MedicalResearch.com Interview with:
Auriel A. Willette, M.S., Ph.D.
Food Science and Human Nutrition
Neuroscience Interdepartmental Graduate Program
Gerontology Interdepartmental Graduate Program
Iowa State University, Ames
Medical Research: What is the background for this study? What are the main findings?
Response: Obesity is a major health concern around the world. Obesity causes insulin resistance, defined in this case as the inability of insulin to bind to its receptor and mediate glucose metabolism. Other researchers and I have recently found that higher insulin resistance is associated with less glucose metabolism in the brains of patients with Alzheimer’s disease. This relationship is found primarily in medial temporal lobe, an area necessary for generating new memories of facts and events. This is important because Alzheimer’s disease is characterized by progressive decreases in glucose metabolism over time, and partly drives worse memory performance. Insulin resistance in midlife also increases the risk of developing Alzheimer’s disease.
We wanted to determine if insulin resistance is linked to similar effects in cognitively normal, late middle-aged participants decades before Alzheimer’s disease typically occurs. If so, insulin resistance might be an important biological marker to track from middle-age onwards. Thus, we examined the association between insulin resistance, regional glucose metabolism using FDG-PET, and memory function in 150 middle-aged participants, many of whom had a mother or father with Alzheimer’s disease.
We found that higher insulin resistance was strongly associated with less glucose metabolism throughout many brain regions, predominantly in areas that are affected by Alzheimer’s disease. The strongest statistical effects were found in left medial temporal lobe, which again is important for generating new memories. This relationship, in turn, predicted worse memory performance, both immediately after learning a list of words and a 20-minute delay thereafter.
The take-home message is that insulin resistance has an Alzheimer’s-like association with glucose metabolism in middle-aged, cognitively normal people at risk for Alzheimer’s, an association which is related to worse memory.
Medical Research: What should clinicians and patients take away from your report?
Response: It is important to prevent, reduce, or reverse insulin resistance. This is not only relevant to people with type 2 diabetes but also those with “pre-diabetes,” metabolic syndrome, or even obese participants without glycemic control problems but who have hyperinsulinemia.
Moderate exercise is the most important intervention to consider. Moderate exercise is defined here as 30 total minutes on a given day for at least 3 times a week. Activities include brisk walking, yard work, house work, yoga, and other motor movement that is not strenuous. Somatic muscle conditioning is critical for ameliorating or preventing insulin resistance. It is especially important for older participants, who may have muscle atrophy (i.e., sarcopenia) and tend to be less active.
Weight loss interventions should also be considered. Standard recommendations include fewer calorie-heavy drinks and avoiding diet soft drinks, as well as eating one light meal and usually moderating portions for other meals in a given day. For patients who strongly desire to lose weight, intermittent calorie restriction has in clinical trials been shown to reduce weight by 6-8% over an 8-week period and significantly reduce insulin resistance.
For patients with type 2 diabetes, aggressive management is required. Beyond diet and exercise recommendations, controlling the disease with metformin, other drugs, and later if necessary insulin may be best at reducing Alzheimer’s disease risk. Clinical trials using intranasal insulin, which provide insulin directly to the brain, seem to maintain glucose metabolism in the brain and also maintain memory function. Further studies are needed to see if normal methods of controlling type 2 diabetes, or intranasal insulin or other new therapies, will reduce or eliminate risk for Alzheimer’s disease, or the development of Alzheimer’s-like pathology or effects in the brain.
Medical Research: What recommendations do you have for future research as a result of this study?
Response: It is important to longitudinally follow middle-aged participants as they begin to age. Longitudinal studies will allow us to see who develops clinically relevant memory impairment and who does not. One will then be able to see if changes in insulin resistance predicts less glucose metabolism over time, and if that has meaningful predictive power for determining who does and does not go on to have memory problems and eventually Alzheimer’s disease.
Our previous work has also implicated insulin resistance in predicting Alzheimer’s-like pathology in middle-age, such as amyloid deposits in the brain. It will be imperative to examine any links with regional deposits of tau filament, a hallmark of Alzheimer’s disease, when tau imaging becomes more commonplace. This will be critical in both Alzheimer’s disease and in middle-age.
Willette AA, Bendlin BB, Starks EJ, et al. Association of Insulin Resistance With Cerebral Glucose Uptake in Late Middle–Aged Adults at Risk for Alzheimer Disease. JAMA Neurol. Published online July 27, 2015. doi:10.1001/jamaneurol.2015.0613.
Auriel A. Willette, M.S., Ph.D (2015). Insulin Resistance Linked to Poor Memory Performance
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