A Prospective Analysis of Elevated Fasting Glucose Levels and Cognitive Function in Older People: Results from PROSPER and the Rotterdam Study

Overview

Journal Diabetes

Specialty Endocrinology

Date 2010 Apr 16

PMID 20393152

Citations 33

Authors

Sjoerd M Euser

Naveed Sattar

Jacqueline C M Witteman

Eduard L E M Bollen

Eric J G Sijbrands

Albert Hofman

Ivan J Perry

Monique M B Breteler

Rudi G J Westendorp

Affiliations

Soon will be listed here.

Abstract

Objective: To investigate the relationship between fasting glucose levels, insulin resistance, and cognitive impairment in old age. Diabetes is associated with cognitive impairment in older people. However, the link between elevated fasting glucose levels and insulin resistance in nondiabetic individuals, and the risk of cognitive impairment is unclear.

Research Design And Methods: We analyzed data from, in total, 8,447 participants in two independent prospective studies: the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), 5,019 participants, aged 69-84 years, and the Rotterdam Study, 3,428 participants, aged 61-97 years. Fasting glucose levels were assessed at baseline in both studies; fasting insulin levels were assessed in the Rotterdam Study only. Cognitive function was assessed in both studies at baseline and during follow-up.

Results: Subjects with diabetes had impaired cognitive function at baseline. In contrast, in people without a history of diabetes, there was no clear association between baseline fasting glucose levels and executive function and memory, nor was there a consistent relationship between elevated baseline fasting glucose levels and the rate of cognitive decline in either cohort. Insulin resistance (homeostasis model assessment index) was also unrelated to cognitive function and decline.

Conclusions: Elevated fasting glucose levels and insulin resistance are not associated with worse cognitive function in older people without a history of diabetes. These data suggest either that there is a threshold for effects of dysglycemia on cognitive function or that factors other than hyperglycemia contribute to cognitive impairment in individuals with frank diabetes.

Citing Articles

Development of PPARγ Agonists for the Treatment of Neuroinflammatory and Neurodegenerative Diseases: Leriglitazone as a Promising Candidate.

Pizcueta P, Vergara C, Emanuele M, Vilalta A, Rodriguez-Pascau L, Martinell M Int J Mol Sci. 2023; 24(4).

PMID: 36834611 PMC: 9961553. DOI: 10.3390/ijms24043201.

Application of Grey Relational Analysis to Predict Dementia Tendency by Cognitive Function, Sleep Disturbances, and Health Conditions of Diabetic Patients.

Huang C, Lin Y, Lu Y, Chen C Brain Sci. 2022; 12(12).

PMID: 36552102 PMC: 9775556. DOI: 10.3390/brainsci12121642.

Effects of raw red beetroot consumption on metabolic markers and cognitive function in type 2 diabetes patients.

Aliahmadi M, Amiri F, Bahrami L, Hosseini A, Abiri B, Vafa M J Diabetes Metab Disord. 2021; 20(1):673-682.

PMID: 34222085 PMC: 8212206. DOI: 10.1007/s40200-021-00798-z.

HbA1c and brain health across the entire glycaemic spectrum.

Garfield V, Farmaki A, Eastwood S, Mathur R, Rentsch C, Bhaskaran K Diabetes Obes Metab. 2021; 23(5):1140-1149.

PMID: 33464682 PMC: 8261644. DOI: 10.1111/dom.14321.

Insulin sensitivity predicts cognitive decline in individuals with prediabetes.

Willmann C, Brockmann K, Wagner R, Kullmann S, Preissl H, Schnauder G BMJ Open Diabetes Res Care. 2020; 8(2).

PMID: 33203727 PMC: 7674089. DOI: 10.1136/bmjdrc-2020-001741.

References

Bonora E, Targher G, Alberiche M, Bonadonna R, Saggiani F, Zenere M . Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care. 2000; 23(1):57-63. DOI: 10.2337/diacare.23.1.57. View

Folstein M, Folstein S, McHugh P . "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975; 12(3):189-98. DOI: 10.1016/0022-3956(75)90026-6. View

Sattar N, McConnachie A, Shaper A, Blauw G, Buckley B, de Craen A . Can metabolic syndrome usefully predict cardiovascular disease and diabetes? Outcome data from two prospective studies. Lancet. 2008; 371(9628):1927-35. DOI: 10.1016/S0140-6736(08)60602-9. View

Shepherd J, Blauw G, Murphy M, Cobbe S, Bollen E, Buckley B . The design of a prospective study of Pravastatin in the Elderly at Risk (PROSPER). PROSPER Study Group. PROspective Study of Pravastatin in the Elderly at Risk. Am J Cardiol. 1999; 84(10):1192-7. DOI: 10.1016/s0002-9149(99)00533-0. View

Kalmijn S, Foley D, White L, Burchfiel C, Curb J, Petrovitch H . Metabolic cardiovascular syndrome and risk of dementia in Japanese-American elderly men. The Honolulu-Asia aging study. Arterioscler Thromb Vasc Biol. 2000; 20(10):2255-60. DOI: 10.1161/01.atv.20.10.2255. View

Vanhanen M, Koivisto K, Moilanen L, Helkala E, Hanninen T, Soininen H . Association of metabolic syndrome with Alzheimer disease: a population-based study. Neurology. 2006; 67(5):843-7. DOI: 10.1212/01.wnl.0000234037.91185.99. View

Shepherd J, Blauw G, Murphy M, Bollen E, Buckley B, Cobbe S . Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002; 360(9346):1623-30. DOI: 10.1016/s0140-6736(02)11600-x. View

. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 2002; 26 Suppl 1:S5-20. DOI: 10.2337/diacare.26.2007.s5. View

Cukierman-Yaffe T, Gerstein H, Williamson J, Lazar R, Lovato L, Miller M . Relationship between baseline glycemic control and cognitive function in individuals with type 2 diabetes and other cardiovascular risk factors: the action to control cardiovascular risk in diabetes-memory in diabetes (ACCORD-MIND) trial. Diabetes Care. 2009; 32(2):221-6. PMC: 2628683. DOI: 10.2337/dc08-1153. View

10.

Welsh K, Butters N, Mohs R, Beekly D, Edland S, Fillenbaum G . The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part V. A normative study of the neuropsychological battery. Neurology. 1994; 44(4):609-14. DOI: 10.1212/wnl.44.4.609. View

11.

Fontbonne A, Berr C, Ducimetiere P, Alperovitch A . Changes in cognitive abilities over a 4-year period are unfavorably affected in elderly diabetic subjects: results of the Epidemiology of Vascular Aging Study. Diabetes Care. 2001; 24(2):366-70. DOI: 10.2337/diacare.24.2.366. View

12.

Yaffe K, Kanaya A, Lindquist K, Simonsick E, Harris T, Shorr R . The metabolic syndrome, inflammation, and risk of cognitive decline. JAMA. 2004; 292(18):2237-42. DOI: 10.1001/jama.292.18.2237. View

13.

van Oijen M, Okereke O, Kang J, Pollak M, Hu F, Hankinson S . Fasting insulin levels and cognitive decline in older women without diabetes. Neuroepidemiology. 2008; 30(3):174-9. PMC: 2821443. DOI: 10.1159/000126909. View

14.

Abbatecola A, Paolisso G, Lamponi M, Bandinelli S, Lauretani F, Launer L . Insulin resistance and executive dysfunction in older persons. J Am Geriatr Soc. 2004; 52(10):1713-8. DOI: 10.1111/j.1532-5415.2004.52466.x. View

15.

Craft S . Insulin resistance and Alzheimer's disease pathogenesis: potential mechanisms and implications for treatment. Curr Alzheimer Res. 2007; 4(2):147-52. DOI: 10.2174/156720507780362137. View

16.

Hofman A, Breteler M, Van Duijn C, Janssen H, Krestin G, Kuipers E . The Rotterdam Study: 2010 objectives and design update. Eur J Epidemiol. 2009; 24(9):553-72. PMC: 2744826. DOI: 10.1007/s10654-009-9386-z. View

17.

Lindahl B, Weinehall L, Asplund K, Hallmans G . Screening for impaired glucose tolerance. Results from a population-based study in 21,057 individuals. Diabetes Care. 1999; 22(12):1988-92. DOI: 10.2337/diacare.22.12.1988. View

18.

Kanaya A, Barrett-Connor E, Gildengorin G, Yaffe K . Change in cognitive function by glucose tolerance status in older adults: a 4-year prospective study of the Rancho Bernardo study cohort. Arch Intern Med. 2004; 164(12):1327-33. DOI: 10.1001/archinte.164.12.1327. View

19.

Fuh J, Wang S, Hwu C, Lu S . Glucose tolerance status and cognitive impairment in early middle-aged women. Diabet Med. 2007; 24(7):788-91. DOI: 10.1111/j.1464-5491.2007.02170.x. View

20.

Craft S . Insulin resistance syndrome and Alzheimer's disease: age- and obesity-related effects on memory, amyloid, and inflammation. Neurobiol Aging. 2005; 26 Suppl 1:65-9. DOI: 10.1016/j.neurobiolaging.2005.08.021. View