Insulin Resistance and Hippocampal Volume in Women at Risk for Alzheimer's Disease

Overview

Journal Neurobiol Aging

Publisher Elsevier

Specialties Geriatrics
Neurology
Physiology

Date 2009 Dec 25

PMID 20031276

Citations 86

Authors

Natalie L Rasgon

Heather A Kenna

Tonita E Wroolie

Ryan Kelley

Daniel Silverman

John Brooks

Katherine E Williams

Bevin N Powers

Joachim Hallmayer

Allan Reiss

Affiliations

Soon will be listed here.

Abstract

Insulin resistance (IR) is the main pathological condition underlying vascular disorders, such as diabetes and cardiovascular disease, which are well established risk factors for cognitive decline and Alzheimer disease (AD). Hippocampal atrophy has been associated with cognitive decline, but little is known about the influence of IR on hippocampus integrity in non-diabetic, cognitively intact individuals. Herein, 50 women ages 50-65, current users of hormone therapy, underwent magnetic resonance imaging, cognitive testing, and homeostatic assessment of insulin resistance (HOMA-IR), as part of a longitudinal study examining brain structure and function in postmenopausal women at risk for AD. Results demonstrated a significant negative relationship between HOMA-IR and right and total hippocampal volume, overall cognitive performance, and selective tests of verbal and non-verbal memory. The main effect of HOMA-IR on brain structure and cognition was not altered by the presence of APOE-ε4 allele or by reproductive history, such as duration of endogenous and exogenous estrogen exposure. These results suggest that IR in middle-aged individuals at risk for AD may be biomarker for dementia risk.

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References

Kumar R, Anstey K, Cherbuin N, Wen W, Sachdev P . Association of type 2 diabetes with depression, brain atrophy, and reduced fine motor speed in a 60- to 64-year-old community sample. Am J Geriatr Psychiatry. 2008; 16(12):989-98. DOI: 10.1097/JGP.0b013e31818b40fc. View

Craft S, Asthana S, Cook D, Baker L, Cherrier M, Purganan K . Insulin dose-response effects on memory and plasma amyloid precursor protein in Alzheimer's disease: interactions with apolipoprotein E genotype. Psychoneuroendocrinology. 2003; 28(6):809-22. DOI: 10.1016/s0306-4530(02)00087-2. View

Maki P, Resnick S . Longitudinal effects of estrogen replacement therapy on PET cerebral blood flow and cognition. Neurobiol Aging. 2000; 21(2):373-83. DOI: 10.1016/s0197-4580(00)00123-8. View

Pierce B, Waring J, Schacter D, Budson A . Effects of distinctive encoding on source-based false recognition: further examination of recall-to-reject processes in aging and Alzheimer disease. Cogn Behav Neurol. 2008; 21(3):179-86. PMC: 2760251. DOI: 10.1097/WNN.0b013e31817d74e7. View

den Heijer T, Vermeer S, van Dijk E, Prins N, Koudstaal P, Hofman A . Type 2 diabetes and atrophy of medial temporal lobe structures on brain MRI. Diabetologia. 2003; 46(12):1604-10. DOI: 10.1007/s00125-003-1235-0. View

Craft S, Peskind E, Schwartz M, Schellenberg G, Raskind M, Porte Jr D . Cerebrospinal fluid and plasma insulin levels in Alzheimer's disease: relationship to severity of dementia and apolipoprotein E genotype. Neurology. 1998; 50(1):164-8. DOI: 10.1212/wnl.50.1.164. View

Starr V, Convit A . Diabetes, sugar-coated but harmful to the brain. Curr Opin Pharmacol. 2007; 7(6):638-42. PMC: 2170066. DOI: 10.1016/j.coph.2007.10.007. View

Jacobson L, Sapolsky R . The role of the hippocampus in feedback regulation of the hypothalamic-pituitary-adrenocortical axis. Endocr Rev. 1991; 12(2):118-34. DOI: 10.1210/edrv-12-2-118. View

Maki P . A systematic review of clinical trials of hormone therapy on cognitive function: effects of age at initiation and progestin use. Ann N Y Acad Sci. 2005; 1052:182-97. DOI: 10.1196/annals.1347.012. View

10.

Barnes L, Wilson R, Schneider J, Bienias J, Evans D, Bennett D . Gender, cognitive decline, and risk of AD in older persons. Neurology. 2003; 60(11):1777-81. DOI: 10.1212/01.wnl.0000065892.67099.2a. View

11.

Yaffe K . Metabolic syndrome and cognitive decline. Curr Alzheimer Res. 2007; 4(2):123-6. DOI: 10.2174/156720507780362191. View

12.

Peila R, Rodriguez B, Launer L . Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study. Diabetes. 2002; 51(4):1256-62. DOI: 10.2337/diabetes.51.4.1256. View

13.

Low L, Anstey K, Maller J, Kumar R, Wen W, Lux O . Hormone replacement therapy, brain volumes and white matter in postmenopausal women aged 60-64 years. Neuroreport. 2005; 17(1):101-4. DOI: 10.1097/01.wnr.0000194385.10622.8e. View

14.

McIntyre R, Vagic D, Swartz S, Soczynska J, Woldeyohannes H, Voruganti L . Insulin, insulin-like growth factors and incretins: neural homeostatic regulators and treatment opportunities. CNS Drugs. 2008; 22(6):443-53. DOI: 10.2165/00023210-200822060-00001. View

15.

Vanhanen M, Koivisto K, Kuusisto J, Mykkanen L, Helkala E, Hanninen T . Cognitive function in an elderly population with persistent impaired glucose tolerance. Diabetes Care. 1998; 21(3):398-402. DOI: 10.2337/diacare.21.3.398. View

16.

Kalmijn S, Feskens E, Launer L, Stijnen T, Kromhout D . Glucose intolerance, hyperinsulinaemia and cognitive function in a general population of elderly men. Diabetologia. 1995; 38(9):1096-102. DOI: 10.1007/BF00402181. View

17.

Convit A, Wolf O, Tarshish C, de Leon M . Reduced glucose tolerance is associated with poor memory performance and hippocampal atrophy among normal elderly. Proc Natl Acad Sci U S A. 2003; 100(4):2019-22. PMC: 149951. DOI: 10.1073/pnas.0336073100. View

18.

Devanand D, Liu X, Tabert M, Pradhaban G, Cuasay K, Bell K . Combining early markers strongly predicts conversion from mild cognitive impairment to Alzheimer's disease. Biol Psychiatry. 2008; 64(10):871-9. PMC: 2613777. DOI: 10.1016/j.biopsych.2008.06.020. View

19.

Hampel H, Burger K, Teipel S, Bokde A, Zetterberg H, Blennow K . Core candidate neurochemical and imaging biomarkers of Alzheimer's disease. Alzheimers Dement. 2008; 4(1):38-48. DOI: 10.1016/j.jalz.2007.08.006. View

20.

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