Type 2 diabetes mellitus, cognitive impairment and dementia

Stewart, Robert; Liolitsa, Danae

doi:10.1046/j.1464-5491.1999.00027.x

Cited by 485 publications

(326 citation statements)

References 153 publications

Supporting

Mentioning

298

Contrasting

Unclassified

Order By: Relevance

“…A substantial body of literature has suggested that chronic hyperglycaemia and/or the occurrence of complications could directly or indirectly affect brain function [32,33]. As virtually all of this work has been conducted in adults with Type 2 diabetes, it is unlikely that those cognitive changes can be attributed to recurrent hypoglycaemia, given the very low rates of hypoglycaemia in patients with Type 2 diabetes [34].…”

Section: Discussionmentioning

confidence: 99%

Cognitive efficiency declines over time in adults with Type 1 diabetes: effects of micro- and macrovascular complications

2003

View full text Add to dashboard Cite

Aims/hypothesis. Mild cognitive dysfunction is not uncommon in adults with Type 1 diabetes, but its pathogenesis remains unclear. Previous cross-sectional studies had suggested that microangiopathy might affect brain integrity and lead to 'central neuropathy.' To assess the relationship between changes in cognitive performance and the incidence of new micro-and macrovascular complications, 103 young and middle-aged adults (mean age: 40 yrs) with childhood-onset Type 1 diabetes were followed over a 7-year period, and were compared to 57 demographically-similar adults without diabetes. Methods. All subjects completed a comprehensive battery of neurocognitive tests on two occasions. Diabetic subjects also received repeated medical assessments to diagnose the onset of clinically significant complications.Results. Relative to control subjects, diabetic adults showed significant declines on measures of psychomotor efficiency; no between-group differences were evident on learning, memory, or problem-solving tasks. The development of proliferative retinopathy and autonomic neuropathy during the follow-up period predicted decline in psychomotor speed (p<0.01), as did incident macrovascular complications (p<0.05), systolic blood pressure at follow-up (p<0.01), and duration of diabetes (p<0.01). Conclusion/interpretation. This study shows that cognitive efficiency may decline over time in diabetic adults, and that this neurocognitive change may be linked, at least in part, to the occurrence of complications like proliferative retinopathy and elevated blood pressure. Therapeutic interventions that reduce the risk of vascular complications may have a similarly beneficial effect on the brain and reduce the risk of neurocognitive dysfunction in diabetic patients. [Diabetologia (2003)

show abstract

Section: Discussionmentioning

confidence: 99%

Cognitive efficiency declines over time in adults with Type 1 diabetes: effects of micro- and macrovascular complications

2003

View full text Add to dashboard Cite

show abstract

“…The experimental model presented in this study can be used to study the pathophysiology of the complex interaction between diabetes and ageing. Better understanding of this interaction may eventually challenge the concept of accelerated cognitive decline in elderly diabetic patients as an irremediable disorder [16].…”

Section: Discussionmentioning

confidence: 99%

“…This hypothesis stems from clinical observations that the effects of diabetes on the brain are most pronounced in the elderly [16]. Moreover, many of the processes which have been implicated in the pathogenesis of brain ageing, in particular oxidative stress, microvascular dysfunction, non-enzymatic protein glycation and disturbed intracellular calcium homeostasis [17,18], are also implicated in the development of diabetic complications [17,19].…”

mentioning

confidence: 99%

Learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: interaction of diabetes and ageing

et al. 2000

View full text Add to dashboard Cite

Peripheral neuropathy is a well-known complication of both clinical and experimental diabetes mellitus. Long-term diabetes also leads to a variety of discrete functional and structural disorders in the central nervous system [1]. Moderate impairment of cognitive function has been observed in middle-aged adults with Type I (insulin-dependent) or Type II (non-insulin-dependent) diabetes mellitus. In the elderly cognitive deficits appear, however, to be more pronounced and can readily be detected with relatively crude tests such as the mini-mental state examination [4,5].The hippocampus is a brain structure involved in certain forms of learning [6,7]. At the cellular level, hippocampal long-term potentiation (LTP) and depression (LTD) are two forms of synaptic plasticity which have attracted considerable attention in the search for the mechanisms of learning and memory [8,9]. We have shown previously that LTP expression was impaired in the CA1 and the CA3 field of the hippocampus of young adult diabetic rats, whereas LTD expression in the CA1 field was enhanced [10, Diabetologia (2000) Abstract Aims/hypothesis. Diabetes mellitus leads to functional and structural changes in the brain which appear to be most pronounced in the elderly. Because the pathogenesis of brain ageing and that of diabetic complications show close analogies, it is hypothesized that the effects of diabetes and ageing on the brain interact. Our study examined the effects of diabetes and ageing on learning and hippocampal synaptic plasticity in rats. Methods. Young adult (5 months) and aged (2 years) rats were examined after 8 weeks of streptozotocindiabetes. Learning was tested in a Morris water maze. Synaptic plasticity was tested ex vivo, in hippocampal slices, in response to trains of stimuli of different frequency (0.05 to 100 Hz). Results. Statiscally significant learning impairments were observed in young adult diabetic rats compared with controls. These impairments were even greater in aged diabetic animals. In hippocampal slices from young adult diabetic animals long-term potentiation induced by 100 Hz stimulation was impaired compared with controls (138 vs 218 % of baseline). In contrast, long-term depression induced by 1 Hz stimulation was enhanced in slices from diabetic rats compared with controls (79 vs 92 %). In non-diabetic aged rats synaptic responses were 149 and 93 % of baseline in response to 100 and 1 Hz stimulation, compared with 106 and 75 % in aged diabetic rats. Conclusion/interpretation. Both diabetes and ageing affect learning and hippocampal synaptic plasticity. The cumulative deficits in learning and synaptic plasticity in aged diabetic rats indicate that the effects of diabetes and ageing on the brain could interact. [Diabetologia (2000) 43: 500±506]

show abstract

“…Some diabetic patients develop cognitive deficits, which are generally moderate in young adults [2] but can be more pronounced in the elderly [3]. Recent epidemiological studies even report an association between diabetes and dementia [3,4]. Given the prevalence of diabetes among the elderly and the effect of cognitive impairment and dementia on the quality of life of patients and health care resources, a better understanding of the effects of diabetes on the brain is needed.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Cerebral metabolism in streptozotocin-diabetic rats: an in vivo magnetic resonance spectroscopy study

et al. 2001

View full text Add to dashboard Cite

It is becoming increasingly clear that the brain is another site of diabetic end-organ damage [1]. Some diabetic patients develop cognitive deficits, which are generally moderate in young adults [2] but can be more pronounced in the elderly [3]. Recent epidemiological studies even report an association between diabetes and dementia [3,4]. Given the prevalence of diabetes among the elderly and the effect of cognitive impairment and dementia on the quality of life of patients and health care resources, a better understanding of the effects of diabetes on the brain is needed.Experimentally diabetic rodents develop cerebral deficits similar to those observed in diabetic patients. Streptozotocin (STZ)-diabetic rats have been found to have impaired learning and memory functions [5] and increases in the peak latencies of brainstem audi- Diabetologia (2001) Abstract Aims/hypothesis. It is increasingly evident that the brain is another site of diabetic end-organ damage. The pathogenesis has not been fully explained, but seems to involve an interplay between aberrant glucose metabolism and vascular changes. Vascular changes, such as deficits in cerebral blood flow, could compromise cerebral energy metabolism. We therefore examined cerebral metabolism in streptozotocin-diabetic rats in vivo by means of localised 31 P and 1 H magnetic resonance spectroscopy. Methods. Rats were examined 2 weeks and 4 and 8 months after diabetes induction. A non-diabetic group was examined at baseline and after 8 months.Results. In 31 P spectra the phosphocreatine:ATP, phosphocreatine:inorganic phosphate and ATP:inorganic phosphate ratios and intracellular pH in diabetic rats were similar to controls at all time points. In 1 H spectra a lactate resonance was detected as frequently in controls as in diabetic rats. Compared with baseline and 8-month controls 1 H spectra did, however, show a statistically significant decrease in N-acetylaspartate:total creatine (±14 % and ±23 %) and Nacetylaspartate:choline (±21 % and ±17 %) ratios after 2 weeks and 8 months of diabetes, respectively. Conclusion/interpretation. No statistically significant alterations in cerebral energy metabolism were observed after up to 8 months of streptozotocin-diabetes. These findings indicate that cerebral blood flow disturbances in diabetic rats do not compromise the energy status of the brain to a level detectable by magnetic resonance spectroscopy. Reductions in Nacetylaspartate levels in the brain of STZ-diabetic rats were shown by 1 H spectroscopy, which could present a marker for early metabolic or functional abnormalities in cerebral neurones in diabetes. [Diabetologia (2001) 44: 346±353]

show abstract

Type 2 diabetes mellitus, cognitive impairment and dementia

Cited by 485 publications

References 153 publications

Cognitive efficiency declines over time in adults with Type 1 diabetes: effects of micro- and macrovascular complications

Cognitive efficiency declines over time in adults with Type 1 diabetes: effects of micro- and macrovascular complications

Learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: interaction of diabetes and ageing

Cerebral metabolism in streptozotocin-diabetic rats: an in vivo magnetic resonance spectroscopy study

Contact Info

Product

Resources

About