Imbalance of formaldehyde metabolism may be one of the various pathomechanisms involved in the onset and progression of age-related cognitive impairment. Provided evidence demonstrated that having been or being occupationally exposed to exogenous formaldehyde can affect cognitive performance. Elderly patients with the postoperative cognitive dysfunction (POCD) suffered from high levels of endogenous formaldehyde after their surgeries, but those without POCD did not. Monkeys fed with low concentration of methanol suffered from loss of working memory. Levels of hippocampal formaldehyde from the patient autopsy are significantly higher than those of age-matched normal controls. Using a double-blind experiment, the correlation between endogenous (urine) formaldehyde and general cognitive abilities was estimated in a community-based elderly population (n = 604). Urine formaldehyde levels were inversely correlated with the Montreal Cognitive Assessment (MoCA) scores of elderly participants. The concentration varied with demographic features: higher odds of a high formaldehyde level occurred among the less educated elderly population. Educational levels are strikingly correlated with the concentration of endogenous formaldehyde for the elderly living in local communities in Beijing. The epidemiological investigation showed that the average concentration of urine formaldehyde of the elderly increases with aging (>75 years old). In clinical study, the concentration of urine formaldehyde of Alzheimer’s patients is inversely correlated with their Mini-Mental State Examination (MMSE) scores. Urine formaldehyde levels were significantly elevated in subjective cognitive decline (SCD) group, compared with cognitively normal controls (NC), objectively defined subtle cognitive decline (Obj-SCD) and mild cognitive impairment (MCI) groups, suggesting that urine formaldehyde could be used as a noninvasive biomarker for early diagnosis before objectively cognitive decline and differential diagnosis of Alzheimer’s disease (AD) at different stages. In distinguishing normal cognitive control from AD patients, the areas under the receiver operating characteristic curves (AUC) of urine formate was 0.797, better than some plasma biomarkers such as Aβ and P-Tau, and similar to that of plasma neurofilament light chain (NfL; AUC = 0.768). We would like to emphasize that employing urine levels of both formate and formaldehyde may improve the accuracy of using the plasma biomarkers to distinguish AD stages. Therefore, endogenous formaldehyde and formic acid could be employed as noninvasive biomarkers for detecting, diagnosing, distinguishing, and monitoring age-related cognitive impairment.

Cognitive Ability and Impairment Related to Formaldehyde

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发表日期：

2025年

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Rongqiao He

摘要

Imbalance of formaldehyde metabolism may be one of the various pathomechanisms involved in the onset and progression of age-related cognitive impairment. Provided evidence demonstrated that having been or being occupationally exposed to exogenous formaldehyde can affect cognitive performance. Elderly patients with the postoperative cognitive dysfunction (POCD) suffered from high levels of endogenous formaldehyde after their surgeries, but those without POCD did not. Monkeys fed with low concentration of methanol suffered from loss of working memory. Levels of hippocampal formaldehyde from the patient autopsy are significantly higher than those of age-matched normal controls. Using a double-blind experiment, the correlation between endogenous (urine) formaldehyde and general cognitive abilities was estimated in a community-based elderly population (n = 604). Urine formaldehyde levels were inversely correlated with the Montreal Cognitive Assessment (MoCA) scores of elderly participants. The concentration varied with demographic features: higher odds of a high formaldehyde level occurred among the less educated elderly population. Educational levels are strikingly correlated with the concentration of endogenous formaldehyde for the elderly living in local communities in Beijing. The epidemiological investigation showed that the average concentration of urine formaldehyde of the elderly increases with aging (>75 years old). In clinical study, the concentration of urine formaldehyde of Alzheimer’s patients is inversely correlated with their Mini-Mental State Examination (MMSE) scores. Urine formaldehyde levels were significantly elevated in subjective cognitive decline (SCD) group, compared with cognitively normal controls (NC), objectively defined subtle cognitive decline (Obj-SCD) and mild cognitive impairment (MCI) groups, suggesting that urine formaldehyde could be used as a noninvasive biomarker for early diagnosis before objectively cognitive decline and differential diagnosis of Alzheimer’s disease (AD) at different stages. In distinguishing normal cognitive control from AD patients, the areas under the receiver operating characteristic curves (AUC) of urine formate was 0.797, better than some plasma biomarkers such as Aβ and P-Tau, and similar to that of plasma neurofilament light chain (NfL; AUC = 0.768). We would like to emphasize that employing urine levels of both formate and formaldehyde may improve the accuracy of using the plasma biomarkers to distinguish AD stages. Therefore, endogenous formaldehyde and formic acid could be employed as noninvasive biomarkers for detecting, diagnosing, distinguishing, and monitoring age-related cognitive impairment.