Thursday, December 26, 2024
12/26/2024
Approaches to ameliorate cognitive decline with aging are few and often require behavioral changes that are difficult to maintain over long periods of time. The novel study proposed in this application 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 our prior studies in humans we propose that brain functioning also can be acutely improved with a reduction in dietary saturated fat. We will use this approach in cognitively normal older adults without dementia, but we propose that acutely 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. We 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, we 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. We will assess the following primary outcomes: working memory performance, activation of working memory networks using functional magnetic resonance imaging (fMRI) and functional connectivity. Specific Aim 1 is to determine in cognitively normal older adults if lowering the dietary PA/OA ratio reversibly affects working memory performance. Hypothesis 1 is that improved working memory performance will result from lowering the dietary PA/OA ratio. Specific Aim 2 is to determine in cognitively normal older adults if lowering the dietary PA/OA ratio reversibly affects brain functioning measured by fMRI activation during a working memory task and functional connectivity during rest. Hypothesis 2a is that increased activation in the working memory network will result from lowering the dietary PA/OA ratio. Hypothesis 2b is that increased local functional connectivity within the working memory network will result from lowering the dietary PA/OA ratio. 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.
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