Alzheimer’s disease (AD) is the most widespread neurological disease among the elderly, causing dementia.

The predominant clinical signs of AD are progressive memory loss and worsening of other cognitive abilities, while extraneuronal neuritic plaques, intraneuronal neurofibrillary tangles, and neuronal death are the neuropathological hallmarks.

Early-onset AD (EOAD) and late-onset AD (LOAD) are the two types of Alzheimer’s disease. LOAD (onset after age 65) accounts for 95 percent or more of AD cases as compared to EOAD (onset before age 65). With the world’s rapidly aging population, more than 50 million people were living with dementia in 2019, with the figure expected to rise to 152 million by 2050. 

Alzheimer’s disease is responsible for 60–80 percent of dementia cases. Because there is no effective cure for Alzheimer’s disease, preventing or delaying its onset is a top concern.

Dietary patterns and nutrition are increasingly being linked to the etiology of Alzheimer’s disease. As a result, a good diet and nutrient balance, especially vitamins, are critical in the prevention of Alzheimer’s disease.

Marginal vitamin A shortage, for example, increases Aβ generation, which is a primary component of neuritic plaques, as well as cognitive deficiencies. A growing body of research suggests that folate, an essential vitamin, plays a key role in the development of Alzheimer’s disease.

The typical range of plasma/serum folate concentrations is between 13.5 and 45.3 nmol/L. Folate deficiency are defined as plasma/serum folate levels of less than 6.8 nmol/L and more than 13.5 nmol/L, respectively.

Previous research has linked low folate levels to not only certain areas of cognitive functioning, such as episodic recall and recognition, but also to all types of dementia, including vascular dementia and Alzheimer’s disease.

Supplementing with folate/folic acid also helps to improve cognitive functioning in elderly people and people with mild cognitive impairment.

Furthermore, a lack of folate leads to an increase in tau phosphorylation, which is the main component of neurofibrillary tangles. However, no meta-analysis study has been conducted to evaluate the link between folate deficiency and the risk of Alzheimer’s disease, as well as the beneficial effect of adequate folate intake in the prevention of AD.

The goal of this study is to look into the role of folate deficiency, as well as the beneficial effect of adequate folate intake in the prevention, as well as to update the relationship between plasma/serum folate levels and AD.

A total of 3,672 studies (including 3,370 in English and 302 in Chinese) in the general population were initially identified from the Meta-analysis Of Observational Studies in Epidemiology (MOOSE).

Findings from Asia and Europe studies

Low levels of Folate Is Associated With the Risk for Dementia And Alzheimer’s Disease

The meta-analysis includes fifteen case-control studies with 971 AD patients and 1,059 controls. A total of eight studies were undertaken in European countries and seven in Asian countries.

According to the findings, folate deficiency is linked to an increased risk of Alzheimer’s disease. It was reported that folate deficiency could raise the risk of Alzheimer’s disease.

Findings from Canada and Europe studies

Low Blood folate Increases the Risk for AD and Dementia

The meta-analysis comprised five investigations from 2001 to 2017. The number of people in the sample ranged from 190 to 816. Three investigations were undertaken in Italy, Sweden, and Switzerland, with two in Canada and three in Italy, Sweden, and Switzerland, respectively.

The folate levels of participants in all cohort studies were separated into two groups: folate deficiency and normal, with folate levels of <13.5 and ≥13.5 nmol/L, respectively. The combined RR for folate deficiency/possible deficiency was 1.88 (95 percent CI: 1.20, 2.57).

According to the findings, a low folate level raises the risk of Alzheimer’s disease.

Findings from North America

Sufficient Intake of Folate Reduces the Risk for Dementia and Alzheimer’s Disease

The meta-analysis comprised eleven cohort studies published between 2005 and 2009. The number of people in the sample ranged from 192 to 727. All of the research was done in the United States.

The meta-analysis included all 11 cohort studies to look at the link between folate intake and Alzheimer’s disease in the elderly. The overall RR was 0.50. (95 percent CI: 0.25, 0.76). A daily intake of 400 μg of folate was used as the cut-off to distinguish the two subgroups because the recommended daily requirement of folate is 400 μg. The combined RR and HR were 1.15 (95 percent CI: 0.28, 2.02) and 0.9 (95 percent CI: 0.6, 1.3), respectively, when the daily folate consumption was 400 μg. The combined RR and HR were 0.44 (95 percent CI: 0.18, 0.71) and 0.76 (95 percent CI: 0.52, 0.99), respectively, when daily folate intake was equivalent to or greater than 400 μg.

It was shown that adequate folate consumption (i.e., ≥400 μg/d) is a preventive factor for Alzheimer’s disease, lowering the risk of the disease considerably.

Source: 10.3389/fnins.2021.661198

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