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Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial.
Arch Neurol. 2012 Jan; 69(1):29-38.AN

Abstract

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.

Authors+Show Affiliations

Geriatric Research, Education, and Clinical Center, S-182, Veterans Affairs Puget Sound Health Care System, 1660 S Columbian Way, Seattle, WA 98108, USA. scraft@uw.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

21911655

Citation

Craft, Suzanne, et al. "Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: a Pilot Clinical Trial." Archives of Neurology, vol. 69, no. 1, 2012, pp. 29-38.
Craft S, Baker LD, Montine TJ, et al. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol. 2012;69(1):29-38.
Craft, S., Baker, L. D., Montine, T. J., Minoshima, S., Watson, G. S., Claxton, A., Arbuckle, M., Callaghan, M., Tsai, E., Plymate, S. R., Green, P. S., Leverenz, J., Cross, D., & Gerton, B. (2012). Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Archives of Neurology, 69(1), 29-38. https://doi.org/10.1001/archneurol.2011.233
Craft S, et al. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: a Pilot Clinical Trial. Arch Neurol. 2012;69(1):29-38. PubMed PMID: 21911655.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. AU - Craft,Suzanne, AU - Baker,Laura D, AU - Montine,Thomas J, AU - Minoshima,Satoshi, AU - Watson,G Stennis, AU - Claxton,Amy, AU - Arbuckle,Matthew, AU - Callaghan,Maureen, AU - Tsai,Elaine, AU - Plymate,Stephen R, AU - Green,Pattie S, AU - Leverenz,James, AU - Cross,Donna, AU - Gerton,Brooke, Y1 - 2011/09/12/ PY - 2011/9/14/entrez PY - 2011/9/14/pubmed PY - 2012/2/22/medline SP - 29 EP - 38 JF - Archives of neurology JO - Arch Neurol VL - 69 IS - 1 N2 - 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. SN - 1538-3687 UR - https://www.unboundmedicine.com/medline/citation/21911655/Intranasal_insulin_therapy_for_Alzheimer_disease_and_amnestic_mild_cognitive_impairment:_a_pilot_clinical_trial_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/archneurol.2011.233 DB - PRIME DP - Unbound Medicine ER -