Differential Effects of Meal Challenges on Cognition, Metabolism, and Biomarkers for Apolipoprotein E ɛ4 Carriers and Adults with Mild Cognitive Impairment.

BACKGROUND: High intake of saturated fat (SF) and glycemic index (GI) foods is a risk factor for sporadic Alzheimer's disease. Meal challenges may elucidate mechanisms that contribute to this risk, enabling development of targeted interventions. OBJECTIVE: To assess cognitive and metabolic changes after a meal high in SF and GI calories (HIGH) versus a meal low in these macronutrients (LOW) in older adults with and without cognitive impairment, and with and without the apolipoprotein E4 risk factor. METHODS: 46 adults with either cognitive impairment (CI) or normal cognition (NC) ingested a LOW (25% total fat, 7% SF, GI <55) and a HIGH meal (50% total fat, 25% SF, GI >70) in a blinded random fashion. Participants then underwent cognitive testing and blood sampling for metabolic and Alzheimer's disease biomarkers. Data were analyzed using repeated measures ANOVA and Spearman correlations. RESULTS: E4-adults with NC demonstrated lower delayed memory scores after the HIGH compared to the LOW meal, whereas normal E4+ and CI E4- groups had higher scores after the HIGH meal (ANOVA p = 0.03). These findings were associated with meal-induced changes in glucose (p = 0.05), insulin (p = 0.004), triglycerides (p <  0.01), and plasma Aß42 (p = 0.05). CONCLUSIONS: These preliminary data suggest that cognitive performance of adults without CI may worsen following high SF and sugar meals, whereas adults with CI or those at risk for CI due to E4 status may benefit acutely from such meals. Furthermore, plasma Aß was affected by meal type, suggesting a relationship between metabolic response and amyloid regulation.

Diet intervention and cerebrospinal fluid biomarkers in amnestic mild cognitive impairment.

OBJECTIVE: To compare the effects of a 4-week high-saturated fat/high-glycemic index (HIGH) diet with a low-saturated fat/low-glycemic index (LOW) diet on insulin and lipid metabolism, cerebrospinal fluid (CSF) markers of Alzheimer disease, and cognition for healthy adults and adults with amnestic mild cognitive impairment (aMCI). DESIGN: Randomized controlled trial. SETTING: Veterans Affairs Medical Center clinical research unit. PARTICIPANTS: Forty-nine older adults (20 healthy adults with a mean [SD] age of 69.3 [7.4] years and 29 adults with aMCI with a mean [SD] age of 67.6 [6.8] years). INTERVENTION: Participants received the HIGH diet (fat, 45% [saturated fat, > 25%]; carbohydrates, 35%-40% [glycemic index, > 70]; and protein, 15%-20%) or the LOW diet (fat, 25%; [saturated fat, < 7%]; carbohydrates, 55%-60% [glycemic index, < 55]; and protein, 15%-20%) for 4 weeks. Cognitive tests, an oral glucose tolerance test, and lumbar puncture were conducted at baseline and during the fourth week of the diet. MAIN OUTCOME MEASURES: The CSF concentrations of ß-amyloid (Aß42 and Aß40), tau protein, insulin, F2-isoprostanes, and apolipoprotein E, plasma lipids and insulin, and measures of cognition. RESULTS: For the aMCI group, the LOW diet increased CSF Aß42 concentrations, contrary to the pathologic pattern of lowered CSF Aß42 typically observed in Alzheimer disease. The LOW diet had the opposite effect for healthy adults, ie, decreasing CSF Aß42, whereas the HIGH diet increased CSF Aß42. The CSF apolipoprotein E concentration was increased by the LOW diet and decreased by the HIGH diet for both groups. For the aMCI group, the CSF insulin concentration increased with the LOW diet, but the HIGH diet lowered the CSF insulin concentration for healthy adults. The HIGH diet increased and the LOW diet decreased plasma lipids, insulin, and CSF F2-isoprostane concentrations. Delayed visual memory improved for both groups after completion of 4 weeks of the LOW diet. CONCLUSION: Our results suggest that diet may be a powerful environmental factor that modulates Alzheimer disease risk through its effects on central nervous system concentrations of Aß42, lipoproteins, oxidative stress, and insulin.

Statin users without an APOE-epsilon4 allele have increased insulin resistance.

The present study examined the relationships among statin use, APOE genotype, and insulin resistance as measured by the homeostasis model assessment of insulin resistance (HOMA-IR) in healthy older adults. APOE epsilon4- (i.e., not having an epsilon4 allele) statin users had higher HOMA-IR values compared with epsilon4+/statin users (p=0.0169), and with non-users who were epsilon4- (p=0.0003) or epsilon4+ (p=0.0006). These results suggest that statin use may modulate insulin levels for individuals without an APOE epsilon4 allele.