Abstract
Aging alters brain structure and function and diabetes mellitus (DM) may accelerate this process. This study investigated the effects of type 2 DM on individual brain aging as well as the relationships between individual brain aging, risk factors, and functional measures. To differentiate a pattern of brain atrophy that deviates from normal brain aging, we used the novel BrainAGE approach, which determines the complex multidimensional aging pattern within the whole brain by applying established kernel regression methods to anatomical brain magnetic resonance images (MRI). The “Brain Age Gap Estimation” (BrainAGE) score was then calculated as the difference between chronological age and estimated brain age. 185 subjects (98 with type 2 DM) completed an MRI at 3Tesla, laboratory and clinical assessments. Twenty-five subjects (12 with type 2 DM) also completed a follow-up visit after 3.8 ± 1.5 years. The estimated brain age of DM subjects was 4.6 ± 7.2 years greater than their chronological age (p = 0.0001), whereas within the control group, estimated brain age was similar to chronological age. As compared to baseline, the average BrainAGE scores of DM subjects increased by 0.2 years per follow-up year (p = 0.034), whereas the BrainAGE scores of controls did not change between baseline and follow-up. At baseline, across all subjects, higher BrainAGE scores were associated with greater smoking and alcohol consumption, higher tumor necrosis factor alpha (TNFα) levels, lower verbal fluency scores and more severe deprepession. Within the DM group, higher BrainAGE scores were associated with longer diabetes duration (r = 0.31, p = 0.019) and increased fasting blood glucose levels (r = 0.34, p = 0.025). In conclusion, type 2 DM is independently associated with structural changes in the brain that reflect advanced aging. The BrainAGE approach may thus serve as a clinically relevant biomarker for the detection of abnormal patterns of brain aging associated with type 2 DM.
Highlights
The global prevalence of type 2 diabetes mellitus (DM) is projected to rise sharply over the coming decades
We further explored the relationships between individual brain aging and clinically significant lifestyle risk factors, clinical laboratory data [i.e., fasting blood glucose level as a potential indicator of hyperglycemia, tumor necrosis factor alpha (TNFα) as a potential indicator of persistent inflammation], and common clinical outcomes
Brain volumes did not differ between the groups, the DM subjects had significantly higher BrainAGE scores than controls (F = 17.2; p = 0.0001; Figure 2)
Summary
The global prevalence of type 2 diabetes mellitus (DM) is projected to rise sharply over the coming decades. Individuals aged 65 years and older have a high risk of developing diabetes complications, due to the combination of both modifiable (i.e., lifestyle), and non-modifiable risk factors (Zimmet et al, 2001) Within this population, type 2 DM has been linked to increased brain atrophy (Araki et al, 1994; Schmidt et al, 2004; Last et al, 2007; De Bresser et al, 2010; Van Elderen et al, 2010; Novak et al, 2011), impaired cognitive function (Reijmer et al, 2011), increased risk of depression (Anderson et al, 2001; Ali et al, 2006) and dementia, including both vascular dementia and Alzheimer’s disease (AD) (Janson et al, 2004; Xu et al, 2004; Biessels et al, 2006; Velayudhan et al, 2010; Tan et al, 2011; Cheng et al, 2012). Recognition and quantification of subtle deviations from aging-related brain atrophy may afford prospective identification
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