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

Study Overview
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Brief Summary
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This study will focus on improving brain health through dietary modification of added sugars in middle aged adults (50- 64 years old). Participants will be fed two 10-day diets (one diet containing 5% of total energy from added sugars and one diet containing 25% of total energy from added sugars) and examine blood vessel function, hippocampus structure using a MRI, and memory performance.

Detailed Description
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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.

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

Conditions
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Aging, Healthy Diet

Intervention / Treatment
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* Other: Low Added Sugar Diet
* Other: High Added Sugar Diet


Participation Criteria
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Eligibility Criteria
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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 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 CNS functions (e.g. long active benzodiazepines); concussion within last 2 years and ≥ 3 lifetime concussions; heavy alcohol consumption (defined by the CDC and USDA 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 MET-hours/week, within the past 3 months.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: A single-blind, randomized-crossover, controlled feeding study. Participants will be provided with 10-days each of a research diet containing low sugar (LS; 5% of energy from added sugars) vs. high sugar (HS; 25% of energy from added sugars) in a random order, separated by a 2-week washout.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Added Sugar Diet<br>Subjects will be provided with a diet that is low in added sugars. | Other: Low Added Sugar Diet<br>* Consumption of 10 days of a diet low in added sugars (5% of total caloric intake)<br>|
| Experimental: High Added Sugar Diet<br>Subjects will be provided with a diet that is high in added sugars. | Other: High Added Sugar Diet<br>* Consumption of 10 days of a diet high in added sugars (25% of total caloric intake)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in systolic blood pressure at the end of each diet | 24-hour ambulatory blood pressure | Over 1.5 months. Once at baseline and again at the end of each 10 day diet (low and high added sugar), separated by a 2 week washout period | 
| Change from baseline in arterial compliance at the end of each diet | Carotid artery compliance will be calculated as the change in cross sectional area of the carotid artery for a given change in carotid pressure using transcutaneous tonometry coupled with duplex ultrasound | Over 1.5 months. Once at baseline and again at the end of each 10 day diet (low and high added sugar), separated by a 2 week washout period | 
| Change from baseline in cerebrovascular reactivity at the end of each diet | Total cerebral perfusion measured using pseudo-continuous arterial spin labeling in response to 3-minutes of hypercapnia (+9 mmHg increase in PETCO2) | Over 1.5 months. Once at baseline and again at the end of each 10 day diet (low and high added sugar), separated by a 2 week washout period | 
| Change from baseline in hippocampal stiffness at the end of each diet | Magnetic Resonance Imaging (MRI) of the brain to collect structural T1- and T2-weighted images | Over 1.5 months. Once at baseline and again at the end of each 10 day diet (low and high added sugar), separated by a 2 week washout period | 
| Change from baseline in hippocampal damping ratio at the end of each diet | Magnetic Resonance Elastography (MRE) of the brain to collect microstructural integrity while the head will be vibrated using the resoundant acoustic driver system | Over 1.5 months. Once at baseline and again at the end of each 10 day diet (low and high added sugar), separated by a 2 week washout period | 
| Change from baseline in delayed recall memory (e.g.words) at the end of each diet | Administration of the Hopkins Verbal Learning Test (HVLT-R) | Over 1.5 months. Once at baseline and again at the end of each 10 day diet (low and high added sugar), separated by a 2 week washout period | 
| Change from baseline in delayed recall memory (e.g. pictures) at the end of each diet | Administration of the Brief Visuospatial Memory Test (BVMT-R) | Over 1.5 months. Once at baseline and again at the end of each 10 day diet (low and high added sugar), separated by a 2 week washout period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in pulse wave velocity at the end of each diet | Pulse wave velocity measured using transcutaneous tonometry | Over 1.5 months. Once at baseline and again at the end of each 10 day diet (low and high added sugar), separated by a 2 week washout period | 
| Change from baseline in cognitive domain (e.g. processing speed) at the end of each diet | Administration of the NIH Toolbox Pattern Comparison test | Over 1.5 months. Once at baseline and again at the end of each 10 day diet (low and high added sugar), separated by a 2 week washout period | 
| Change from baseline in cognitive domain (e.g. inhibition) at the end of each diet | Administration of the NIH Toolbox Flanker test | Over 1.5 months. Once at baseline and again at the end of each 10 day diet (low and high added sugar), separated by a 2 week washout period | 
| Change from baseline in lipid profile at the end of each diet | Blood biomarkers of lipid profile (e.g. cholesterol, triglycerides, HDL, LDL, and VLDL) | Over 1.5 months. Once at baseline and again at the end of each 10 day diet (low and high added sugar), separated by a 2 week washout period | 
| Change from baseline in inflammation at the end of each diet | Blood biomarkers of inflammation (e.g. cytokines and interleukins) | Over 1.5 months. Once at baseline and again at the end of each 10 day diet (low and high added sugar), separated by a 2 week washout period | 
| Change from baseline in oxidative stress at the end of each diet | Blood biomarkers of oxidative stress (e.g. superoxide) | Over 1.5 months. Once at baseline and again at the end of each 10 day diet (low and high added sugar), separated by a 2 week washout period | 
| Change from baseline in sleep quality compared to each diet | Sleep quality will be continuously measured for 10 days using an Actiwatch. | Over 1.5 months. Once at baseline and again at the end of each 10 day diet (low and high added sugar), separated by a 2 week washout period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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added sugars, arterial stiffness, cerebrovascular function, cognitive function