One-Carbon Metabolism Biomarkers and Risks of Incident Neurocognitive Disorder among Cognitively Normal Older Adults
Paulina Maria Przybycien-Gaweda,
Tih Shih Lee,
Wee Shiong Lim,
Mei Sian Chong,
Philip Yap,
Chin Yee Cheong,
Iris Rawtaer,
Tau Ming Liew,
Xinyi Gwee,
Qi Gao,
Keng Bee Yap,
Tze Pin Ng
Affiliations
Paulina Maria Przybycien-Gaweda
Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
Tih Shih Lee
Laboratory of Neurobehavioural Genomics, Duke-NUS Medical School, Singapore 169857, Singapore
Wee Shiong Lim
Institute of Geriatrics and Active Aging, Tan Tock Seng Hospital, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308433, Singapore
Mei Sian Chong
Geriatric Education and Research Institute, Singapore 768024, Singapore
Philip Yap
Department of Geriatric Medicine, Khoo Teck Puat Hospital, Singapore 768828, Singapore
Chin Yee Cheong
Department of Geriatric Medicine, Khoo Teck Puat Hospital, Singapore 768828, Singapore
Iris Rawtaer
Department of Psychiatry, Sengkang General Hospital, Singapore 544886, Singapore
Tau Ming Liew
Department of Psychiatry, Singapore General Hospital, Singapore 169608, Singapore
Xinyi Gwee
Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
Qi Gao
Department of Clinical Epidemiology, Tan Tock Seng Hospital, Singapore 308433, Singapore
Keng Bee Yap
Department of Medicine, Ng Teng Fong General Hospital, Singapore 609606, Singapore
Tze Pin Ng
Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
There is a lack of evidence supporting an association between folate and vitamin B12 exposure with cognitive outcomes. We examined serum folate and vitamin B12 and plasma homocysteine in 690 cognitively-normal adults (aged ≥ 55) from the Singapore Longitudinal Aging Study (SLAS-2) followed-up over 4.5 years on incident neurocognitive disorder (NCD): mild cognitive impairment (MCI) and dementia. At follow-up, 5.7% (39) of participants developed NCD (34 MCI and 5 dementia). Comparing with those who remained cognitively-normal, participants progressed to NCD had significantly lower mean baseline vitamin B12 (420 [SD ± 221] vs. 510 [SD ± 290] pmol/L, p = 0.026), higher homocysteine (14.6 [SD ± 4.2] vs. 12.9 [SD ± 4.3], p = 0.018) and lower one-carbon index (Z-scores: −0.444 [SD ± 0.819] vs. −0.001 [SD ± 0.990], p = 0.006). Adjusted for confounders, significant associations with incident NCD were found for lower vitamin B12 (per-SD OR = 2.10, 95%CI = 1.26–3.52), higher homocysteine (per-SD OR = 1.96, 95%CI = 1.18–3.24) and lower one-carbon index (per-SD OR = 1.67, 95%CI = 1.06–2.64). Folate was not significantly associated with progression to NCD. Notably, low B12 in the presence of high folate was significantly associated with incident NCD (adjusted OR = 3.81, 95%CI = 1.04–13.9). Low B12, high homocysteine, low B12 in the presence of high folate, and a one-carbon index of hypo-methylation were independently associated with progression to NCD among cognitively normal.