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Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment

2011· article· en· 1 234 citations· W2153284686 sur OpenAlex· 10.1001/archneurol.2011.233

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Résumé

OBJECTIVE: To examine the effects of intranasal insulin administration on cognition, function, cerebral glucose metabolism, and cerebrospinal fluid biomarkers in adults with amnestic mild cognitive impairment or Alzheimer disease (AD). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Clinical research unit of a Veterans Affairs medical center. PARTICIPANTS: The intent-to-treat sample consisted of 104 adults with amnestic mild cognitive impairment (n = 64) or mild to moderate AD (n = 40). Intervention Participants received placebo (n = 30), 20 IU of insulin (n = 36), or 40 IU of insulin (n = 38) for 4 months, administered with a nasal drug delivery device (Kurve Technology, Bothell, Washington). MAIN OUTCOME MEASURES: Primary measures consisted of delayed story recall score and the Dementia Severity Rating Scale score, and secondary measures included the Alzheimer Disease's Assessment Scale-cognitive subscale (ADAS-cog) score and the Alzheimer's Disease Cooperative Study-activities of daily living (ADCS-ADL) scale. A subset of participants underwent lumbar puncture (n = 23) and positron emission tomography with fludeoxyglucose F 18 (n = 40) before and after treatment. RESULTS: Outcome measures were analyzed using repeated-measures analysis of covariance. Treatment with 20 IU of insulin improved delayed memory (P < .05), and both doses of insulin (20 and 40 IU) preserved caregiver-rated functional ability (P < .01). Both insulin doses also preserved general cognition as assessed by the ADAS-cog score for younger participants and functional abilities as assessed by the ADCS-ADL scale for adults with AD (P < .05). Cerebrospinal fluid biomarkers did not change for insulin-treated participants as a group, but, in exploratory analyses, changes in memory and function were associated with changes in the Aβ42 level and in the tau protein-to-Aβ42 ratio in cerebrospinal fluid. Placebo-assigned participants showed decreased fludeoxyglucose F 18 uptake in the parietotemporal, frontal, precuneus, and cuneus regions and insulin-minimized progression. No treatment-related severe adverse events occurred. CONCLUSIONS: These results support longer trials of intranasal insulin therapy for patients with amnestic mild cognitive impairment and patients with AD. Trial Registration clinicaltrials.gov Identifier: NCT00438568.

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La notice

Revue
Archives of Neurology
Thématique
Advanced Drug Delivery Systems
Domaine
Pharmacology, Toxicology and Pharmaceutics
Établissements canadiens
Organismes subventionnaires
NIH Clinical CenterNational Institute on AgingUniversity of WashingtonNancy and Buster Alvord EndowmentU.S. Department of Veterans Affairs
Mots-clés
MedicineMontreal Cognitive AssessmentInsulinInternal medicineClinical Dementia RatingPlaceboDementiaAlzheimer's diseasePhysical therapyDiseasePathology
Résumé présent dans OpenAlex
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