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

As life expectancy in the United States continues to increase, the projected numbers of elderly people who will develop dementia will grow rapidly. This paper reviews four well-established cardiovascular risk factors (type 2 diabetes, hypertension, cholesterol, and inflammation), for which there is longitudinal epidemiological evidence of increased risk of dementia, Alzheimer's disease, mild cognitive impairment, and cognitive decline. These risk factors are of special interest because of their potential modifiability, which may affect the course of cognitive compromise. Diabetes is the cardiovascular risk factor (CvRF) most consistently associated with cognition. Hypertension in midlife is consistently associated with cognition, but its associations with late-life hypertension are less clear. Total cholesterol is not consistently associated with cognition. Interleukin-6 and C-reactive protein are inflammatory markers relatively consistently associated with cognition. Composites of the CvRFs increase the risk for dementia in a dose-dependent fashion, suggesting a cumulative effect of these factors on neuronal stress. In the relatively few studies that have reported interactions of risk factors, they potentiate each other. The effect of each of these risk factors varies according to apolipoprotein E genotype. It may be that the effect of these risk factors varies according to the presence of the others, and these complex relationships underlie the biological mechanisms of cognitive compromise. This may be crucial for understanding the effects on cognition of drugs and other approaches, such as lifestyle change, for treating these risk factors.
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PMID:The effects of cardiovascular risk factors on cognitive compromise. 1958 55

Obesity is associated with cognitive dysfunction, for which changes in the hippocampus plausibly play a pivotal role. We tested the hypothesis that an elevated level of visceral fat accumulation (VFA) correlates with hippocampus volume and insulin resistance in non-dementia patients with type 2 diabetes. Subjects included 48 non-dementia patients with type 2 diabetes, who were divided into two groups, high VFA group (mean+/-standard deviation: age=65+/-6 years, n=30) and normal VFA group (65+/-5 years, n=18). Hippocampus volume has been quantitated with computer-assisted analysis using a magnetic resonance imaging (MRI) voxel-based specific regional analysis system developed for the study of Alzheimer's disease (VSRAD), which yields a Z-score as the end point for assessment of hippocampal volume. The Z-score was higher in the high VFA group than in the normal VFA group (p<0.0001). The fasting plasma glucose (p<0.05) and insulin concentrations (p<0.0001) and the homeostasis model assessment (HOMA) index (p<0.0001) were higher in the high VFA group than in the normal VFA group. Multiple regression analysis showed that VFA levels were independently predicted by Z-score and HOMA index. Our results indicate that the elevated level of VFA in Japanese non-dementia patients with type 2 diabetes is characterized by increased hippocampus volume and insulin resistance, and that the Z-score and HOMA index are independent predictors of VFA.
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PMID:Abdominal visceral fat accumulation is associated with hippocampus volume in non-dementia patients with type 2 diabetes mellitus. 1968 83

Persons with type 2 diabetes have a high risk of late-life cognitive impairment, and physical activity might be a potential target for modifying this risk. Therefore, the authors evaluated the association between physical activity level and cognition in women with type 2 diabetes. Beginning in 1995-2000, cognitive function was assessed in 1,550 Nurses' Health Study participants aged > or =70 years with type 2 diabetes. Follow-up assessments were completed twice thereafter, at 2-year intervals. Multivariate-adjusted linear regression models were used to obtain mean differences in baseline cognitive scores and cognitive decline across tertiles of long-term physical activity. Initial results from age- and education-adjusted models indicated that greater physical activity levels were associated with better baseline cognition (for a global score averaging scores from 6 cognitive tests, P-trend = 0.02). However, results were substantially attenuated after adjustment for multiple potential confounders, largely because of physical disability indicators (global score: P-trend = 0.06); for example, the mean difference for the global score was 0.07 standard units (95% confidence interval: -0.01, 0.15) when comparing extreme tertiles. Results were similar for cognitive decline. These findings indicate little overall association between physical activity and cognition after adjustment for disability factors in older women with type 2 diabetes.
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PMID:Physical activity levels and cognition in women with type 2 diabetes. 1972 85

Recent studies have linked obesity, type 2 diabetes mellitus (T2DM) or non-alcoholic steatohepatitis (NASH) to insulin resistance in the brain, cognitive impairment and neurodegeneration. Insulin resistance compromises cell survival, metabolism and neuronal plasticity, and increases oxidative stress, cytokine activation and apoptosis. T2DM/NASH has been demonstrated to be associated with increased ceramide generation, suggesting a mechanistic link between peripheral insulin resistance and neurodegeneration because ceramides mediate insulin resistance and can cross the blood-brain barrier (BBB). Peripheral insulin resistance diseases may potentially cause brain insulin resistance via a liver-brain axis of neurodegeneration as a result of the trafficking of ceramides across the BBB. Therapy that includes insulin-sensitizing agents may help prevent brain insulin resistance-mediated cognitive impairment.
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PMID:Insulin resistance and neurodegeneration: roles of obesity, type 2 diabetes mellitus and non-alcoholic steatohepatitis. 1977 93

The association of type II diabetes mellitus (DM2) with Alzheimer's disease (AD) has received considerable attention in recent years. In the present paper, a hypothesis for this association from an evolutionary perspective, with emphasis on the close interplay between exercise and cognitive function, will be advanced in order to provide a biological rationale for the notion that the fundamental metabolic features of DM2 act in the brain over a protracted time span to induce the neuropathological characteristics of Alzheimer's disease thereby producing cognitive impairment. It is hoped that this hypothesis puts the association of DM2 and AD on firm conceptual grounds from a biological perspective and offers directions for further research.
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PMID:Exercise and cognitive function: a hypothesis for the association of type II diabetes mellitus and Alzheimer's disease from an evolutionary perspective. 1982 99

Alzheimer's disease (AD) has characteristic histopathological, molecular, and biochemical abnormalities, including cell loss; abundant neurofibrillary tangles; dystrophic neurites; amyloid precursor protein, amyloid-beta (APP-Abeta) deposits; increased activation of prodeath genes and signaling pathways; impaired energy metabolism; mitochondrial dysfunction; chronic oxidative stress; and DNA damage. Gaining a better understanding of AD pathogenesis will require a framework that mechanistically interlinks all these phenomena. Currently, there is a rapid growth in the literature pointing toward insulin deficiency and insulin resistance as mediators of AD-type neurodegeneration, but this surge of new information is riddled with conflicting and unresolved concepts regarding the potential contributions of type 2 diabetes mellitus (T2DM), metabolic syndrome, and obesity to AD pathogenesis. Herein, we review the evidence that (1) T2DM causes brain insulin resistance, oxidative stress, and cognitive impairment, but its aggregate effects fall far short of mimicking AD; (2) extensive disturbances in brain insulin and insulin-like growth factor (IGF) signaling mechanisms represent early and progressive abnormalities and could account for the majority of molecular, biochemical, and histopathological lesions in AD; (3) experimental brain diabetes produced by intracerebral administration of streptozotocin shares many features with AD, including cognitive impairment and disturbances in acetylcholine homeostasis; and (4) experimental brain diabetes is treatable with insulin sensitizer agents, i.e., drugs currently used to treat T2DM. We conclude that the term "type 3 diabetes" accurately reflects the fact that AD represents a form of diabetes that selectively involves the brain and has molecular and biochemical features that overlap with both type 1 diabetes mellitus and T2DM.
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PMID:Alzheimer's disease is type 3 diabetes-evidence reviewed. 1988 99

Recent studies have revealed that type 2 diabetes mellitus (T2DM) is a risk factor for cognitive dysfunction or dementia, especially those related to Alzheimer's disease (AD). Basic research suggests that insulin accelerates Alzheimer-related pathology through its effects on the amyloid beta (Abeta). Several pathological studies with autopsy samples have demonstrated, however, that dementia subjects with diabetes have less AD-related neuropathology than subjects without diabetes. We and others have reported that small vessel diseases affect cognitive function in older diabetics. Asymptomatic ischemic lesions in T2DM subjects may lower the threshold for the development of dementia and this may explain the inconsistency between the basic research and clinicopathological studies. Longitudinal follow-up of T2DM subjects without overt dementia using both amyloid imaging and magnetic resonance imaging may elucidate these issues. Following up until the development of overt dementia would make it possible to compare both amyloid load and ischemic lesions before and after the development of dementia. Moreover, amyloid imaging in non-demented older people with or without insulin resistance would verify the role of insulin in the processing and deposition of Abeta. Vascular risk factors may represent a therapeutic target, while neurodegenerative pathologies have not yet been amenable to treatment. It remains to be investigated whether medical interventions on vascular risk factors have protective effects against the development and progress of dementia.
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PMID:Pathophysiology of cognitive dysfunction in older people with type 2 diabetes: vascular changes or neurodegeneration? 2010 36

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of Alzheimer's disease, which involves hippocampus-mediated cognitive impairment. The present study investigated whether the resting-state functional connectivity of the hippocampus would be changed in patients with T2DM. A region of interest-based resting-state functional magnetic resonance imaging (fMRI) approach was applied to explore functional connectivity differences between 21 elderly patients with T2DM and 19 well-matched healthy controls, with all participants assessed by multi-dimensional neuropsychological tests. We found that T2DM patients performed significantly worse in the Auditory Verbal Learning Test (AVLT) (especially for Delayed Recall and Recognition) and Clock Drawing Test (CDT) when compared with the control group, and cognitive function was negatively related to BMI and HbA(1c). Importantly, the hippocampus showed reduced functional connectivity bilaterally to widespread regions, including fusiform gyrus, frontal gyrus, temporal gyrus, anterior cingulate gyrus, medial frontal gyrus, posterior cingulate gyrus, precuneus and inferior parietal lobule in T2DM patients compared to healthy controls. T2DM is associated with an impaired pattern of default network function, and the specific disconnection pattern identified may be involved in the neuropathophysiology of this disease.
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PMID:Impairments in cognition and resting-state connectivity of the hippocampus in elderly subjects with type 2 diabetes. 2012 14

People with diabetes mellitus are at increased risk of cognitive dysfunction. This review explores the relation between caffeine intake, diabetes, cognition and dementia, focusing on type 2 diabetes (T2DM). Epidemiological studies on caffeine/coffee intake and T2DM risk are reviewed. Next, the impact of T2DM on cognition is addressed. Finally, the potential for caffeine to modulate the risk of cognitive decline in the context of diabetes is explored. The conclusion is that, although epidemiological studies indicate that coffee/caffeine consumption is associated with a decreased risk of T2DM and possibly also with a decreased dementia risk, we can at present not be certain that these associations are causal. For now, recommendations for coffee consumption in individuals with T2DM or pre-diabetic stages are therefore difficult to establish, but it should be acknowledged that caffeine does appear to have several properties that warrant further investigations in this field.
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PMID:Caffeine, diabetes, cognition, and dementia. 2018 38

Cognitive speed, inhibitory function, and memory decline with age while crystallised, particularly verbal, abilities remain largely intact. Poor health, fewer years of education, lower activity, the presence of the APOE E4 allele, and high BP appear to predict faster cognitive decline. Dementia is diagnosed in the presence of objective cognitive impairment, both long- and short-term memory, plus at least one additional (cortical) cognitive deficit, such as dysphasia, dyspraxia, agnosia, or disturbance in executive functioning. In addition, patients have to show significant impairment in social or occupational functioning and a significant decline from previous levels. Both smoking and diabetes increase the risk of all types of dementia, not smoking or even stopping smoking reduces this risk, but better control of type 2 diabetes does not appear to have a measurable effect. Drinking small to moderate amounts of alcohol appears to confer some benefit in ameliorating cognitive decline. There is some evidence that HRT, DHEA, BP lowering in patients without prior cerebrovascular disease, statins, vitamin B6 and procaine are NOT helpful. There is insufficient evidence to establish or refute a beneficial effect for exercise, treatment of type 2 diabetes, omega-3 fatty acids, folic acid with/without vitamin B12, antioxidant vitamins, or ginkgo biloba. Depressive symptoms are more prevalent than dementia. Clinical (major) depression can present with cognitive deterioration, often associated with subjective complaints. Patients with subjective or objective memory impairment, but without functional deterioration, can be referred to the local memory clinic, while demented patients eligible for acetylcholinesterase inhibitor treatment, patients whose diagnosis is unclear and who may need some specific investigations, as well as patients who may benefit from a combined approach with psychotropic drugs and behavioural support should be referred to the local mental health team.
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PMID:Normal cognitive decline or dementia? 2019 32


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