Type 2 Diabetes and Memory: Using Neuroimaging to Understand the Mechanisms

Abstract

Abstract:The most robust and frequently reported cognitive deficits in type 2 diabetes (DM2) are those that relate to memory. Behavioural research has identified a number of potential contributory physiological factors, including abnormalities in glucose metabolism, such as hyperglycaemia and hypoglycaemia. The impact of these mechanisms on memory has been further investigated through the use of both structural and functional neuroimaging. Structural brain imaging has indicated that memory impairments in DM2 are associated with global atrophy of the brain. Further data suggest that localised atrophy in the hippocampal area, a brain region critical to memory formation and consolidation, may be primarily responsible for the memory deficits seen in this population. Functional imaging data has corroborates these findings, with functional magnetic resonance imaging (fMRI) suggesting reduced connectivity between the hippocampus and surrounding brain regions, particularly the frontal and temporal gyri. Despite this, little functional neuroimaging research has directly investigated differences in regional brain activity between healthy and DM2 participants whilst memory tasks are being performed. By using neuroimaging techniques to their full potential, we can acquire a fuller, more comprehensive picture of the impact that DM2 has on memory.Keywords: Brain, cognition, EEG, memory, MRI, neuroimaging, type 2 diabetes.Type 2 diabetes (DM2) in older adults is associated with cognitive impairment, reflecting accelerated cognitive decline relative to that expected in normal ageing [1][2][3]. The most frequently reported and most robust deficits are seen in verbal episodic memory [4], although other domains of memory such as face recognition and working memory may also be affected [5,6]. However, it is still unclear whether these deficits reflect impairments in their encoding or retrieval. These memory impairments have been attributed to varied physiological mechanisms, including abnormalities in glucose metabolism, insulin resistance, dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and vascular complications [7,8]. The role of these physiological mechanisms in neurocognitive functioning in individuals withDM2 has been investigated using a variety of neuroimaging techniques. Methods such as magnetic resonance imaging (MRI) and electroencephalography (EEG), have allowed researchers to examine both the structural and functional impact of DM2 on the brain. This review will consider these neuroimaging studies and speculate on how these innovative techniques could be informative in identifying underlying mechanisms of memory deficits in DM2. DM2 AND COGNITIVE IMPAIRMENT: THE MECHANISMSDisturbances in glucose metabolism, including hyperglycaemia and hypoglycaemia, have been associated with cognitive dysfunction [7,9]. Summerfield, Deary and Frier [7] observed that induced acute hyperglycaemia in adults with DM2 impaired cognitive performance, most notably in the working memory domain. Relatively few studies have inve...

Higher GABA concentration in the medial prefrontal cortex of Type 2 diabetes patients is associated with episodic memory dysfunction

“…In this regard, previous work has mainly investigated T2D related decline in single item memory, for example, word list learning (Jones et al, 2014;Stewart & Liolitsa, 1999), which is a different process with distinct neural substrates as compared to associative memory (Ranganath, 2010;Wang, Li, Li, & Zhang, 2013). As associative memory, compared to single item memory, is more affected in Alzheimer's disease (Blackwell et al, 2004;Fowler, Saling, Conway, Semple, & Louis, 2002;O'Connell et al, 2004;Parra et al, 2009;Swainson et al, 2001) and T2D patients exhibit an increased risk in developing Alzheimer disease (Kuusisto et al, 1997;Leibson et al, 1997;Ott et al, 1999), our study of associative episodic memory in T2D provides a relevant contribution to the understanding of cognitive decline in T2D.…”

“…, psychomotor speed (Gregg et al, 2000;Reaven et al, 1990), processing speed (Messier, 2005), verbal fluency (Kanaya, Barrett-Connor, Gildengorin, & Yaffe, 2004;Reaven et al, 1990), executive function (Munshi et al, 2006;Perlmuter et al, 1984;Reaven et al, 1990), attention (Fontbonne, Berr, Ducimetiere, & Alperovitch, 2001), and several domains of memory (Grodstein, Chen, Wilson, & Manson, 2001;Messier, 2005;Mooradian, Perryman, Fitten, Kavonian, & Morley, 1988;Munshi et al, 2006;Perlmuter et al, 1984). Among these impairments, the most robust and frequently reported cognitive deficits in T2D are episodic memory dysfunction (Jones, Riby, Mitchell, & Smith, 2014). Not surprisingly, T2D associates with a greater prevalence of neurocognitive disorders and Alzheimer's disease in particular (Biessels, van der Heide, Kamal, Bleys, & Gispen, 2002;Leibson et al, 1997;Ott et al, 1996Ott et al, , 1999.…”

Cognitive Dysfunction in Persons with Type 2 Diabetes Mellitus: A Concept Analysis

“…The hippocampus is a brain region important for learning, and memory formation and consolidation. Some preliminary data suggest that atrophy in the hippocampal area may be primarily responsible for memory impairment reported in this population (Jones, Riby, Mitchell, & Smith, 2014). Using the diffusion magnetic resonance imaging technique, Reijmer, Brundel, et al (2013) found microstructural white matter abnormalities and disruptions in the white matter network in persons with T2DM compared with age-, sex-, and education-matched controls.…”

Markers of cognitive impairment in patients with type 2 diabetes

“…Functional imaging data further suggests diminished connectivity between the hippocampus and the frontal and temporal regions (23). Thus, atrophy in the hippocampal area and altered neuronal connectivity might be responsible for the memory impairment in subjects with T2D (23).…”

“…In fact, there is some evidence that higher blood glucose levels, even in the normal range, are associated with atrophy in the hippocampus and amygdala, brain regions critically important for memory (22). Functional imaging data further suggests diminished connectivity between the hippocampus and the frontal and temporal regions (23). Thus, atrophy in the hippocampal area and altered neuronal connectivity might be responsible for the memory impairment in subjects with T2D (23).…”