Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer's Disease Biomarkers: A Pilot Clinical Trial

Suzanne Craft, Amy Claxton, Laura D. Baker, Angela J. Hanson, Brenna Cholerton, Emily H. Trittschuh, Deborah Dahl, Erin Caulder, Bryan Neth, Thomas J. Montine, Youngkyoo Jung, Joseph A Maldjian, Christopher Whitlow, Seth Friedman, Suzanne De La Monte

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Background: Long acting insulin detemir administered intranasally for three weeks enhanced memory for adults with Alzheimer's disease dementia (AD) or amnestic mild cognitive impairment (MCI). The investigation of longer-term administration is necessary to determine whether benefits persist, whether they are similar to benefits provided by regular insulin, and whether either form of insulin therapy affects AD biomarkers. Objective: The present study aimed to determine whether four months of treatment with intranasal insulin detemir or regular insulin improves cognition, daily functioning, and AD biomarkers for adults with MCI or AD. Methods: This randomized, double-blind, placebo-controlled trial included an intent-to-treat sample consisting of 36 adults diagnosed with MCI or mild to moderate AD. Participants received placebo (n = 12), 40 IU of insulin detemir (n = 12), or 40 IU of regular insulin (n = 12) daily for four months, administered with a nasal delivery device. A cognitive battery was administered at baseline and after two and four months of treatment. MRI was administered for all participants and lumbar puncture for a subset (n = 20) at baseline and four months. The primary outcome was change from baseline to four months on a memory composite (sum of Z scores for delayed list and story recall). Secondary outcomes included: global cognition (Alzheimer's Disease Assessment Scale-Cognition), daily functioning (Dementia Severity Rating Scale), MRI volume changes in AD-related regions of interest, and cerebrospinal fluid AD markers. Results: The regular insulin treated group had better memory after two and four months compared with placebo (p < 0.03). No significant effects were observed for the detemir-assigned group compared with the placebo group, or for daily functioning for either group. Regular insulin treatment was associated with preserved volume on MRI. Regular insulin treatment was also associated with reduction in the tau-P181/Aβ42 ratio. Conclusion: Future research is warranted to examine the mechanistic basis of treatment differences, and to further assess the efficacy and safety of intranasal insulin.

Original languageEnglish (US)
Pages (from-to)1325-1334
Number of pages10
JournalJournal of Alzheimer's Disease
Volume57
Issue number4
DOIs
StatePublished - Jan 1 2017

Fingerprint

Long-Acting Insulin
Cognition
Alzheimer Disease
Biomarkers
Clinical Trials
Insulin
Placebos
Therapeutics
Spinal Puncture

Keywords

  • Alzheimer's disease
  • clinical trial
  • insulin
  • intranasal
  • magnetic resonance imaging
  • memory

ASJC Scopus subject areas

  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Craft, S., Claxton, A., Baker, L. D., Hanson, A. J., Cholerton, B., Trittschuh, E. H., ... De La Monte, S. (2017). Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer's Disease Biomarkers: A Pilot Clinical Trial. Journal of Alzheimer's Disease, 57(4), 1325-1334. https://doi.org/10.3233/JAD-161256

Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer's Disease Biomarkers : A Pilot Clinical Trial. / Craft, Suzanne; Claxton, Amy; Baker, Laura D.; Hanson, Angela J.; Cholerton, Brenna; Trittschuh, Emily H.; Dahl, Deborah; Caulder, Erin; Neth, Bryan; Montine, Thomas J.; Jung, Youngkyoo; Maldjian, Joseph A; Whitlow, Christopher; Friedman, Seth; De La Monte, Suzanne.

In: Journal of Alzheimer's Disease, Vol. 57, No. 4, 01.01.2017, p. 1325-1334.

Research output: Contribution to journalArticle

Craft, S, Claxton, A, Baker, LD, Hanson, AJ, Cholerton, B, Trittschuh, EH, Dahl, D, Caulder, E, Neth, B, Montine, TJ, Jung, Y, Maldjian, JA, Whitlow, C, Friedman, S & De La Monte, S 2017, 'Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer's Disease Biomarkers: A Pilot Clinical Trial', Journal of Alzheimer's Disease, vol. 57, no. 4, pp. 1325-1334. https://doi.org/10.3233/JAD-161256
Craft, Suzanne ; Claxton, Amy ; Baker, Laura D. ; Hanson, Angela J. ; Cholerton, Brenna ; Trittschuh, Emily H. ; Dahl, Deborah ; Caulder, Erin ; Neth, Bryan ; Montine, Thomas J. ; Jung, Youngkyoo ; Maldjian, Joseph A ; Whitlow, Christopher ; Friedman, Seth ; De La Monte, Suzanne. / Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer's Disease Biomarkers : A Pilot Clinical Trial. In: Journal of Alzheimer's Disease. 2017 ; Vol. 57, No. 4. pp. 1325-1334.
@article{1664a63215be4431af6c20e47131bb2d,
title = "Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer's Disease Biomarkers: A Pilot Clinical Trial",
abstract = "Background: Long acting insulin detemir administered intranasally for three weeks enhanced memory for adults with Alzheimer's disease dementia (AD) or amnestic mild cognitive impairment (MCI). The investigation of longer-term administration is necessary to determine whether benefits persist, whether they are similar to benefits provided by regular insulin, and whether either form of insulin therapy affects AD biomarkers. Objective: The present study aimed to determine whether four months of treatment with intranasal insulin detemir or regular insulin improves cognition, daily functioning, and AD biomarkers for adults with MCI or AD. Methods: This randomized, double-blind, placebo-controlled trial included an intent-to-treat sample consisting of 36 adults diagnosed with MCI or mild to moderate AD. Participants received placebo (n = 12), 40 IU of insulin detemir (n = 12), or 40 IU of regular insulin (n = 12) daily for four months, administered with a nasal delivery device. A cognitive battery was administered at baseline and after two and four months of treatment. MRI was administered for all participants and lumbar puncture for a subset (n = 20) at baseline and four months. The primary outcome was change from baseline to four months on a memory composite (sum of Z scores for delayed list and story recall). Secondary outcomes included: global cognition (Alzheimer's Disease Assessment Scale-Cognition), daily functioning (Dementia Severity Rating Scale), MRI volume changes in AD-related regions of interest, and cerebrospinal fluid AD markers. Results: The regular insulin treated group had better memory after two and four months compared with placebo (p < 0.03). No significant effects were observed for the detemir-assigned group compared with the placebo group, or for daily functioning for either group. Regular insulin treatment was associated with preserved volume on MRI. Regular insulin treatment was also associated with reduction in the tau-P181/Aβ42 ratio. Conclusion: Future research is warranted to examine the mechanistic basis of treatment differences, and to further assess the efficacy and safety of intranasal insulin.",
keywords = "Alzheimer's disease, clinical trial, insulin, intranasal, magnetic resonance imaging, memory",
author = "Suzanne Craft and Amy Claxton and Baker, {Laura D.} and Hanson, {Angela J.} and Brenna Cholerton and Trittschuh, {Emily H.} and Deborah Dahl and Erin Caulder and Bryan Neth and Montine, {Thomas J.} and Youngkyoo Jung and Maldjian, {Joseph A} and Christopher Whitlow and Seth Friedman and {De La Monte}, Suzanne",
year = "2017",
month = "1",
day = "1",
doi = "10.3233/JAD-161256",
language = "English (US)",
volume = "57",
pages = "1325--1334",
journal = "Journal of Alzheimer's Disease",
issn = "1387-2877",
publisher = "IOS Press",
number = "4",

}

TY - JOUR

T1 - Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer's Disease Biomarkers

T2 - A Pilot Clinical Trial

AU - Craft, Suzanne

AU - Claxton, Amy

AU - Baker, Laura D.

AU - Hanson, Angela J.

AU - Cholerton, Brenna

AU - Trittschuh, Emily H.

AU - Dahl, Deborah

AU - Caulder, Erin

AU - Neth, Bryan

AU - Montine, Thomas J.

AU - Jung, Youngkyoo

AU - Maldjian, Joseph A

AU - Whitlow, Christopher

AU - Friedman, Seth

AU - De La Monte, Suzanne

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Background: Long acting insulin detemir administered intranasally for three weeks enhanced memory for adults with Alzheimer's disease dementia (AD) or amnestic mild cognitive impairment (MCI). The investigation of longer-term administration is necessary to determine whether benefits persist, whether they are similar to benefits provided by regular insulin, and whether either form of insulin therapy affects AD biomarkers. Objective: The present study aimed to determine whether four months of treatment with intranasal insulin detemir or regular insulin improves cognition, daily functioning, and AD biomarkers for adults with MCI or AD. Methods: This randomized, double-blind, placebo-controlled trial included an intent-to-treat sample consisting of 36 adults diagnosed with MCI or mild to moderate AD. Participants received placebo (n = 12), 40 IU of insulin detemir (n = 12), or 40 IU of regular insulin (n = 12) daily for four months, administered with a nasal delivery device. A cognitive battery was administered at baseline and after two and four months of treatment. MRI was administered for all participants and lumbar puncture for a subset (n = 20) at baseline and four months. The primary outcome was change from baseline to four months on a memory composite (sum of Z scores for delayed list and story recall). Secondary outcomes included: global cognition (Alzheimer's Disease Assessment Scale-Cognition), daily functioning (Dementia Severity Rating Scale), MRI volume changes in AD-related regions of interest, and cerebrospinal fluid AD markers. Results: The regular insulin treated group had better memory after two and four months compared with placebo (p < 0.03). No significant effects were observed for the detemir-assigned group compared with the placebo group, or for daily functioning for either group. Regular insulin treatment was associated with preserved volume on MRI. Regular insulin treatment was also associated with reduction in the tau-P181/Aβ42 ratio. Conclusion: Future research is warranted to examine the mechanistic basis of treatment differences, and to further assess the efficacy and safety of intranasal insulin.

AB - Background: Long acting insulin detemir administered intranasally for three weeks enhanced memory for adults with Alzheimer's disease dementia (AD) or amnestic mild cognitive impairment (MCI). The investigation of longer-term administration is necessary to determine whether benefits persist, whether they are similar to benefits provided by regular insulin, and whether either form of insulin therapy affects AD biomarkers. Objective: The present study aimed to determine whether four months of treatment with intranasal insulin detemir or regular insulin improves cognition, daily functioning, and AD biomarkers for adults with MCI or AD. Methods: This randomized, double-blind, placebo-controlled trial included an intent-to-treat sample consisting of 36 adults diagnosed with MCI or mild to moderate AD. Participants received placebo (n = 12), 40 IU of insulin detemir (n = 12), or 40 IU of regular insulin (n = 12) daily for four months, administered with a nasal delivery device. A cognitive battery was administered at baseline and after two and four months of treatment. MRI was administered for all participants and lumbar puncture for a subset (n = 20) at baseline and four months. The primary outcome was change from baseline to four months on a memory composite (sum of Z scores for delayed list and story recall). Secondary outcomes included: global cognition (Alzheimer's Disease Assessment Scale-Cognition), daily functioning (Dementia Severity Rating Scale), MRI volume changes in AD-related regions of interest, and cerebrospinal fluid AD markers. Results: The regular insulin treated group had better memory after two and four months compared with placebo (p < 0.03). No significant effects were observed for the detemir-assigned group compared with the placebo group, or for daily functioning for either group. Regular insulin treatment was associated with preserved volume on MRI. Regular insulin treatment was also associated with reduction in the tau-P181/Aβ42 ratio. Conclusion: Future research is warranted to examine the mechanistic basis of treatment differences, and to further assess the efficacy and safety of intranasal insulin.

KW - Alzheimer's disease

KW - clinical trial

KW - insulin

KW - intranasal

KW - magnetic resonance imaging

KW - memory

UR - http://www.scopus.com/inward/record.url?scp=85018745780&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018745780&partnerID=8YFLogxK

U2 - 10.3233/JAD-161256

DO - 10.3233/JAD-161256

M3 - Article

C2 - 28372335

AN - SCOPUS:85018745780

VL - 57

SP - 1325

EP - 1334

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

IS - 4

ER -