Intranasal Insulin Reduces White Matter Hyperintensity Progression in Association with Improvements in Cognition and CSF Biomarker Profiles in Mild Cognitive Impairment and Alzheimer's Disease.
Activities of Daily Living
Administration, Intranasal
Aged
Alzheimer Disease
/ drug therapy
Biomarkers
/ cerebrospinal fluid
Brain
/ physiopathology
Cognition
/ drug effects
Cognitive Dysfunction
/ drug therapy
Female
Humans
Hypoglycemic Agents
/ therapeutic use
Image Processing, Computer-Assisted
/ statistics & numerical data
Insulin
/ therapeutic use
Insulin, Regular, Human
/ therapeutic use
Magnetic Resonance Imaging
Male
Neuropsychological Tests
/ statistics & numerical data
White Matter
/ pathology
Alzheimer’s disease
CSF
clinical trial
intranasal insulin
white matter
Journal
The journal of prevention of Alzheimer's disease
ISSN: 2426-0266
Titre abrégé: J Prev Alzheimers Dis
Pays: Switzerland
ID NLM: 101638820
Informations de publication
Date de publication:
Historique:
entrez:
8
6
2021
pubmed:
9
6
2021
medline:
28
10
2021
Statut:
ppublish
Résumé
Intranasally administered insulin has shown promise in both rodent and human studies in Alzheimer's disease; however, both effects and mechanisms require elucidation. We assessed the effects of intranasally administered insulin on white matter health and its association with cognition and cerebral spinal fluid biomarker profiles in adults with mild cognitive impairment or Alzheimer's disease in secondary analyses from a prior phase 2 clinical trial (NCT01767909). A randomized (1:1) double-blind clinical trial. Twelve sites across the United States. Adults with mild cognitive impairment or Alzheimer's disease. Participants received either twice daily placebo or insulin (20 IU Humulin R U-100 b.i.d.) intranasally for 12 months. Seventy-eight participants were screened, of whom 49 (32 men) were enrolled. Changes from baseline in global and regional white matter hyperintensity volume and gray matter volume were analyzed and related to changes in cerebral spinal fluid biomarkers, Alzheimer's Disease Assessment Scale-Cognition, Clinical Disease Rating-Sum of Boxes, Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale, and a memory composite. The insulin-treated group demonstrated significantly reduced changes in white matter hyperintensity volume in deep and frontal regions after 12 months, with a similar trend for global volume. White matter hyperintensity volume progression correlated with worsened Alzheimer's disease cerebral spinal fluid biomarker profile and cognitive function; however, patterns of correlations differed by treatment group. Intranasal insulin treatment for 12 months reduced white matter hyperintensity volume progression and supports insulin's potential as a therapeutic option for Alzheimer's disease.
Sections du résumé
BACKGROUND
BACKGROUND
Intranasally administered insulin has shown promise in both rodent and human studies in Alzheimer's disease; however, both effects and mechanisms require elucidation.
OBJECTIVE
OBJECTIVE
We assessed the effects of intranasally administered insulin on white matter health and its association with cognition and cerebral spinal fluid biomarker profiles in adults with mild cognitive impairment or Alzheimer's disease in secondary analyses from a prior phase 2 clinical trial (NCT01767909).
DESIGN
METHODS
A randomized (1:1) double-blind clinical trial.
SETTING
METHODS
Twelve sites across the United States.
PARTICIPANTS
METHODS
Adults with mild cognitive impairment or Alzheimer's disease.
INTERVENTION
METHODS
Participants received either twice daily placebo or insulin (20 IU Humulin R U-100 b.i.d.) intranasally for 12 months. Seventy-eight participants were screened, of whom 49 (32 men) were enrolled.
MEASUREMENTS
METHODS
Changes from baseline in global and regional white matter hyperintensity volume and gray matter volume were analyzed and related to changes in cerebral spinal fluid biomarkers, Alzheimer's Disease Assessment Scale-Cognition, Clinical Disease Rating-Sum of Boxes, Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale, and a memory composite.
RESULTS
RESULTS
The insulin-treated group demonstrated significantly reduced changes in white matter hyperintensity volume in deep and frontal regions after 12 months, with a similar trend for global volume. White matter hyperintensity volume progression correlated with worsened Alzheimer's disease cerebral spinal fluid biomarker profile and cognitive function; however, patterns of correlations differed by treatment group.
CONCLUSION
CONCLUSIONS
Intranasal insulin treatment for 12 months reduced white matter hyperintensity volume progression and supports insulin's potential as a therapeutic option for Alzheimer's disease.
Identifiants
pubmed: 34101779
doi: 10.14283/jpad.2021.14
pmc: PMC10233712
mid: NIHMS1892908
doi:
Substances chimiques
Biomarkers
0
Hypoglycemic Agents
0
Insulin
0
Insulin, Regular, Human
0
Banques de données
ClinicalTrials.gov
['NCT01767909']
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
240-248Subventions
Organisme : NIA NIH HHS
ID : P30 AG072947
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG041845
Pays : United States
Déclaration de conflit d'intérêts
The authors have no conflict of interest to report.
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