Intranasal insulin administration dose-dependently modulates verbal memory and plasma amyloid-beta in memory-impaired older adults.
Intranasal insulin administration raises central nervous system (CNS) insulin levels in humans and acutely facilitates verbal memory in patients with Alzheimer's disease (AD), an effect that may differ by APOE genotype. The purpose of this study was to examine the cognitive dose response curves for intranasal insulin administration, and determine whether the effects of insulin differ between participants with (epsilon4+) and without (epsilon4-) the APOE- epsilon4 allele. On separate mornings, 33 memory-impaired adults with AD or amnestic mild cognitive impairment and 59 normal adults each underwent five intranasal treatment conditions consisting of insulin (10, 20, 40, or 60 IU) or placebo. Cognition was tested 15-minutes post-treatment, and blood was acquired at baseline and 45-minutes post-treatment. Plasma insulin and glucose levels were unaffected by treatment. Insulin administration facilitated recall on two measures of verbal memory in memory-impaired epsilon4- adults, with performance generally peaking at 20 IU. In contrast, memory-impaired epsilon4+ subjects demonstrated a relative decline in verbal memory. Insulin also differentially modulated plasma amyloid-beta for memory-impaired subjects and normal controls, effects that again differed by APOE genotype. These findings suggest that groups with different genetic risks for AD may show differential dose-response curves following intranasal insulin administration.
Reger
Mark A
MA
Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.
Watson
G Stennis
GS
Green
Pattie S
PS
Baker
Laura D
LD
Cholerton
Brenna
B
Fishel
Mark A
MA
Plymate
Stephen R
SR
Cherrier
Monique M
MM
Schellenberg
Gerard D
GD
Frey
William H
WH
Craft
Suzanne
S
D000281:Administration, Intranasal; D000544:Alzheimer Disease / Q000453:epidemiology*; D016229:Amyloid beta-Peptides / Q000187:drug effects; D053327:Apolipoprotein E4 / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D003704:Dementia / Q000175:diagnosis / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000175:diagnosis / Q000453:epidemiology*; D009483:Neuropsychological Tests; D012720:Severity of Illness Index; D014705:Verbal Behavior / Q000187:drug effects*
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D007004:Hypoglycemic Agents; D007328:Insulin