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Media type:
E-Article
Title:
Anti‐N‐homocysteine‐protein autoantibodies are associated with impaired cognition
Contributor:
Włoczkowska, Olga;
Perła‐Kaján, Joanna;
Smith, A. David;
de Jager, Celeste;
Refsum, Helga;
Jakubowski, Hieronim
Published:
Wiley, 2021
Published in:
Alzheimer's & Dementia: Translational Research & Clinical Interventions, 7 (2021) 1
Language:
English
DOI:
10.1002/trc2.12159
ISSN:
2352-8737
Origination:
Footnote:
Description:
AbstractIntroductionElevated 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 N‐Hcy‐protein. We tested a hypothesis that anti‐N‐Hcy‐protein autoantibodies predict cognition in individuals with MCI participating in a randomized, double‐blind, placebo‐controlled VITACOG trial of B vitamins.MethodsParticipants 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 N‐Hcy‐protein auto‐antibodies were quantified by enzyme‐linked immunosorbent assay. Associations among anti‐N‐Hcy‐protein autoantibodies, cognition, and brain atrophy were examined by multiple regression analysis.ResultsAt baseline, anti‐N‐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‐N‐Hcy‐protein autoantibodies were associated with impaired global cognition (MMSE) and attention/processing speed (Trail Making A). In the placebo group, baseline anti‐N‐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‐N‐Hcy‐protein autoantibodies with cognition.DiscussionThese findings suggest that anti‐N‐Hcy‐protein autoantibodies can impair functional (attention/processing speed and global cognition), but not structural (brain atrophy), aspects of cognition. Anti‐N‐Hcy‐protein autoantibodies are a new factor associated with impaired cognition, which could be ameliorated by B vitamins.