Diabetes and cognitive impairment

Biessels, Geert Jan; Koffeman, Aafke R; Scheltens, Philip

doi:10.1007/s00415-005-0036-4

Cited by 70 publications

(24 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Metabolic syndrome is a risk factor for neurological disorders including stroke, dementia, and depression (Baker et al, 2010; Biessels et al, 2006; Correia et al, 2011; de la Monte, 2009; Haan, 2006; Neumann et al, 2008; Profenno et al, 2010; Zhao and Townsend, 2009). Several studies have demonstrated that factors associated with metabolic syndrome have a negative impact on cognitive health (Dahl and Hassing, 2013; Farr et al, 2008; Luchsinger et al, 2007; Novak and Hajjar, 2010; Takahashi et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

The role of endoplasmic reticulum stress in hippocampal insulin resistance

Sims‐Robinson

Bakeman

Glasser

et al. 2016

Experimental Neurology

View full text Add to dashboard Cite

Metabolic syndrome, which includes hypertension, hyperglycemia, obesity, insulin resistance, and dyslipidemia, has a negative impact on cognitive health. Endoplasmic reticulum (ER) stress is activated during metabolic syndrome, however it is not known which factor associated with metabolic syndrome contributes to this stress. ER stress has been reported to play a role in the development of insulin resistance in peripheral tissues. The role of ER stress in the development of insulin resistance in hippocampal neurons is not known. In the current study, we investigated ER stress in the hippocampus of 3 different mouse models of metabolic syndrome: the C57BL6 mouse on a high fat (HF) diet; apolipoprotein E, leptin, and apolipoprotein B-48 deficient (ApoE 3KO) mice; and the low density lipoprotein receptor, leptin, and apolipoprotein B-48 deficient (LDLR 3KO) mice. We demonstrate that ER stress is activated in the hippocampus of HF mice, and for the first time, in ApoE 3KO mice, but not LDLR 3KO mice. The HF and ApoE 3KO mice are hyperglycemic; however, the LDLR 3KO mice have normal glycemia. This suggests that hyperglycemia may play a role in the activation of ER stress in the hippocampus. Similarly, we also demonstrate that impaired insulin signaling is only present in the HF and ApoE 3KO mice, which suggests that ER stress may play a role in insulin resistance in the hippocampus. To confirm this we pharmacologically induced ER stress with thapsigargin in human hippocampal neurons. We demonstrate for the first time that thapsigargin leads to ER stress and impaired insulin signaling in human hippocampal neurons. Our results may provide a potential mechanism that links metabolic syndrome and cognitive health.

show abstract

Section: Introductionmentioning

confidence: 99%

The role of endoplasmic reticulum stress in hippocampal insulin resistance

Sims‐Robinson

Bakeman

Glasser

et al. 2016

Experimental Neurology

View full text Add to dashboard Cite

show abstract

“…Using such brain phenotypes, many studies have investigated factors of morphological brain aging such as sex (Coffey et al, 1998; Resnick et al, 2003; Lemaître et al, 2005b; Abe et al, 2010; Hua et al, 2010; O'Dwyer et al, 2012; Ryan et al, 2014), genetics (Lemaître et al, 2005a; Crivello et al, 2010; Boada et al, 2012; Stein et al, 2012; Ryan et al, 2014) or lifestyle (Coffey et al, 1999; Sabia et al, 2014; Shpanskaya et al, 2014; Umene-Nakano et al, 2014). Others have demonstrated the effect on brain atrophy of cardiovascular risk factors such as obesity (Driscoll et al, 2012; Xu et al, 2013; Debette et al, 2014, 2011; Franke et al, 2014), hypertension (Debette et al, 2011; Maillard et al, 2012; Peters, 2012; Beauchet et al, 2013; Franke et al, 2014), hypercholesterolemia (Tendolkar et al, 2012; Van Velsen et al, 2013; Franke et al, 2014), diabetes (Biessels et al, 2005; Debette et al, 2011; Cherbuin et al, 2012; Franke et al, 2014) and tobacco smoking (Enzinger et al, 2005; Ikram et al, 2008; Debette et al, 2011; Durazzo et al, 2012; Hoogendam et al, 2012). …”

Section: Introductionmentioning

confidence: 99%

Sex-related and tissue-specific effects of tobacco smoking on brain atrophy: assessment in a large longitudinal cohort of healthy elderly

Duriez

Crivello

Mazoyer

2014

Front. Aging Neurosci.

View full text Add to dashboard Cite

We investigated the cross-sectional and longitudinal effects of tobacco smoking on brain atrophy in a large cohort of healthy elderly participants (65–80 years). MRI was used for measuring whole brain (WB), gray matter (GM), white matter (WM), and hippocampus (HIP) volumes at study entry time (baseline, N = 1451), and the annualized rates of variation of these volumes using a 4-year follow-up MRI in a subpart of the cohort (N = 1111). Effects of smoking status (never, former, or current smoker) at study entry and of lifetime tobacco consumption on these brain phenotypes were studied using sex-stratified AN(C)OVAs, including other health parameters as covariates. At baseline, male current smokers had lower GM, while female current smokers had lower WM. In addition, female former smokers exhibited reduced baseline HIP, the reduction being correlated with lifetime tobacco consumption. Longitudinal analyses demonstrated that current smokers, whether men or women, had larger annualized rates of HIP atrophy, as compared to either non or former smokers, independent of their lifetime consumption of tobacco. There was no effect of smoking on the annualized rate of WM loss. In all cases, measured sizes of these tobacco-smoking effects were of the same order of magnitude than those of age, and larger than effect sizes of any other covariate. These results demonstrate that tobacco smoking is a major factor of brain aging, with sex- and tissue specific effects, notably on the HIP annualized rate of atrophy after the age of 65.

show abstract

“…In addition to the accelerated cognitive decline observed in DM2, it is also reported that people with DM2 are at greater risk of dementia [2,17]. This risk is most often attributed to the effects of hyperglycaemia on the brain, although severe episodes of hypoglycaemia may also increase its probability [18].…”

Section: Dm2 and Cognitive Impairment: The Mechanismsmentioning

confidence: 99%

“…Despite its apparent detrimental effects, the occurrence of hypoglycaemia in DM2 is not commonly reported, possibly due to patients being unaware of its symptoms when mild hypoglycaemia occurs [15,16]. Further long term investigation of hypoglycaemia's effects on cognitive performance in DM2 is clearly needed.In addition to the accelerated cognitive decline observed in DM2, it is also reported that people with DM2 are at greater risk of dementia [2,17]. This risk is most often attributed to the effects of hyperglycaemia on the brain, although severe episodes of hypoglycaemia may also increase its probability [18].…”

mentioning

confidence: 99%

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

Jones¹,

Riby²,

Mitchell³

et al. 2014

CDR

View full text Add to dashboard Cite

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...

show abstract

Diabetes and cognitive impairment

Cited by 70 publications

References 28 publications

The role of endoplasmic reticulum stress in hippocampal insulin resistance

The role of endoplasmic reticulum stress in hippocampal insulin resistance

Sex-related and tissue-specific effects of tobacco smoking on brain atrophy: assessment in a large longitudinal cohort of healthy elderly

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

Contact Info

Product

Resources

About