title: Parameters of glucose metabolism and the aging brain: a magnetization transfer imaging study of brain macro- and micro-structure in older adults without diabetes.
abstract: Given the concurrent, escalating epidemic of diabetes mellitus and neurodegenerative diseases, two age-related disorders, we aimed to understand the relation between parameters of glucose metabolism and indices of pathology in the aging brain. From the Leiden Longevity Study, 132 participants (mean age 66 years) underwent a 2-h oral glucose tolerance test to assess glucose tolerance (fasted and area under the curve (AUC) glucose), insulin sensitivity (fasted and AUC insulin and homeostatic model assessment of insulin sensitivity (HOMA-IS)) and insulin secretion (insulinogenic index). 3-T brain MRI was used to detect macro-structural damage (atrophy, white matter hyper-intensities, infarcts and/or micro-bleeds) and magnetization transfer imaging (MTI) to detect loss of micro-structural homogeneity that remains otherwise invisible on conventional MRI. Macro-structurally, higher fasted glucose was significantly associated with white matter atrophy (P = 0.028). Micro-structurally, decreased magnetization transfer ratio (MTR) peak height in gray matter was associated with higher fasted insulin (P = 0.010), AUCinsulin (P = 0.001), insulinogenic index (P = 0.008) and lower HOMA-IS index (P < 0.001). Similar significant associations were found for white matter. Thus, while higher glucose was associated with macro-structural damage, impaired insulin action was associated more strongly with reduced micro-structural brain parenchymal homogeneity. These findings offer some insight into the association between different parameters of glucose metabolism (impairment of which is characteristic of diabetes mellitus) and brain aging.
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Centre, Leiden, the Netherlands, a.a.akintola@lumc.nl.
authors.forename: Abimbola A
authors.initials: AA
authors.lastname: Akintola
authors.forename: Annette
authors.initials: A
authors.lastname: van den Berg
authors.forename: Irmhild
authors.initials: I
authors.lastname: Altmann-Schneider
authors.forename: Steffy W
authors.initials: SW
authors.lastname: Jansen
authors.forename: Mark A
authors.initials: MA
authors.lastname: van Buchem
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.forename: Rudi G
authors.initials: RG
authors.lastname: Westendorp
authors.forename: Diana
authors.initials: D
authors.lastname: van Heemst
authors.forename: Jeroen
authors.initials: J
authors.lastname: van der Grond
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000473:pathology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D005215:Fasting / Q000502:physiology; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male
chemical_list: D005947:Glucose