TY - JOUR
T1 - A feasibility study of the combination of intranasal insulin with oral semaglutide for cognition in older adults with metabolic syndrome at high dementia risk- Study rationale and design
AU - Davidy, Tal
AU - Yore, Iscka
AU - Cukierman-Yaffe, Tali
AU - Ravona-Springer, Ramit
AU - Livny, Abigail
AU - Lesman-Segev, Orit H.
AU - Azuri, Yossi
AU - Carmichael, Owen
AU - Kapogiannis, Dimitrios
AU - Zetterberg, Henrik
AU - Lin, Hung Mo
AU - Sano, Mary
AU - Beeri, Michal Schnaider
N1 - Publisher Copyright:
© 2024
PY - 2024/4
Y1 - 2024/4
N2 - Introduction: We present the rationale and design of a double-blind placebo-controlled feasibility trial combining intranasal insulin (INI) with semaglutide, a GLP-1 receptor agonist, to improve cognition in older adults with metabolic syndrome (MetS) and mild cognitive impairment (MCI). Since both INI and dulaglutide have beneficial effects on the cerebrovascular disease (CVD), we anticipate that improved CVD will underlie the hypothesized cognitive benefits. Methods: This 12-months trial will include 80 older adults aged > 60 with MetS and MCI, randomized to 4 groups: INI/oral semaglutide, intranasal placebo/oral semaglutide, INI/oral placebo, and intranasal placebo/oral placebo. Feasibility of combining INI with semaglutide will be tested by examining the ease of use of INI (20IU, twice/day) with semaglutide (14 once daily), adherence, and safety profile are the efficacy of combination therapy on global cognition and neurobiological markers: cerebral blood flow, cerebral glucose utilization, white matter hyperintensities, Alzheimer's related blood biomarkers and expression of insulin signaling proteins measured in brain-derived exosomes. Efficacy will be assessed for the intent-to-treat sample. Discussion: This feasibility study is anticipated to provide the basis for a multi-center large-scale randomized clinical trial (RCT) of the cognitive benefits of the combination of INI with semaglutide in individuals enriched for CVD and at high dementia risk.
AB - Introduction: We present the rationale and design of a double-blind placebo-controlled feasibility trial combining intranasal insulin (INI) with semaglutide, a GLP-1 receptor agonist, to improve cognition in older adults with metabolic syndrome (MetS) and mild cognitive impairment (MCI). Since both INI and dulaglutide have beneficial effects on the cerebrovascular disease (CVD), we anticipate that improved CVD will underlie the hypothesized cognitive benefits. Methods: This 12-months trial will include 80 older adults aged > 60 with MetS and MCI, randomized to 4 groups: INI/oral semaglutide, intranasal placebo/oral semaglutide, INI/oral placebo, and intranasal placebo/oral placebo. Feasibility of combining INI with semaglutide will be tested by examining the ease of use of INI (20IU, twice/day) with semaglutide (14 once daily), adherence, and safety profile are the efficacy of combination therapy on global cognition and neurobiological markers: cerebral blood flow, cerebral glucose utilization, white matter hyperintensities, Alzheimer's related blood biomarkers and expression of insulin signaling proteins measured in brain-derived exosomes. Efficacy will be assessed for the intent-to-treat sample. Discussion: This feasibility study is anticipated to provide the basis for a multi-center large-scale randomized clinical trial (RCT) of the cognitive benefits of the combination of INI with semaglutide in individuals enriched for CVD and at high dementia risk.
KW - Cerebral blood flow
KW - Cognition
KW - Dulaglutide
KW - Intranasal insulin
KW - Metabolic syndrome
KW - Mild cognitive impairment
UR - http://www.scopus.com/inward/record.url?scp=85184206435&partnerID=8YFLogxK
U2 - 10.1016/j.mad.2023.111898
DO - 10.1016/j.mad.2023.111898
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C2 - 38159613
AN - SCOPUS:85184206435
SN - 0047-6374
VL - 218
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
M1 - 111898
ER -
