Sanne M. Manschot

A detailed profile of cognitive dysfunction and its relation to psychological distress in patients with type 2 diabetes mellitus

Type 2 diabetes mellitus (DM2) is a common metabolic disorder. DM2 is associated with cognitive impairments, and with depressive symptoms, which occur in about one third of patients. In the current study we compared the cognitive profile and psychological well-being of 119 patients with DM2 (mean age: 66 +/- 6; mean duration: 9 +/- 6 years) with 55 age and education matched-control participants. Groups were compared on cognitive performance in five major cognitive domains, psychological wellbeing [assessed by Symptom Checklist (SCL)-90-R and the Beck Depression Inventory (BDI-II)] and abnormalities on brain MRI. We hypothesized an interrelationship between cognition, MRI abnormalities, and psychological well-being. DM2 patients performed significantly worse than controls on cognitive tasks, especially on tasks that required more mental efficiency, although the differences were modest (effect sizes Cohen d < .6). We speculate that DM2 patients have a diminished ability to efficiently process unstructured information. Patients with DM2 had significantly higher scores on the SCL-90-R (p < .001) and on the BDI-II (p < .001) and worse MRI ratings than controls, but psychological distress did not correlate with cognition, MRI ratings or biomedical characteristics. Contrary to our hypothesis, cognitive disturbances and psychological distress thus seem independent symptoms of the same disease.

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.

Peripheral and central neurologic complications in type 2 diabetes mellitus: No association in individual patients

Diabetes mellitus is associated with end-organ complications in the peripheral and central nervous system. It is unknown if these complications share a common aetiology, and if they co-occur in the same patient. The aim of the present study was to relate different measures of peripheral neuropathy in patients with type 2 diabetes mellitus (DM2) to cognition and brain MRI. A standardized neurological examination and questionnaire, neuropsychological examination and brain MRI were performed in 122 patients with DM2 and 56 matched controls. Measures of peripheral neuropathy were vibration threshold, a sensory examination sum score and the Toronto Clinical Neuropathy Scoring System. Neuropsychological test scores were expressed in standardized z-values across five predetermined cognitive domains. White matter lesions and cortical and subcortical atrophy were rated on MRI. Overall 38% of the patients with DM2 and 12% of the controls were classified as having any neuropathy (p<0.001). Patients with DM2 had a lower performance on the neuropsychological tests, more white matter lesions (p<0.01) and more atrophy (p<0.01) than controls. Within the DM2 group none of the measures of peripheral neuropathy was related to MRI abnormalities or cognitive dysfunction (linear regression analyses, adjusted for age, education, sex). We conclude that peripheral neuropathy in patients with DM2 is not related to cognitive dysfunction and brain abnormalities. This indicates that central and peripheral neurological complications of DM2 might have different etiologies.

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

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.

Cerebrovascular Reserve Capacity Is Preserved in a Population-Based Sample of Patients with Type 2 Diabetes Mellitus

Background and Purpose: Type 2 diabetes mellitus (DM2) is associated with an increased risk of stroke. DM2 is also associated with cognitive impairments. Vascular dysfunction, such as impaired cerebrovascular reserve capacity (CVR), may be a determinant of these changes, but previous studies on CVR in DM2 have provided variable results in selected populations of patients. We aimed to examine CVR in a population-based sample of DM2 patients. Methods: The CO2 reactivity of the middle cerebral artery was examined using transcranial Doppler ultrasonography in 81 DM2 patients and 38 controls. In DM2 patients CVR was correlated with diabetic parameters, vascular risk factors and cognitive functioning.Results: CVR was similar in patients and controls (51 vs. 49%). Within the DM2 group, there was no statistically significant relationship between CVR and DM duration, HbA1c, albuminuria, blood pressure, intima-media thickness and cognition. CVR tended to be lower in diabetic patients with retinopathy [46 vs. 55%, mean difference: –7.9 (confidence interval –18.0, 2.2)]. Conclusion: We conclude that CVR is not impaired in unselected patients with DM2 and probably does not, therefore, play a major role in the aetiology of cognitive impairment.

Erratum to “Peripheral and central neurologic complications in type 2 diabetes mellitus: No association in individual patients” [J Neurol Sci 264 (2008) 157–162]

a Rudolf Magnus Institute of Neuroscience, Department of Neurology, University Medical Center, Utrecht, The Netherlands b Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands c Helmholtz Research Institute, Utrecht University, University Medical Center, Utrecht, The Netherlands a Rudolf Magnus Institute of Neuroscience, Department of Medical Pharmacology, University Medical Center, Utrecht, The Netherlands

Peripheral and central neurologic complications in type 2 diabetes mellitus

a Rudolf Magnus Institute of Neuroscience, Department of Neurology, University Medical Center, Utrecht, The Netherlands b Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands c Helmholtz Research Institute, Utrecht University, University Medical Center, Utrecht, The Netherlands a Rudolf Magnus Institute of Neuroscience, Department of Medical Pharmacology, University Medical Center, Utrecht, The Netherlands