van Uffelen 2008.
Methods | The FACT study (Folate physical Activity Cognition Trial). 2 x 2 factorial, randomised controlled trial (RCT) comparing the effects of (1) a walking programme with a placebo activity programme, and (2) vitamin B supplementation with placebo supplementation over 1 year. |
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Participants |
Location: Netherlands. Setting of recruitment and treatment: Community setting in a Dutch town. Sample size:
Participant baseline characteristics:
Inclusion criteria:
Exclusion criteria:
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Interventions |
Active intervention: 5 mg folic acid, 0.4 mg vitamin B‐12 (cyanocobalamin) and 50 mg vitamin B‐6 (pyridoxine hydrochloride) once daily for a year. Comparator: Placebo. |
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Outcomes |
Outcomes of interest in the review: Overall cognitive functioning: MMSE; Specific cognitive functioning subdomain: episodic memory: Auditory Verbal Learning Test (AVLT); Specific cognitive functioning subdomain: executive functioning: Stroop Colour Word Test‐Abridged (SCWT‐A), (also measured: letter fluency); Specific cognitive functioning subdomain: speed of processing: Digit Symbol Substitution Test (DSST); Quality of life: Dementia ‐ quality‐of‐life (D‐QOL), (also measured: health‐related QoL with SF‐12); Adverse events. |
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Source of Funding | Funded by Body@Work, Research Center Physical Activity, Work and Health, TNO‐VU University Medical Center. External financial support was obtained from the municipality of Alkmaar and the ‘‘Stichting Fonds voor het Hart’’. VIATRIS provided the FA/B12/B6 pills and placebo pills. |
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Declaration of Interest | "None of the external sources had input into protocol development, data collection, analyses, and interpretation or drafting this manuscript. | |
Notes | International Standard Randomised Controlled Trial Number Register (ISCTRN) 19227688 | |
Risk of bias | ||
Bias | Authors' judgement | Support for judgement |
Random sequence generation (selection bias) | Low risk | Quote: After the baseline interview, participants were randomised using the option ‘‘random sample of cases’’ in SPSS. Comment: Computer software used for randomisation leading to adequate sequence generation in the study. |
Allocation concealment (selection bias) | Unclear risk | Quote: "Participants and exercise instructors were blinded to group allocation by being left unaware of which exercise programme was supposed to be effective. The pills were coded as A or B by the manufacturer. The key was decoded after data analysis". Comment: Further information required. |
Blinding of participants and personnel (performance bias) All outcomes | Low risk | Quote: "Pills were coded A or B by manufacturer and then decoded only after data analysis". Comment: Participants and personnel were blinded to the intervention a participant received. |
Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "All cognitive outcome measures were assessed by trained examiners, who were also blinded to group allocation". Comment: Low risk of detection bias as the examiners were blinded to group allocation. |
Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: "For both interventions, data were analysed on a modified intention‐to‐treat basis, including participants with at least one post‐baseline assessment". Comment: All participants accounted for and data analysed from all participants with an intention‐to‐treat method. |
Selective reporting (reporting bias) | Low risk | Quote: "The walking program and/or FA/B12/B6 supplementation were not effective in improving cognition within one year". Comment: The only outcome measure tested was cognitive function and this was included in the results. |
Other bias | Low risk | No other potential biases detected. |
AD: Alzheimer's disease ADAS‐cog: Alzheimer's Disease Assessment Scale ‐ cognitive ADCS: Alzheimer's Disease Cooperative Study ADL: Activities of Daily Living APOE ϵ4: Apolipoprotein‐E gene, ϵ4 allele AVLT: Auditory Verbal Learning Test CAMDEX: Cambridge Mental Disorders of the Elderly Examination CDR: Clinical Dementia Rating scale CIND: Cognitive Impairment ‐ no dementia CLOX: Clock drawing executive test CrPic: Chromium picolinate CT: Computerised tomography CVLT: California Verbal Learning Test D‐QOL: Dementia Quality of Life questionnaire DSM‐IV: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition DSST: Digit Symbol Substitution Test EQ‐5D: Euroqol‐5D: a standardized instrument for use as a measure of health outcome FA: Folic acid GARS: Groningen Activity Restriction Scale HVLT: Hopkins Verbal Learning Test holoTC: Holotranscobalamin IQCODE: Informant Questionnaire on Cognitive Decline in the Elderly IQR: Interquartile range ISRCTN: International Standard Randomised Controlled Trial Number MCI: Mild cognitive impairment MMA: Methylmalonic acid MMSE: Mini‐Mental State Examination MoCA: Montreal Cognitive Assessment MRI: Magnetic resonance imaging PAL: Paired Associate Learning QoL: Quality of life RBC: Red blood cell SCWT‐A: Stroop Color‐Word Test ‐ Abridged SDMT: Symbol Digit Modalities Test SF‐12: 12‐item Short Form Survey TIA: Transient Ischaemic Attack TICS28: 28‐item Telephone Interview for Cognitive Status TICSm: Modified Telephone Interview for Cognitive Status vit: vitamin WAIS: Wechsler Adult Intelligence Scale wk: week 10 WLT: 10 Word Learning Test