title: Cognitively impaired elderly exhibit insulin resistance and no memory improvement with infused insulin.
abstract: Insulin resistance is a risk factor for Alzheimer's disease (AD), although its role in AD etiology is unclear. We assessed insulin resistance using fasting and insulin-stimulated measures in 51 elderly subjects with no dementia (ND; n = 37) and with cognitive impairment (CI; n = 14). CI subjects exhibited either mild CI or AD. Fasting insulin resistance was measured using the homeostatic model assessment of insulin resistance (HOMA-IR). Insulin-stimulated glucose disposal was assessed using the hyperinsulinemic-euglycemic clamp to calculate glucose disposal rate into lean mass, the primary site of insulin-stimulated glucose disposal. Because insulin crosses the blood-brain barrier, we also assessed whether insulin infusion would improve verbal episodic memory compared to baseline. Different but equivalent versions of cognitive tests were administered in counterbalanced order in the basal and insulin-stimulated state. Groups did not differ in age or body mass index. Cognitively impaired subjects exhibited greater insulin resistance as measured at fasting (HOMA-IR; ND: 1.09 [1.1] vs. CI: 2.01 [2.3], p = 0.028) and during the hyperinsulinemic clamp (glucose disposal rate into lean mass; ND: 9.9 (4.5) vs. AD 7.2 (3.2), p = 0.040). Cognitively impaired subjects also exhibited higher fasting insulin compared to ND subjects, (CI: 8.7 [7.8] vs. ND: 4.2 [3.8] μU/mL; p = 0.023) and higher fasting amylin (CI: 24.1 [39.1] vs. 8.37 [14.2]; p = 0.050) with no difference in fasting glucose. Insulin infusion elicited a detrimental effect on one test of verbal episodic memory (Free and Cued Selective Reminding Test) in both groups (p < 0.0001) and no change in performance on an additional task (delayed logical memory). In this study, although insulin resistance was observed in cognitively impaired subjects compared to ND controls, insulin infusion did not improve memory. Furthermore, a significant correlation between HOMA-IR and glucose disposal rate was present only in ND (p = 0.0002) but not in cognitively impaired (p = 0.884) subjects, indicating potentially important physiological differences between these cohorts.
authors.affiliation: Alzheimer's Disease Center, University of Kansas Medical Center, Fairway, KS, USA; Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA. Electronic address: jmorris2@kumc.edu.
authors.forename: Jill K
authors.initials: JK
authors.lastname: Morris
authors.affiliation: Alzheimer's Disease Center, University of Kansas Medical Center, Fairway, KS, USA; Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Vidoni
authors.affiliation: Alzheimer's Disease Center, University of Kansas Medical Center, Fairway, KS, USA; Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Mahnken
authors.affiliation: Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Montgomery
authors.affiliation: Alzheimer's Disease Center, University of Kansas Medical Center, Fairway, KS, USA; Department of Psychology, University of Kansas, Lawrence, KS, USA.
authors.forename: David K
authors.initials: DK
authors.lastname: Johnson
authors.affiliation: Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Thyfault
authors.affiliation: Alzheimer's Disease Center, University of Kansas Medical Center, Fairway, KS, USA; Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Burns
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000209:etiology / Q000503:physiopathology; D001812:Blood-Brain Barrier / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology* / Q000523:psychology*; D015331:Cohort Studies; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D061212:Memory, Episodic; D012307:Risk Factors
chemical_list: D007328:Insulin; D005947:Glucose
keywords: Aging; Alzheimer's disease; Cognitive impairment; Hyperinsulinemia; Insulin; Insulin resistance