White matter lesions and glucose regulation in early Alzheimer's disease

Abstract

Intro: While the brain’s anatomic changes due to Alzheimer’s disease have been well documented, the importance of accompanying White Matter Lesions (WMLs) as seen on MRI has not yet been clearly defined. Recent evidence has suggested a possible vascular origin in the development of WML. Insulin and glucose levels are known to have vascular effects so we sought to determine if there was a relationship between glucoregulation and WML in early AD. Methods: Nondemented individuals (n = 32) and individuals with early-stage AD (n = 30) were evaluated with clinical, psychometric, neuroimaging and laboratory tests as part of the KU Brain Aging Project. Exclusion criteria included neurological disorders other than AD, ischemic heart disease and diabetes. Areas of abnormal white matter signal as observed on FLAIR MRI were traced using semi-automated techniques and volumes were quantitated using a software imaging suite (Analyze 6.0) A 3-hour Intravenous Glucose Tolerance Test (IVGTT) was conducted to determine insulin sensitivities and results were analyzed using a software program (MINMOD Millennium). Results: There was no significant difference in the volume of white matter lesions (WMLs) between groups. WML volume in the demented group was 13073 mm3 (n=28), while volume in the non-demented group was 11790 mm3 (n=30). Using preliminary glucose data (demented=14, non-demented=20) there appears to a significant difference (p=0.05) between groups in the values for blood glucose 3 hrs after the initial glucose challenge; demented glucose = 89.8(12.4)mg/dl and non-demented glucose = 83.3(6.3)mg/dl. Initial demented group correlation calculations between baseline glucose and WML volume (n=14, r=.45, p=0.11), and baseline insulin and WML volumes (n=15, r=0.29, p=0.29), showed no significance, although a potential trend in that direction. Conclusions: WMLs are prevalent in both early AD and nondemented aging groups and may be associated with impaired glucoregulation. Further analysis, with a larger sample size should clarify the developing picture. Initial WML volumes do not appear able to distinguish between demented and non-demented patients, a more focused analysis using regional volumes may yield different results and should be attempted in the future.