Abstract

Prior observational studies have suggested correlations between saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) with cognitive function. However, causal relationships remains unclear. We assessed the causal impact of two SFAs (palmitic acid [PA] and stearic acid [SA]) and two MUFAs (oleic acid [OA] and palmitoleic acid [POA]) on cognitive function-related traits, and dementia-related traits by univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) analyses. UVMR indicated β of 0.060 (P = 4.05E-06) for cognitive performance score and 0.066 (P = 4.21E-04) for fluid intelligence per standard deviation (SD) increase in OA level. MVMR indicated: (i) β of -0.608 (P = 8.37E-05) for fluid intelligence score per SD increase in POA; (ii) β of 0.074 (P = 0.018) for fluid intelligence score per SD increase in OA; (iii) β of 0.029 (P = 0.033) for number of incorrect matches in round per SD increase in PA; and (iv) β of 0.039 (P = 0.032) for number of incorrect matches in round per SD increase in SA. In addition, a secondary MVMR analysis after excluding the effect of polyunsaturated fatty acids suggested that: (i) β of -0.043 (P = 1.97E-02) for cognitive performance score per SD increase in PA and (ii) β of -0.079 (P = 1.79E-03) for cognitive performance score per SD increase in SA. Overall, UVMR and MVMR suggest that OA may be beneficial for cognitive function, while POA, PA, and SA may have detrimental effects on cognitive function.

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