{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:32:05Z","timestamp":1791203525142,"version":"4.2.0"},"reference-count":46,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2015,11,27]]},"abstract":"<jats:p>Background: Homocysteine has been identified as a potential risk factor for stroke, cerebral small-vessel diseases (SVD), and dementia. Objective: The present study aimed to investigate the predictive value of homocysteine levels on incident dementia while simultaneously controlling for MRI findings and vascular risk factors. Methods: Within a Japanese cohort of participants with vascular risk factors in an observational study, we evaluated the association between baseline total homocysteine (tHcy) levels (per 1 \u03bcmol\/L and the tertile of tHcy), the prevalence of MRI-findings at baseline, and incident all-cause dementia. Baseline brain MRI was used to determine SVD (lacunas, white matter hyperintensities, and cerebral microbleeds [CMBs]) and atrophy (medial-temporal lobe atrophy and bicaudate ratio). Logistic regression analyses were used to estimate the cross-sectional association between tHcy and each of MRI findings. Cox proportional hazards analyses were performed to estimate the longitudinal association between tHcy and dementia. Results: In the 643 subjects (age: 67.2 \u00b1 8.4 years, male: 59% ; education: 12.9 \u00b1 2.6 years), multivariable analyses adjusted for several potential confounders, including estimated glomerular filtration rate (eGFR) and intima-media thickness, showed that highest tHcy tertile was associated with lacunas, CMBs, and strictly deep CMBs. During the mean 7.3-year follow-up (range: 2\u201313), 47 patients were diagnosed with dementia (Alzheimer\u2019s disease: 24; vascular dementia: 18; mixed-type: 3; other: 2). After adjusting for age, gender, APOE \u025b4, education, BMI, MMSE, hypertension, cerebrovascular events, eGFR, and MRI-findings, tHcy level (hazard ratios [HR]: 1.08, p\u200a=\u200a0.043) and the highest tertile of tHcy (HR: 2.50, p\u200a=\u200a0.047) for all-cause dementia remained significant. Conclusions: Our results provide additional evidence of tHcy that contributes to increased susceptibility to dementia risk.<\/jats:p>","DOI":"10.3233\/jad-150458","type":"journal-article","created":{"date-parts":[[2015,11,27]],"date-time":"2015-11-27T08:36:20Z","timestamp":1448613380000},"page":"503-513","source":"Crossref","is-referenced-by-count":56,"title":["Increased Total Homocysteine Levels Predict\u00a0the Risk of Incident Dementia Independent of Cerebral Small-Vessel Diseases and Vascular Risk Factors"],"prefix":"10.1177","volume":"49","author":[{"given":"Kaori","family":"Miwa","sequence":"first","affiliation":[{"name":"Department of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makiko","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Strokology, Stroke Center, Hoshigaoka Medical Center, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Okazaki","sequence":"additional","affiliation":[{"name":"Department of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Yagita","sequence":"additional","affiliation":[{"name":"Department of Stroke Medicine, Kawasaki Medical University, Kurashiki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Sakaguchi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Mochizuki","sequence":"additional","affiliation":[{"name":"Department of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Kitagawa","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tokyo Women\u2019s Medical University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-150458_ref1","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1056\/NEJM199104253241701","article-title":"Hyperhomocysteinemia: An independent risk factor for vascular disease","volume":"324","author":"Clarke","year":"1991","journal-title":"N Engl J Med"},{"key":"10.3233\/JAD-150458_ref2","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1001\/jama.288.16.2015","article-title":"Homocysteine and risk of ischemic heart disease and stroke: A meta-analysis","volume":"288","author":"Homocysteine Studies Collaboration","year":"2002","journal-title":"JAMA"},{"key":"10.3233\/JAD-150458_ref3","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1093\/brain\/awh023","article-title":"Homocysteine is a risk factor for cerebral small vessel disease, acting via endothelial dysfunction","volume":"127","author":"Hassan","year":"2004","journal-title":"Brain"},{"key":"10.3233\/JAD-150458_ref4","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1161\/STR.0b013e3182299496","article-title":"Vascular contributions to cognitiveimpairment and dementia: A statement for healthcare professionalsfrom the American Heart Association\/American Stroke Association","volume":"42","author":"Gorelick","year":"2011","journal-title":"Stroke"},{"key":"10.3233\/JAD-150458_ref5","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1056\/NEJMoa011613","article-title":"Plasma homocysteine as a risk factor for dementia and Alzheimer\u2019s disease","volume":"346","author":"Seshadri","year":"2002","journal-title":"N Engl J Med"},{"key":"10.3233\/JAD-150458_ref6","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.neurobiolaging.2009.02.024","article-title":"Midlife homocysteine and late-life dementia in women. 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