Effects of Functional Oils on Obesity With Mild Cognitive Impairment

Obesity is a significant risk factor for the development of cognitive impairment, making precise nutritional interventions a vital strategy for preventing and managing this condition. Based on an established cohort, this randomized controlled trial aims to evaluate the efficacy of substituting regular dietary oil with functional diacylglycerol (DAG) oil in obese patients with MCI.

The study will analyze changes in overall cognitive function, body composition, and dietary quality before and after the 6-month intervention. Furthermore, the study will explore the underlying mechanisms by analyzing biological samples (blood and feces) for alterations in lipid metabolites, gut microbiota composition, inflammatory cytokines, and specific markers of white adipose tissue browning. The findings will help determine the therapeutic potential of DAG oil in regulating lipid metabolism and delaying cognitive decline.

• Rapeseed Oil (RSO) (Dietary supplement), also known as Conventional rapeseed oil: A commercially available conventional rapeseed oil for daily household cooking use, containing diacylglycerol (DAG) only at the trace level naturally occurring in regular vegetable oil.
• Diacylglycerol Oil (DAG Oil) (Dietary supplement), also known as Rapeseed oil-based DAG oil: A rapeseed oil-based functional oil produced via lipase-catalyzed enzymatic conversion, with a diacylglycerol content ≥40% (national standard requirement), for daily household cooking use in place of conventional cooking oil.

Primary outcomes

• Change From Baseline in Cognitive Function [Baseline and 6 months]: Change from baseline in cognitive function assessed by the Montreal Cognitive Assessment (MoCA), which evaluates visuospatial/executive function, naming, memory, attention, language, abstraction, delayed recall, and orientation. Total score ranges from 0 to 30, with higher scores indicating better cognitive function.
• Change From Baseline in Body Weight [Baseline and 6 months]: Change from baseline in body weight (kg) measured by bioelectrical impedance analysis (InBody body composition analyzer).
• Change From Baseline in Body Fat Percentage [Baseline and 6 months]: Change from baseline in body fat percentage measured by bioelectrical impedance analysis (InBody body composition analyzer).

Secondary outcomes

• Change From Baseline in Visceral Fat Area [Baseline and 6 months]: Change from baseline in visceral fat area measured by bioelectrical impedance analysis (InBody body composition analyzer).
• Change From Baseline in Serum Lipid Concentrations [Baseline and 6 months]: Change from baseline in serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), measured by automated biochemical analyzer.
• Change in Gut Microbiota Composition and Metabolites [Baseline and 6 months]: Change from baseline in fecal gut microbiota composition, alpha/beta diversity, and microbial abundance assessed by 16S ribosomal RNA sequencing, and in microbial metabolites including short-chain fatty acids (e.g., butyrate) assessed by untargeted metabolomics.

Sex: All, ages: 45 Years to 75 Years

Inclusion Criteria:

* Meets the diagnostic criteria for obesity combined with mild cognitive impairment (MCI) (obesity: BMI ≥28.0 kg/m\^2 per the 2022 Chinese Expert Consensus on Obesity Prevention and Treatment; MCI: Montreal Cognitive Assessment \[MoCA\] score below the education-adjusted cutoff, confirmed by a neurologist)
* Aged 45 to 75 years
* Has not been on a diet or has discontinued dieting for at least 3 months, and has not taken fish oil or similar supplements, or is willing to discontinue such supplements for 3 months prior to the intervention
* Able to accept and consume DAG oil as part of daily diet
* Voluntarily agrees to participate and signs the informed consent form

Exclusion Criteria:

* History of neuropsychiatric disorders such as stroke, epilepsy, or schizophrenia
* Cognitive impairment attributable to depression, thyroid disease, traumatic brain injury, or drug- or alcohol-induced intoxication
* History of cerebrovascular disease, or cognitive decline due to severe impairment of cardiac, hepatic, pulmonary, or renal function
* Use of antibiotics, health products, or nutritional supplements within 2 weeks prior to fecal sample collection; or gastrointestinal symptoms (trauma, inflammation/infection, abdominal pain, diarrhea, or constipation) or vaccination history within the same period

• Rong Xiao, PhD, Principal investigator, Capital Medical University