Formaldehyde Exposure Linked to Cognitive Impairment

Occupational formaldehyde exposure was linked to cognitive deficits at relatively young ages in a French cohort study.

Adults ages 45 and older had a higher risk of global cognitive impairment if they had been exposed to formaldehyde at work (adjusted RR 1.17, 95% CI 1.11-1.23), reported Noemie Letellier, PhD, of University of Montpellier in France, and co-authors.

This higher risk of impairment spanned all cognitive domains. Both high exposure duration and high lifetime dose were associated with worse cognition, with duration showing a dose-effect relationship, the researchers wrote in Neurology.

“Despite the restrictions on the use of formaldehyde due to better knowledge of its toxicity, especially its carcinogenic effect, formaldehyde is still widely used in many sectors,” Letellier told MedPage Today.

“The effect of formaldehyde on the brain has been previously shown mainly in animal experiments, but very few studies have been done on humans,” she added.

Formaldehyde is classified as carcinogenic for humans by the International Agency for Research on Cancer. Occupational exposure has been linked to leukemia in some studies.

Letellier and colleagues looked at 75,322 people in France in the CONSTANCES cohort, of whom 6,047 had been exposed to formaldehyde during their working life. Agricultural and self-employed workers were excluded. Participants exposed to formaldehyde had a median age of 57.5, and 68% were women.

Nurses, caregivers, and medical technicians represented more than half of the people exposed, Letellier noted.

“The vast majority of those exposed are workers in the care sector,” she said. In the hospital, activities that use formalin (an aqueous solution of formaldehyde) include tissue fixation in anatomy laboratories and biopsy departments; reagents in medical biology analysis laboratories; sterilization of the operating room, intensive care unit, and medical devices; and embalming.

The study measured lifetime formaldehyde exposure with a Job-Exposure Matrix (JEM), a tool that assessed occupational formaldehyde exposure from all job types in France from 1950 to 2018. The JEM provided indices for probability, intensity, and frequency of exposure.

Cognitive function was assessed by trained neuropsychologists who used a standardized battery of tests to evaluate global cognitive function, episodic verbal memory, language abilities, and executive functions. The French version of the Mini Mental State Examination (MMSE) was used to evaluate global cognitive function. Findings were adjusted for age, sex, education, income, solvent exposure, effort-reward imbalance, night-shift hours, and repetitive or noisy work.

Participants exposed to formaldehyde were more often exposed to night-shift work (52% vs 17% for those not exposed to formaldehyde), and to other solvents, repetitive work, and noisy work.

Workers exposed to formaldehyde for 22 years or longer had a 21% higher risk of global cognitive impairment than those never exposed (adjusted RR 1.21, 95% CI 1.11-1.32). Workers with the highest cumulative exposure to formaldehyde had a 19% greater risk of cognitive impairment compared with those unexposed (adjusted RR 1.19, 95% CI 1.09-1.28).

“Participants who were exposed in the past (i.e., exposure before 2001) had a lower risk of cognitive impairment compared with those recently exposed (i.e., exposure after 2002), suggesting a potential reversibility of the effect of formaldehyde exposure on cognitive performance, as shown in a previous work on occupational solvent exposure in the CONSTANCES cohort,” Letellier and co-authors noted.

“However, our findings also suggest that cognitive deficits associated with formaldehyde persist after occupational exposure, even for moderate lifetime exposure,” they wrote.

The study had several limitations, Letellier and colleagues acknowledged. It relied on a JEM, which may have nomenclature codes that grouped together heterogeneous occupations or activities with potentially different formaldehyde exposure assessments. It also did consider non-occupational formaldehyde exposure.

Findings should be confirmed in longitudinal analyses that track cognitive changes over time, the researchers said.