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Geert Jan Biessels

Publications and source records attributed to Geert Jan Biessels.

14 recordsLinked to original sources
PubMed2006

Risk of dementia in diabetes mellitus: a systematic review.

The relation between diabetes and major types of dementia is controversial. This systematic review examines the incidence of dementia in people with diabetes mellitus. We identified 14 eligible longitudinal population-based studies of variable methodological quality. The incidence of "any dementia" was higher in individuals with diabetes than in those without diabetes in seven of ten studies reporting this aggregate outcome. This high risk included both Alzheimer's disease and vascular dementia (eight of 13 studies and six of nine studies respectively). Detailed data on modulating and mediating effects of glycaemic control, microvascular complications, and comorbidity (eg, hypertension and stroke) were generally absent. The findings of mechanistic studies suggest that vascular disease and alterations in glucose, insulin, and amyloid metabolism underlie the pathophysiology, but which of these mechanisms are clinically relevant is unclear. Further high quality studies need to be initiated, with objective diabetes assessment, together with reliable methods to establish the contribution of vascular disease and other comorbidity to dementia.

Community Health Planning↗
PubMed2006

Cognitive performance, psychological well-being, and brain magnetic resonance imaging in older patients with type 1 diabetes.

Modest cognitive impairment has been reported in young-adult patients with type 1 diabetes. In older patients with type 2 diabetes, cognitive impairments are more pronounced, which might be due to age but also to differential effects of type 1 diabetes and type 2 diabetes on the brain. This study therefore assessed cognitive performance and magnetic resonance imaging (MRI) of the brain in older type 1 diabetic patients. Forty type 1 diabetic patients (age >50 years) and 40 age-matched control subjects were included. Neuropsychological assessment included all major cognitive domains, and psychological well-being was assessed with questionnaires. Atrophy, white-matter abnormalities, and infarcts were rated on MRI scans. Type 1 diabetic patients performed slightly (effect sizes <0.4) worse on cognitive tasks, but only "speed of information processing" reached statistical significance. No significant between-group differences were found on any of the MRI parameters. Type 1 diabetic patients tended to report more cognitive and depressive problems than control subjects, but this did not correlate with the performance on cognitive tests. We conclude that cognition in older type 1 diabetic patients is only mildly disturbed. Chronic exposure to hyperglycemia is in itself, even at older age, apparently not sufficient to have considerable impact on the brain.

Aged↗
PubMed2006

Brain magnetic resonance imaging correlates of impaired cognition in patients with type 2 diabetes.

The structural correlates of impaired cognition in type 2 diabetes are unclear. The present study compared cognition and brain magnetic resonance imaging (MRI) between type 2 diabetic patients and nondiabetic control subjects and assessed the relationship between cognition and MRI findings and blood pressure and metabolic control. The study included 113 patients and 51 control subjects. Brain MRI scans were rated for white matter lesions (WMLs), cortical and subcortical atrophy, and infarcts. Neuropsychological test scores were divided into five cognitive domains and expressed as standardized Z values. Type 2 diabetes was associated with deep WMLs (P = 0.02), cortical (P < 0.001) and subcortical (P < 0.05) atrophy, (silent) infarcts (P = 0.06), and impaired cognitive performance (attention and executive function, information-processing speed, and memory, all P < 0.05). Adjustment for hypertension did not affect the results. Within the type 2 diabetic group, cognitive function was inversely related with WMLs, atrophy, and the presence of infarcts (adjusted for age, sex, and estimated IQ), and there was a modest association with HbA1c and diabetes duration. This association was strongest for age, even more so than in control subjects. We conclude that cognitive impairments in patients with type 2 diabetes are not only associated with subcortical ischemic changes in the brain, but also with increased brain atrophy.

Aged↗
PubMed2005

Diabetes and cognitive impairment. Clinical diagnosis and brain imaging in patients attending a memory clinic.

BACKGROUND: Diabetes is a risk factor for dementia,but the issue whether this concerns only vascular dementia or also Alzheimer's disease is debated. We compared the clinical diagnoses and abnormalities on brain MRI in patients with or without diabetes who received standardised, detailed diagnostic studies at a memory clinic, in order to establish whether one specific type of dementia or specific MRI abnormalities were more common in diabetes. PATIENTS AND METHODS: Patients who visited our memory clinic between January 2002 and June 2004 were divided into a group with (n = 42) or without diabetes (n = 389). The diagnoses were recorded, and MRI scans were rated for (sub)cortical atrophy, medial temporal lobe atrophy, infarctions, and white matter changes. RESULTS: The proportion of Alzheimer's disease (36% versus 28%; OR 1.1 (95% CI 0.5-2.2), adjusted for age and sex), vascular dementia (5% versus 2%; OR 2.4 (0.5-12.1)), and so called "cognitive impairment no dementia" (24% versus 17%; 1.3 (0.6-2.9)) was similar in patients with or without diabetes. On MRI lacunar and cortical infarctions were more common and cortical atrophy more pronounced among diabetic patients. By contrast, the severity of white matter changes was similar in the two groups. CONCLUSION: The relative frequency of different diagnoses among diabetic and non-diabetic patients attending a memory clinic was similar, indicating that diabetes does not predispose to one particular subtype of dementia. The imaging findings support the notion that the increased risk of cognitive decline and dementia in elderly subjects with diabetes is due to dual pathology, involving both cerebrovascular disease and cortical atrophy.

Aged↗
PubMed2005

The impact of diabetes on cognition: what can be learned from rodent models?

Diabetes mellitus is associated with modest impairments in cognition, particularly in the elderly. In addition, the risk of dementia is increased. We review herein studies in rodent models that may help to identify the mechanisms that underlie these adverse effects of diabetes on the brain. Abnormalities in learning and memory, synaptic plasticity, and glutamatergic neurotransmission have now been identified in a number of these models. In general, observations in models characterized by chronic hyperglycaemia and hypoinsulinaemia (referred to as models of type 1 diabetes) are quite consistent, and these models are being increasingly used to study the pathogenesis and to develop new treatments. However, results from models characterized by insulin resistance, hyperinsulinaemia, and modest hyperglycaemia (referred to as models of type 2 diabetes) are much more variable. Moreover, the possible interaction between diabetes and aging has not been examined in sufficient detail. Because clinically relevant cognitive deficits mainly occur in elderly patients with type 2 diabetes, the challenge for researchers in this field will be to further develop adequate models.

Aging↗
PubMed2005

Effects of the Ca2+ antagonist nimodipine on functional deficits in the peripheral and central nervous system of streptozotocin-diabetic rats.

Diabetes mellitus can lead to functional and structural deficits in both the peripheral and central nervous system. The pathogenesis of these deficits is multifactorial, probably involving, among others, microvascular dysfunction and alterations in intracellular calcium homeostasis. The present study examined the effects of treatment with the Ca2+ antagonist nimodipine (20 mg/kg, intraperitoneal injection, every 48 h) on functional deficits in the peripheral and central nervous system in streptozotocin-diabetic rats. In a prevention experiment, treatment was initiated immediately after diabetes induction and continued for 10 weeks. In a reversal experiment, treatment was initiated 16 weeks after diabetes induction and continued for 12 weeks. Sciatic nerve motor and sensory conduction velocity, brainstem auditory-evoked potentials, and visual-evoked potentials were measured in control, untreated, and nimodipine-treated diabetic rats. In addition, long-term potentiation, a form of synaptic plasticity used as a model for learning and memory at the cellular level, was examined in hippocampal slices. Nimodipine treatment partially prevented deficits in nerve conduction velocity and hippocampal long-term potentiation in diabetic rats. However, nimodipine intervention treatment was unable to reverse established deficits in nerve conduction velocity, evoked potential latencies, or long-term potentiation. It is concluded that nimodipine can partially prevent early functional deficits in the peripheral and central nervous system of streptozotocin-diabetic rats but is unable to reverse late deficits.

Analysis of Variance↗
PubMed2005

The effects of type 1 diabetes on cognitive performance: a meta-analysis.

OBJECTIVE: To investigate the exact nature and magnitude of cognitive impairments in patients with type 1 diabetes and the possible association with other disease variables, such as recurrent episodes of hypoglycemia and metabolic control. RESEARCH DESIGN AND METHODS: MedLine and PsycLit search engines were used to identify studies on cognitive performance in patients with type 1 diabetes. Effect sizes (Cohen's d), which are the standardized differences between the experimental and the control group, were calculated. In the meta-analysis, a combined d value was calculated, expressing the magnitude of associations across studies. RESULTS: A total of 33 studies were identified that met the inclusion criteria. Compared with nondiabetic control subjects, the type 1 diabetic group demonstrated a significantly lowered performance on the following cognitive domains: intelligence (d = -0.7), speed of information processing (d = -0.3), psychomotor efficiency (d = -0.6), visual (d = -0.4) and sustained attention (d = -0.3), cognitive flexibility (d = -0.5), and visual perception (d = -0.4). Lowered cognitive performance in diabetic patients appeared to be associated with the presence of microvascular complications but not with the occurrence of severe hypoglycemic episodes or with poor metabolic control. CONCLUSIONS: In patients with type 1 diabetes, cognitive dysfunction is characterized by a slowing of mental speed and a diminished mental flexibility, whereas learning and memory are spared.The magnitude of the cognitive deficits is mild to moderate, but even mild forms of cognitive dysfunction might hamper everyday activities since they can be expected to present problems in more demanding situations.

Attention↗
PubMed2004

Cerebral dysfunction in type 1 diabetes: effects of insulin, vascular risk factors and blood-glucose levels.

Type 1 diabetes can lead to several well-described complications such as retinopathy, nephropathy and peripheral neuropathy. Evidence is accumulating that it is also associated with gradually developing end-organ damage in the central nervous system. This relatively unknown complication can be referred to as "diabetic encephalopathy" and is characterised by electrophysiological and neuroradiological changes, such as delayed latencies of evoked potentials, modest cerebral atrophy and (periventricular) white matter lesions. Furthermore, individuals with type 1 diabetes may show performance deficits in a wide range of cognitive domains. The exact mechanisms underlying this diabetic encephalopathy are only partially known. Chronic metabolic and vascular changes appear to play an important role. Interestingly, the differences in the "cognitive profile" between type 1 and type 2 diabetes also suggest a critical role for disturbances of insulin action in the central nervous system.

Animals↗
PubMed2004

Glucose, insulin and the brain: modulation of cognition and synaptic plasticity in health and disease: a preface.

The brain has long been viewed as an insulin-insensitive organ. Following the demonstration of insulin receptors in the brain, this assumption has been challenged, and a whole new field of research has emerged. Insulin appears to play a role in brain physiology, and disturbances of cerebral insulin signalling and glucose homeostasis are implicated in brain pathology. This special issue of the European Journal of Pharmacology provides an overview of research into the involvement of glucose and insulin in the modulation of cognition and synaptic plasticity in health and in disease. In three sections, the effects of glucose and insulin on the brain will be discussed from a physiological perspective, in relation to brain ageing and Alzheimer's disease, and in relation to diabetes mellitus, respectively. These subjects will be covered from various angles, from the level of molecular neurosciences, to the level of applied neuropsychology.

Alzheimer Disease↗
PubMed2003

Angiotensin converting enzyme inhibition partially prevents deficits in water maze performance, hippocampal synaptic plasticity and cerebral blood flow in streptozotocin-diabetic rats.

Vascular dysfunction is important in the pathogenesis of peripheral complications of diabetes. However, the effects of diabetes on cerebral blood flow and the role of vascular deficits in the pathogenesis of diabetic encephalopathy are still unknown. The present study examined whether experimental diabetes is associated with reduced cerebral blood flow and whether treatment with enalapril can improve cerebral perfusion and function (blood flow and functional cerebral deficits). Streptozotocin-diabetic rats were treated with the ACE inhibitor enalapril (24 mg/kg) from onset of diabetes. After 14 weeks of diabetes, 12 enalapril treated and 12 untreated diabetic rats, and 12 nondiabetic age-matched control rats were tested in a spatial version of the Morris water maze. After 16 weeks of diabetes, in the same groups, blood flow in the hippocampus and thalamus was measured by hydrogen clearance microelectrode polarography. In a separate study, hippocampal long-term potentiation was measured after 26 weeks of diabetes. Water maze performance and hippocampal long-term potentiation were impaired in diabetic rats. Furthermore, blood flow in diabetic rats was reduced by 30% (P<0.001) in the hippocampus and by 37% (P<0.005) in the thalamus compared to nondiabetic controls. Enalapril treatment significantly improved water maze performance (P<0.05), hippocampal long term potentiation (P<0.05) and hippocampal blood flow (P<0.05). Cerebral perfusion is reduced in diabetic rats compared to controls. Treatment aimed at the vasculature can improve cerebral blood flow, deficits in Morris maze performance and long term potentiation. These findings suggest that vasculopathy plays a role in the development of cerebral dysfunction in diabetic rats.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Neuronal Ca2+ disregulation in diabetes mellitus.

The Ca(2+) hypothesis of brain ageing and dementia may account for part of the available data on the pathogenesis of dementia and certain neurodegenerative disorders. The hypothesis proposes that disturbances in the homeostasis of neuronal cytosolic free Ca(2+) are part of a final common pathway, ultimately leading to neuronal dysfunction and cell death. The hypothesis also proposes that a small change in cytosolic free Ca(2+) sustained over a long period of time will result in similar damage as a large change over a short period. Diabetes mellitus is associated with neurological complications in the peripheral and central nervous system, as reflected in peripheral neuropathy, modest cognitive impairments and an increased risk of dementia. In animal models of diabetes, learning impairments are associated with alterations in Ca(2+) -dependent forms of hippocampal synaptic plasticity. Disturbances in the homeostasis of cytosolic free Ca(2+) may present a final common pathway in the multifactorial pathogenesis of neurological complications of diabetes, which involves vascular changes, oxidative stress, and non-enzymatic protein glycation. In line with the Ca(2+) hypothesis of neurodegenerative disorders, a prolonged, small increase in basal cytosolic Ca(2+) levels indeed exists in sensory neurones of diabetic animals. In addition, Ca(2+) dynamics are affected. Ca(2+) channel blockers, such as nimodipine, have been shown to improve experimental peripheral neuropathy, through a vascular mechanism, possibly in combination with direct neuronal effects. Preliminary studies indicate that nimodipine may also improve Ca(2+)-dependent forms of synaptic plasticity in the hippocampus of diabetic rats.

Aging↗
PubMed2002

Ageing and diabetes: implications for brain function.

Diabetes mellitus is associated with moderate cognitive deficits and neurophysiological and structural changes in the brain, a condition that may be referred to as diabetic encephalopathy. Diabetes increases the risk of dementia, particularly in the elderly. The emerging view is that the diabetic brain features many symptoms that are best described as "accelerated brain ageing." The clinical characteristics of diabetic encephalopathy are discussed, as well as behavioural (e.g. spatial learning) and neurophysiological (e.g. hippocampal synaptic plasticity) findings in animal models. Animal models can make a substantial contribution to our understanding of the pathogenesis, which shares many features with the mechanisms underlying brain ageing. By unravelling the pathogenesis, targets for pharmacotherapy can be identified. This may allow treatment or prevention of this diabetic complication in the future. We discuss changes in glutamate receptor subtypes, in second-messenger systems and in protein kinases that may account for the alterations in synaptic plasticity. In addition, the possible role of cerebrovascular changes, oxidative stress, nonenzymatic protein glycation, insulin and alterations in neuronal calcium homeostasis are addressed.

Aging↗
PubMedDate not supplied

Nerve conduction velocity and evoked potential latencies in streptozotocin-diabetic rats: effects of treatment with an angiotensin converting enzyme inhibitor.

BACKGROUND: Diabetes mellitus is associated with deficits in cerebral function. Vascular disorders may play a role in the pathogenesis and provide a potential target for treatment. The present study examined if prevention and intervention treatment with the angiotensin converting enzyme inhibitor enalapril could improve peripheral and central neurophysiological deficits in streptozotocin-diabetic rats. METHODS: Sciatic nerve conduction velocities were measured prior to diabetes induction and again every three weeks. In the prevention study, the final nerve conduction measurements were performed at 15 weeks and in the intervention study at 24 weeks. Brain stem auditory and visual evoked potential latencies were measured every 3 weeks from 10 weeks after diabetes induction. In the prevention study, the final evoked potential measurements were performed at 16 weeks and in the intervention study at 25 weeks. Treatment with the angiotensin converting enzyme inhibitor enalapril was started directly after diabetes induction (prevention treatment) and after 15 weeks of diabetes (intervention treatment). RESULTS: Nerve conduction velocity, brain stem auditory and visual evoked potential latencies were impaired in diabetic rats. Enalapril prevented deficits in nerve conduction velocity (p < 0.001), brain stem auditory evoked potential latencies (p < 0.01) and visual evoked potential latencies (p < 0.005). Enalapril intervention treatment had no effect on nerve conduction velocity and on visual evoked potential latencies, but improved brain stem auditory evoked potential latencies (p < 0.05) after 10 weeks of treatment. CONCLUSION: Enalapril partially prevents the development of neurophysiological alterations in the peripheral and central nervous system and partially reverses deficits in brain stem auditory evoked potential latencies in STZ-diabetic rats.

Angiotensin-Converting Enzyme Inhibitors↗