A single-dose pilot trial of intranasal rapid-acting insulin in apolipoprotein E4 carriers with mild-moderate Alzheimer's disease.
BACKGROUND
Intranasal (IN) insulin acutely improves verbal memory in mild cognitive impairment (MCI)/Alzheimer's disease (AD), but its therapeutic effects may be attenuated in apolipoprotein E4 (ApoE4) carriers. Furthermore, rapid-acting (RA) insulins may have superior therapeutic effects compared with regular insulin types.


OBJECTIVE
To measure the safety and efficacy of intranasally delivered RA glulisine in ApoE4 carriers with mild-moderate AD.


METHODS
We performed a double-blinded, randomized, cross-over study of RA insulin glulisine in nine mild-moderate AD subjects to better understand the relationship between RA insulin, ApoE4 carrier status and memory performance.


RESULTS
IN glulisine was well tolerated but failed to have an acute impact on cognition in ApoE4 carriers with AD. Serum insulin levels acutely dropped following treatment, but peripheral glucose levels remained unchanged.


CONCLUSIONS
Larger clinical trials of longer duration are necessary to better understand the relationships between RA insulin, ApoE4 carrier status and cognitive performance in AD.
HealthPartners Center for Memory and Aging, Regions Hospital, 401 Phalen Blvd., Mail Stop 41104C, St. Paul, MN, 55130, USA, Michael.H.Rosenbloom@HealthPartners.com.
Michael H
MH
Rosenbloom
Terry R
TR
Barclay
Maria
M
Pyle
Brian L
BL
Owens
Amanda B
AB
Cagan
Christopher P
CP
Anderson
William H
WH
Frey
Leah R
LR
Hanson
D000281:Administration, Intranasal; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy* / Q000235:genetics* / Q000523:psychology; D053327:Apolipoprotein E4 / Q000235:genetics*; D054316:Biomarkers, Pharmacological; D001786:Blood Glucose / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006579:Heterozygote; D006801:Humans; D007328:Insulin / Q000097:blood; D061266:Insulin, Short-Acting / Q000008:administration & dosage*; D008297:Male; D008568:Memory / Q000187:drug effects; D018697:Nootropic Agents / Q000008:administration & dosage*; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome
D053327:Apolipoprotein E4; D054316:Biomarkers, Pharmacological; D001786:Blood Glucose; D007328:Insulin; D061266:Insulin, Short-Acting; D018697:Nootropic Agents