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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic patients have impaired learning/memory, brain atrophy, and two-fold increased risk of dementia. The cause of cognitive disturbances that progress to dementia is unknown. Because neurotrophic insulin-like growth factor (IGF) levels are reduced in diabetic patients and rodents, and IGF can cross the blood-central nervous system barrier (B-CNS-B), the hypothesis was tested that IGF administered systemically can prevent cognitive disturbances, independently of hyperglycemia and a generalized catabolic state. Latency to escape to a hidden platform in the Morris Water Maze is used widely to test spatial memory, a hippocampus-dependent task. Adult rats were rendered diabetic with streptozotocin and implanted 4 weeks later with subcutaneous pumps that released either vehicle (D + Veh) or 20 microg/day IGF-I (D + IGF). Latency to escape to the hidden platform was prolonged in (D + Veh) versus non-diabetic rats (P < 0.003) 10.5 weeks after the onset of diabetes. Such prolongation was prevented in (D + IGF) versus (D + Veh) rats (P < 0.03). The data show that IGF-I can act across the B-CNS-B to prevent loss of cognition-related performance in the water maze independently of ongoing hyperglycemia and reduction in brain (P < 0.001) and whole body weight (P < 0.001) in diabetic rats. The hypothesis that brain IGF contributes to learning/memory was tested. An anti-IGF antibody, or preimmune serum, was infused into the lateral ventricles in non-diabetic rats. Learning in a passive avoidance task was impaired significantly in the IGF antibody versus preimmune serum-treated groups on test Days 1, 2, and 3 (P = 0.04, 0.02 and 0.004, respectively). The data together are consistent with a model in which brain IGF is essential for learning/memory, and a loss of IGF activity due to diabetes may contribute to cognitive disturbances.
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PMID:Systemic insulin-like growth factor-I administration prevents cognitive impairment in diabetic rats, and brain IGF regulates learning/memory in normal adult rats. 1459 95

Diabetic patients are at increased risk for stroke, but little is known about the presence of other brain lesions. We studied the association of magnetic resonance imaging-detected brain lesions to diabetes in 1,252 individuals aged 65-75 years who were randomly selected from eight European population registries or defined working populations. All scans were centrally read for brain abnormalities, including infarcts, white matter lesions, and atrophy. We used a three-point scale to rate periventricular white matter lesions, and the volume of subcortical lesions was calculated according to their number and size. Subjective grading of cortical atrophy by lobe and summation of the lobar grades resulted in a total cortical atrophy score. The mean of three linear measurements of the ventricular diameter relative to the intracranial cavity defined the severity of subcortical atrophy. After adjustment for possible confounders, diabetes was associated with cortical brain atrophy but not with any focal brain lesions or subcortical atrophy. There was a strong interaction of diabetes and hypertension, such that the association between diabetes and cortical atrophy existed only in hypertensive but not in normotensive participants. Cognitive and pathological data are needed to determine the clinical significance of these findings as well as to understand the mechanisms underlying these associations.
Diabetes 2004 Mar
PMID:Magnetic resonance imaging of the brain in diabetes: the Cardiovascular Determinants of Dementia (CASCADE) Study. 1498 53

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.
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PMID:Cerebral dysfunction in type 1 diabetes: effects of insulin, vascular risk factors and blood-glucose levels. 1509 82

We investigated the influence of brain atrophy and white matter lesions on cognitive function in elderly people. We selected 33 subjects (mean age, 79.2 +/- 5.1yrs) with a MMSE score from 14 to 30 who had no previous history of stroke from the outpatients in the Memory Clinic of our hospital. These subjects were divided into four groups on the basis of their MMSE score as follows: 14-20; moderate dementia (Moderate-D, n = 9), 21-23; mild dementia (Mild-D, n = 9), 24-27; mild cognitive impairment (MCI, n = 10), 28-30; normal (Normal, n = 5). Among these four groups, we compared the frequency of the associated risk factors for cerebral infarction (hypertension, diabetes mellitus, hyperlipidemia, heart disease), and the severity of brain atrophy and cerebral white matter lesion which were visually evaluated by MRI technique. Brain atrophy and white matter lesions were assessed by reviewing the cerebral cortex and hippocampus, and deep white matter lesion (DWML) and periventricular hyperintensity (PVH), respectively. Brain atrophy was divided into three grades (mild, moderate, severe) and white matter lesions were classified into four grades (0-3) using Fazekas's criteria. We performed statistical analysis to detect t parameters which correlate with and influence MMSE scores from among the MRI findings. The cases with dementia were all diagnosed as Alzheimer's disease. There were no significant differences among the four groups in mean age, the incidence of individual associated risk factors, the severity of cortical atrophy, or the grade of DWML (< or = 2) and PVH (< or = 2). However, the frequency of hippocampal atrophic change greater than a moderate grade increased in parallel with the exacerbation of reduced cognitive function (Normal; 20%, MCI: 40%, Mild-D; 56%, Moderate-D 89%), and approximately 76% with such a change were AD cases. Statistical analysis showed a significant negative correlation between the grade of hippocampal atrophy and MMSE score (r = -0.518, p < 0.005) and a great influence of hippocampal atrophy on that score (step-wise regression analysis: r = 0.518, p < 0.005). From the above results, it was suggested that more than moderate atrophic change in the hippocampus might possibly be related with cognitive impairment and that both DWML and PVH less than the second grade had little influence on the decline of brain function.
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PMID:[A neuroradiological study on the influence of cerebral atrophy and white matter lesion on cognitive function in the elderly]. 1551 34

A clinico-instrumental study of 78 young patients (mean age 41.3 +/- 4.2 years) with ischemic stroke was carried out. A prevalence of such risk factors as severe arterial hypertension, innate and acquired heart valvular disease, familial loading were characteristic of these patients, while ischemic heart disease and diabetes mellitus occurred less often. Comparing to elderly patients, no significant differences in dynamics of neurological deficit were found in young patients with ischemic stroke. The data of neuroimaging examination indicated less frequency of the signs of cerebral atrophy and leucoareosis in young patients. The results obtained confirm the presence of modifying risk factors for ischemic stroke in young patients that grounds realization of preventive measures.
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PMID:[Clinical and pathogenetical features of ischemic stroke of young age]. 1555 19

Human diabetes is associated with cognitive impairment and structural abnormalities in the brain such as cerebral atrophy. The aetiology of these abnormalities is not known. The BB/E rat is a well-established model of type 1 (insulin dependent) diabetes. A cohort of 34 BB/E rats with diabetes was divided into three sub-groups according to age (and duration of diabetes). Basal ganglia calcification (BGC) was present in the brains of more than 50% of diabetic animals, but not in any of 37 non-diabetic BB/E rats. BGC occurred more commonly in those animals which had the longest duration of diabetes (p=0.001), such that BGC was present in only 8% of animals with diabetes for 20 weeks, but in 100% of animals with diabetes for 60 weeks. There were no other significant light microscopic neuropathologic changes in diabetic animals. It will be important to investigate the mechanism of brain calcification, whether a similar process occurs in humans with diabetes, and its possible relationship to cognitive decline.
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PMID:Basal ganglia calcification in BB/E rats with diabetes. 1563 13

Risk of dementia increases after stroke, and poststroke dementia (PSD) is an important cause of disability in the elderly. The prevalence rates of PSD vary from 12.2% to 31.8% within 3 months to 1 year after stroke, depending on patient populations and the diagnostic criteria used in the numerous studies. Incidence rates of PSD increase with time after the stroke. Although vascular lesions and white matter changes can explain the cognitive disorders seen in stroke patients, an underlying neurodegenerative disorder may contribute to the development of PSD. Cognitive decline may pre-date the stroke and follow a progressive course after the stroke. The vascular and degenerative processes involved share common environmental and genetic risk factors. This review explains the mechanisms of dementia in stroke patients and identifies predictive factors for PSD. The following points are successively considered: (i) demographic characteristics of the patients, including age and level of education; (ii) prestroke cognitive decline; (iii) vascular risk factors, including diabetes mellitus and prior strokes; (iv) stroke characteristics, including severity and location of the vascular lesion; (v) co-morbid disorders; and (vi) abnormalities on brain imaging, including location, size and number of vascular lesions, white matter changes and cerebral atrophy. Older age, prestroke cognitive decline, stroke recurrence, hypoxic-ischaemic disorders, left-side infarcts, strategic infarcts and white matter lesions appear to be the main predictive factors of PSD. Prevention of stroke should reduce the morbidity and mortality associated with PSD. In addition, management of PSD with secondary prevention treatments could reduce occurrence of further strokes. Cholinesterase inhibitors may be beneficial not only in Alzheimer's disease associated with cerebrovascular lesions, but also for the treatment of cholinergic dysfunction arising from pure vascular dementia. Better knowledge of the risk factors for PSD, including environmental and genetic factors, should increase the effectiveness of preventive strategies in patients with this condition.
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PMID:Poststroke dementia in the elderly. 1597 39

Brain atrophy in diabetic dementia (DD) may be due to a catabolic state with DNA loss. Insulin-like growth factor (IGF) levels are reduced in diabetes, and IGF replacement may ameliorate brain protein loss. Subcutaneous minipumps released vehicle (Db + Veh) or IGF-I (Db + IGF-I) in diabetic rats. Brain wet, dry, and water weights as well as DNA, rRNA, poly(A)+ RNA, and protein contents per brain were significantly reduced in diabetic rats. In the remaining brain cells, there was a significant decline in ratios of (rRNA/DNA) and (protein/DNA). IGF-I administration partially prevented the loss of brain protein content independently of hyperglycemia (P < 0.03). This is the first demonstration of a severe disturbance in the brain protein regulatory pathway together with DNA loss in diabetes. Because Alzheimer's Disease (AD) is associated with a diabetes-like brain environment, a catabolic state may contribute to brain atrophy in sporadic AD as well as DD.
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PMID:Effect of IGF-I on DNA, RNA, and protein loss associated with brain atrophy and impaired learning in diabetic rats. 1618 84

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.
Diabetes 2006 Apr
PMID:Brain magnetic resonance imaging correlates of impaired cognition in patients with type 2 diabetes. 1656 35

Longstanding diabetes mellitus damages kidney, retina, peripheral nerve and blood vessels, but brain is not usually considered a primary target. We describe direct involvement of the brain, particularly white matter, in long-term (9 months) experimental diabetes of mice, not previously modeled, correlating magnetic resonance (MR) imaging with quantitative histological assessment. Leukoencephalopathy and cerebral atrophy, resembling that encountered in diabetic humans, developed in diabetic mice and was accompanied by time-related development of cognitive changes in behavioural testing. Increased RAGE (receptor for advanced glycation end products) expression, a mediator of widespread diabetic complications, increased dramatically at sites of white matter damage in regions of myelination. RAGE expression was also elevated within neurons, astrocytes and microglia in grey matter and within oligodendrocytes in white matter. RAGE null diabetic mice had significantly less neurodegenerative changes when compared to wild-type diabetic mice. Our findings identify a robust and novel model of cerebral, particularly white matter, involvement with diabetes associated with abnormal RAGE signaling.
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PMID:Diabetes, leukoencephalopathy and rage. 1681 28


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