Glucose levels and risk of dementia.

BACKGROUND Diabetes is a risk factor for dementia. It is unknown whether higher glucose levels increase the risk of dementia in people without diabetes. METHODS We used 35,264 clinical measurements of glucose levels and 10,208 measurements of glycated hemoglobin levels from 2067 participants without dementia to examine the relationship between glucose levels and the risk of dementia. Participants were from the Adult Changes in Thought study and included 839 men and 1228 women whose mean age at baseline was 76 years; 232 participants had diabetes, and 1835 did not. We fit Cox regression models, stratified according to diabetes status and adjusted for age, sex, study cohort, educational level, level of exercise, blood pressure, and status with respect to coronary and cerebrovascular diseases, atrial fibrillation, smoking, and treatment for hypertension. RESULTS During a median follow-up of 6.8 years, dementia developed in 524 participants (74 with diabetes and 450 without). Among participants without diabetes, higher average glucose levels within the preceding 5 years were related to an increased risk of dementia (P=0.01); with a glucose level of 115 mg per deciliter (6.4 mmol per liter) as compared with 100 mg per deciliter (5.5 mmol per liter), the adjusted hazard ratio for dementia was 1.18 (95% confidence interval [CI], 1.04 to 1.33). Among participants with diabetes, higher average glucose levels were also related to an increased risk of dementia (P=0.002); with a glucose level of 190 mg per deciliter (10.5 mmol per liter) as compared with 160 mg per deciliter (8.9 mmol per liter), the adjusted hazard ratio was 1.40 (95% CI, 1.12 to 1.76). CONCLUSIONS Our results suggest that higher glucose levels may be a risk factor for dementia, even among persons without diabetes. (Funded by the National Institutes of Health.)

[1]  J. Kalbfleisch,et al.  The Statistical Analysis of Failure Time Data , 1980 .

[2]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[3]  M. Emi,et al.  Genotyping and sequence analysis of apolipoprotein E isoforms. , 1988, Genomics.

[4]  D. T. Vernier,et al.  Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. , 1990, Journal of lipid research.

[5]  E. Teng,et al.  The Cognitive Abilities Screening Instrument (CASI): A Practical Test for Cross-Cultural Epidemiological Studies of Dementia , 1994, International Psychogeriatrics.

[6]  G. Schellenberg,et al.  Dementia and Alzheimer disease incidence: a prospective cohort study. , 2002, Archives of neurology.

[7]  Laurence L. George,et al.  The Statistical Analysis of Failure Time Data , 2003, Technometrics.

[8]  Eric R. Ziegel,et al.  The Elements of Statistical Learning , 2003, Technometrics.

[9]  D. Arterburn,et al.  The Coming Epidemic of Obesity in Elderly Americans , 2004, Journal of the American Geriatrics Society.

[10]  P. Matthews,et al.  Risk factors for progression of brain atrophy in aging , 2005, Neurology.

[11]  K. Yaffe,et al.  Glycosylated hemoglobin level and development of mild cognitive impairment or dementia in older women. , 2006, The journal of nutrition, health & aging.

[12]  C. Rochester,et al.  EXERCISE IS ASSOCIATED WITH REDUCED RISK FOR INCIDENT DEMENTIA AMONG PERSONS 65 YEARS OF AGE AND OLDER , 2006 .

[13]  R. Westendorp,et al.  The impact of diabetes mellitus on cognitive decline in the oldest of the old: a prospective population-based study , 2006, Diabetologia.

[14]  S. Haneuse,et al.  Pathological correlates of dementia in a longitudinal, population‐based sample of aging , 2007, Annals of neurology.

[15]  D. Schoenfeld,et al.  Translating the A1C Assay Into Estimated Average Glucose Values , 2008, Diabetes Care.

[16]  Geert Jan Biessels,et al.  Diabetes and other vascular risk factors for dementia: which factor matters most? A systematic review. , 2008, European journal of pharmacology.

[17]  L. Lannfelt,et al.  Glucose metabolism and the risk of Alzheimer’s disease and dementia: a population-based 12 year follow-up study in 71-year-old men , 2009, Diabetologia.

[18]  M. Strachan R D Lawrence Lecture 2010 ^ . The brain as a target organ in Type 2 diabetes: exploring the links with cognitive impairment and dementia , 2011, Diabetic medicine : a journal of the British Diabetic Association.

[19]  A. Sharrett,et al.  Glycated haemoglobin and cognitive decline: the Atherosclerosis Risk in Communities (ARIC) study , 2011, Diabetologia.

[20]  S. Black,et al.  Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association , 2011, Stroke.

[21]  Ramit Ravona-Springer,et al.  Changes in glycemic control are associated with changes in cognition in non diabetic elderly , 2011, Alzheimer's & Dementia.

[22]  小原 知之 Glucose tolerance status and risk of dementia in the community : the Hisayama study , 2011 .

[23]  Paula I. Moreira,et al.  Insulin signaling, glucose metabolism and mitochondria: Major players in Alzheimer's disease and diabetes interrelation , 2012, Brain Research.

[24]  Peter Riederer,et al.  Different effects of soluble and aggregated amyloid β42 on gene/protein expression and enzyme activity involved in insulin and APP pathways , 2012, Journal of Neural Transmission.

[25]  N. Belyaev,et al.  Are amyloid‐degrading enzymes viable therapeutic targets in Alzheimer’s disease? , 2012, Journal of neurochemistry.

[26]  R. Mayeux,et al.  Epidemiology of Alzheimer disease. , 2012, Cold Spring Harbor perspectives in medicine.

[27]  D. Leroith,et al.  The worldwide diabetes epidemic , 2012, Current opinion in endocrinology, diabetes, and obesity.

[28]  S. Correia,et al.  The impairment of insulin signaling in Alzheimer's disease , 2012, IUBMB life.

[29]  G. Pandini,et al.  Insulin has multiple antiamyloidogenic effects on human neuronal cells. , 2013, Endocrinology.