{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:31:53Z","timestamp":1791567113099,"version":"4.3.4"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T00:00:00Z","timestamp":1684800000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The association between markers of vitamin B12 status and cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD), which precede cognitive impairment, has been investigated by only a few small studies and results have been inconsistent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>The aim of this study was to investigate the associations of vitamin B12\u2010related markers with CSF biomarkers of AD and cognitive performance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data included 462 patients aged 40 to 94\u2009years referred to the Memory Clinic of the Ulm University Hospital, Ulm, Germany. Vitamin B12, holotranscobalamin (HoloTC), homocysteine (tHcy), and methylmalonic acid (MMA) have been measured. CSF values of amyloid \u03b2<jats:sub>42<\/jats:sub> (A\u03b2<jats:sub>42<\/jats:sub>) and total\u2010tau have been assessed in 227 participants. CERAD battery was administered to examine the cognitive status, and different domains were derived. Regression models were used to investigate the associations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the multi\u2010adjusted model, higher levels of MMA were associated with raised CSF total\u2010tau values: the odds ratios (ORs) 95% confidence intervals (CIs) were 3.25 (95% CI\u2009=\u20091.35\u20137.76) for the highest quartile of MMA compared to the lowest. Furthermore, moderately increased MMA were related to lower A\u03b2<jats:sub>42<\/jats:sub> levels: the ORs and 95% CIs were 3.06 (95% CI\u2009=\u20091.22\u20137.67) for the third quartile of MMA compared to the lowest. All B12 indicators except B12 itself were related to several cognitive domains, such as episodic memory and executive functioning.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Markers of vitamin B12 may be independent predictors of CSF biomarkers of AD and cognitive functioning, with MMA showing the most consistent effects. Randomized controlled trials are needed to determine the importance of vitamin B12 supplementation on slowing structural brain changes and cognitive decline. 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