Observational studies have shown a controversial relationship between dietary fat intake and Alzheimer's disease, and the causal effects are unclear.

To assess the causal effects of total fat, saturated fat and polyunsaturated fat (PUF) intakes on the risk of Alzheimer's disease.

A two-sample Mendelian randomisation analysis was performed using genome-wide association study summary statistics on different types of fat intake from UK Biobank (n = 51 413) and on late-onset Alzheimer's disease (LOAD; 4282 cases, n = 307 112) and all forms of Alzheimer's disease (6281 cases, n = 309 154) from the FinnGen consortium. In addition, a multivariable Mendelian randomisation (MVMR) analysis was conducted to estimate the effects independent of carbohydrate and protein intakes.

Genetically predicted per standard deviation increase in the total fat and saturated fat intakes were associated with 44 and 38% higher risks of LOAD (total fat: odds ratio = 1.44, 95% CI 1.03–2.02; saturated fat: odds ratio = 1.38, 95% CI 1.002–1.90; P = 0.049). The associations remained significant in the MVMR analysis (total fat: odds ratio = 3.31, 95% CI 1.74–6.29; saturated fat: odds ratio = 2.04, 95% CI 1.16–3.59). Total fat and saturated fat intakes were associated with a higher risk of all forms of Alzheimer's disease in the MVMR analysis (total fat: odds ratio = 2.09, 95% CI 1.22–3.57; saturated fat: odds ratio = 1.60, 95% CI 1.01–2.52). The PUF intake was not associated with LOAD or all forms of Alzheimer's disease.

This study indicated that total dietary fat intake, especially saturated fat, contributed to the risk of Alzheimer's disease, and the effects were independent of other nutrients. These findings informed prevention strategies and management for Alzheimer's disease directly towards reducing dietary saturated fat intake.

观察性研究表明，膳食脂肪摄入量与阿尔茨海默病之间存在争议关系，其因果效应尚不清楚。

评估总脂肪、饱和脂肪和多不饱和脂肪 （PUF） 摄入量对阿尔茨海默病风险的因果影响。

使用来自英国生物样本库 （n = 51 413） 和晚发性阿尔茨海默病 （LOAD;4282 例，n = 307 112） 和所有形式的阿尔茨海默病 （6281 例，n = 309 154） 的全基因组关联研究摘要统计数据进行双样本孟德尔随机化分析来自 FinnGen 财团。此外，还进行了多变量孟德尔随机化 （MVMR） 分析，以估计独立于碳水化合物和蛋白质摄入量的影响。

遗传预测总脂肪和饱和脂肪摄入量的每个标准差增加与 LOAD 风险增加 44% 和 38% 相关（总脂肪：比值比 = 1.44,95% CI 1.03-2.02;饱和脂肪：比值比 = 1.38,95% CI 1.002-1.90;P = 0.049）。在 MVMR 分析中，相关性仍然显著（总脂肪：比值比 = 3.31,95% CI 1.74-6.29;饱和脂肪：比值比 = 2.04,95% CI 1.16-3.59）。在 MVMR 分析中，总脂肪和饱和脂肪摄入量与各种形式的阿尔茨海默病风险较高相关（总脂肪：比值比 = 2.09,95% CI 1.22-3.57;饱和脂肪：比值比 = 1.60,95% CI 1.01-2.52）。PUF 摄入量与 LOAD 或所有形式的阿尔茨海默病无关。

这项研究表明，膳食脂肪总摄入量，尤其是饱和脂肪，会增加患阿尔茨海默病的风险，并且其影响独立于其他营养素。这些发现为阿尔茨海默病的预防策略和管理提供了信息，直接减少了膳食饱和脂肪的摄入量。