The Effects of Added Sugar Intake on Brain Blood Flow and Hippocampal Function in Midlife Adults

Aging is the primary risk factor for Alzheimer's disease (AD) which is the most common form of dementia and among the fastest growing causes of morbidity and mortality in the United States. The risk factors for AD emerge during midlife and are similar to cardiovascular and cerebrovascular diseases. The impact of midlife peripheral vascular changes on cardiovascular risk are worsened by poor lifestyle habits, including eating a diet that contains a lot of added sugars (defined as all caloric sweeteners added to food during processing or preparation). One effect of eating a high added sugar diet is an elevation in blood triglycerides (TGs), which impairs blood vessel function by causing inflammation; however, it is not known whether eating a lot of added sugars affects the blood vessels in the brain. The purpose of this project is to determine if there is a link between added sugar intake and brain health in midlife adults. Our hypothesis is that eating excess added sugar impairs the structure and function of an area of the brain called the hippocampus by increasing plasma TGs and systemic inflammation. To test this, we will have people eat a high and low sugar diet for 10 days each (in a random order) and test how each diet affects their blood vessel function, the structure of their hippocampus, and their memory performance. We expect to show that eating a diet that contains a lot of added sugars worsens brain health compared to a diet that contains few added sugars. The data generated from this project will help us better understand risk factors for dementia and will be used to support a future grant proposal to the National Institutes of Health aimed at lowering added sugar intake in mid-life adults and individuals with mild cognitive impairment.

Inclusion criteria

• ability to provide informed consent;
• men and postmenopausal women aged 50-64 years;
• habitual intake of added sugars ≤15% of total calories;
• systolic BP < 130 mmHg; diastolic BP < 90 mmHg;
• body mass index (BMI) <30 kg/m2 and % body fat < 25% for men and < 33% for women;
• fasting triglycerides < 200 mg/dl (< 2.3 mmol/L);
• LDL cholesterol <160 mg/dl (4.14 mmol/L);
• fasting plasma glucose <126 mg/dl (<7.0 mmol/L) and hemoglobin A1C < 6.5% at screening;
• weight stable in the prior 6 months (≤ 2 kg weight change);
• blood chemistries indicative of normal liver enzymes and renal function (estimated glomerular filtration rate using the Modification of Diet in Renal Disease (MDRD) prediction equation must be >60 ml/min/1.73 m^2).

Exclusion criteria

• current use of medications or supplements known to lower blood triglycerides or cholesterol (e.g., fibrates, statins, high dose niacin, high dose omega-3 supplement);
• chronic clinical diseases (e.g., coronary artery/peripheral artery/cerebrovascular diseases, heart failure, diabetes, chronic kidney disease requiring dialysis, neurological or autoimmune conditions affecting cognition (e.g. Alzheimer's disease or other form of dementia, Parkinson's disease, epilepsy, multiple sclerosis, large vessel infarct);
• major psychiatric disorder (e.g. schizophrenia, bipolar disorder);
• major depressive disorder (PHQ-9 ≥ 10);
• current or past (i.e., last 3 months) use of anti-hypertensive or other cardiovascular-acting medications known to influence vascular function and/or arterial stiffness;
• current medication use likely to affect central nervous system (CNS) functions (e.g. long active benzodiazepines);
• concussion within last 2 years and ≥ 3 lifetime concussions;
• heavy alcohol consumption (defined by the Centers for Disease Control and Prevention and United States Department of Agriculture as ≥8 drinks/week for women and ≥15 drinks/week for men).
• claustrophobia, metal implants, pacemaker or other factors affecting feasibility and/or safety of MRI scanning;
• recent major change in health status within previous 6 months (i.e., surgery, significant infection or illness);
• current smoking within the past 3 months;
• High degree of physical activity as defined by ≥ 25 leisure metabolic equivalent (MET)-hours/week, within the past 3 months.