Type 2 diabetes mellitus is associated with brain atrophy and hypometabolism in the ADNI cohort

Abstract

Objective: We investigated type 2 diabetes mellitus (T2DM) as a risk factor for brain atrophy and glucose hypometabolism in older adults with or at risk of cognitive impairment.Methods: Participants with the T2DM were identified from the Alzheimer's Disease Neuroimaging Initiative (ADNI-1/GO/2 cohorts). Analysis of covariance models were used to compare participants with and without T2DM, controlling for potential confounding factors.Results: Whole brain volume and whole brain [18 F]-fluorodeoxyglucose (FDG) uptake were significantly different as a function of T2DM status, independent of baseline clinical diagnosis. On post hoc analysis, a lower whole brain volume was seen in participants with both mild cognitive impairment (MCI) and T2DM (n 5 76) compared with participants who had MCI but not T2DM (n 5 747; p 5 0.009). Similarly, mean FDG uptake in gray matter and white matter was lower in participants with both MCI and T2DM (n 5 72) than in participants with MCI without T2DM (n 5 719; p 5 0.04). Subsequent regional analysis revealed that the decreased FDG uptake in participants with both MCI and T2DM was mainly manifested in 3 brain regions: frontal lobe, sensory motor cortex, and striatum. Type 2 diabetes mellitus (T2DM) is a risk factor for cognitive impairment, 1 as more than 30% of patients with T2DM have mild cognitive impairment (MCI).2,3 T2DM not only is associated with a high MCI prevalence but may also shorten the conversion time from normal cognition to MCI. 4,5 In 1997, a population-based cohort study reported that T2DM could significantly increase Alzheimer disease (AD) risk. 6 In 1999, the Rotterdam Study reported that T2DM could almost double the AD risk.7 However, no direct link has been found between T2DM and AD from the pathophysiologic perspective.8 In addition, it is not clear how T2DM interacts with existing cognitive impairment in the form of MCI or AD. Thus, the goal of this study was to evaluate how T2DM affects brain structure and glucose metabolism in participants with normal cognition, MCI, or AD. Specifically, the effects of T2DM were examined in a secondary data analysis of the structural brain atrophy and glucose metabolism measures from older adults with normal cognition, MCI, or AD, who were enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI). The findings may provide important insight into the biological mechanisms by which T2DM increases the risk of cognitive impairment.From Master of Physician Assistant Studies,

Diabetes and Alzheimer’s Disease: A Link not as Simple as it Seems

“…On the other hand, T2DM patients with mild cognitive impairment (MCI) showed a general reduction in brain [ 18 F]-fluorodeoxyglucose (FDG) uptake in gray and white matter [22]. Insulin resistance has also been associated with a reduced cerebral glucose metabolic rate in frontal, temporal-parietal, and cingulate regions in patients with T2DM [23,24].…”

“…Interestingly, brain hypometabolism (observed by FDG uptake) is associated with an increased risk for AD and can be observed years before the dementia onset in the same brain regions affected in T2DM patients [25,26]. Thus, the reduced cerebral glucose metabolic rate observed in diabetic patients could be a predisposing factor for AD and MCI [22]. b) Vascular and structural brain abnormalities T2DM is linked to alterations in cerebral microvasculature, including amyloid angiopathy [16,27].…”

Diabetes, adult neurogenesis and brain remodeling: New insights from rodent and zebrafish models

“…Functional MRI studies showed a dysfunction in glucose metabolism in patient having Alzheimer disease and also in small subcortical structures in patients with Parkinson disease. 89,90 Besides showing significantly more cognitive deficits, T1D and T2D patients display equally more behavioral alterations such as depression, related to their condition. 4,10 In fact, depression is a risk factor for developing diabetes 91 as glycemic control is affected by lifestyle (e.i.…”

Moderating Effect of Insulin Resistance on the Relationship between Gray Matter Volumes and Cognitive Function

“…Many previous studies have investigated the relationship between diabetes-associated factors (such as HbA1c, diabetes status, blood glucose, cognitive function, and brain atrophy and/or metabolism), in addition to insulin resistance and cognitive impairment [ 33 , 34 , 35 ]. The current study indicates that only insulin resistance has a significant effect on the relationship between structural changes in key brain regions sensitive to insulin and cognitive deterioration.…”