Brain Aging in Very Old Men With Type 2 Diabetes

Korf, Esther S.C.; White, Lon R.; Scheltens, Philip; Launer, Lenore J.

doi:10.2337/dc06-0243

Cited by 182 publications

(120 citation statements)

References 46 publications

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“…Investigators studying cases from a large epidemiological sample have shown that, relative to nondiabetic control subjects, elderly (average age 77.8 years) individuals with type 2 diabetes exhibit reductions in hippocampal and amygdalar volumes [7]; however, no neuropsychological data were reported in this sample. A moderately elevated risk of hippocampal atrophy (odds ratio 1.7, 95% CI 0.9-2.9) has been demonstrated among very old men with type 2 diabetes [8], but it should be noted that this study included individuals with dementia, Alzheimer's disease, strokes, lacunes and high rates of white matter disease.…”

Section: Introductionmentioning

confidence: 83%

Hippocampal damage and memory impairments as possible early brain complications of type 2 diabetes

et al. 2007

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Aims/hypothesis There is evidence that type 2 diabetes mellitus is associated with cognitive impairment. Most studies investigating this association have evaluated elderly individuals, after many years of diabetes, who generally have poor glycaemic control and significant vascular disease. The aim of the current study was to investigate the early cognitive consequences and associated brain correlates of type 2 diabetes. Materials and methods With regard to cognition and brain measures, we compared 23 age-, sex-and educationmatched control subjects with 23 mostly middle-aged individuals with relatively well-controlled diabetes of less than 10 years from the time of diagnosis. Results We found deficits in hippocampal-based memory performance and preservation of other cognitive domains. Relative to control subjects, individuals with diabetes had reductions in brain volumes that were restricted to the hippocampus. There was an inverse relationship between glycaemic control and hippocampal volume; in multivariate regression analysis, HbA 1c was the only significant predictor of hippocampal volume, accounting for 33% of the observed variance. Other variables commonly associated with type 2 diabetes, such as elevated BMI, hypertension or dyslipidaemia, did not independently contribute to the variance in hippocampal volume. Conclusions/interpretation These results suggest that the medial temporal lobe may be the first brain site affected by type 2 diabetes and that individuals in poorer metabolic control may be affected to a greater extent.

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Section: Introductionmentioning

confidence: 83%

Hippocampal damage and memory impairments as possible early brain complications of type 2 diabetes

et al. 2007

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“…The glucose-mediated effects on cognition and brain structure might accelerate brain ageing. In addition, neurotoxic AGE caused by hyperglycaemia may contribute to the formation of neurofibrillary tangles and neuritic plaques [47]. Second, insulin resistance, especially in earlystage diabetes, is associated with compensatory hyperinsuli-naemia.…”

Section: Discussionmentioning

confidence: 99%

“…Insulin appears to stimulate beta-amyloid peptide secretion and inhibit the extracellular degradation of beta-amyloid by competition for insulin-degrading enzyme (IDE) [48]. Insulin signalling defects may increase hyperphosphorylation of tau protein, which can lead to neurofibrillary tangles [47]. Third, inflammatory markers, including C-reactive protein, IL-6 and TNF-α1 are associated with diabetes and also contribute to the development of Alzheimer's disease [49].…”

Section: Discussionmentioning

confidence: 99%

Uncontrolled diabetes increases the risk of Alzheimer’s disease: a population-based cohort study

et al. 2009

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Aims/hypothesis Diabetes has been related to Alzheimer's disease with inconsistent findings. We aimed to clarify the association of diabetes with different dementing disorders taking into account glycaemic control, and to explore the link between glucose dysregulation and neurodegeneration. Methods A dementia-free cohort (n=1,248) aged ≥75 years was longitudinally examined to detect dementia, Alzheimer's disease and vascular dementia (VaD) cases (Diagnostic and

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“…Diabetes also is associated with cognitive disorders (13-15) and with brain structural changes in large and small vessels (16,17). Therefore, it is biologically plausible to hypothesize that the strength of association between retinal and cerebral microvascular lesions may be greater in people with diabetes compared with those without the disease.…”

Section: Results-evidencementioning

confidence: 99%

Retinal and Cerebral Microvascular Signs and Diabetes

et al. 2008

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OBJECTIVE-Diabetes increases the risk for microvascular disease. The retina and the brain both have intricate microvascular systems that are developmentally similar. We sought to examine whether microvascular lesions in the retina and in the brain are associated and whether this association differs among people with and without diabetes. RESEARCH DESIGN AND METHODS-The analysis included 4,218 participants of the Icelandic population-based Age, Gene/Environment Susceptibility-Reykjavik Study who were born in 1907-1935 and who were previously followed as a part of the Reykjavik Study. Retinal focal arteriolar narrowing, arteriovenous (AV) nicking, and microaneurysms/hemorrhages were evaluated on digital retinal images of both eyes. Cerebral microbleeds (CMBs) were evaluated from magnetic resonance images. Data were analyzed with logistic and multinomial logistic regression models controlling for demographics, major cardiovascular risk factors, cerebral infarcts, and white matter lesions. D evelopmentally, the retina is an outgrowth of the brain and shares with the brain similar microvascular properties in anatomy, physiology, and metabolic activities (1,2). Microvascular systems in both the retina and the brain may be affected by atherosclerotic, hemodynamic, or other metabolic factors that affect large, small, and microblood vessels (3,4). Population-based epidemiological studies have shown that retinal microvascular abnormalities, such as arteriovenous (AV) nicking, microaneurysms, and hemorrhages, are associated with an increased risk of clinical stroke and cerebral white matter lesions (WMLs) (5-8), a marker for small-vessel disease. To date, no population-based studies have examined the relation of retinal microvascular signs to cerebral microbleeds (CMBs), which indicate the presence of hemorrhagic microvascular lesions or microangiopathy in the brain (9). CMBs are histopathologically confirmed signals on magnetic resonance image (MRI) that signify hemosiderin deposits due to frank minor hemorrhages or blood leakage through small blood vessels (10). Clinical studies suggest that CMBs are associated with an increased risk for intracerebral hemorrhages and serve as the basis for a clinical diagnosis of cerebral amyloid angiopathy (9,11,12). RESULTS-EvidenceIndividuals with diabetes are known to be at an increased risk for microvascular lesions of both the retina and the brain. Diabetes also is associated with cognitive disorders (13-15) and with brain structural changes in large and small vessels (16,17). Therefore, it is biologically plausible to hypothesize that the strength of association between retinal and cerebral microvascular lesions may be greater in people with diabetes compared with those without the disease.In this population-based study of older adults, we sought to investigate whether retinal microvascular signs are associated with microbleeds in the brain and whether the association between retinal microvascular lesions and brain microbleeds varies by diabetes status. RESEARCH DESIGN AND METHODS...

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Brain Aging in Very Old Men With Type 2 Diabetes

Cited by 182 publications

References 46 publications

Hippocampal damage and memory impairments as possible early brain complications of type 2 diabetes

Hippocampal damage and memory impairments as possible early brain complications of type 2 diabetes

Uncontrolled diabetes increases the risk of Alzheimer’s disease: a population-based cohort study

Retinal and Cerebral Microvascular Signs and Diabetes

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