The Risk of Dementia among Persons with Diabetes Mellitus: A Population‐Based Cohort Study<sup>a</sup>

Leibson, Cynthia L.; Rocca, Walter A.; Hanson, Virginia; Cha, Ruitao; Kokmen, Emre; O’Brien, Peter C.; Palumbo, Pasquale

doi:10.1111/j.1749-6632.1997.tb48496.x

Cited by 217 publications

(166 citation statements)

References 12 publications

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“…Over the last decade, many population-based studies have reported a relationship between diabetes and dementia with some inconsistent findings. In fact, some longitudinal studies reported an association between diabetes and Alzheimer's disease [4,7,11,25,43] or observed such an association only in specific subgroups [12,13,15], but others did not [5,6,8]. We found that well-controlled diabetes (diabetes with random blood glucose <7.8 mmol/l) was not significantly related to dementia risk.…”

Section: Discussioncontrasting

confidence: 52%

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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Section: Discussioncontrasting

confidence: 52%

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

et al. 2009

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“…The recent rise in interest in insulin signaling and its relationship with AD is driven to a large extent by the increasing number of prospective and retrospective epidemiological findings, which indicate that type II diabetes mellitus is a significant risk factor for developing AD (Ott et al, 1996(Ott et al, , 1999Leibson et al, 1997). Type II diabetes mellitus is characterized by insulin resistance, reduced insulin secretion, and overt hyperglycemia (Olson and Norris, 2004).…”

Section: Introductionmentioning

confidence: 99%

Insulin-Degrading Enzyme as a Downstream Target of Insulin Receptor Signaling Cascade: Implications for Alzheimer's Disease Intervention

Zhao¹,

Teter²,

Morita³

et al. 2004

J. Neurosci.

303

188

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Insulin-degrading enzyme (IDE) is one of the proteins that has been demonstrated to play a key role in degrading ␤-amyloid (A␤) monomer in vitro and in vivo, raising the possibility of upregulating IDE as an approach to reduce A␤. Little is known, however, about the cellular and molecular regulation of IDE protein. Because one of the main functions of IDE is to degrade insulin, we hypothesized that there is a negative feedback mechanism whereby stimulation of insulin receptor-mediated signaling upregulates IDE to prevent chronic activation of the pathway. We show that treatment of primary hippocampal neurons with insulin increased IDE protein levels by ϳ25%. Insulin treatment also led to phosphatidylinositol-3 (PI3) kinase activation evidenced by Akt phosphorylation, which was blocked by PI3 kinase inhibitors, wortmannin and LY 294002. Inhibition of PI3 kinase abolished the IDE upregulation by insulin, indicating a causeeffect relationship between insulin signaling and IDE upregulation. Further support for this link was provided by the findings that deficient insulin signaling (decreased PI3 kinase subunit P85) was correlated with reduced IDE in Alzheimer's disease (AD) brains and in Tg2576 Swedish amyloid precursor protein transgenic mice fed a safflower oil-enriched ("Bad") diet used to accelerate pathogenesis. Consistent with IDE function in the degradation of A␤ monomer, the IDE decrease in the Bad diet-fed Tg2576 mice was associated with increased A␤ monomer levels. These in vitro and in vivo analyses validate the use of enhanced CNS insulin signaling as a potential strategy for AD intervention to correct the IDE defects occurring in AD.

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“…In epidemiological population studies, there is an increase in the risk for dementia among individuals with T2DM [16]. However, epidemiological studies have to be interpreted carefully.…”

Section: Diabetes and Dementiamentioning

confidence: 99%

Diabetes, sugar-coated but harmful to the brain

Starr

Convit

2007

Current Opinion in Pharmacology

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The Risk of Dementia among Persons with Diabetes Mellitus: A Population‐Based Cohort Study^a

Cited by 217 publications

References 12 publications

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

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

Insulin-Degrading Enzyme as a Downstream Target of Insulin Receptor Signaling Cascade: Implications for Alzheimer's Disease Intervention

Diabetes, sugar-coated but harmful to the brain

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The Risk of Dementia among Persons with Diabetes Mellitus: A Population‐Based Cohort Studya

Cited by 217 publications

References 12 publications

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

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

Insulin-Degrading Enzyme as a Downstream Target of Insulin Receptor Signaling Cascade: Implications for Alzheimer's Disease Intervention

Diabetes, sugar-coated but harmful to the brain

Contact Info

Product

Resources

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The Risk of Dementia among Persons with Diabetes Mellitus: A Population‐Based Cohort Study^a