Serum folate deficiency and the risks of dementia and all-cause mortality: a national study of old age

Abstract

BackgroundThe association between serum folate deficiency and the risk of dementia in old age is unclear, perhaps owing to small sample sizes, the competing risk of mortality or reverse causation.ObjectiveTo examine the associations between serum folate deficiency and the risks of incident dementia and all-cause mortality in a large national sample of older adults.MethodsA prospective cohort aged 60–75 years (n=27 188) without pre-existing dementia for at least 10 years, was tested for serum concentrations of folate and followed up for dementia or all-cause mortality. Serum folate deficiency was classified as present (<4.4 ng/mL), otherwise absent. HRs and 95% CIs from competing risks Cox models were fitted to quantify the associations between serum folate deficiency and the risks of dementia and all-cause mortality. To examine reverse causation, the analysis was stratified by duration of follow-up.FindingsThe presence compared with the absence of serum folate deficiency was associated with higher risks of dementia (HR=1.68; 95% CI 1.32 to 2.13; p<0.001) and all-cause mortality (HR=2.98; 95% CI 2.52 to 3.52; p<0.001). Evidence for reverse causation were moderate for dementia and mild for all-cause mortality.ConclusionsSerum concentrations of folate may function as a biomarker used to identify those at risk of dementia and mortality; however, reverse causation is likely. Further research is needed to examine the role of serum folate deficiency in dementia aetiology.Clinical implicationsSerum folate deficiency in older adults requires monitoring and treatment for preventative measures and/or as part of implemented therapeutic strategies.

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“…The role of folic acid in prenatal development has been extensively investigated, having critical roles in neurodevelopment and neuroprotective effects [ 154 ]. Serum folate deficiency was associated with higher risks of dementia and all-cause mortality in the elderly (60–75 years) [ 155 ], but vitamin B9 deficiency is correlated with other metal symptoms, especially depression and cognitive decline in epileptic, neurological, psychiatric, geriatric, and psychogeriatric populations [ 156 ]. Folic acid supplementation (400 μg) significantly improved cognitive function and reduced inflammation responses in elderly subjects with MCI after 12 months of intervention [ 157 ].…”

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“…A recent review of nutritional requirements for adults aged ≥ 65 years proposed that intakes of 400 μg were deemed more appropriate for this age group than the current UK recommendation of 200 μg [ 30 , 34 ]. This is due to the increased risk of deficiency in older people, which is associated with neurological damage and potentially increased risk of dementia [ 35 ]. A secondary analysis of the NDNS data found that ‘health conscious’ egg consumers (consuming > 3 eggs/week and low intake of red or processed meat) had significantly higher intakes of folate than those consuming high amounts of red and processed meats and no eggs [ 36 ].…”

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“…Folate intake is associated with a reduced risk of AD [ 91 ]. Furthermore, serum folate deficiency is linked to a greater incidence of dementia [ 92 ]. In patients with AD, serum homocysteine (Hcy) levels are substantially higher, and serum folate and vitamin B12 levels are lower than in non-dementia patients [ 93 ].…”