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

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% atscreening;

• weight stable in the prior 6 months (≤ 2 kg weight change);

• blood chemistries indicative of normal liver enzymes and renal function (estimatedglomerular 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 orcholesterol (e.g., fibrates, statins, high dose niacin, high dose omega-3supplement);

• chronic clinical diseases (e.g., coronary artery/peripheral artery/cerebrovasculardiseases, heart failure, diabetes, chronic kidney disease requiring dialysis,neurological or autoimmune conditions affecting cognition (e.g. Alzheimer's diseaseor other form of dementia, Parkinson's disease, epilepsy, multiple sclerosis, largevessel 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 othercardiovascular-acting medications known to influence vascular function and/orarterial 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 Preventionand United States Department of Agriculture as ≥8 drinks/week for women and ≥15drinks/week for men).

• claustrophobia, metal implants, pacemaker or other factors affecting feasibilityand/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.