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Relationship between Insulin-Resistance Processing Speed and Specific Executive Function Profiles in Neurologically Intact Older Adults

Published online by Cambridge University Press:  14 August 2015

Darvis T. Frazier ,
Brianne M. Bettcher ,
Shubir Dutt ,
Nihar Patel ,
Dan Mungas ,
Joshua Miller ,
Ralph Green  and
Joel H. Kramer
Darvis T. Frazier*
Affiliation:
Memory and Aging Center, University of California, San Francisco, San Francisco, California Department of Neurology, University of California, San Francisco, San Francisco, California
Brianne M. Bettcher
Affiliation:
Memory and Aging Center, University of California, San Francisco, San Francisco, California Department of Neurology, University of California, San Francisco, San Francisco, California
Shubir Dutt
Affiliation:
Memory and Aging Center, University of California, San Francisco, San Francisco, California Department of Neurology, University of California, San Francisco, San Francisco, California
Nihar Patel
Affiliation:
Memory and Aging Center, University of California, San Francisco, San Francisco, California Department of Neurology, University of California, San Francisco, San Francisco, California
Dan Mungas
Affiliation:
Department of Neurology, School of Medicine, University of California, Davis, Davis, California
Joshua Miller
Affiliation:
Department of Pathology and Laboratory Medicine, University of California, Davis, Davis, California
Ralph Green
Affiliation:
Department of Pathology and Laboratory Medicine, University of California, Davis, Davis, California
Joel H. Kramer
Affiliation:
Memory and Aging Center, University of California, San Francisco, San Francisco, California Department of Neurology, University of California, San Francisco, San Francisco, California
*
Correspondence and reprint requests to: Darvis T. Frazier, UCSF Memory and Aging Center, 675 Nelson Rising Lane, Suite 190 San Francisco, CA 94143-1207. E-mail: [email protected]
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Abstract

This study investigated the relationship between insulin-resistance and constituent components of executive function in a sample of neurologically intact older adult subjects using the homeostasis model assessment (HOMA-IR) and latent factors of working memory, cognitive control and processing speed derived from confirmatory factor analysis. Low-density lipoprotein (LDL), mean arterial pressure (MAP), along with body mass index (BMI) and white matter hypointensity (WMH) were used to control for vascular risk factors, adiposity and cerebrovascular injury. The study included 119 elderly subjects recruited from the University of California, San Francisco Memory and Aging Center. Subjects underwent neuropsychological assessment, fasting blood draw and brain magnetic resonance imaging (MRI). Partial correlations and linear regression models were used to examine the HOMA-IR-executive function relationship. Pearson correlation adjusting for age showed a significant relationship between HOMA-IR and working memory (rp=−.18; p=.047), a trend with cognitive control (rp=−.17; p=.068), and no relationship with processing speed (rp=.013; p=.892). Linear regression models adjusting for demographic factors (age, education, and gender), LDL, MAP, BMI, and WMH indicated that HOMA-IR was negatively associated with cognitive control (r=−.256; p=.026) and working memory (r=−.234; p=.054). These results suggest a greater level of peripheral insulin-resistance is associated with decreased cognitive control and working memory. After controlling for demographic factors, vascular risk, adiposity and cerebrovascular injury, HOMA-IR remained significantly associated with cognitive control, with working memory showing a trend. These findings substantiate the insulin-resistance-executive function hypothesis and suggest a complex interaction, demonstrated by the differential impact of insulin-resistance on processing speed and specific aspects of executive function. (JINS, 2015, 21, 622–628)

Keywords

Homeostatic model assessmentInsulin-resistanceConfirmatory factor analysisExecutive functionWorking memoryCognitive controlProcessing speedWhite matter hypointensity
Type
Research Articles
Information
Journal of the International Neuropsychological Society , Volume 21 , Issue 8 , September 2015 , pp. 622 - 628
Copyright
Copyright © The International Neuropsychological Society 2015 

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References

Abbatecola, A.M., Paolisso, G., Lamponi, M., Bandinelli, S., Lauretani, F., Launer, L., & Ferrucci, L. (2004). Insulin resistance and executive dysfunction in older persons. Journal of the American Geriatrics Society, 52(10), 1713–1718. doi: 10.1111/j.1532-5415.2004.52466.xCrossRefGoogle ScholarPubMed
Baker, L.D., Cross, D.J., Minoshima, S., Belongia, D., Watson, G.S., & Craft, S. (2011). Insulin resistance and Alzheimer-like reductions in regional cerebral glucose metabolism for cognitively normal adults with prediabetes or early type 2 diabetes. Archives of neurology, 68(1), 51–57. doi:10.1001/archneurol.2010.225.CrossRefGoogle ScholarPubMed
Banks, W.A., Owen, J.B., & Erickson, M.A. (2012). Insulin in the brain: There and back again. Pharmacology & Therapeutics, 136(1), 82–93. doi:10.1016/j.pharmthera.2012.07.006CrossRefGoogle Scholar
Benedict, C., Brooks, S.J., Kullberg, J., Burgos, J., Kempton, M.J., Nordenskjöld, R., & Schiöth, H.B. (2012). Impaired insulin sensitivity as indexed by the HOMA score is associated with deficits in verbal fluency and temporal lobe gray matter volume in the elderly. Diabetes Care, 35(3), 488–494. doi:10.2337/dc11-2075CrossRefGoogle ScholarPubMed
Bettcher, B.M., Watson, C.L., Walsh, C.M., Lobach, I.V., Neuhaus, J., Miller, J.W., & Kramer, J.H. (2014). Interleukin-6, age, and corpus callosum integrity. PLoS One, 9(9), e106521. doi:10.1371/journal.pone.0106521CrossRefGoogle ScholarPubMed
Boeka, A.G., & Lokken, K.L. (2008). Neuropsychological performance of a clinical sample of extremely obese individuals. Archives of Clinical Neuropsychology, 23(4), 467–474. doi:10.1016/j.acn.2008.03.003CrossRefGoogle ScholarPubMed
Bove, R.M., Brick, D.J., Healy, B.C., Mancuso, S.M., Gerweck, A.V., Bredella, M.A., & Miller, K.K. (2013). Metabolic and endocrine correlates of cognitive function in healthy young women. Obesity, 21(7), 1343–1349. doi:10.1002/oby.20212CrossRefGoogle ScholarPubMed
Cholerton, B., Baker, L.D., & Craft, S. (2013). Insulin, cognition, and dementia. European Journal of Pharmacology, 719(1), 170–179. doi:10.1016/j.ejphar.2013.08.008CrossRefGoogle ScholarPubMed
Craft, S. (2005). Insulin resistance syndrome and Alzheimer’s disease: Age-and obesity-related effects on memory, amyloid, and inflammation. Neurobiology of Aging, 26(1), 65–69. doi:10.1016/j.neurobiolaging.2005.08.021CrossRefGoogle ScholarPubMed
Dik, M.G., Jonker, C., Comijs, H.C., Deeg, D.J., Kok, A., Yaffe, K., & Penninx, B.W. (2007). Contribution of metabolic syndrome components to cognition in older individuals. Diabetes Care, 30(10), 2655–2660. doi:10.2337/dc06-1190CrossRefGoogle ScholarPubMed
Geroldi, C., Frisoni, G.B., Paolisso, G., Bandinelli, S., Lamponi, M., Abbatecola, A.M., & Ferrucci, L. (2005). Insulin resistance in cognitive impairment: The InCHIANTI study. Archives of Neurology, 62(7), 1067–1072. doi:10.1001/archneur.62.7.1067CrossRefGoogle ScholarPubMed
Gunstad, J., Paul, R.H., Cohen, R.A., Tate, D.F., & Gordon, E. (2006). Obesity is associated with memory deficits in young and middle-aged adults. Eating and Weight Disorders-Studies on Anorexia, Bulimia and Obesity, 11(1), e15–e19. doi:10.1007/BF03327747CrossRefGoogle Scholar
Gunstad, J., Paul, R.H., Cohen, R.A., Tate, D.F., Spitznagel, M.B., & Gordon, E. (2007). Elevated body mass index is associated with executive dysfunction in otherwise healthy adults. Comprehensive Psychiatry, 48(1), 57–61. doi:10.1016/j.comppsych.2006.05.001CrossRefGoogle ScholarPubMed
Jastreboff, A.M., Sinha, R., Lacadie, C., Small, D.M., Sherwin, R.S., & Potenza, M.N. (2013). Neural Correlates of Stress- and Food Cue–Induced Food Craving in Obesity Association with insulin levels. Diabetes Care, 36(2), 394–402. doi:10.2337/dc12-1112.CrossRefGoogle ScholarPubMed
Jiang, H., Hampel, H., Prvulovic, D., Wallin, A., Blennow, K., Li, R., & Shen, Y. (2011). Elevated CSF levels of TACE activity and soluble TNF receptors in subjects with mild cognitive impairment and patients with Alzheimer’s disease. Molecular Neurodegeneration, 6, 69. doi:10.1186/1750-1326-6-69CrossRefGoogle ScholarPubMed
Kern, P.A., Ranganathan, S., Li, C., Wood, L., & Ranganathan, G. (2001). Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. American Journal of Physiology-Endocrinology and Metabolism, 280(5), E745–E751. Retrieved from http://ajpendo.physiology.org/content/280/5/E745.long.CrossRefGoogle ScholarPubMed
Miyake, A., Friedman, N.P., Emerson, M.J., Witzki, A.H., Howerter, A., & Wager, T.D. (2000). The unity and diversity of executive functions and their contributions to complex “frontal lobe” tasks: A latent variable analysis. Cognitive Psychology, 41(1), 49–100. doi:10.1006/cogpCrossRefGoogle ScholarPubMed
Muthén, B.O., & Muthén, L.K. (2010). Mplus (Version 6). Los Angeles: Muthen & Muthen.Google Scholar
Ryan, J.P., Sheu, L.K., Verstynen, T.D., Onyewuenyi, I.C., & Gianaros, P.J. (2013). Cerebral blood flow links insulin resistance and baroreflex sensitivity. PloS One, 8(12), e83288. doi:10.1371/journal.pone.0083288CrossRefGoogle ScholarPubMed
Ryu, S.Y., Coutu, J.P., Rosas, H.D., & Salat, D.H. (2014). Effects of insulin resistance on white matter microstructure in middle-aged and older adults. Neurology, 82(21), 1862–1870. doi:10.1212/WNLCrossRefGoogle ScholarPubMed
Schuur, M., Henneman, P., van Swieten, J.C., Zillikens, M.C., de Koning, I., Janssens, A. C. J. W., & van Duijn, C.M. (2010). Insulin-resistance and metabolic syndrome are related to executive function in women in a large family-based study. European Journal of Epidemiology, 25(8), 561–568. doi:10.1007/s10654-010-9476-yCrossRefGoogle Scholar
Shoelson, S.E., Lee, J., & Goldfine, A.B. (2006). Inflammation and insulin resistance. The Journal of Clinical Investigation, 116(7), 1793–1801. doi:10.1172/JCI29069CrossRefGoogle ScholarPubMed
Spielman, L.J., & Klegeris, A. (2014). The Role of Insulin and Incretins in Neuroinflammation and Neurodegeneration. Immunoendocrinology, 1(1), 1–8. doi: 10.14800/Immunoendocrinology.391Google Scholar
Tam, C., Xie, W., Johnson, W.D., Cefalu, W.T., Redman, L.M., & Ravussin, E. (2012). Defining insulin resistance from hyperinsulinemic-euglycemic clamps. Diabetes Care, 35(7), 1605–1610. doi:10.2337/dc11-2339CrossRefGoogle ScholarPubMed
van den Berg, E., Dekker, J.M., Nijpels, G., Kessels, R.P., Kappelle, L.J., de Haan, E.H., & Biessels, G.J. (2008). Cognitive functioning in elderly persons with type 2 diabetes and metabolic syndrome: The Hoorn study. Dementia and Geriatric Cognitive Disorders, 26(3), 261–269. doi:10.1159/000160959CrossRefGoogle ScholarPubMed
Willette, A.A., Xu, G., Johnson, S.C., Birdsill, A.C., Jonaitis, E.M., Sager, M.A., & Bendlin, B.B. (2013). Insulin resistance, brain atrophy, and cognitive performance in late middle–aged adults. Diabetes Care, 36(2), 443–449. doi:10.2337/dc12-0922CrossRefGoogle ScholarPubMed