123","article-title":"Interactive associations of vascular risk and beta-amyloid burden with cognitive decline in clinically normal elderly individuals: Findings from the Harvard Aging Brain Study","volume":"75","author":"Rabin","year":"2018","journal-title":"JAMA Neurol"},{"key":"2023070317480987300_awac354-B19","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.neurobiolaging.2013.06.011","article-title":"Blood pressure decrease correlates with tau pathology and memory decline in hypertensive elderly","volume":"35","author":"Glodzik","year":"2014","journal-title":"Neurobiol Aging"},{"key":"2023070317480987300_awac354-B20","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1001\/jamaneurol.2019.3774","article-title":"Associations between vascular risk across adulthood and brain pathology in late life: Evidence from a British birth cohort","volume":"77","author":"Lane","year":"2020","journal-title":"JAMA Neurol"},{"key":"2023070317480987300_awac354-B21","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2018-023664","article-title":"Associations of lifestyle and vascular risk factors with Alzheimer\u2019s brain biomarker changes during middle age: A 3-year longitudinal study in the broader New York city area","volume":"8","author":"Walters","year":"2018","journal-title":"BMJ Open"},{"key":"2023070317480987300_awac354-B22","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1212\/WNL.0b013e31826c1b9d","article-title":"Alzheimer\u2019s disease neuroimaging I. Vascular burden and Alzheimer disease pathologic progression","volume":"79","author":"Lo","year":"2012","journal-title":"Neurology"},{"key":"2023070317480987300_awac354-B23","doi-asserted-by":"crossref","first-page":"827.e11","DOI":"10.1016\/j.neurobiolaging.2011.06.020","article-title":"Blood pressure is associated with higher brain amyloid burden and lower glucose metabolism in healthy late middle-age persons","volume":"33","author":"Langbaum","year":"2012","journal-title":"Neurobiol Aging"},{"key":"2023070317480987300_awac354-B24","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1212\/01.wnl.0000436935.47657.78","article-title":"Pulse pressure is associated with Alzheimer biomarkers in cognitively normal older adults","volume":"81","author":"Nation","year":"2013","journal-title":"Neurology"},{"key":"2023070317480987300_awac354-B25","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.neurobiolaging.2018.11.001","article-title":"Influence of hypertension on brain amyloid deposition and Alzheimer\u2019s disease signature neurodegeneration","volume":"75","author":"Jeon","year":"2019","journal-title":"Neurobiol Aging"},{"key":"2023070317480987300_awac354-B26","doi-asserted-by":"crossref","first-page":"26801","DOI":"10.1038\/srep26801","article-title":"Plasma \u03b2-amyloid in Alzheimer\u2019s disease and vascular disease","volume":"6","author":"Janelidze","year":"2016","journal-title":"Sci Rep"},{"key":"2023070317480987300_awac354-B27","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1001\/jamaneurol.2013.1342","article-title":"Risk factors for beta-amyloid deposition in healthy aging: Vascular and genetic effects","volume":"70","author":"Rodrigue","year":"2013","journal-title":"JAMA Neurol"},{"key":"2023070317480987300_awac354-B28","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1001\/jamaneurol.2013.5390","article-title":"Associations between serum cholesterol levels and cerebral amyloidosis","volume":"71","author":"Reed","year":"2014","journal-title":"JAMA Neurol"},{"key":"2023070317480987300_awac354-B29","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1001\/jamaneurol.2017.0244","article-title":"Evaluation of amyloid protective factors and Alzheimer disease neurodegeneration protective factors in elderly individuals","volume":"74","author":"Vemuri","year":"2017","journal-title":"JAMA Neurol"},{"key":"2023070317480987300_awac354-B30","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.3233\/JAD-200232","article-title":"Pre-diabetes, but not type 2 diabetes, is related to brain amyloid in late middle-age","volume":"75","author":"Luchsinger","year":"2020","journal-title":"J Alzheimers Dise"},{"key":"2023070317480987300_awac354-B31","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1001\/jama.2017.3090","article-title":"Association between midlife vascular risk factors and estimated brain amyloid deposition","volume":"317","author":"Gottesman","year":"2017","journal-title":"JAMA"},{"key":"2023070317480987300_awac354-B32","doi-asserted-by":"crossref","DOI":"10.1002\/alz.12343","article-title":"Association of cardiovascular risk burden with risk of dementia and brain pathologies: A population-based cohort study","author":"Song","year":"2021","journal-title":"Alzheimers Dement"},{"key":"2023070317480987300_awac354-B33","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.neurobiolaging.2021.10.017","article-title":"Cerebrospinal fluid dynamics and discordant amyloid biomarkers","volume":"110","author":"Graff-Radford","year":"2022","journal-title":"Neurobiol Aging"},{"key":"2023070317480987300_awac354-B34","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/s10654-020-00640-5","article-title":"Objectives, design and main findings until 2020 from the Rotterdam Study","volume":"35","author":"Ikram","year":"2020","journal-title":"Eur J Epidemiol"},{"key":"2023070317480987300_awac354-B35","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.neuroimage.2006.01.021","article-title":"An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest","volume":"31","author":"Desikan","year":"2006","journal-title":"Neuroimage"},{"key":"2023070317480987300_awac354-B36","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.nicl.2017.04.025","article-title":"Optimized classification of (18)F-florbetaben PET scans as positive and negative using an SUVR quantitative approach and comparison to visual assessment","volume":"15","author":"Bullich","year":"2017","journal-title":"Neuroimage Clin"},{"key":"2023070317480987300_awac354-B37","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S1474-4422(08)70001-2","article-title":"Imaging of amyloid beta in Alzheimer\u2019s disease with 18F-BAY94-9172, a novel PET tracer: Proof of mechanism","volume":"7","author":"Rowe","year":"2008","journal-title":"Lancet Neurol"},{"key":"2023070317480987300_awac354-B38","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1007\/s00259-016-3601-4","article-title":"Quantitation of PET signal as an adjunct to visual interpretation of florbetapir imaging","volume":"44","author":"Pontecorvo","year":"2017","journal-title":"Eur J Nucl Med Mol Imag"},{"key":"2023070317480987300_awac354-B39","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1186\/s13195-021-00836-1","article-title":"Validation of amyloid PET positivity thresholds in centiloids: A multisite PET study approach","volume":"13","author":"Royse","year":"2021","journal-title":"Alzheimers Res Ther"},{"key":"2023070317480987300_awac354-B40","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1097\/00004872-200306000-00001","article-title":"2003 European Society of Hypertension\u2013European Society of Cardiology guidelines for the management of arterial hypertension","volume":"21","author":"European Society of Hypertension\u2013European Society of Cardiology Guidelines","year":"2003","journal-title":"J Hypertens"},{"key":"2023070317480987300_awac354-B41","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1001\/jama.285.19.2486","article-title":"Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)","volume":"285","author":"Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults","year":"2001","journal-title":"JAMA"},{"key":"2023070317480987300_awac354-B42","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1001\/jama.2018.3060","article-title":"Trends in obesity and severe obesity prevalence in US youth and adults by sex and age, 2007\u20132008 to 2015\u20132016","volume":"319","author":"Hales","year":"2018","journal-title":"JAMA"},{"key":"2023070317480987300_awac354-B43","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1249\/01.MSS.0000078924.61453.FB","article-title":"International physical activity questionnaire: 12-Country reliability and validity","volume":"35","author":"Craig","year":"2003","journal-title":"Med Sci Sports Exerc"},{"key":"2023070317480987300_awac354-B44","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/978-1-4939-0446-4_6","article-title":"Bi-allelic SNP genotyping using the TaqMan\u00ae assay","volume":"1145","author":"Woodward","year":"2014","journal-title":"Methods Mol Biol"},{"key":"2023070317480987300_awac354-B45","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/S1474-4422(18)30053-X","article-title":"The effect of APOE and other common genetic variants on the onset of Alzheimer\u2019s disease and dementia: A community-based cohort study","volume":"17","author":"van der Lee","year":"2018","journal-title":"Lancet Neurol"},{"key":"2023070317480987300_awac354-B46","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.neurobiolaging.2016.04.017","article-title":"Impaired fasting glucose is associated with increased regional cerebral amyloid","volume":"44","author":"Morris","year":"2016","journal-title":"Neurobiol Aging"},{"key":"2023070317480987300_awac354-B47","doi-asserted-by":"crossref","first-page":"e253","DOI":"10.1212\/WNL.0000000000006780","article-title":"Cerebral microbleeds: Prevalence and relationship to amyloid burden","volume":"92","author":"Graff-Radford","year":"2019","journal-title":"Neurology"},{"key":"2023070317480987300_awac354-B48","doi-asserted-by":"crossref","first-page":"e1799","DOI":"10.1212\/WNL.0000000000012770","article-title":"Cerebral amyloid angiopathy pathology and its association with amyloid-\u03b2 PET signal","volume":"97","author":"McCarter","year":"2021","journal-title":"Neurology"},{"key":"2023070317480987300_awac354-B49","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1161\/STROKEAHA.117.016990","article-title":"Diagnosis of cerebral amyloid angiopathy: Evolution of the Boston criteria","volume":"49","author":"Greenberg","year":"2018","journal-title":"Stroke"},{"key":"2023070317480987300_awac354-B50","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/S1474-4422(19)30228-5","article-title":"Associations between blood pressure across adulthood and late-life brain structure and pathology in the neuroscience substudy of the 1946 British birth cohort (Insight 46): An epidemiological study","volume":"18","author":"Lane","year":"2019","journal-title":"Lancet Neurol"},{"key":"2023070317480987300_awac354-B51","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/S1474-4422(05)70284-2","article-title":"Risk of dementia in diabetes mellitus: A systematic review","volume":"5","author":"Biessels","year":"2006","journal-title":"Lancet Neurol"},{"key":"2023070317480987300_awac354-B52","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.ejphar.2008.02.049","article-title":"Diabetes and other vascular risk factors for dementia: Which factor matters most? A systematic review","volume":"585","author":"Kloppenborg","year":"2008","journal-title":"Eur J Pharmacol"},{"key":"2023070317480987300_awac354-B53","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1212\/WNL.0b013e3181eee25f","article-title":"Insulin resistance is associated with the pathology of Alzheimer disease: The Hisayama Study","volume":"75","author":"Matsuzaki","year":"2010","journal-title":"Neurology"},{"key":"2023070317480987300_awac354-B54","doi-asserted-by":"crossref","first-page":"759","DOI":"10.2967\/jnumed.113.132647","article-title":"Diabetes and elevated hemoglobin A1c levels are associated with brain hypometabolism but not amyloid accumulation","volume":"55","author":"Roberts","year":"2014","journal-title":"J Nucl Med"},{"key":"2023070317480987300_awac354-B55","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1212\/WNL.0000000000001982","article-title":"Type 2 diabetes mellitus and biomarkers of neurodegeneration","volume":"85","author":"Moran","year":"2015","journal-title":"Neurology"},{"key":"2023070317480987300_awac354-B56","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1111\/j.1365-2990.2008.00948.x","article-title":"\u03b2-Amyloid deposition in brains of subjects with diabetes","volume":"35","author":"Alafuzoff","year":"2009","journal-title":"Neuropathol Appl Neurobiol"},{"key":"2023070317480987300_awac354-B57","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1001\/jamaneurol.2013.284","article-title":"Glucose intolerance, insulin resistance, and pathological features of Alzheimer disease in the Baltimore longitudinal study of aging","volume":"70","author":"Thambisetty","year":"2013","journal-title":"JAMA Neurol"},{"key":"2023070317480987300_awac354-B58","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.jalz.2014.03.011","article-title":"Insulin resistance predicts brain amyloid deposition in late middle-aged adults","volume":"11","author":"Willette","year":"2015","journal-title":"Alzheimers Dement"},{"key":"2023070317480987300_awac354-B59","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1001\/jama.2015.4668","article-title":"Prevalence of cerebral amyloid pathology in persons without dementia: A meta-analysis","volume":"313","author":"Jansen","year":"2015","journal-title":"JAMA"},{"key":"2023070317480987300_awac354-B60","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1161\/ATVBAHA.120.311911","article-title":"Vascular hypothesis of Alzheimer disease","volume":"41","author":"Scheffer","year":"2021","journal-title":"Arterioscler Thromb Vascr Biol"},{"key":"2023070317480987300_awac354-B61","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.mad.2019.03.008","article-title":"Crucial players in Alzheimer\u2019s disease and diabetes mellitus: Friends or foes?","volume":"181","author":"Kubis-Kubiak","year":"2019","journal-title":"Mech Ageing Dev"},{"key":"2023070317480987300_awac354-B62","doi-asserted-by":"crossref","first-page":"4162","DOI":"10.1073\/pnas.0230450100","article-title":"Insulin-degrading enzyme regulates the levels of insulin, amyloid \u03b2-protein, and the \u03b2-amyloid precursor protein intracellular domain in vivo","volume":"100","author":"Farris","year":"2003","journal-title":"Proc Natl Acad Sci"},{"key":"2023070317480987300_awac354-B63","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1172\/JCI79742","article-title":"Hyperglycemia modulates extracellular amyloid-\u03b2 concentrations and neuronal activity in vivo","volume":"125","author":"Macauley","year":"2015","journal-title":"J Clin Invest"},{"key":"2023070317480987300_awac354-B64","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1001\/archneurol.2009.913","article-title":"APOE epsilon4 genotype and longitudinal changes in cerebral blood flow in normal aging","volume":"67","author":"Thambisetty","year":"2010","journal-title":"Arch Neurol"},{"key":"2023070317480987300_awac354-B65","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/s41582-019-0228-7","article-title":"Apolipoprotein E and Alzheimer disease: Pathobiology and targeting strategies","volume":"15","author":"Yamazaki","year":"2019","journal-title":"Nat Rev Neurol"},{"key":"2023070317480987300_awac354-B66","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.3233\/JAD-201609","article-title":"Hypertension and hypercholesterolemia modify dementia risk in relation to APOE\u025b4 status","volume":"81","author":"Pillai","year":"2021","journal-title":"J Alzheimers Dis"},{"key":"2023070317480987300_awac354-B67","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2019.20780","article-title":"Association of vascular risk factors with \u03b2-amyloid peptide and tau burdens in cognitively unimpaired individuals and its interaction with vascular medication use","volume":"3","author":"K\u00f6be","year":"2020","journal-title":"JAMA Netw Open"},{"key":"2023070317480987300_awac354-B68","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.neurobiolaging.2020.03.015","article-title":"The association between midlife lipid levels and late-life brain amyloid deposition","volume":"92","author":"Bennett","year":"2020","journal-title":"Neurobiol Aging"},{"key":"2023070317480987300_awac354-B69","first-page":"739","article-title":"ApoE4-induced cholesterol dysregulation and its brain cell type-specific implications in the pathogenesis of Alzheimer\u2019s disease","volume":"42","author":"Jeong","year":"2019","journal-title":"Mol Cells"},{"key":"2023070317480987300_awac354-B70","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/S1474-4422(20)30412-9","article-title":"APOE and Alzheimer\u2019s disease: Advances in genetics, pathophysiology, and therapeutic approaches","volume":"20","author":"Serrano-Pozo","year":"2021","journal-title":"Lancet Neurol"},{"key":"2023070317480987300_awac354-B71","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1161\/01.ATV.0000120374.59826.1b","article-title":"Brain cholesterol: Long secret life behind a barrier","volume":"24","author":"Bj\u00f6rkhem","year":"2004","journal-title":"Arterioscler Thromb Vasc Biol"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awac354\/47029833\/awac354.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/146\/1\/337\/50785711\/awac354.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/146\/1\/337\/50785711\/awac354.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T15:02:14Z","timestamp":1688396534000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/146\/1\/337\/6825245"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,12]]},"references-count":71,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,11,12]]},"published-print":{"date-parts":[[2023,1,5]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awac354","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,1,4]]},"published":{"date-parts":[[2022,11,12]]}}}