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Impaired insulin secretion increases the risk of Alzheimer disease
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences. (Geriatrics)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences. (Geriatrics)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences. (Geriatrics)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.ORCID iD: 0000-0003-2247-8454
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2008 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 71, no 14, 1046-47 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Subjects with diabetes are reported to have an increased risk of dementia and cognitive impairment. However, the underlying causes remain unknown. We investigated the longitudinal associations between midlife insulin secretion, glucose metabolism, and the subsequent development of Alzheimer disease (AD) and dementia. METHODS: The population-based Uppsala Longitudinal Study of Adult Men started 1970 when the 2,322 participants were 50 years old. Investigation at baseline included determinations of acute insulin response and glucose tolerance using the IV glucose tolerance test and Homeostasis Model Assessment insulin resistance index. During a median follow up of 32 years, 102 participants were diagnosed with AD, 57 with vascular dementia, and 394 with any dementia or cognitive impairment. Associations were analyzed using Cox proportional hazard models. RESULTS: A low insulin response at baseline was associated with a higher cumulative risk of AD (hazard ratio for 1 SD decrease, 1.31; 95% CI, 1.10-1.56) also after adjustment for age, systolic blood pressure, body mass index, serum cholesterol, smoking, education level, and insulin resistance. This association was stronger in subjects without the APOE epsilon4 allele. Impaired glucose tolerance increased the risk of vascular dementia (hazard ratio for 1 SD decrease, 1.45; 95% CI, 1.05-2.00) but not AD. Impaired insulin secretion, glucose intolerance, and estimates of insulin resistance were all associated with higher risk of any dementia and cognitive impairment. CONCLUSIONS: In this longitudinal study, impaired acute insulin response at midlife was associated with an increased risk of Alzheimer disease (AD) up to 35 years later suggesting a causal link between insulin metabolism and the pathogenesis of AD.

Place, publisher, year, edition, pages
2008. Vol. 71, no 14, 1046-47 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-16349DOI: 10.1212/01.wnl.0000310646.32212.3aISI: 000259649100006PubMedID: 18401020OAI: oai:DiVA.org:uu-16349DiVA: diva2:44120
Available from: 2008-05-19 Created: 2008-05-19 Last updated: 2017-12-08Bibliographically approved
In thesis
1. Predictors of Dementia: Insulin, Fatty Acids and Vascular Risk Factors
Open this publication in new window or tab >>Predictors of Dementia: Insulin, Fatty Acids and Vascular Risk Factors
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Identification of modifiable risk factors for Alzheimer’s disease (AD) is crucial in order to diminish suffering from this devastating disease. The aim of this thesis was to investigate if different aspects of glucose metabolism, insulin, fatty-acid composition or other vascular risk factors predict the future development of AD and dementia.

This thesis is based on the Uppsala Longitudinal Study of Adult Men (ULSAM) cohort, which started in 1970. A total of 2322 men at age 50 were examined with focus on vascular risk factors. The cohort was re-examined at ages 60, 71, 77, 82 and 88. Incident diagnoses of AD, vascular dementia, other dementias and cognitive impairment were assessed in 2005–2010.

The risk of AD was increased in subjects with lower early insulin response measured with both an intravenous glucose tolerance test at 50 years and an oral glucose tolerance test at 71 years of age. The presence of vascular risk factors such as hypertension, obesity, hypercholesterolemia and smoking increased the risk of future vascular dementia but not of AD. Furthermore, saturated fatty acids at midlife were inversely associated with risk of AD. No evidence of a protective effect of omega-3 fatty acids against dementia was found.

The susceptibility allele, APOE ε4, was the strongest individual risk factor. APOE ε4 carriers with vascular risk factors had the greatest risk of developing dementia. Low insulin response was a risk factor for AD mainly in APOE ε4 non-carriers.

Disturbances in insulin and glucose metabolism, vascular risk factors and fatty acids are linked differentially to the pathogenesis of AD and vascular dementia. These observations should be considered when future clinical approaches are planned to prevent and postpone the onset of dementia.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 69 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 734
Keyword
dementia, Alzheimer’s disease, vascular dementia, insulin secretion, diabetes, fatty acids, epidemiology, vascular risk factors
National Category
Clinical Medicine
Research subject
Geriatrics
Identifiers
urn:nbn:se:uu:diva-164528 (URN)978-91-554-8248-0 (ISBN)
Public defence
2012-02-15, Enghoffssalen, Akademiska sjukhuset ing 50 bv, Uppsala, 13:00 (English)
Opponent
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Projects
ULSAM
Available from: 2012-01-23 Created: 2011-12-20 Last updated: 2012-01-24

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Rönnemaa, EZethelius, BSundelöf, JSundström, JBerne, CLannfelt, LKilander, L

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