biostudies-literatureWloczkowska OAmerican Heart Associatione12159https://www.ebi.ac.uk/biostudies/studies/S-EPMC8010366biostudies-literatureUnknown7(1)<h4>Introduction</h4>Elevated homocysteine (Hcy) and related metabolites accelerate Alzheimer's disease. Hcy-lowering B vitamins slow brain atrophy/cognitive decline in mild cognitive impairment (MCI). Modification with Hcy-thiolactone generates auto-immunogenic <i>N</i>-Hcy-protein. We tested a hypothesis that anti-<i>N</i>-Hcy-protein autoantibodies predict cognition in individuals with MCI participating in a randomized, double-blind, placebo-controlled VITACOG trial of B vitamins.<h4>Methods</h4>Participants with MCI (n = 196, 76.8 years old, 60% women) were randomly assigned to receive a daily dose of folic acid (0.8 mg), vitamin B₁₂ (0.5 mg), and B₆ (20 mg) (n = 98) or placebo (n = 98) for 2 years. Cognition was analyzed by neuropsychological tests. Brain atrophy was quantified in a subset of patients (n = 167) by magnetic resonance imaging. Anti <i>N</i>-Hcy-protein auto-antibodies were quantified by enzyme-linked immunosorbent assay. Associations among anti-<i>N</i>-Hcy-protein autoantibodies, cognition, and brain atrophy were examined by multiple regression analysis.<h4>Results</h4>At baseline, anti-<i>N</i>-Hcy-protein autoantibodies were significantly associated with impaired global cognition (Mini-Mental State Examination [MMSE]), episodic memory (Hopkins Verbal Learning Test-revised), and attention/processing speed (Map Search). At the end of the study, anti-<i>N</i>-Hcy-protein autoantibodies were associated with impaired global cognition (MMSE) and attention/processing speed (Trail Making A). In the placebo group, baseline anti-<i>N</i>-Hcy-protein autoantibodies predicted, independently of Hcy, global cognition (Telephone Inventory for Cognitive Status modified [TICS-m]; MMSE) and attention/processing speed (Trail Making A) but not brain atrophy, at the end of study. B-vitamin treatment abrogated association of anti-<i>N</i>-Hcy-protein autoantibodies with cognition.<h4>Discussion</h4>These findings suggest that anti-<i>N</i>-Hcy-protein autoantibodies can impair functional (attention/processing speed and global cognition), but not structural (brain atrophy), aspects of cognition. Anti-<i>N</i>-Hcy-protein autoantibodies are a new factor associated with impaired cognition, which could be ameliorated by B vitamins.Alzheimer's & dementia (New York, N. Y.)Anti-<i>N</i>-homocysteine-protein autoantibodies are associated with impaired cognition.PMC801036617GRNT32910002de Jager CWloczkowska OSmith ADJakubowski HPerla-Kajan JRefsum HfalseAnti-<i>N</i>-homocysteine-protein autoantibodies are associated with impaired cognition.<h4>Introduction</h4>Elevated homocysteine (Hcy) and related metabolites accelerate Alzheimer's disease. Hcy-lowering B vitamins slow brain atrophy/cognitive decline in mild cognitive impairment (MCI). Modification with Hcy-thiolactone generates auto-immunogenic <i>N</i>-Hcy-protein. We tested a hypothesis that anti-<i>N</i>-Hcy-protein autoantibodies predict cognition in individuals with MCI participating in a randomized, double-blind, placebo-controlled VITACOG trial of B vitamins.<h4>Methods</h4>Participants with MCI (n = 196, 76.8 years old, 60% women) were randomly assigned to receive a daily dose of folic acid (0.8 mg), vitamin B₁₂ (0.5 mg), and B₆ (20 mg) (n = 98) or placebo (n = 98) for 2 years. Cognition was analyzed by neuropsychological tests. Brain atrophy was quantified in a subset of patients (n = 167) by magnetic resonance imaging. Anti <i>N</i>-Hcy-protein auto-antibodies were quantified by enzyme-linked immunosorbent assay. Associations among anti-<i>N</i>-Hcy-protein autoantibodies, cognition, and brain atrophy were examined by multiple regression analysis.<h4>Results</h4>At baseline, anti-<i>N</i>-Hcy-protein autoantibodies were significantly associated with impaired global cognition (Mini-Mental State Examination [MMSE]), episodic memory (Hopkins Verbal Learning Test-revised), and attention/processing speed (Map Search). At the end of the study, anti-<i>N</i>-Hcy-protein autoantibodies were associated with impaired global cognition (MMSE) and attention/processing speed (Trail Making A). In the placebo group, baseline anti-<i>N</i>-Hcy-protein autoantibodies predicted, independently of Hcy, global cognition (Telephone Inventory for Cognitive Status modified [TICS-m]; MMSE) and attention/processing speed (Trail Making A) but not brain atrophy, at the end of study. B-vitamin treatment abrogated association of anti-<i>N</i>-Hcy-protein autoantibodies with cognition.<h4>Discussion</h4>These findings suggest that anti-<i>N</i>-Hcy-protein autoantibodies can impair functional (attention/processing speed and global cognition), but not structural (brain atrophy), aspects of cognition. Anti-<i>N</i>-Hcy-protein autoantibodies are a new factor associated with impaired cognition, which could be ameliorated by B vitamins.2021-01-01T00:00:00Z20212025-04-05T14:33:45.088Z2022-02-09T12:48:09.621ZS-EPMC80103663381676410.1002/trc2.12159