Vascular risk factors like hypertension, hyperlipidemia and diabetes mellitus are risk factors for Alzheimer's disease (AD). White matter lesions (WMLs) have been recognized as the imaging characteristics of cerebral small vessel diseases. WMLs are a risk factor for stroke, cognitive decline, and dementia and their prevalence increases with age. In magnetic resonance imaging (MRI), white matter hypointensities in T1‐weighted images, and white matter hyperintensities in T2‐weighted and FLAIR images are regarded as visualizations of WMLs. Peripheral insulin resistance (IR) may contribute to the etiopathogenesis of AD. Here we evaluated whether insulin resistance exerts its effects on non‐diabetic AD subjects by influencing WMLs.
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. Insulin resistance was calculated by the homeostatic model assessment (HOMA‐IR). Hypointensity volumetrics determined as WMLs were estimated using the FreeSurfer analysis (http://surfer.nmr.mgh.harvard.edu/) on T1 MRI acquired on 3T scans. Glucose metabolism (rCMRGlc) was calculated by parametric images generated using spectral analysis with an arterial plasma input function.
In this non‐diabetic AD population, the prevalence of IR was about 16%. WMLs volume was not correlated to HOMA‐IR. However, WMLs was negatively correlated with left hippocampal volume (Spearman's rho=−.208, p=.02). WMLs volume was positively correlated with age and with serum triglyceride levels and negatively correlated with serum HDL cholesterol levels.
In this study in a non‐diabetic AD population, white matter lesions were not correlated with peripheral insulin resistance. This suggests that in non‐diabetic AD subjects, vascular changes are not influenced by peripheral insulin resistance.
|Journal||Alzheimer's & Dementia: The Journal of the Alzheimer's Association|
|Issue number||7S Part 20|
|Publication status||Published - 01 Jul 2019|
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Supervisor: Santos, E. (Supervisor)
Student thesis: Doctoral Thesis › Doctor of PhilosophyFile