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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.

SUBMITTER: Akintola AA

PROVIDER: S-EPMC4446544 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Associations between insulin action and integrity of brain microstructure differ with familial longevity and with age.

Akintola Abimbola A AA van den Berg Annette A van Buchem Mark A MA Jansen Steffy W SW Slagboom Eline P EP Westendorp Rudi G RG van der Grond Jeroen J van Heemst Diana D

Frontiers in aging neuroscience 20150528

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 ...[more]

PMID: 26074813

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Project description:ImportanceCognitive impairment occurs across the psychosis spectrum and is associated with functional outcome. However, it is unknown whether these shared manifestations of cognitive dysfunction across diagnostic categories also reflect shared neurobiological mechanisms or whether the source of impairment differs.ObjectiveTo examine whether the general cognitive deficit observed across psychotic disorders is similarly associated with functional integrity of 2 brain networks widely implicated in supporting many cognitive domains.Design, setting, and participantsA total of 201 healthy control participants and 375 patients with psychotic disorders from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium were studied from September 29, 2007, to May 31, 2011. The B-SNIP recruited healthy controls and stable outpatients from 6 sites: Baltimore, Maryland; Boston, Massachusetts; Chicago, Illinois; Dallas, Texas; Detroit, Michigan; and Hartford, Connecticut. All participants underwent cognitive testing and resting-state functional magnetic resonance imaging. Data analysis was performed from April 28, 2015, to February 21, 2017.Main outcomes and measuresThe Brief Assessment of Cognition in Schizophrenia was used to measure cognitive ability. A principal axis factor analysis on the Brief Assessment of Cognition in Schizophrenia battery yielded a single factor (54% variance explained) that served as the measure of general cognitive ability. Functional network integrity measures included global and local efficiency of the whole brain, cingulo-opercular network (CON), frontoparietal network, and auditory network and exploratory analyses of all networks from the Power atlas. Group differences in network measures, associations between cognition and network measures, and mediation models were tested.ResultsThe final sample for the current study included 201 healthy controls, 143 patients with schizophrenia, 103 patients with schizoaffective disorder, and 129 patients with psychotic bipolar disorder (mean [SD] age, 35.1 [12.0] years; 281 male [48.8%] and 295 female [51.2%]; 181 white [31.4%], 348 black [60.4%], and 47 other [8.2%]). Patients with schizophrenia (Cohen d = 0.36, P < .001) and psychotic bipolar disorder (Cohen d = 0.33, P = .002) had significantly reduced CON global efficiency compared with healthy controls. All patients with psychotic disorders had significantly reduced CON local efficiency, but the clinical groups did not differ from one another. The CON global efficiency was significantly associated with general cognitive ability across all groups (β = 0.099, P = .009) and significantly mediated the association between psychotic disorder status and general cognition (β = -0.037; 95% CI, -0.076 to -0.014). Subcortical network global efficiency was also significantly reduced in psychotic disorders (F3,587 = 4.01, P = .008) and positively predicted cognitive ability (β = 0.094, P = .009).Conclusions and relevanceThese findings provide evidence that reduced CON and subcortical network efficiency play a role in the general cognitive deficit observed across the psychosis spectrum. They provide new support for the dimensional hypothesis that a shared neurobiological mechanism underlies cognitive impairment in psychotic disorders.

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Associations between insulin action and integrity of brain microstructure differ with familial longevity and with age.

Publications

Associations between insulin action and integrity of brain microstructure differ with familial longevity and with age.

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