Objective: To obtain a glucose brain uptake survey of Parkinson’s Disease (PD) patients with or without insulin resistance (IR).

Background: IR is common in PD and impaired insulin signaling is believed to cause or exacerbate neurodegeneration. However, while peripheral IR can be measured by several methods including the Homeostatic Model Assessment or HOMA-IR and hemoglobin A1C (HbA1C), it is currently impossible to determine the degree of brain or central IR in PD. Based on previous studies in neurodegeneration, fludeoxyglucose positron emission tomography ([¹⁸F]FDG-PET) is a potential biomarker of central IR in PD. We hypothesize that peripheral IR will negatively correlate with brain glucose metabolism in relevant regions of interest.

Method: A [¹⁸F]FDG-PET scan was obtained in non-diabetic PD patients. DICOM images were quantitatively analyzed with NeuroSTAT. A stereotactic surface projection (3D-SSP) technique mapped hit counts onto surface voxels, and the mean voxel hit counts were normalized by comparing each voxel to the global hit counts. Finally, a Z-score was determined using a two tailed t-test. Peripheral IR was defined by HbA1C ≥ 5.7 or HOMA-IR ≥ 2.0. Subjects were compared by IR status and to a database of elderly controls (Alzheimer’s Disease Neuroimaging Initiative) using t-test comparison with a significance level set at p>0.01. Areas with decreased glucose metabolism were identified by neuroradiologists (AW, PL) blinded to IR status.

Results: 20 subjects were recruited in the study, of which 10 (50%) had peripheral IR. Independent of IR status, PD subjects (n=20) showed areas of relative hypometabolism in the occipital, parietal, and posterior frontal lobes (z ≥ 3-5, p<0.01) when compared to a group of controls (n=29). When compared to PD patients with normal peripheral glucose metabolism (n=10), those with peripheral IR (n=10) showed scattered areas of focal hypometabolism in the parietal and frontal lobes, including the pre-central gyrus (z ≥ 2-3, p<0.05).

Conclusion: As previously described, [¹⁸F]FDG-PET documented a relative reduction in glucose metabolism in our cohort of non-diabetic PD patients. Interestingly, peripheral IR appears to be associated with at least some of these abnormalities, in particular those affecting frontal and motor planning areas. While limited by a small study sample, our results suggest that [¹⁸F]FDG-PET may play a role as an imaging biomarker for central IR in PD.

References: Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf Minoshima, S., Frey, K.A., Koeppe, R.A., Foster, N.L., and Kuhl, D.E. (1995). A Diagnostic Approach in Alzheimer’s Disease Using Three-Dimensional Stereotactic Surface Projections of Fluorine-18-FDG PET. J Nucl Med 36, 1238–1248.

« Back to 2019 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/imaging-brain-insulin-resistance-in-parkinsons-disease-using-%c2%b9%e2%81%b8ffdg-pet/