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Glucose metabolism and the risk of Alzheimer's disease and dementia: a population-based 12 year follow-up study in 71-year-old men
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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2009 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 52, no 8, 1504-1510 p.Article in journal (Refereed) Published
Abstract [en]

AIMS/HYPOTHESIS: Accumulating evidence suggests that diabetes increases the risk of dementia, but few studies have addressed possible mechanisms underlying this relationship. The aim of our study was to investigate the longitudinal association of glucose metabolism, insulin secretion and insulin action with the development of Alzheimer's disease and vascular dementia. METHODS: The Uppsala Longitudinal Study of Adult Men is an ongoing observational study in Sweden in which 1,125 men aged 71 years and free from dementia underwent an OGTT and a euglycaemic insulin clamp between 1990 and 1995. During a median follow-up of 12 years, 257 persons developed dementia or cognitive impairment, of whom 81 had Alzheimer's disease and 26 vascular dementia. Associations were analysed with the Cox proportional hazards method. RESULTS: Low early insulin response to oral glucose challenge, but not low insulin sensitivity, was associated with a higher risk of Alzheimer's disease (HR for 1 SD decrease 1.32; 95% CI 1.02, 1.69) after adjustment for diabetes, blood pressure, body mass index, cholesterol, smoking and educational level. Low insulin sensitivity was associated with a higher risk of vascular dementia (HR for 1 SD decrease 1.55; 95% CI 1.02, 2.35), but not after multiple adjustments. Diabetes increased the risk of any dementia and cognitive impairment by 63%. CONCLUSIONS/INTERPRETATION: In this community-based study, low early insulin response was associated with increased risk of subsequent Alzheimer's disease, whereas low insulin sensitivity was not. Vascular dementia was not related to early insulin response. We suggest that glucometabolic disturbances are linked differentially to the pathogenesis of these two main dementia subtypes.

Place, publisher, year, edition, pages
2009. Vol. 52, no 8, 1504-1510 p.
Keyword [en]
Alzheimer's disease, Diabetes, Insulin, Insulin resistance, Vascular dementia
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-123412DOI: 10.1007/s00125-009-1393-9ISI: 000268006200007PubMedID: 19455303OAI: oai:DiVA.org:uu-123412DiVA: diva2:313915
Available from: 2010-04-27 Created: 2010-04-27 Last updated: 2016-01-18Bibliographically 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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