Lotte Truin1, Simone Eussen2, Stine Ulven3, Tahreem Ghazal Siddiqui3, Thomas Olsen4, Sebastian Köhler5, Marleen van Greevenbroek1.
1Department of Internal Medicine, Maastricht University, Maastricht, Netherlands, 2Department of Epidemiology, Maastricht University, Maastricht, Netherlands, 3Department of Nutrition, University of Oslo, Oslo, Norway, 4Department of Forensic Sciences, Oslo University Hospital, Oslo, Norway, 5Alzheimer Center Limburg, Maastricht University, Maastricht, Netherlands.
Background: Elevated plasma homocysteine, reflecting low B-vitamin status, and lower plasma docosahexaenoic acid (DHA; an omega-3 fatty acid) levels have been associated with poorer cognition, and emerging evidence suggests a synergistic interaction between B-vitamins and DHA. People with type 2 diabetes mellitus (T2DM) are at increased risk of cognitive decline, making modifiable nutritional targets particularly relevant in this group. This study examined the interaction between plasma homocysteine and DHA on cognition in the Dutch population-based cohort The Maastricht Study, focusing on differences by T2DM status.
Methods: Cross-sectional data were used from The Maastricht Study (n = 1,092, 59.8 ± 7.9 years, 50.0% women). Plasma homocysteine levels were measured by liquid chromatography (LC) tandem mass spectrometry (MS) (LC/MS-MS) and plasma DHA levels by nuclear magnetic resonance (NMR) spectroscopy. Cognitive functioning was tested across three domains: verbal memory, information processing speed, and executive functioning and attention. Cognitive impairment was defined as 1.5 SD below the norm for age, sex and education in any domain. Multiple linear and binary logistic regression analyses were used, adjusted for demographic, somatic and lifestyle factors, and prespecified stratified by T2DM. A p-value < 0.1 was considered significant for interaction terms.
Results: A significant interaction between homocysteine and DHA in their relation to cognitive functioning indicated that at lower homocysteine concentrations, higher DHA was related to better cognitive functioning (pinteraction = 0.019) and lower odds of cognitive impairment (pinteraction = 0.050). T2DM-stratified analyses revealed this interaction was significant only in participants with T2DM (cognitive functioning: pinteraction = 0.012; cognitive impairment: pinteraction = 0.094). Neither homocysteine nor DHA showed independent associations with cognitive outcomes.
Conclusion: These preliminary findings suggest that DHA may benefit cognition when homocysteine is low and possibly more so in people with T2DM, although this requires confirmation. Given that nutritional factors such as B-vitamins and DHA are modifiable, these may represent potential targets for dementia risk reduction in this high-risk group.