Title: Insulin resistance predicts brain amyloid deposition in late middle-aged adults
Legend: Healthy late middle-aged adults with higher insulin resistance (based on fasting glucose and insulin levels) show greater amyloid deposition on [C11]PIB-PET imaging. The results suggest that metabolic dysfunction in midlife may contribute to Alzheimer’s pathology. Shown on the left for illustrative purposes are voxel-wise regression results; regions in hot colors are those where higher insulin resistance predicted greater amyloid deposition on [C11]PIB-PET imaging. Shown on the right is a scatter plot (Figure 3 from Willette et al., 2015) indicating a positive relationship between insulin resistance and frontal amyloid deposition. PIB distribution volume ratio (DVR) values were adjusted for age, sex, apolipoprotein ε4 status, family history of Alzheimer’s disease (AD), use of type 2 diabetes medication, body mass index, and the main effects of HOMA-IR and glycemic status.
Citation: Willette AA, Johnson SC, Birdsill AC, Sager MA, Christian B, Baker LD, Craft S, Oh J, Statz E, Hermann BP, Jonaitis EM, Koscik RL, La Rue A, Asthana S, Bendlin BB (2015). Insulin resistance predicts brain amyloid deposition in late middle-aged adults. Alzheimer’s & Dementia.11(5):504-510.e1.
Abstract: Insulin resistance (IR) increases Alzheimer’s disease (AD) risk. IR is related to greater amyloid burden post-mortem and increased deposition within areas affected by early AD. No studies have examined if IR is associated with an in vivo index of amyloid in the human brain in late middle-aged participants at risk for AD. Asymptomatic, late middle-aged adults (N = 186) from the Wisconsin Registry for Alzheimer’s Prevention underwent [C-11]Pittsburgh compound B (PiB) positron emission tomography. The cross-sectional design tested the interaction between insulin resistance and glycemic status on PiB distribution volume ratio in three regions of interest (frontal, parietal, and temporal). In participants with normoglycemia but not hyperglycemia, higher insulin resistance corresponded to higher PiB uptake in frontal and temporal areas, reflecting increased amyloid deposition. This is the first human study to demonstrate that insulin resistance may contribute to amyloid deposition in brain regions affected by AD.
About the investigator: Bendlin’s work focuses on brain structure and function in middle and late age, especially in people with increased risk of developing AD due to parental family history, genotype and vascular risk factors. Understanding early brain changes in people who may go on to develop AD is expected to lead to earlier diagnosis, prevention, and the development of new therapies for AD. Her current projects use MRI as a tool to understand the effect of risk factors (parental family history, genotype, Metabolic Syndrome) on brain blood flow and structure. Additionally, she is funded to examine the relationship between cerebrospinal fluid biomarkers and brain structure to learn more about early mechanisms of brain damage in AD.