24 March 2022

Watch out for folates!

XX2 century

Low levels of folic acid in the blood of the elderly may be associated with an increased risk of dementia and death from any cause. Such conclusions are made by the authors of a study published in the journal Evidence Based Mental Health (Rotstein et al., Serum folate deficiency and the risks of dementia and all-cause mortality: a national study of old age).

It is useful for elderly people to regularly monitor and, if necessary, adjust the level of folic acid in the blood. This is important because this indicator tends to decrease with age, and, according to researchers, every fifth elderly person is deficient in folic acid. At the same time, the data available to date indicate that folic acid deficiency affects cognitive abilities and the transmission of nerve impulses in the brain, which makes it a possible risk factor for dementia.

However, few studies that have considered this issue before have been conducted on a small number of participants and have shown mixed results.

In addition, it is difficult to rule out an inverse causal relationship, in which folic acid deficiency may not be the cause of dementia, but the consequence of some other processes that cause and accompany its development.

Therefore, the authors of the recent study wanted to investigate whether a deficiency of folic acid in the blood serum could be associated with the risk of dementia and death from any cause, in a large sample of elderly people. They also tried to clarify whether there is an inverse causal relationship here.

The researchers relied on the medical records of 27,188 people served by one national health care provider in Israel. All participants were between the ages of 60 and 75 and had not previously been diagnosed with dementia for at least 10 years before blood folic acid tests began in 2013.

Records in medical records were monitored for the diagnosis of dementia until the end of 2017 (or until the death of the patient, if it happened earlier).

About 3,418 (slightly less than 13%) participants had a deficiency of folic acid in the blood — below 4.4 ng/ml. Folic acid deficiency has been linked to a significantly increased risk of both dementia and death from any cause.

Among those with folic acid deficiency, the incidence of dementia was estimated at 7.96 cases per 10,000 person-years, while death from any cause was estimated at 19.2 cases per 10,000 person-years.

Compare with the situation among those who did not have folic acid deficiency: 4.24 cases of dementia and 5.36 cases of death from any cause per 10,000 person-years.

After taking into account various factors that can have one or another effect on the development of dementia and/or cause death (or, conversely, delay it), including concomitant diabetes, depression, vitamin B12 deficiency, smoking and the use of folic acid supplements, the probability of diagnosing dementia in people with folic acid deficiency was 68% higher and the probability of death from any cause is almost three times higher.

Further analysis did not significantly weaken the observed associations, however, it was not possible to statistically reliably exclude an inverse causal relationship.

The authors note that the study is observational and, by virtue of this, cannot establish the cause of dementia, especially given the potential role of reverse causation.

But it is quite possible, they note, that folic acid deficiency affects homocysteine levels and, therefore, may be the cause or one of the causes of vascular risk of dementia. Also, a lack of folic acid can induce processes that prevent DNA repair of neurons, making them vulnerable to oxidative damage, which, in turn, accelerates aging and damage to brain cells.

The researchers believe that the concentration of folic acid in the blood serum can serve as a biomarker of the risks of dementia and mortality in old age, and add that older people should be regularly checked for deficiency of this substance.

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