Inflammation-associated declines in cerebral vasoreactivity and cognition in type 2 diabetes

Abstract

Objective: The aim of this prospective study was to investigate the relationships between inflammation, cerebral vasoregulation, and cognitive decline in type 2 diabetes mellitus (T2DM) over a 2-year span.Methods: Sixty-five participants (aged 66 6 9.2 years, 35 with T2DM, 33 women) were enrolled for this 2-year prospective study. Continuous arterial spin labeling at 3-tesla MRI was used to measure global and regional cerebral perfusion and vasoreactivity. Neuropsychological measures were evaluated at the beginning and completion of the study. The associations between serum inflammatory markers, regional cerebral vasoreactivity, and cognitive functions were examined using least squares models.Results: After 2 years of follow-up, participants with T2DM had diminished global and regional cerebral vasoreactivity and a decline in multiple cognitive tasks compared with baseline (p , 0.0001-0.012). In the T2DM group, lower cerebral vasoreactivity was associated with a greater decrease in daily living activities score (r Type 2 diabetes mellitus (T2DM) has been recognized as an independent risk for development of cognitive impairment and dementia.1,2 Endothelial dysfunction and impaired cerebral vasoregulation associated with hyperglycemia and elevated proinflammatory cytokine levels have been linked to functional decline in T2DM.3-5 The aim of this study was to prospectively determine the associations between inflammation, cerebral vasoregulation, and cognitive performance over a 2-year span in older adults with and without T2DM. We hypothesized that (1) inflammation and hyperglycemia are associated with impaired vasoregulation in the brain, and (2) impaired vasoregulation is associated with cognitive decline in T2DM.

Humans with Type-2 Diabetes Show Abnormal Long-Term Potentiation-Like Cortical Plasticity Associated with Verbal Learning Deficits

“…While the sample size is consistent with recently-published work on diabetes and cognitive aging [7, 56, 57], it is relatively small when compared to large-scale epidemiological studies [58]. Further, we enrolled a relatively homogenous population of non-demented adults.…”

“…Presumably as a consequence of this damage, T2DM accelerates cognitive decline [4] and increases risk of dementia [5, 6]. Cognitive dysfunction in T2DM has been linked to inflammation and altered vasoreactivity [7]. Even in the absence of vascular complications, T2DM can alter synaptic plasticity in the mouse hippocampus resulting in cognitive deficits [8], and mice with T2DM are less likely to recover from stroke due to impaired neuroplastic mechanisms [9].…”

Cognitive decline in metabolic syndrome is linked to microstructural white matter abnormalities

“…The reasons for predilection of WM microstructural abnormalities are likely to stem from multiple mechanisms exerting their effects on WM structure and integrity. T2DM has been associated with large and small vessel disease, altered regional vasoreactivity [43], worse vasodilatation capacity [44] and reduced regional gray matter perfusion [45]. Given the fact that WM is more susceptible to ischemia compared to GM [46, 47], it is be possible that a vascular mechanism plays a central WM pathology which is further supported by several studies demonstrating reduced perfusion and vasoreactivity in areas of leukoaraiosis [44–46].…”

The resting perfusion pattern associates with functional decline in type 2 diabetes

“…Type 2 diabetes mellitus (T2DM) is associated with altered cerebral vasoreactivity (Novak et al 2011; Chung et al 2015; Last et al 2007), cerebral atrophy (Franke et al 2013; Novak et al 2011; van Elderen et al 2010), cognitive impairment (Chung et al 2015; Wong, Scholey, and Howe 2014) and functional decline (Chung et al 2015). T2DM-related endothelial dysfunction secondary to a chronic state of hyperglycemia, inflammation and insulin resistance (Kim et al 2006; Starr et al 2003; Brownlee 2005), has been associated with alterations in the blood brain barrier (Mogi and Horiuchi 2011; Starr et al 2003), neuronal damage (Umegaki 2014), and arterial stiffness (Zhou, Zhang, and Lu 2014), thus negatively affecting cerebral metabolism and cerebral blood flow (CBF)(Roberts et al 2014).…”