| ObjectiveThe aim of this study was to explore the effect of folic acid combined with vitamin B12 on patients with Alzheimer's disease?AD?and its underlying mechanisms,so as to provide scientific evidence for prevention and treatment of AD and other neurodegenerative diseases as well as for slowing their development and progress.MethodsA single-center,single-blind,randomized controlled trial was conducted.All subjects were recruited from the cognitive impairment clinic of Tianjin Huanhu Hospital between June 2016 and June 2018.According to the inclusion and exclusion criteria,156 patients with AD were finally enrolled and 1 patient with normal pressure hydrocephalus?NPH?was excluded.The subjects randomly assigned to intervention group or control group according to gender,mini-mental state examination?MMSE?score,education level and age.Finally the sample size of the two groups were 79 and77,respectively.Patients in the intervention group received folic acid 1.2 mg/d and vitamin B12(VB12)50?g/d,and those in the control group took the identical placebo.MMSE and Alzheimer's disease assessment scale-cognitive subscale?ADAS-Cog?were used to assess cognitive function of AD patients.Serum folate and VB12 levels were measured by chemiluminescence method.Plasma S-adenosylmethionine?SAM?,S-adenosylhomocysteine?SAH?and SAM/SAH were detected by high performance liquid chromatography?HPLC?.Serum homocysteine?Hcy?concentration was measured by enzyme cycle method.Interleukin 2?IL-2?,interleukin 6?IL-6?,interleukin 10?IL-10?,monocyte chemotactic protein 1?MCP-1?and tumor necrosis factor alpha?TNF-??were determined by the Merck Millipore liquid-chip multi-factor product detection technology.The expressions of APP–mRNA,PS1-mRNA,PS2-mRNA,TNF?-mRNA and IL6-mRNA were detected by RT-qPCR.ResultsAfter 6 months'intervention,the scores of MMSE,orientation,language&praxis in the intervention group were 0.799 points,0.536 points,and 0.530 points higher than those of the control group,respectively.The differences were statistically significant?P<0.05?.Registration,recall,attention&calculation were not significantly different?P>0.05?.The scores of ADAS-Cog,language,memory and praxis in the intervention group decreased by 2.274 points,1.045 points,0.851 points,and 0.422 points,respectively,and the differences were statistically significant?P<0.05?.It suggests that folic acid combined with VB122 can delay the decline of cognitive function in AD patients.After 6 months'intervention,the levels of folate,VB12,SAM and SAM/SAH in the intervention group were significantly increased,and the concentrations of Hcy and SAH were significantly lower than those in the control group?P<0.025?.APP-mRNA and PS2-mRNA in the intervention group were decreased compared with those in the control group,and the differences were statistically significant?P<0.025?PS1-mRNA was decreased compared with the control group,but the difference was not statistically significant?P>0.025?.It suggests that folic acid combined with VB12 may delay the progress of cognitive function impairment by decreasing the expression levels of APP-mRNA,PS2-mRNA and PS1-mRNA.The levels of TNF?and IL-6,TNF?-mRNA and IL6-mRNA in the intervention group were significantly lower than those in the control group,and the differences were statistically significant?P<0.025?.Decrease of MCP-1 and the IL-10 was lower in the intervention group than the control group,but the difference was not statistically significant?P>0.025?.This suggests that folic acid combined with VB12 may delay cognitive decline by reducing the expression levels and concentrations of TNF?and IL-6.ConclusionsOn the basis of conventional anti-dementia drug therapy,folic acid combined with VB12 intervention can delay the decline of cognitive function in AD patients.On one hand,the underlying mechanism may be the reduced expression levels and concentrations of TNF?and IL-6.On the other hand,delayed cognitive decline may be the decreasing expression levels of APP-mRNA,PS2-mRNA and PS1-mRNA. |
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