Risk Factors for “brain aging”
1. Obesity
2. Type 2 Diabetes
3. Cardiovascular Disease
4. High Cholesterol
All have been linked to INSULIN RESISTANCE
Kalaria RN (2010) Vascular basis for brain degeneration: faltering controls and risk factors for dementia. Nutrition Reviews. 68:S74-S87
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).
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
Alzheimer’s Disease?
Observation
The prevalence of nutrition related ailments has
dramatically increased. The prevalence of
Alzheimer’s Disease has dramatically increased.
Can we manipulate diet to improve memory and
increase positive outcomes in the elder years?
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 Alzheimer’s Disease, and
consequently, a negative effect on memory.
Macronutrient pattern associated with
T2DM and IR
•
•
•
45% FAT (25% Saturated)
35-40% CARBOHYDRATES
15-20% PROTEIN
Normal Memory or Amnestic
Mild Cognitive Impairment
(aMCI)
•
•
•
25% FAT (<7% Saturated)
55-60% CARBOHYDRATES
15-20% PROTEIN
Normal Memory or Amnestic
Mild Cognitive Impairment
(aMCI)
Screening Visit
o Safety Blood Draw
o Memory Evaluation
o Physical Exam
3 Visits
• OGTT
• Spinal Tap
• Memory test
Eligible
4 WEEKS OF FREE
MEALS
Fill out 3-Day Food
Record to determine
isocaloric diet
3 Visits (during week 4)
• OGTT
• Spinal Tap
• Memory test
20 Normal Memory & 29 Impaired Memory
(n=49)
 Amyloid – beta (AB)
 Tau
 Insulin
 Apolipoprotein-E (ApoE)
 Helps to clear AB from the system
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 Alzheimer’s
Disease in the spinal fluid, the
fluid that surrounds the brain.
Results
• Changes in spinal fluid
– AB42
Implicated in Alzheimer’s as causing “plaques” in the brain, reducing brain function
Results
• Changes in spinal fluid
– ApoE
Helps with clearance of the AB protein that causes “plaques” in Alzheimer’s
Results
• Improved delayed memory on the LOW diet!
P<0.05
Conclusion
• Normal adults on the HIGH diet showed a
pattern that is theoretically similar to what
someone would look like on their way to
Alzheimer’s disease.
• Little was seen with MCI’s on the HIGH diet
– Already started the process of AD?
– More intensive intervention needed to worsen the
damage already done?
Conclusion
• LOW diet helped both groups
– Improved memory
– Less oxidative stress (isoprostanes)
– Less AD biomarkers
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.