Low folate linked to risk of cognitive decline in later life – new TILDA study

Posted on: 14 January 2022

A new study from researchers at The Irish Longitudinal Study on Ageing (TILDA) at Trinity College Dublin has found strong links between low levels of folate (the natural form of the dietary supplement, folic acid) and accelerated cognitive decline.

The study, published in the European Journal of Clinical Nutrition, uses data from over 3,000 community dwelling participants aged 50 years and older in Ireland, and is the largest sample to date to investigate longitudinal associations of folate and cognitive function, using repeated assessments of cognitive tests.

The study examines older adults who provided blood samples of folate at Wave 1 of TILDA, with repeated measurements of cognitive function assessed over eight years. Researchers found that older persons with low folate faced a greater risk of poorer cognitive function overall over eight years, particularly evidenced in memory tests. TILDA’s study is the largest representative study of its kind, with the findings revealing important information for at-risk older adults, clinicians, public health stakeholders and policymakers alike.

Folate status in Ireland and risk of cognitive impairment

Dementia is a disease that affects 7% of the world’s population, and is a major cause of disability and death, while the risk of developing dementia greatly increases with age. Cognitive impairment is a known precursor to dementia, resulting in a deterioration in attention, executive function, learning and memory. Low folate is associated with an accelerated decline in cognitive function, and is an important marker for cognitive decline among older people.

Older adults in Ireland face a significant risk of folate deficiency with TILDA research showing that 1 in 7 in Ireland have low or deficient folate levels. Folate is important for the synthesis and repair of DNA, formation of healthy blood cells and other genetic material, as it is necessary for cells to divide. Deficiency causes anaemia and is associated with cardiovascular disease and certain cancers. Furthermore, low intakes of natural folates and folic acid and low blood status have been observed among all age groups in the Irish population. Low folate status is a modifiable risk factor for cognitive decline, and is a widespread issue for older adults in Ireland and countries where folic acid fortification is not mandated.

What are the key findings?

• The study finds that low folate was associated with an accelerated decline in overall cognitive function.
• The results are more pronounced for tests of episodic memory – memory being a sensitive indicator for early cognitive decline and mild cognitive impairment. The findings suggest that low folates may have differential relationships with specific cognitive domains, particularly with memory .
• Low folate may be a useful early marker of risk of accelerated cognitive decline.
• The study demonstrates that even among the relatively healthy and cognitively robust group surveyed, that low folate status predicts accelerated cognitive decline across several cognitive domains, over an 8-year time period.

Why does this matter?

Older people are at significant risk of folate deficiency and the result of this study clearly shows that low folate predicts the risk of accelerated cognitive decline. At the other end of the spectrum, deficiency of folate in early pregnancy can lead to neural tube defects (NTDs) such as spina bifida and anencephaly in new-born babies. Ireland has one the highest rates of NTDs in Europe. Almost 80 countries worldwide have introduced mandatory fortification of flour with folic acid, for the prevention of NTDs starting with the US in 1998. However, to date no country in Europe has implemented mandatory folic acid fortification. The results in this latest TILDA study further demonstrate that low folate status is of major concern in later life too, adding to the argument that the addition of folic acid to the food supply could be of benefit to young and old alike.

Lead author Deirdre O’Connor, Registered Nutritionist and TILDA researcher said:

These findings are hugely important and provide robust evidence to show low folate as a useful early indicator of accelerated cognitive decline in older people. It is crucial that we better understand how to identify the risks factors for cognitive decline and mitigate against them early on. We know that voluntary fortification with folic acid is ineffective for maintaining folate status in this population group. Despite growing support, Ireland remains on the fence with respect to mandatory fortification. We know that it is an effective population strategy if it is carefully established, controlled and monitored. Our study on this important Irish cohort of over 3,000 older individuals indicates that improving folate levels in the population may have positive health consequences for both young and old.

Professor Rose Anne Kenny, Principal Investigator of TILDA, said:

Currently more than 55 million people live with dementia worldwide, and there are nearly 10 million new cases every year. In Ireland, 64,000 people have dementia and this is expected to double over the next 25 years. Cognitive decline is an early stage of dementia. Our work now shows that low folate is a new risk factor for cognitive decline. Any new risk factor which we can change is an important discovery. Folate is an easily modified risk factor – both for individuals to ensure that they have adequate blood levels and for policy makers to now review the Irish policy of fortification. Examples are adding folate to all flour and breakfast cereals. Foods high in folate include spinach, kale, brussels sprouts, cabbage, broccoli, beans and legumes, yeast and beef extracts, oranges and orange juice, wheat bran and other whole grain foods, poultry, pork, shellfish and liver.

Some of the established risk factors for dementia are early detection and treatment of hypertension, high cholesterol, diabetes, hearing vision problems; management of life behaviours such as smoking, physical activity and obesity;  and social engagement, stress and sleep. Dementia is currently the seventh leading cause of death among all diseases and one of the major causes of disability and dependency among older people globally. This underscores the important impact of this study.

The paper is published in the European Journal of Clinical Nutrition , ‘Low folate predicts accelerated cognitive decline: 8-year follow-up of 3,140 older adults in Ireland’ can be found here: https://www.nature.com/articles/s41430-021-01057-3