A randomized placebo-controlled trial of using B vitamins to prevent cognitive decline in older mild cognitive impairment patients

Abstract

Background & aims: Mild cognitive impairment (MCI) patients are at risk of cognitive decline, while elevated serum homocysteine is also associated with cognitive impairment. Thus, older people with MCI and hyperhomocysteinemia may be under greater risk of cognitive decline. We therefore performed a randomized trial of homocysteine-lowering by B vitamins supplementation to prevent cognitive decline in older MCI patients with elevated serum homocysteine. Methods: 279 MCI outpatients aged !65 years with serum homocysteine !10.0 mmol/L were randomly assigned to take either methylcobalamin 500 mg and folic acid 400 mg once daily, or two placebo tablets for 24 months. All subjects were followed up at 12 monthly intervals. The primary outcome was cognitive decline as defined by an increase in clinical dementia rating scale (CDR) sum of boxes (CDR_SOB). The secondary outcomes were global CDR, memory Z score, executive function Z score and Hamilton depression rating scale (HDRS) score. Results: The clinical characteristics between two groups were well matched, except that the supplement group had better executive function. The supplement effectively lowered serum homocysteine (mean 13.9 ± sd 3.5 mmol at baseline to 9.3 ± 2.4 mmol/L at month 24). At month 24, there was no significant group difference in CDR_SOB or any secondary outcomes (mean changes in CDR_SOB 0.36 versus 0.22 in supplement and placebo groups respectively). At month 12, the supplement group significantly improved in executive function and had lower HDRS score (P ¼ 0.004 and 0.012 respectively). Group difference was significant for HDRS, but borderline significant for executive function. (P ¼ 0.01; 0.06 respectively) These effects were not significant at month 24. Subgroup analysis showed that aspirin use had significant interaction with B supplements in CDR_SOB at month 24 (Beta 0.189, P ¼ 0.005). Conclusions: Vitamin B 12 and folic acid supplementation did not reduce cognitive decline in older people with MCI and elevated serum homocysteine, though the cognitive decline over two years in placebo group was small. The supplement led to a significant reduction in depressive symptoms at month 12, though this effect was not sustained. Aspirin use had a negative interaction effect on cognitive functioning with B supplements. Clinical trial registration: Centre for Clinical Research and Biostatistics (CCRB) Clinical Trials Registry: CUHK_CCT00373.

Diet, Stress and Mental Health

“…Long-term supplementation with folate and vitamin B12 did not prevent the development of depression in healthy women [ 165 ]. Studies in patients with depression showed that folate and/or Vitamin B12, including as an augmentation to antidepressants, resulted in improved symptoms of depression in some studies [ 166 , 167 , 168 , 169 , 170 ] but not others [ 164 , 171 , 172 ]. Greater reductions in depression were seen in depressed patients with the MHTFR polymorphism [ 167 , 173 ].…”

Impact of supplementation with vitamins B6, B12, and/or folic acid on the reduction of homocysteine levels in patients with mild cognitive impairment: A systematic review

“…MCI patients sample sizes ranged from 16 51 to 279. 52 Seven primary studies used the Mini-Mental State Examination (MMSE) as diagnostic criteria for inclusion, [17][18][19]32,53,54 and one study did not report the diagnostic criteria, but was included since mean, minimum and maximum MMSE was reported and fit the MCI criteria 35 (Table S3).…”

The preventive efficacy of vitamin B supplement on the cognitive decline of elderly adults: a systematic review and meta-analysis

“…They were recruited from homes, communities or hospitals. The participants of six studies [28][29][30][36][37][38] were MCI patients and the other fteen studies [26,35,[39][40][41][42][43][44][45][46][47][48][49][50][51] were elderly adults without cognitive impairment. Some of these participants were accompanied with one or more chronic diseases, such as mental disorders, stroke, diabetes mellitus, transient ischemic attack or hypertension.…”

“…The mean age of participants ranged from 60.0 to 83 in the intervention group and 60.0 to 82 in the control group. The treatment duration ranged from 1 month to 3.4 years, eleven studies [28,37,38,40,41,[46][47][48][49][50][51]] ≤ 12 months and ten studies [26,29,30,35,36,39,[42][43][44][45]] > 12 months. The detail characteristics of 21 included studies were presented in Table 1.…”