In this post, I link to and excerpt from The preventive efficacy of vitamin B supplements on the cognitive decline of elderly adults: a systematic review and meta-analysis [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. BMC Geriatr. 2021 Jun 16;21(1):367. doi: 10.1186/s12877-021-02253-3.
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Abstract
Background: The irreversibility of cognitive impairment of Alzheimer’s disease (AD) prompts that preventing or delaying the onset of AD should be a public health priority. Vitamin B supplements can lower the serum homocysteine (Hcy) level, but whether it can prevent cognitive decline or not remains unclear. We aimed to evaluate the preventive efficacy of vitamin B supplements on the cognitive decline of elderly adults.
Methods: We searched PubMed, Embase, The Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, Science Direct, PsycINFO from inception to December 1, 2019, and then updated the retrieved results on June 1, 2020. The randomized controlled trials (RCTs) which evaluated the efficacy of vitamin B in mild cognitive impairment (MCI) patients or elderly adults without cognitive impairment were selected. Standardized mean difference (SMD) or mean difference (MD) as well as their 95 % confidence interval (CI) were calculated by performing random effects models or fixed effects models.
Results: A total of 21 RCTs involving 7571 participants were included for meta-analysis. The forest plots showed that there is significant effect in global cognitive function (15 RCTs, SMD: 0.36; 95 % CI: 0.18 to 0.54, P < 0.01) and Hcy (11 RCTs, MD: -4.59; 95 %CI: -5.51 to -3.67, P < 0.01), but there is no effect in information processing speed (10 RCTs, SMD: 0.06; 95 % CI: -0.12 to 0.25, P = 0.49), episodic memory (15 RCTs, SMD: 0.10; 95 % CI: -0.04 to 0.25, P = 0.16), executive function (11 RCTs, SMD: -0.21; 95 % CI: -0.49 to 0.06, P = 0.13). The value of effect size and heterogeneity did not vary apparently when excluding the low-quality studies, so we could believe that the results of meta-analysis were robust.
Conclusions: Vitamin B supplements might delay or maintain the cognitive decline of elderly adults. We can recommend that the vitamin B supplements should be considered as a preventive medication to MCI patients or elderly adults without cognitive impairment. More well-designed RCTs with large sample sizes were required to clarify the preventive efficacy in the future.
Keywords: Cognitive function; Elderly adults; Meta-analysis; Preventive efficacy; Randomized controlled trials; Vitamin B.
Background
The main pathological characteristics of AD are the amyloid plaques due to the accumulation of β-amyloid peptide (Aβ) and the neurofibrillary tangles (NFTs) that contains hyperphosphorylated microtubule-associated tau proteins [10, 11]. Homocysteine (Hcy) is a neurotoxic amino acid as a by-product of methionine transmethylation, which can cause the accumulation of Aβ and brain atrophy [12]. Vitamin B12, folate and vitamin B6 are cofactors for the methylation of Hcy and play a vital role in lowering the levels of serum Hcy [13]. Low serum status of vitamin B and high Hcy levels may cause brain atrophy through oxidative stress and lead to the cognitive decline of elderly adults [14–17]. The elimination of excess Hcy could be a potential therapeutic intervention to improve cognitive function or delay the onset of AD [18]. Folate and the metabolically related vitamin B are considered promising for preventing or delaying aged-related cognitive decline to people with high serum levels of Hcy [19–21].
Up to now, there is as yet no effective medication to improve the cognitive function by alter the course of AD [31]. In view of the irreversibility of cognitive impairment, we should pay more attention to MCI patient or elderly adults without cognitive impairment rather than AD patients. Meanwhile, several randomized controlled trials (RCTs) concerning evaluating the preventive efficacy of vitamin B supplements on the cognitive decline of elderly adults were screened, but the conclusions are inconsistent. Therefore, it is necessary to conduct a systematic review and meta-analysis to verify the preventive efficacy. We expected that our research results will assist in guiding clinicians and health educator to optimize the prescription patterns for the MCI patients and elderly adults without cognitive impairment.
Discussion
Summary of results
This systematic review explored the preventive efficacy of vitamin B supplements on the cognitive decline of MCI patients or elderly adults without cognitive impairment by synthesizing 21 eligible RCTs. We found that vitamin B supplements can significantly lower the levels of serum Hcy and prevent the decline of global cognitive function. The substantial reduction of the levels of serum Hcy verified that vitamins B are cofactors for the methylation of Hcy and play a vital role in lowering the levels of serum Hcy. Besides, the high levels of serum Hcy of participants may also be a crucial factor. In view of this, we can draw the conclusions that vitamin B supplements can prevent or delay aged-related cognitive decline by lowering the levels of Hcy. As for the other three outcome measures (information processing speed, episodic memory, executive function), the vitamin B supplements was invalid. The difference in conclusions may be related to the assumption that the vitamin B supplements have efficacy on global cognitive function rather than the other three outcome measures. Besides, the assumption that the outcome measure of global cognitive function was more sensitive than the other three outcome measures to detect the change of cognitive function may also be related to the difference.
The heterogeneity of every outcome measure was substantial and was caused by various reasons. First, both MCI patients and elderly adults without cognitive impairment were included in our meta-analysis. Because of age-related of degeneration, elderly adults were at high risk of chronic disease, such as mental disorders, stroke, diabetes mellitus, transient ischemic attack or hypertension. Different chronic diseases may influence the metabolism of vitamin B or the assessment of cognitive function; second, the baseline levels of serum Hcy of participants varied significantly. The therapeutic efficacy of vitamin B supplements in participants was significantly associated with the baseline levels of serum Hcy [52]; third, the treatment duration of studies included ranged from 1 month to 3.4 years. It is generally believed that longer treatment duration is more likely to achieve better therapeutic efficacy; last, the cognitive function scales utilized in studies were diversified. The 21 included studies involved 53 different cognitive function scales in total. One outcome measure was assessed by several cognitive function scales in most cases.
Conclusions and recommendations
According to the results of meta-analysis, we can draw the conclusions that vitamin B supplements can low the serum Hcy levels and improve the global cognitive function, but cannot improve the information processing speed, episodic memory, executive function of MCI patients and elderly adults without cognitive impairment. On the whole, the effect sizes among vitamin B supplements appear to be trivial. Prevention measures are never likely to exert remarkable effect sizes on individual. But for the population level, the trivial effect sizes can be amplified and result in substantial improvement.
In view of the results of different cognitive domain categories and serum Hcy, we thought that vitamin B supplements might delay or maintain the cognitive decline of elderly adults. In consideration of the vitamin B supplements is cheap and accessible, the vitamin B supplements should be considered as a preventive medicine to MCI patients or elderly adults without cognitive impairment. More well-designed RCTs with large sample sizes were required to clarify the preventive efficacy in the future. In order to obtain smaller heterogeneity, some consistency and universal cognitive function scales are necessary to evaluate the cognitive function. Moreover, we can conduct a network meta-analysis to identify the optimal dosage and combination of vitamin B12, vitamin B6, or folic acid to the cognitive decline of MCI patients and elderly adults without cognitive impairment for future work plan.
