2. Insulin Resistance Inability of insulin to perform its normal functions which could lead to… – High blood sugar Cant be used by cells due to improper insulin function – Reduced glycogen synthesis in liver – Increased fatty acids in blood – And more! More problems occur as the years pass (previous slide).

3. Memory Wellness Program Interested in why memory changes as we get older How our body and brain use sugar and insulin Which risk factors may lead to Alzheimers Disease?

6. Observation The prevalence of nutrition related ailments has dramatically increased. The prevalence of Alzheimers Disease has dramatically increased. Can we manipulate diet to improve memory and increase positive outcomes in the elder years?

7. Hypothesis A low fat / low glycemic index diet will prove beneficial to brain function and a high fat / high glycemic index diet will have an effect on certain proteins and hormones associated with insulin resistance and Alzheimers Disease, and consequently, a negative effect on memory.

8. Macronutrient pattern associated with T2DM and IR 45% FAT (25% Saturated) 35-40% CARBOHYDRATES 15-20% PROTEIN 25% FAT (<7% Saturated) 55-60% CARBOHYDRATES 15-20% PROTEIN Normal Memory or Amnestic Mild Cognitive Impairment (aMCI)

9. Screening Visit o Safety Blood Draw o Memory Evaluation o Physical Exam Screening Visit o Safety Blood Draw o Memory Evaluation o Physical Exam Eligible Fill out 3-Day Food Record to determine isocaloric diet 3 Visits OGTT Spinal Tap Memory test 3 Visits OGTT Spinal Tap Memory test 4 WEEKS OF FREE MEALS 3 Visits (during week 4) OGTT Spinal Tap Memory test 3 Visits (during week 4) OGTT Spinal Tap Memory test 20 Normal Memory & 29 Impaired Memory (n=49)

11. Amyloid – beta (AB) Tau Insulin Apolipoprotein-E (ApoE) Helps to clear AB from the system

12. RESULTS Diet Intervention Modulated Insulin & Lipid Metabolism – High diet increased Insulin (AUC), Low diet reduced Insulin (AUC) – Adults with aMCI had a two-fold change in total cholesterol across diets! These changes were important and indicated that the diets worked allowing us to see how this would affect certain proteins and hormones associated with Alzheimers Disease in the spinal fluid, the fluid that surrounds the brain.

13. Results Changes in spinal fluid – AB42 Implicated in Alzheimers as causing plaques in the brain, reducing brain function

14. Results Changes in spinal fluid – ApoE Helps with clearance of the AB protein that causes plaques in Alzheimers

15. Results Improved delayed memory on the LOW diet! P<0.05

16. Conclusion Normal adults on the HIGH diet showed a pattern that is theoretically similar to what someone would look like on their way to Alzheimers disease. Little was seen with MCIs on the HIGH diet – Already started the process of AD? – More intensive intervention needed to worsen the damage already done?

17. Conclusion LOW diet helped both groups – Improved memory – Less oxidative stress (isoprostanes) – Less AD biomarkers

18. In the future Hifat/HiGI vs Lofat/LoGI vs Hifat/LoGI vs Lofat/HiGI – 10 blood draws over the course of 5 hours – Meal tolerance test Look at younger folks (45-65) with Pre-diabetes and Pre-Hypertension vs controls and combinations.