Microvascular Determinants of Cognitive Decline and Brain Volume Change in Elderly Patients with Type 2 Diabetes

Abstract

Background/Aims: The present study examined the relationship between microvascular complications and cognitive decline and the development of structural brain abnormalities over a period of 4 years in patients with type 2 diabetes mellitus (T2DM). Methods: Sixty-eight elderly patients with T2DM had 2 cognitive assessments with a 4-year interval. Two MRI scans, performed at the same time as the cognitive assessments, were available from 55 patients. Changes in cognitive performance over time were expressed as a regression-based index (RBI). Automated volumetric measurements of total brain, lateral ventricles and white matter hyperintensities were performed. The relationship between baseline microvascular complications [diabetic retinopathy, peripheral neuropathy or albuminuria (micro- or macroalbuminuria)] and cognition and brain volumes was examined with linear regression analyses adjusted for age and sex (for cognition also for IQ). Results: At baseline, diabetic retinopathy was present in 18% of patients, peripheral neuropathy in 36%, albuminuria in 15%. Retinopathy or neuropathy were not significantly associated with baseline cognition or brain volumes, or changes in these measures over time. Albuminuria was associated with a lower composite RBI score, indicating accelerated cognitive decline (adjusted mean difference between patients with or without albuminuria: –0.58, 95% CI –0.85 to –0.31, p < 0.001). Conclusion: Albuminuria predicted accelerated cognitive decline in patients with T2DM, but other microvascular complications were unrelated to accelerated cognitive decline or brain MRI abnormalities.

Subclinical albuminuria is linked to gray matter atrophy in type 2 diabetes mellitus

“…Albuminuria, a marker of chronic vascular kidney disease, is associated with accelerated cognitive decline in diabetic patients [2]. Cerebromicrovascular disease manifests as impaired vasoreactivity [7, 8], hypoperfusion and decreased metabolism that may lead to hypoxia and brain tissue loss [9-12].…”

Cognitive decline in newly diagnosed Type 2 Diabetes and the effect of good glycemic control on cognitive function

“…Also the study by de bresser et al examining the relationship between microvascular complications and cognitive decline and the development of structural brain abnormalities in Diabetics, reported that presence of albuminuria predicted accelerated cognitive decline in Type2 diabetes (P<0.001). (17) In our study, 10.7% already had Diabetic Retinopathy when they were diagnosed with Diabetes or developed it within six months. This prevalence of Diabetic Retinopathy in our study on newly diagnosed diabetics is somewhat similar to that of a study by Abdollahi et al in 2006, where the prevalence reported was 13.4%.…”

Pharmacologically induced impairment of neurovascular coupling responses alters gait coordination in mice

“…In that regard, it is important that a significant association between serum ADMA level and slower gait speed was demonstrated among elderly individuals (Obayashi et al 2016). Type 2 diabetes mellitus (Duarte et al 2015) also leads to neurovascular dysfunction, which is associated with increased risk for brain function loss and long-term cognitive impairment (Biessels and Reijmer 2014;Brundel et al 2012Brundel et al , 2014de Bresser et al 2010;Palta et al 2014;Reijmer et al 2011;Ruis et al 2009;Ryan et al 2014Ryan et al , 2016van den Berg et al 2008van den Berg et al , 2009van den Berg et al , 2010. Increased oxidative stress and heightened inflammation associated with cardiovascular risk factors may also affect arachidonic acid metabolism, decreasing production of vasodilator prostaglandins and EETs and/or increasing synthesis of vasoconstrictor eicosanoids, such as 20-hydroxyeicosatetraenoic acid (20-HETE), contributing to neurovascular dysfunction.…”