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Study of Nasal Insulin to Fight Forgetfulness - Device Study

Primary Purpose

Mild Cognitive Impairment, Cognitive Impairment

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Insulin
Placebo
intranasal nebulizer-like device
Sponsored by
Wake Forest University Health Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mild Cognitive Impairment focused on measuring Intranasal Delivery of Insulin, Cognitive Testing, Nasal Insulin

Eligibility Criteria

55 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Fluent in English
  • Cognitively normal or diagnosis of aMCI
  • Stable medical condition for 3 months prior to screening visit
  • Stable medications for 4 weeks prior to the screening and study visits
  • Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be clinically insignificant by the study physician

Exclusion Criteria:

  • A diagnosis of dementia
  • History of a clinically significant stroke
  • Current evidence or history in past two years of epilepsy, head injury with loss of consciousness, any major psychiatric disorder including psychosis, major depression, bipolar disorder
  • Diabetes (type I or type II) insulin dependent and non-insulin dependent diabetes mellitus
  • Current or past use of insulin or any other anti-diabetic medication within 5 years of Screening visit.
  • History of cancer five years prior to screening (history of skin melanoma or stable prostate cancer are not exclusionary)
  • History of seizure within past five years
  • Pregnancy or possible pregnancy.
  • Use of anticoagulants warfarin (Coumadin) and dabigatran (Pradaxa)
  • Residence in a skilled nursing facility at screening
  • Use of an investigational agent within two months of screening visit
  • Regular use of alcohol, narcotics, anticonvulsants, antiparkinsonian medications, or any other exclusionary medications

Sites / Locations

  • Wake Forest University Health Sciences

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Insulin first, then placebo

Placebo first, then insulin

Arm Description

Participants will be randomly assigned to receive regular insulin (U100, 20 IU) administered with an intranasal nebulizer-like device. Participants in this arm will then receive placebo at visit 3 during second intervention period.

Participants will be randomly assigned to receive placebo administered with an intranasal nebulizer-like device. At visit 3 during second intervention period, participants in this arm will receive insulin.

Outcomes

Primary Outcome Measures

CSF insulin levels
Levels of insulin in CS fluid after being delivered with the device. This will help to determine the ability of an intranasal delivery device to increase levels of insulin in cerebrospinal fluid (CSF)

Secondary Outcome Measures

The Auditory-Verbal Learning Test (AVLT)
memory measure in which participant hears a list of 12 words over 3 trials, and is asked to recall them immediately after hearing them, then again after a 45 minute delay. Total possible score is 36 for immediate recall and 12 for delayed recall. Higher scores are better.
CSF Levels of AB42
Levels of the 42 amino acid isoform of the beta amyloid peptide
CSF Levels of total tau
Levels of the tau protein
CSF Levels phospho-tau 181
Levels of the tau phosphorylated at isotope 181

Full Information

First Posted
February 22, 2019
Last Updated
January 27, 2023
Sponsor
Wake Forest University Health Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT03857321
Brief Title
Study of Nasal Insulin to Fight Forgetfulness - Device Study
Official Title
Device Study for Intranasal Delivery of Insulin
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 12, 2019 (Actual)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
August 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wake Forest University Health Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The SNIFF Device study will involve using a device to administer insulin through each participant's nose or intra-nasally. Insulin is a hormone that is produced in the body. It works by lowering levels of glucose (sugar) in the blood. This study is measuring how much insulin the device delivers. In addition, this study will look at the effects of insulin or placebo administered intra-nasally using a nebulizer-like device on memory, blood, and cerebral spinal fluid.
Detailed Description
The aim of this study is to determine the ability of an intranasal delivery device to increase levels of insulin in cerebrospinal fluid (CSF). A growing body of evidence suggests that insulin plays a role in normal memory processes and that insulin abnormalities may contribute to cognitive and brain changes associated with Alzheimer's disease (AD). Interestingly, insulin administered to the nasal cavity is transported within a few minutes into the brain, but does not affect blood sugar or insulin levels. The study will consist of a single site, randomized, double-blind trial comparing the acute effects of INI (20 International Units) or placebo delivered with nebulizer-like device on CSF insulin levels, AD biomarkers and memory. At study entry, participants will be randomized to receive either an acute dose of insulin or placebo first, and the other substance on a second visit. Participants who are cognitively normal or who have aMCI (n=30) will be enrolled. The primary outcome measure will be to test the hypothesis that CSF insulin levels will increase 30 minutes after receiving a 20 International Units dose of insulin delivered with a nebulizer-like device, compared to levels achieved 30 minutes after placebo.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mild Cognitive Impairment, Cognitive Impairment
Keywords
Intranasal Delivery of Insulin, Cognitive Testing, Nasal Insulin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Model Description
At study entry, participants will be randomized to receive either an acute dose of insulin or of placebo first and the other substance on a second visit.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Neither participants or site personnel will know whether insulin or saline is being administered. Exceptions will be the study nurse who is directly involved in preparing the insulin or placebo, as well as preparing DSMB reports.
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Insulin first, then placebo
Arm Type
Experimental
Arm Description
Participants will be randomly assigned to receive regular insulin (U100, 20 IU) administered with an intranasal nebulizer-like device. Participants in this arm will then receive placebo at visit 3 during second intervention period.
Arm Title
Placebo first, then insulin
Arm Type
Experimental
Arm Description
Participants will be randomly assigned to receive placebo administered with an intranasal nebulizer-like device. At visit 3 during second intervention period, participants in this arm will receive insulin.
Intervention Type
Drug
Intervention Name(s)
Insulin
Other Intervention Name(s)
Humulin® R U-100
Intervention Description
20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly & Company)
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
placebo to Humulin® R U-100, Sterile saline
Intervention Description
Matching placebo (sterile saline) to 20 IU Humulin® R U-100
Intervention Type
Device
Intervention Name(s)
intranasal nebulizer-like device
Intervention Description
Participants will be assigned to receive placebo or regular insulin (U100, 20 IU) administered through an intranasal nebulizer-like device.
Primary Outcome Measure Information:
Title
CSF insulin levels
Description
Levels of insulin in CS fluid after being delivered with the device. This will help to determine the ability of an intranasal delivery device to increase levels of insulin in cerebrospinal fluid (CSF)
Time Frame
30 minutes after intervention administration
Secondary Outcome Measure Information:
Title
The Auditory-Verbal Learning Test (AVLT)
Description
memory measure in which participant hears a list of 12 words over 3 trials, and is asked to recall them immediately after hearing them, then again after a 45 minute delay. Total possible score is 36 for immediate recall and 12 for delayed recall. Higher scores are better.
Time Frame
5 minutes before lumbar puncture, and immediately following lumbar puncture
Title
CSF Levels of AB42
Description
Levels of the 42 amino acid isoform of the beta amyloid peptide
Time Frame
30 minutes after intervention administration
Title
CSF Levels of total tau
Description
Levels of the tau protein
Time Frame
30 minutes after intervention administration
Title
CSF Levels phospho-tau 181
Description
Levels of the tau phosphorylated at isotope 181
Time Frame
30 minutes after intervention administration

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Fluent in English Cognitively normal or diagnosis of aMCI Stable medical condition for 3 months prior to screening visit Stable medications for 4 weeks prior to the screening and study visits Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be clinically insignificant by the study physician Exclusion Criteria: A diagnosis of dementia History of a clinically significant stroke Current evidence or history in past two years of epilepsy, head injury with loss of consciousness, any major psychiatric disorder including psychosis, major depression, bipolar disorder Diabetes (type I or type II) insulin dependent and non-insulin dependent diabetes mellitus Current or past use of insulin or any other anti-diabetic medication within 5 years of Screening visit. History of cancer five years prior to screening (history of skin melanoma or stable prostate cancer are not exclusionary) History of seizure within past five years Pregnancy or possible pregnancy. Use of anticoagulants warfarin (Coumadin) and dabigatran (Pradaxa) Residence in a skilled nursing facility at screening Use of an investigational agent within two months of screening visit Regular use of alcohol, narcotics, anticonvulsants, antiparkinsonian medications, or any other exclusionary medications
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Suzanne Craft, PhD
Organizational Affiliation
Wake Forest University Health Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Wake Forest University Health Sciences
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
21514249
Citation
Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):270-9. doi: 10.1016/j.jalz.2011.03.008. Epub 2011 Apr 21.
Results Reference
background
PubMed Identifier
3758265
Citation
Baker H, Spencer RF. Transneuronal transport of peroxidase-conjugated wheat germ agglutinin (WGA-HRP) from the olfactory epithelium to the brain of the adult rat. Exp Brain Res. 1986;63(3):461-73. doi: 10.1007/BF00237470.
Results Reference
background
PubMed Identifier
20837822
Citation
Baker LD, Cross DJ, Minoshima S, Belongia D, Watson GS, Craft S. Insulin resistance and Alzheimer-like reductions in regional cerebral glucose metabolism for cognitively normal adults with prediabetes or early type 2 diabetes. Arch Neurol. 2011 Jan;68(1):51-7. doi: 10.1001/archneurol.2010.225. Epub 2010 Sep 13.
Results Reference
background
PubMed Identifier
3782501
Citation
Balin BJ, Broadwell RD, Salcman M, el-Kalliny M. Avenues for entry of peripherally administered protein to the central nervous system in mouse, rat, and squirrel monkey. J Comp Neurol. 1986 Sep 8;251(2):260-80. doi: 10.1002/cne.902510209.
Results Reference
background
PubMed Identifier
15288712
Citation
Benedict C, Hallschmid M, Hatke A, Schultes B, Fehm HL, Born J, Kern W. Intranasal insulin improves memory in humans. Psychoneuroendocrinology. 2004 Nov;29(10):1326-34. doi: 10.1016/j.psyneuen.2004.04.003.
Results Reference
background
PubMed Identifier
18230654
Citation
Benedict C, Kern W, Schultes B, Born J, Hallschmid M. Differential sensitivity of men and women to anorexigenic and memory-improving effects of intranasal insulin. J Clin Endocrinol Metab. 2008 Apr;93(4):1339-44. doi: 10.1210/jc.2007-2606. Epub 2008 Jan 29.
Results Reference
background
Citation
Bodian, D. and H. A. Howe (1941).
Results Reference
background
PubMed Identifier
11992114
Citation
Born J, Lange T, Kern W, McGregor GP, Bickel U, Fehm HL. Sniffing neuropeptides: a transnasal approach to the human brain. Nat Neurosci. 2002 Jun;5(6):514-6. doi: 10.1038/nn849. No abstract available.
Results Reference
background
PubMed Identifier
2418083
Citation
Broadwell RD, Balin BJ. Endocytic and exocytic pathways of the neuronal secretory process and trans-synaptic transfer of wheat germ agglutinin-horseradish peroxidase in vivo. J Comp Neurol. 1985 Dec 22;242(4):632-50. doi: 10.1002/cne.902420410.
Results Reference
background
PubMed Identifier
16399806
Citation
Cavanna AE, Trimble MR. The precuneus: a review of its functional anatomy and behavioural correlates. Brain. 2006 Mar;129(Pt 3):564-83. doi: 10.1093/brain/awl004. Epub 2006 Jan 6.
Results Reference
background
PubMed Identifier
18549783
Citation
Chiu SL, Chen CM, Cline HT. Insulin receptor signaling regulates synapse number, dendritic plasticity, and circuit function in vivo. Neuron. 2008 Jun 12;58(5):708-19. doi: 10.1016/j.neuron.2008.04.014.
Results Reference
background
PubMed Identifier
21911655
Citation
Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, Arbuckle M, Callaghan M, Tsai E, Plymate SR, Green PS, Leverenz J, Cross D, Gerton B. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol. 2012 Jan;69(1):29-38. doi: 10.1001/archneurol.2011.233. Epub 2011 Sep 12.
Results Reference
background
PubMed Identifier
9443474
Citation
Craft S, Peskind E, Schwartz MW, Schellenberg GD, Raskind M, Porte D Jr. Cerebrospinal fluid and plasma insulin levels in Alzheimer's disease: relationship to severity of dementia and apolipoprotein E genotype. Neurology. 1998 Jan;50(1):164-8. doi: 10.1212/wnl.50.1.164.
Results Reference
background
PubMed Identifier
14980532
Citation
Craft S, Watson GS. Insulin and neurodegenerative disease: shared and specific mechanisms. Lancet Neurol. 2004 Mar;3(3):169-78. doi: 10.1016/S1474-4422(04)00681-7.
Results Reference
background
PubMed Identifier
19188609
Citation
De Felice FG, Vieira MN, Bomfim TR, Decker H, Velasco PT, Lambert MP, Viola KL, Zhao WQ, Ferreira ST, Klein WL. Protection of synapses against Alzheimer's-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers. Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):1971-6. doi: 10.1073/pnas.0809158106. Epub 2009 Feb 2. Erratum In: Proc Natl Acad Sci U S A. 2009 May 5;106(18):7678.
Results Reference
background
Citation
Faber, H. K. (1938).
Results Reference
background
Citation
Fairbrother, R. W. and E. W. Hurst (1930).
Results Reference
background
PubMed Identifier
16216936
Citation
Fishel MA, Watson GS, Montine TJ, Wang Q, Green PS, Kulstad JJ, Cook DG, Peskind ER, Baker LD, Goldgaber D, Nie W, Asthana S, Plymate SR, Schwartz MW, Craft S. Hyperinsulinemia provokes synchronous increases in central inflammation and beta-amyloid in normal adults. Arch Neurol. 2005 Oct;62(10):1539-44. doi: 10.1001/archneur.62.10.noc50112.
Results Reference
background
PubMed Identifier
19015157
Citation
Francis GJ, Martinez JA, Liu WQ, Xu K, Ayer A, Fine J, Tuor UI, Glazner G, Hanson LR, Frey WH 2nd, Toth C. Intranasal insulin prevents cognitive decline, cerebral atrophy and white matter changes in murine type I diabetic encephalopathy. Brain. 2008 Dec;131(Pt 12):3311-34. doi: 10.1093/brain/awn288. Epub 2008 Nov 16.
Results Reference
background
PubMed Identifier
9720972
Citation
Frolich L, Blum-Degen D, Bernstein HG, Engelsberger S, Humrich J, Laufer S, Muschner D, Thalheimer A, Turk A, Hoyer S, Zochling R, Boissl KW, Jellinger K, Riederer P. Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease. J Neural Transm (Vienna). 1998;105(4-5):423-38. doi: 10.1007/s007020050068.
Results Reference
background
PubMed Identifier
9236950
Citation
Galasko D, Bennett D, Sano M, Ernesto C, Thomas R, Grundman M, Ferris S. An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997;11 Suppl 2:S33-9.
Results Reference
background
PubMed Identifier
11306609
Citation
Gasparini L, Gouras GK, Wang R, Gross RS, Beal MF, Greengard P, Xu H. Stimulation of beta-amyloid precursor protein trafficking by insulin reduces intraneuronal beta-amyloid and requires mitogen-activated protein kinase signaling. J Neurosci. 2001 Apr 15;21(8):2561-70. doi: 10.1523/JNEUROSCI.21-08-02561.2001.
Results Reference
background
PubMed Identifier
20847404
Citation
Gil-Bea FJ, Solas M, Solomon A, Mugueta C, Winblad B, Kivipelto M, Ramirez MJ, Cedazo-Minguez A. Insulin levels are decreased in the cerebrospinal fluid of women with prodomal Alzheimer's disease. J Alzheimers Dis. 2010;22(2):405-13. doi: 10.3233/JAD-2010-100795.
Results Reference
background
PubMed Identifier
17848936
Citation
Hallschmid M, Benedict C, Schultes B, Born J, Kern W. Obese men respond to cognitive but not to catabolic brain insulin signaling. Int J Obes (Lond). 2008 Feb;32(2):275-82. doi: 10.1038/sj.ijo.0803722. Epub 2007 Sep 11.
Results Reference
background
PubMed Identifier
9235959
Citation
Hong M, Lee VM. Insulin and insulin-like growth factor-1 regulate tau phosphorylation in cultured human neurons. J Biol Chem. 1997 Aug 1;272(31):19547-53. doi: 10.1074/jbc.272.31.19547.
Results Reference
background
PubMed Identifier
7104545
Citation
Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL. A new clinical scale for the staging of dementia. Br J Psychiatry. 1982 Jun;140:566-72. doi: 10.1192/bjp.140.6.566.
Results Reference
background
PubMed Identifier
12547019
Citation
Illum L. Nasal drug delivery: new developments and strategies. Drug Discov Today. 2002 Dec 1;7(23):1184-9. doi: 10.1016/s1359-6446(02)02529-1.
Results Reference
background
PubMed Identifier
10078556
Citation
Kern W, Born J, Schreiber H, Fehm HL. Central nervous system effects of intranasally administered insulin during euglycemia in men. Diabetes. 1999 Mar;48(3):557-63. doi: 10.2337/diabetes.48.3.557.
Results Reference
background
PubMed Identifier
5126829
Citation
Kristensson K, Olsson Y. Uptake of exogenous proteins in mouse olfactory cells. Acta Neuropathol. 1971;19(2):145-54. doi: 10.1007/BF00688493. No abstract available.
Results Reference
background
PubMed Identifier
12951650
Citation
Kupila A, Sipila J, Keskinen P, Simell T, Knip M, Pulkki K, Simell O. Intranasally administered insulin intended for prevention of type 1 diabetes--a safety study in healthy adults. Diabetes Metab Res Rev. 2003 Sep-Oct;19(5):415-20. doi: 10.1002/dmrr.397.
Results Reference
background
PubMed Identifier
17692997
Citation
Lee CC, Kuo YM, Huang CC, Hsu KS. Insulin rescues amyloid beta-induced impairment of hippocampal long-term potentiation. Neurobiol Aging. 2009 Mar;30(3):377-87. doi: 10.1016/j.neurobiolaging.2007.06.014. Epub 2007 Aug 10.
Results Reference
background
PubMed Identifier
7622680
Citation
Minoshima S, Frey KA, Foster NL, Kuhl DE. Preserved pontine glucose metabolism in Alzheimer disease: a reference region for functional brain image (PET) analysis. J Comput Assist Tomogr. 1995 Jul-Aug;19(4):541-7. doi: 10.1097/00004728-199507000-00006.
Results Reference
background
PubMed Identifier
8071705
Citation
Minoshima S, Koeppe RA, Frey KA, Kuhl DE. Anatomic standardization: linear scaling and nonlinear warping of functional brain images. J Nucl Med. 1994 Sep;35(9):1528-37.
Results Reference
background
PubMed Identifier
9191756
Citation
Morris JC, Ernesto C, Schafer K, Coats M, Leon S, Sano M, Thal LJ, Woodbury P. Clinical dementia rating training and reliability in multicenter studies: the Alzheimer's Disease Cooperative Study experience. Neurology. 1997 Jun;48(6):1508-10. doi: 10.1212/wnl.48.6.1508.
Results Reference
background
PubMed Identifier
11735772
Citation
Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, Ritchie K, Rossor M, Thal L, Winblad B. Current concepts in mild cognitive impairment. Arch Neurol. 2001 Dec;58(12):1985-92. doi: 10.1001/archneur.58.12.1985.
Results Reference
background
PubMed Identifier
6800439
Citation
Pontiroli AE, Alberetto M, Secchi A, Dossi G, Bosi I, Pozza G. Insulin given intranasally induces hypoglycaemia in normal and diabetic subjects. Br Med J (Clin Res Ed). 1982 Jan 30;284(6312):303-6. doi: 10.1136/bmj.284.6312.303.
Results Reference
background
PubMed Identifier
15964100
Citation
Reger MA, Watson GS, Frey WH 2nd, Baker LD, Cholerton B, Keeling ML, Belongia DA, Fishel MA, Plymate SR, Schellenberg GD, Cherrier MM, Craft S. Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype. Neurobiol Aging. 2006 Mar;27(3):451-8. doi: 10.1016/j.neurobiolaging.2005.03.016. Epub 2005 Jun 16.
Results Reference
background
PubMed Identifier
18430999
Citation
Reger MA, Watson GS, Green PS, Baker LD, Cholerton B, Fishel MA, Plymate SR, Cherrier MM, Schellenberg GD, Frey WH 2nd, Craft S. Intranasal insulin administration dose-dependently modulates verbal memory and plasma amyloid-beta in memory-impaired older adults. J Alzheimers Dis. 2008 Apr;13(3):323-31. doi: 10.3233/jad-2008-13309.
Results Reference
background
PubMed Identifier
17942819
Citation
Reger MA, Watson GS, Green PS, Wilkinson CW, Baker LD, Cholerton B, Fishel MA, Plymate SR, Breitner JC, DeGroodt W, Mehta P, Craft S. Intranasal insulin improves cognition and modulates beta-amyloid in early AD. Neurology. 2008 Feb 5;70(6):440-8. doi: 10.1212/01.WNL.0000265401.62434.36. Epub 2007 Oct 17. Erratum In: Neurology. 2008 Sep 9;71(11):866.
Results Reference
background
PubMed Identifier
16340083
Citation
Rivera EJ, Goldin A, Fulmer N, Tavares R, Wands JR, de la Monte SM. Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer's disease: link to brain reductions in acetylcholine. J Alzheimers Dis. 2005 Dec;8(3):247-68. doi: 10.3233/jad-2005-8304.
Results Reference
background
Citation
Rubin, D. B. (1987). Multiple Imputation for Nonresponse in Surveys. Hoboken, New Jersey, John Wiley & Sons, Inc
Results Reference
background
PubMed Identifier
7494186
Citation
Sakane T, Akizuki M, Taki Y, Yamashita S, Sezaki H, Nadai T. Direct drug transport from the rat nasal cavity to the cerebrospinal fluid: the relation to the molecular weight of drugs. J Pharm Pharmacol. 1995 May;47(5):379-81. doi: 10.1111/j.2042-7158.1995.tb05814.x.
Results Reference
background
PubMed Identifier
20921876
Citation
Sano M, Raman R, Emond J, Thomas RG, Petersen R, Schneider LS, Aisen PS. Adding delayed recall to the Alzheimer Disease Assessment Scale is useful in studies of mild cognitive impairment but not Alzheimer disease. Alzheimer Dis Assoc Disord. 2011 Apr-Jun;25(2):122-7. doi: 10.1097/WAD.0b013e3181f883b7.
Results Reference
background
PubMed Identifier
18359102
Citation
Selkoe DJ. Soluble oligomers of the amyloid beta-protein impair synaptic plasticity and behavior. Behav Brain Res. 2008 Sep 1;192(1):106-13. doi: 10.1016/j.bbr.2008.02.016. Epub 2008 Feb 17.
Results Reference
background
PubMed Identifier
3840049
Citation
Shipley MT. Transport of molecules from nose to brain: transneuronal anterograde and retrograde labeling in the rat olfactory system by wheat germ agglutinin-horseradish peroxidase applied to the nasal epithelium. Brain Res Bull. 1985 Aug;15(2):129-42. doi: 10.1016/0361-9230(85)90129-7.
Results Reference
background
PubMed Identifier
15501490
Citation
Stockhorst U, de Fries D, Steingrueber HJ, Scherbaum WA. Insulin and the CNS: effects on food intake, memory, and endocrine parameters and the role of intranasal insulin administration in humans. Physiol Behav. 2004 Oct 30;83(1):47-54. doi: 10.1016/j.physbeh.2004.07.022.
Results Reference
background
PubMed Identifier
8548316
Citation
Thorne RG, Emory CR, Ala TA, Frey WH 2nd. Quantitative analysis of the olfactory pathway for drug delivery to the brain. Brain Res. 1995 Sep 18;692(1-2):278-82. doi: 10.1016/0006-8993(95)00637-6.
Results Reference
background
PubMed Identifier
15262337
Citation
Thorne RG, Pronk GJ, Padmanabhan V, Frey WH 2nd. Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration. Neuroscience. 2004;127(2):481-96. doi: 10.1016/j.neuroscience.2004.05.029.
Results Reference
background
PubMed Identifier
17855343
Citation
Townsend M, Mehta T, Selkoe DJ. Soluble Abeta inhibits specific signal transduction cascades common to the insulin receptor pathway. J Biol Chem. 2007 Nov 16;282(46):33305-33312. doi: 10.1074/jbc.M610390200. Epub 2007 Sep 13.
Results Reference
background
PubMed Identifier
16591462
Citation
Weiss P, Holland Y. Neuronal dynamics and axonal flow, ii. The olfactory nerve as model test object. Proc Natl Acad Sci U S A. 1967 Feb;57(2):258-64. doi: 10.1073/pnas.57.2.258. No abstract available.
Results Reference
background
PubMed Identifier
1400644
Citation
Worsley KJ, Evans AC, Marrett S, Neelin P. A three-dimensional statistical analysis for CBF activation studies in human brain. J Cereb Blood Flow Metab. 1992 Nov;12(6):900-18. doi: 10.1038/jcbfm.1992.127.
Results Reference
background
PubMed Identifier
15590928
Citation
Zhao L, Teter B, Morihara T, Lim GP, Ambegaokar SS, Ubeda OJ, Frautschy SA, Cole GM. Insulin-degrading enzyme as a downstream target of insulin receptor signaling cascade: implications for Alzheimer's disease intervention. J Neurosci. 2004 Dec 8;24(49):11120-6. doi: 10.1523/JNEUROSCI.2860-04.2004.
Results Reference
background
PubMed Identifier
19026743
Citation
Zhao WQ, Townsend M. Insulin resistance and amyloidogenesis as common molecular foundation for type 2 diabetes and Alzheimer's disease. Biochim Biophys Acta. 2009 May;1792(5):482-96. doi: 10.1016/j.bbadis.2008.10.014. Epub 2008 Nov 5.
Results Reference
background

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Study of Nasal Insulin to Fight Forgetfulness - Device Study

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