Study: Low Vitamin B9 Levels in Older Age May Increase Risk of Dementia

Vitamin B9 levels should be regularly checked to correct any deficiencies in older age.

Low vitamin B9 levels in the blood may be associated with a greater risk of dementia and death from any cause in older adults, according to a study published online in Evidence Based Mental Health.

The investigators noted that vitamin B9 levels should be regularly checked to correct any deficiencies in older age, especially because folate blood levels typically decline with age. The investigators added that up to 1 in 5 older adults are estimated to be folate deficient.

Current evidence indicates that folate deficiency can impact cognition and nerve signaling in the brain, which suggests it is a potential risk factor for dementia, according to the study; however, the limited research that has been performed to examine this potential link included a small patient population and has shown mixed results. Because of the time it takes for dementia to develop, the researchers said it is unclear whether folate deficiency is actually a result of pre-clinical dementia instead of its cause.

To explore this issue further, the investigators examined a large national sample of older adults to determine whether serum folate deficiency is associated with the risks of incident dementia and death from any cause, as well as to evaluate the possible role of reverse causation.

The sample included medical records from 27,188 people between 60 and 75 years of age served by a national health care provider in Israel. None of the participants had pre-existing dementia for at least 10 years prior to when blood folate level checks began in 2013. Individuals were monitored through the end of 2017 for a diagnosis of dementia or death.

Approximately 13% (3418 participants) of the study population were folate deficient, which was defined as levels below 4.4 ng/ml. Folate deficiency was linked to a substantially greater risk of both dementia and death from any cause, according to the study.

Among folate deficient individuals, the incidence of dementia was an estimated 7.96 per 10,000 person years, whereas death from any cause was an estimated 19.20 per 10,000 person years. Among individuals who were not folate deficient, estimated dementia incidence was 4.24 per 10,000 person years and death from any cause was 5.36 per 10,000 person years.

Among individuals with folate deficiency, rates of dementia were approximately 3.5% and death from any cause was approximately 8% compared with dementia rates of approximately 3% and death from any cause rates of approximately 4% among individuals who were not folate deficient.

After accounting for factors that could influence the findings, such as co-existing diabetes, depression, cognitive decline, vitamin B12 deficiency, smoking, and folic acid supplement use, individuals who were folate deficient were found to be 68% more likely to be diagnosed with dementia and nearly 3 times as likely to die from any cause, according to the study.

The results of the observational study were not found to significantly weaken upon further examination; however, when stratified by the length of the monitoring period, the investigators noted that reverse causation could not be ruled out.

However, folate deficiency could potentially impact homocysteine levels, thereby affecting the vascular risk of dementia, and/or compromising the DNA repair of neurons, which leaves them vulnerable to oxidative damage. This, in turn, could potentially hasten the aging and damage of brain cells, according to the investigators.

“Serum concentrations of folate may function as a biomarker used to modify the risks of dementia and mortality in old age,” they wrote in the study. “The implications for public health policy appear to be to reliably monitor serum concentrations of folate in older adults and treat deficiency for preventative measures and/or as part of implemented therapeutic strategies while regularly reviewing patients’ clinical outcomes.”


Low blood folate may be linked to heightened dementia and death risks in older people. EurekAlert. [news release]. March 15, 2022.

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