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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type 2 diabetes mellitus and cognitive impairment are 2 of the most common chronic conditions found in persons aged > or = 60 years. Clinical studies have shown a greater prevalence of global cognitive impairment, incidence of cognitive decline, and incidence of Alzheimer disease in patients with type 2 diabetes. To date, there have been no randomized trials of the effects of long-term glycemic control on cognitive function and structural brain changes in patients with type 2 diabetes. The primary aim of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Memory in Diabetes Study (ACCORD-MIND) is to test whether there is a difference in the rate of cognitive decline and structural brain change in patients with diabetes treated with standard-care guidelines compared with those treated with intensive-care guidelines. This comparison will be made in a subsample of 2,977 patients with diabetes participating in the ongoing ACCORD trial, a clinical trial sponsored by the National Heart, Lung, and Blood Institute (NHLBI) with support from the National Institute on Aging (NIA). Data from this ACCORD substudy on the possible beneficial or adverse effects of intensive treatment on cognitive function will be obtained from a 30-minute test battery, administered at baseline and 20-month and 40-month visits. In addition, full-brain magnetic resonance imaging will be performed on 630 participants at baseline and at 40 months to assess the relation between the ACCORD treatments and structural brain changes. The general aim of ACCORD-MIND is to determine whether the intensive treatment of diabetes, a major risk factor for Alzheimer disease and vascular dementia, can reduce the early decline in cognitive function that could later evolve into more cognitively disabling conditions. This report presents the design, rationale, and methods of the ACCORD-MIND substudy.
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PMID:The Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes Study (ACCORD-MIND): rationale, design, and methods. 1759 21

Diabetes is a major public health burden. Even a modest effect of diabetes on cognitive function has significant public health implications. Several lines of mechanistic evidence implicate a role of insulin and glucose metabolism on risk of developing dementia, including Alzheimer's disease. Population-based studies have shown that those with type 2 diabetes mellitus have an increased risk of cognitive impairment, dementia, and neurodegeneration. There are many mechanisms through which diabetes could increase risk of dementia, including glycemia, insulin resistance, oxidative stress, advanced glycation endproducts, inflammatory cytokines, and microvascular and macrovascular disease. This paper presents a review of the evidence on diabetes and increased risk of dementia and cognitive impairment, a discussion of different possible mechanisms, and remaining gaps in our knowledge.
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PMID:Type 2 diabetes and risk of cognitive impairment and dementia. 1776 26

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.
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PMID:Peripheral and central neurologic complications in type 2 diabetes mellitus: no association in individual patients. 1785 Aug 22

Nifedipine, a calcium channel blocker, has been reported to exert pleiotropic effects on atherosclerosis, mainly through its antioxidative properties. However, the effect of the calcium channel blocker on cognitive impairment associated with type 2 diabetes mellitus is not well known. Here, we examined the possibility that a calcium channel blocker could improve cognitive function in a type 2 diabetic mouse model, KK-A(y). KK-A(y) mice subjected to 20 trials of a passive avoidance task every week from 7 weeks of age exhibited impairment of the increase in avoidance rate and, moreover, exaggeration of its age-dependent decline, especially after 12 weeks of age. Oral administration of nifedipine at a nonhypotensive dose (0.001% in laboratory chow) to KK-A(y) mice from 10 weeks of age improved cognitive function. Nifedipine treatment decreased serum insulin level to one fifth of that in KK-A(y) mice without nifedipine. Moreover, nifedipine treatment significantly reduced superoxide anion production in the brain. Furthermore, treatment with nifedipine markedly reduced the mRNA level of Id-1, inhibitor of neural differentiation, in the brain hippocampus. We also observed the increase in blood flow in the brain in KK-A(y) mice with nifedipine treatment compared with nontreated mice. Taken together, our findings suggest that nifedipine ameliorates impaired cognitive function in type 2 diabetic mice, at least because of attenuation of hyperinsulinemia and superoxide production in the brain and possible upregulation of the neural differentiation-controlling gene, Id-1.
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PMID:Diabetes-associated cognitive impairment is improved by a calcium channel blocker, nifedipine. 1819 65

The deleterious effects of diabetes mellitus on the retinal, renal, cardiovascular, and peripheral nervous systems are widely acknowledged. Less attention has been given to the effect of diabetes on cognitive function. Both type 1 and type 2 diabetes mellitus have been associated with reduced performance on numerous domains of cognitive function. The exact pathophysiology of cognitive dysfunction in diabetes is not completely understood, but it is likely that hyperglycemia, vascular disease, hypoglycemia, and insulin resistance play significant roles. Modalities to study the effect of diabetes on the brain have evolved over the years, including neurocognitive testing, evoked response potentials, and magnetic resonance imaging. Although much insightful research has examined cognitive dysfunction in patients with diabetes, more needs to be understood about the mechanisms and natural history of this complication in order to develop strategies for prevention and treatment.
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PMID:Cognitive dysfunction and diabetes mellitus. 1843 9

Alzheimer's disease, AD, is the most common form of dementia. AD initially targets memory and progressively destroys the mind. The brain atrophies as the neocortex suffers neuronal, synaptic, and dendritic losses, and the hallmark amyloid plaques and neurofibrillary tangles proliferate. Pharmacological management, at best, is palliative and transiently effective, with marked adverse effects. Certain nutrients intrinsic to human biochemistry (orthomolecules) match or exceed pharmacological drug benefits in double-blind, randomized, controlled trials, with superior safety. Early intervention is feasible because its heritability is typically minimal and pathological deterioration is detectable years prior to diagnosis. The syndrome amnestic mild cognitive impairment exhibits AD pathology and to date has frustrated attempts at intervention. The condition age-associated memory impairment is a nonpathological extreme of normal brain aging, but with less severe cognitive impairment than amnestic mild cognitive impairment. Age-associated memory impairment is a feasible target for early intervention against AD, beginning with the modifiable AD risk factors - smoking, hypertension, homocysteine, type 2 diabetes, insulin resistance, and obesity. Stress reduction, avoidance of toxins, and mental and physical exercise are important aspects of prevention. The diet should emphasize omega-3 fatty acids docosahexaenoic acid and eicosapentaenoic acid; flavonoids and other antioxidant nutrients; and B vitamins, especially folate, B6 and B12. Dietary supplementation is best focused on those proven from randomized, controlled trials: the phospholipids phosphatidylserine and glycerophosphocholine, the energy nutrient acetyl-L-carnitine, vitamins C and E, and other antioxidants. A comprehensive integrative strategy initiated early in cognitive decline is the most pragmatic approach to controlling progression to Alzheimer's disease.
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PMID:Alzheimer's disease, amnestic mild cognitive impairment, and age-associated memory impairment: current understanding and progress toward integrative prevention. 1859 Mar 47

The Pro12Ala polymorphism in the PPAR-gamma gene has been associated with reduced incidence of type 2 diabetes. Although diabetes has been implicated as a risk factor for dementia, the association of Pro12Ala with cognitive impairment is unclear. Dementia and cognitive impairment without dementia (CIND) were determined during six annual follow-up evaluations in a cohort of 929 older Latinos. Among those with diabetes at baseline, there was an increased rate of dementia/CIND for Ala carriers compared to non-carriers (adjusted hazard ratio (HR)=2.5, 95% confidence interval (CI): 1.3-4.9) but not among non-diabetic participants (adjusted HR=0.94; 95% CI: 0.49-1.8). Among males, there was also an increased rate for Ala carriers (adjusted HR=2.7, 95% CI: 1.4-5.2) but not among female carriers (adjusted HR=0.88; 95% CI: 0.47-1.6). The rate of dementia/CIND was highest in diabetic male Ala carriers (adjusted HR=4.2; 95% CI: 1.5-11) compared to non-diabetic male carriers (adjusted HR=2.9; 95% CI: 1.1-7.4), diabetic female carriers (HR=1.6; 95% CI: 0.66-4.1), and non-diabetic female carriers (HR=0.52; 95% CI: 0.21-1.3). These data suggest that although the Ala variant is associated with a reduced risk of type 2 diabetes, it may increase the risk of cognitive impairment in individuals once diabetes has developed. Male Ala carriers may also have a greater risk of dementia/CIND.
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PMID:The PPAR-gamma Pro12Ala polymorphism and risk of cognitive impairment in a longitudinal study. 1863 67

The occurrence of diabetes and dementia is very high in older patients. The fact that both conditions are concurrent raises the question of a possible link between the two. Cognitive functions of non-demented patients with diabetes have been extensively studied. In type 1 diabetes, only a mild decrease of the speed of information processing and of the psychomotor efficiency has been shown. Cognitive decline seems to be related to poor metabolic control and not to hypoglycaemia. In older patients with type 2 diabetes, memory and executive functions have been found impaired. Longitudinal studies of the literature have shown that diabetic patients have a higher chance of developing dementia than non-diabetic patient, with a relative risk (RR) between 1.26 and 2.83. The risk of vascular dementia was increased in 3 out of 5 studies, with a RR ranging between 2 and 2.6. With regard to Alzheimer's disease, the results are conflicting. Half of the studies found an increased risk in diabetic patients (RR: 1.3-2). The possible causal mechanisms of dementia in diabetic patients remain hypothetical. MRI studies showed varying degrees of cortical atrophy, cerebral infarcts and deep white matter lesions. In neuropathological studies, senile plaques and neurofibrillary tangle were not found with higher severity in the brain of diabetic patients than in the brain of age-matched controls. Several hypotheses have been raised to explain the relationship between diabetes and cognitive decline. Micro and macrovascular changes in the brain could induce cerebral hypoxia and ischemic conditions resulting in cellular death or white matter lesions. The occurrence of vascular lesions might reduce the threshold at which dementia will occur in Alzheimer disease. The deposition of advanced glycation end products doesn't spare the brain and they have been found in senile plaques, where they can reduce the solubility of proteins such as the beta amyloid and Tau proteins. Some authors favour the hypothesis of a brain insulin resistance because, in a few small studies, insulin was found to improve memory.
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PMID:[Diabetes mellitus and cognition: is there a link?]. 1878 78

Persons with type 2 diabetes are at increased risk of cognitive dysfunction. Less is known about which cognitive abilities are affected and how undiagnosed diabetes and impaired fasting glucose relate to cognitive performance. The authors explored this question using data from 1,917 nondemented men and women (average age = 76 years) in the population-based Age, Gene/Environment Susceptibility-Reykjavik Study (2002-2006). Glycemic status groups included diagnosed diabetes (self-reported diabetes or diabetic medication use; n = 163 (8.5%)), undiagnosed diabetes (fasting blood glucose >or=7.0 mmol/L without diagnosed diabetes; n = 55 (2.9%)), and impaired fasting glucose (fasting blood glucose 5.6-6.9 mmol/L; n = 744 (38.8%)). Composites of memory, processing speed (PS), and executive function were constructed from a neuropsychological battery. Linear regression was used to investigate cross-sectional differences in cognitive performance between glycemic groups, adjusted for demographic and health factors. Persons with diagnosed diabetes had slower PS than normoglycemics (beta = -0.12; P < 0.05); diabetes duration of >or=15 years was associated with significantly poorer PS and executive function. Undiagnosed diabetics had slower PS (beta = -0.22; P < 0.01) and poorer memory performance (beta = -0.22; P < 0.05). Persons with type 2 diabetes have poorer cognitive performance than normoglycemics, particularly in PS. Those with undiagnosed diabetes have the lowest cognitive performance.
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PMID:Cognitive impairment: an increasingly important complication of type 2 diabetes: the age, gene/environment susceptibility--Reykjavik study. 1883 52

Vascular risk factors, such as type 2 diabetes mellitus, hypertension, dyslipidemia and obesity, have been associated with an increased risk of cognitive dysfunction, particularly in the elderly. The aim of this systematic review was to compare these risk factors with regard to the nature and magnitude of the associated cognitive decrements. Cross-sectional and longitudinal studies that assessed cognitive functioning in non-demented persons in relation to diabetes/impaired glucose metabolism (k = 36), hypertension (k = 24), dyslipidemia (k = 7) and obesity (k = 6) and that adjusted or matched for age, gender and education were included. When possible, effect sizes (Cohen's d) were computed per cognitive domain. Diabetes and hypertension were clearly associated with cognitive decrements; the results for obesity and dyslipidemia were less consistent. Effect sizes were moderate (median approximately -0.3) for all risk factors. Decline was found in all cognitive domains, although the effects on cognitive speed, mental flexibility and memory were most consistent. Methodological aspects of included studies and implications of these findings are discussed.
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PMID:Type 2 diabetes mellitus, hypertension, dyslipidemia and obesity: A systematic comparison of their impact on cognition. 1884 80


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