Glucose metabolism and the risk of Alzheimer's disease and dementia: a population-based 12 year follow-up study in 71-year-old men.
OBJECTIVE
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
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.
Rönnemaa
E
E
Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala Science Park, 751 85 Uppsala, Sweden. elina.ronnemaa@pubcare.uu.se
Zethelius
B
B
Sundelöf
J
J
Sundström
J
J
Degerman-Gunnarsson
M
M
Lannfelt
L
L
Berne
C
C
Kilander
L
L
D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology*; D053327:Apolipoprotein E4 / Q000235:genetics; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure; D015992:Body Mass Index; D005500:Follow-Up Studies; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008137:Longitudinal Studies; D008297:Male; D013548:Sweden
D053327:Apolipoprotein E4; D001786:Blood Glucose; D007328:Insulin