title: Associations between insulin action and integrity of brain microstructure differ with familial longevity and with age.
abstract: Impaired glucose metabolism and type 2 diabetes have been associated with cognitive decline, dementia, and with structural and functional brain features. However, it is unclear whether these associations differ in individuals that differ in familial longevity or age. Here, we investigated the association between parameters of glucose metabolism and microstructural brain integrity in offspring of long-lived families ("offspring") and controls; and age categories thereof. From the Leiden Longevity Study (LLS), 132 participants underwent an oral glucose tolerance test (OGTT) to assess glycemia [fasted glucose and glucose area-under-the-curve (AUC)], insulin resistance [fasted insulin, AUCinsulin, and homeostatic model assessment of insulin resistance (HOMA-IR)], and pancreatic Beta cell secretory capacity (insulinogenic index). 3 Tesla MRI and Magnetization Transfer (MT) imaging MT-ratio (MTR) peak-height was used to quantify differences in microstructural brain parenchymal tissue homogeneity that remain invisible on conventional MRI. Analyses were performed in offspring and age-matched controls, with and without stratification for age. In the full offspring group only, reduced MTR peak-height in gray and white matter was inversely associated with AUCinsulin, fasted insulin, HOMA-IR and insulinogenic-index (all p < 0.01). When dichotomized for age (≤65 years and >65 years): in younger controls, significantly stronger inverse associations were observed between MTR peak-height and fasted glucose, AUCglucose, fasted insulin, AUCinsulin and HOMA-IR in gray matter; and for AUCglucose, fasted insulin and HOMA-IR in white matter (all P-interaction < 0.05). Although the strength of the associations tended to attenuate with age in the offspring group, the difference between age groups was not statistically significant. Thus, associations between impaired insulin action and reduced microstructural brain parenchymal tissue homogeneity were stronger in offspring compared to controls, and seemed to diminish with age.
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Centre Leiden, Netherlands.
authors.forename: Abimbola A
authors.initials: AA
authors.lastname: Akintola
authors.affiliation: Department of Radiology, Leiden University Medical Centre Leiden, Netherlands.
authors.forename: Annette
authors.initials: A
authors.lastname: van den Berg
authors.affiliation: Department of Radiology, Leiden University Medical Centre Leiden, Netherlands ; Netherlands Consortium for Healthy Ageing Leiden, Netherlands ; Leiden Institute for Brain and Cognition, Leiden University Leiden, Netherlands.
authors.forename: Mark A
authors.initials: MA
authors.lastname: van Buchem
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Centre Leiden, Netherlands.
authors.forename: Steffy W
authors.initials: SW
authors.lastname: Jansen
authors.affiliation: Netherlands Consortium for Healthy Ageing Leiden, Netherlands ; Department of Molecular Epidemiology, Leiden University Medical Centre Leiden, Netherlands.
authors.forename: Eline P
authors.initials: EP
authors.lastname: Slagboom
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Centre Leiden, Netherlands ; Department of Public Health, University of Copenhagen Copenhagen, Denmark.
authors.forename: Rudi G
authors.initials: RG
authors.lastname: Westendorp
authors.affiliation: Department of Radiology, Leiden University Medical Centre Leiden, Netherlands ; Netherlands Consortium for Healthy Ageing Leiden, Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: van der Grond
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Centre Leiden, Netherlands ; Netherlands Consortium for Healthy Ageing Leiden, Netherlands.
authors.forename: Diana
authors.initials: D
authors.lastname: van Heemst
keywords: Magnetic Resonance Imaging (MRI); Magnetization Transfer Imaging (MTI); age; brain; familial longevity; glucose; insulin