Fatty Acid Modulation of Brain Function in Older Adults

In this crossover study, the investigtors will administer two experimental diets in a random order for one week, and each experimental diet will be preceded by a one-week, low fat control diet for a total four-week study period. The goal is to study how the fatty acid content of the diet affects brain functioning in healthy adults aged 65-75 years. One experimental diet will have a high palmitic acid (PA)/oleic acid (OA) ratio (HPA), typical of the North American diet. The other experimental diet will have a low PA/OA ratio (HOA), typical of the Mediterranean Diet. All allowed food and drink (except water) will be provided by the investigative team, and compliance will be enhanced by constant, intense dietary surveillance by a registered dietitian.

This study will examine how manipulating dietary fatty acids affects brain functioning in older adults. Prior studies have shown that there are behavioral changes that can be made to improve cognition in adults on an acute time scale including improving sleep and physical activity. Based on preclinical data and prior studies in humans the investigators propose that brain functioning also can be acutely improved with a reduction in dietary saturated fat. This approach will first be used in cognitively normal older adults without dementia, but in the future it may be that improving baseline cognition is beneficial in patients with mild cognitive impairment and Alzheimer's disease even if the overall course of the patient's neurological condition is increasingly impaired cognitive function.

The investigators will manipulate the dietary ratios of palmitic acid (PA) and oleic acid (OA), which are the most prevalent saturated and monounsaturated fatty acids, respectively in the diet and body lipids. Using a crossover study of men and women, aged 65-75 years, the investigators will administer two experimental diets in a random order for one week and each experimental diet will be preceded by a one-week, low fat control diet for a four-week total study period. One experimental diet will have a high PA/OA ratio typical of the usual North American Diet and the other experimental diet will have a low PA/OA ratio typical of the Mediterranean Diet. The following primary outcomes will be assessed: working memory performance, activation of working memory networks using functional magnetic resonance imaging (fMRI) and functional connectivity.

The impact of this study is that these data may suggest one mechanism for acutely improving cognition in healthy older adults and potentially in those with cognitive impairment such as mild cognitive impairment and Alzheimer's disease. While changing dietary behavior long term requires additional investigation, there are potential immediate benefits to acute improvements in cognition on quality of life for older adults.

Eligibility Criteria:
Inclusion Criteria:

* Men and women age range 65-75 years
* Normal cognition (see Research Strategy for details on cognitive assessments)
* "Healthy" (body mass index (BMI) of 20-40 kg/m2)

Exclusion Criteria:

* Significant cognitive or behavioral impairment (see Research Strategy for testing and exclusions) or pharmacological treatment for this (e.g. antipsychotics, anxiolytics, and sedative medications).
* Hormone replacement therapy, past 3 months.
* Hyper-androgenic condition.
* HbA1C≥7.5% and or Fasting plasma glucose concentration ≥130 mg/dL.
* Type 2 Diabetes if receiving any other therapy than metformin.
* Use of nicotine or ingestion of caffeine or alcohol during the study.
* Habitual fat intake \< 25% of kcal or strict vegetarian diet.
* Sleep apnea requiring continuous positive airway pressure at night.
* Lung, cardiac (heart failure or its treatment), liver disease, renal disease, cancer, and any other medical disorder known or thought to cause inflammation or abnormalities of cognition
* Actively training for an athletic event or participating in competitive sports (such as league play or tournaments)
* Intolerance or allergy to any of the food provided in the study.