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    Insulin resistance influences hippocampal glucose metabolism rather than hippocampal volume in non-diabetic Alzheimer disease patients

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    Author
    Junaid, Kehinde
    Keyword
    Alzheimer disease
    Drug therapy
    Temporal lobe
    Nerve degeneration
    Diabetes mellitus
    Magnetic resonance imaging
    Motor cortex
    Drug resistance
    Date
    2019
    
    Metadata
    Show full item record
    DOI
    10.1016/j.jalz.2019.06.2765
    Publisher's URL
    https://www.alzheimersanddementia.com/article/S1552-5260(19)32915-2/fulltext
    Abstract
    Background: Type 2 diabetes is a risk factor for Alzheimer disease (AD) and it has been demonstated that AD brain shows impaired insulin signalling. Progressive brain hypometabolism is a hallmark of AD and can be evaluated using [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). Medial temporal lobe atrophy evaluated on magnetic resonance imaging (MRI) is also a marker of neurodegeneration in AD. Peripheral insulin resistance (IR) may contribute to the etiopathogenesis of AD. Here we evaluated the association between IR, brain glucose metabolism and hippocampal volume in non-diabetic AD subjects.
    Method(s): 121 AD subjects form the Evaluating Liraglutide in Alzheimer's Disease (ELAD) trial (NCT01843075) were enrolled. Glucose and insulin levels were measured after a 4-hour fast on the day of the visit for the brain MRI and FDG-PET scan. Insulin resistance was calculated by the homeostatic model assessment (HOMA-IR). For [18F]FDG analysis, rCMRGlc parametric images were generated using spectral analysis with an arterial plasma input function. T1 volumetric MRI were acquired on 3T scans and automated hippocampal segmentation was done using FreeSurfer.
    Result(s): In this non-diabetic AD population, the prevalence of IR was about 16%. HOMA-IR was negatively correlated with the hippocampal rCMRGlc (Spearman's rho= -.232, p=.04). The correlation remained significant after correcting for age. Subjects above the cut-off value for IR (2.9) showed significant lower rCMRGlc in the hippocampus, medial temporal lobe and precentral gyrus compared to those below the cut-off. No significant correlation was observed between HOMA-IR and hippocampal volume.
    Conclusion(s): In this study in a non-diabetic AD population, peripheral insulin resistance correlates with reduced hippocampal glucose metabolism but not with hippocampal volume. This suggests that the peripheral insulin resistance influence AD pathology by its action on cerebral glucose metabolism and central insulin resistance.
    Copyright © 2019
    Citation
    Femminella, G. D., van der Doef, T., Wang, Y. T., Frangou, E., Love, S., Calsolaro, V., Carver, S., Holmes, C., Ritchie, C. W., Lawrence, R. M., et al. (2019). Insulin resistance influences hippocampal glucose metabolism rather than hippocampal volume in non-diabetic Alzheimer's disease patients. Alzheimer's Association International Conference, 14-18 July 2019 California, United States. Chicago: Alzheimer's and Dementia, p.P736.
    Type
    Conference Proceeding
    URI
    http://hdl.handle.net/20.500.12904/8021
    Note
    This is a conference abstract from the Alzheimer's Association International Conference in Los Angeles, California from 14-18 July 2019.
    Collections
    Diabetes, Endocrine, Metabolic and Nutritional
    Dementia

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