Lower Water-soluble Vitamins and Higher Homocysteine Levels Contribute to Cognitive Decline in Patients with Neurodegenerative Diseases: a retrospective case-control study

Background : Evidence of the effectsof water-soluble vitamins (e.g., vitaminB, vitamin C, and folic acid [FA]) on cognitive function in patients with neurodegenerative diseases is mixed. Furthermore, the relationships among homocysteine (Hcy) metabolism, water-soluble vitamins, and cognitive decline remain unclear. Therefore, we aimed to investigate the role of the levels of water-soluble vitamins (e.g., vitamins B1, B2, B3, B5, B6, B9, B12, and C and FA) and Hcy in dementia progression in patients with neurodegenerative diseases. Methods : In this retrospective cohort study, we enrolled 280 healthy controls and 646 patients with a neurodegenerative disease. Patientswere classified into a Parkinson’s disease (PD) group (n = 312), Alzheimer’s disease (AD) group (n = 219), orother dementia group (n = 115) according to pathological features. The other dementia group comprised 25 patients with frontotemporal dementia, 38 with Lewy body dementia, 34 with vascular dementia, and 18 with semantic dementia. Serum vitamins (i.e., B1, B2, B3, B5, VB6, B9, and C) were measured via liquid chromatography-mass spectrometry/mass spectrometry. Total Hcy and plasma vitamin B12 and FA levels were measured using commercial electrochemiluminescence immunoassays. Results : The serum levels of vitamins B1, B2, B5, B6, B9, and C were lower in all patient groups than in the control group. The logistic regression results revealed that lower levels of serum vitamins B2, B6, B9, and B12 were associated with a higher risk of dementia in PD patients, and higher Hcy levels and lower serum vitamin B6 and B9 levels were associated with a higher risk of AD-relatedcognitive impairment. In addition, the level of vitamins was positivelycorrelated with neuropsychological assessment scoresand negatively correlated with Hcy level and stage of dementia. Conclusions : The levels of several water-soluble vitamins are lower in dementia patients. Moreover, lower levels of water-soluble vitamins and higher levels of Hcy may be associated with a higher risk of developing dementia. These findings suggest that estimating water-soluble vitamin levels in older adults may be valuable given that they may help improve cognitive function.