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.