O4-08-01: Intranasal Insulin- And Biomarker-associated Improvement in Memory and Functional Status in Mild Cognitive Impairment and Alzheimer's Disease: Results of a Randomized, Double-blind, Placebo-controlled Pilot Trial

2010 ◽  
Vol 6 ◽  
pp. e18-e18
Author(s):  
Suzanne Craft ◽  
Laura D. Baker ◽  
Thomas J. Montine ◽  
Jing Zhang ◽  
G. Stennis Watson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Functional Status ◽  
Pilot Trial ◽  
Intranasal Insulin ◽  
Double Blind ◽  
Double Blind Placebo

scholarly journals Antidiabetic Drugs in Alzheimer’s Disease and Mild Cognitive Impairment: A Systematic Review

2020 ◽  
pp. 1-12 ◽  
Author(s):  
Mario Muñoz-Jiménez ◽  
Alí Zaarkti ◽  
Juan Antonio García-Arnés ◽  
Natalia García-Casares
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Antidiabetic Drugs ◽  
Secondary Outcome ◽  
Diabetic Patients ◽  
Intranasal Insulin

<b><i>Introduction:</i></b> Considering that Alzheimer’s disease (AD) and diabetes mellitus share pathophysiological features and AD remains with no cure, antidiabetic drugs like intranasal insulin, glitazones, metformin, and liraglutide are being tested as a potential treatment. <b><i>Objective:</i></b> The aim of this systematic review was to assess the efficacy of antidiabetic drugs in patients with AD, mild cognitive impairment (MCI), or subjective cognitive complaints (SCCs). Cognition was studied as the primary outcome and modulation of AD biomarkers, and imaging was also assessed as a secondary outcome. <b><i>Methods:</i></b> We conducted a search in the electronic databases PubMed/MEDLINE, EMBASE, and Scopus seeking clinical trials evaluating the effect on cognition of antidiabetic drugs in patients with AD, MCI, or SCCs. <b><i>Results:</i></b> A total of 23 articles were found eligible. Intranasal regular insulin improved verbal memory in most studies, especially in apoE4− patients, but results in other cognitive domains were unclear. Detemir improved cognition after 2 months of treatment, but it did not after 4 months. Pioglitazone improved cognition in diabetic patients with AD or MCI in 3 clinical trials, but it is controversial as 2 other studies did not show effect. Metformin and liraglutide showed promising results, but further research is needed as just 2 clinical trials involved each of these drugs. Almost all drugs tested were shown to modulate AD biomarkers and imaging. <b><i>Conclusions:</i></b> Intranasal insulin, pioglitazone, metformin, and liraglutide are promising drugs that could be useful in the treatment of AD. However, many questions remain to be answered in future studies, so no particular antidiabetic drug can currently be recommended to treat AD.

scholarly journals Bacterial rhamnolipids (RLs) in saliva of Alzheimer's disease and Mild Cognitive Impairment patients and correlation with neuroinflammation and cognitive state

2021 ◽  
Vol 06 (03) ◽  
pp. 209-219
Author(s):  
Eleni G. Andreadou ◽  
Georgios Katsipis ◽  
Magda Tsolaki ◽  
Anastasia A. Pantazaki
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Mental State ◽  
Biological Fluids ◽  
Pilot Trial ◽  
Control Group ◽  
Cognitive State ◽  
Cox 2

Alzheimer’s disease (AD) is increasingly affecting the aging population and the estimated prevalence reaches 50 million people worldwide. The need for the discovery of new biomarkers for AD diagnosis is urgent and especially in biological fluids other than cerebrospinal fluid (CSF), as its collection is invasive. Arguments are numerous that chronic bacterial infections might be considered as one of the possible causes of AD. Rhamnolipids (RLs) are bacterial virulence factors, suspicious for dysfunctions and disorders including AD. The aim of this pilot trial was to investigate RLs levels in saliva of Mild Cognitive Impairment (MCI) and AD patients with indirect ELISA. Specifically, salivary RLs were determined in 30 AD patients, 24 MCI patients and 15 cognitively healthy individuals and were found elevated in AD and MCI patients compared to those of the control group. The established biomarkers of AD, tau and Aβ42 amyloid, and the inflammatory markers cyclooxygenases (COX-1 and COX-2) were also determined, to evaluate their possible interdependence from RLs levels. Levels of RLs positively correlate with COX-2 levels and negatively with the mental state according to Mini–Mental State Examination (MMSE) score of donors. Multilinear regression verified the tight interrelation of RLs with COX-2 in saliva of MCI and AD patients. The results of this study stand by the hypothesis of inflammatory involvement in AD and indicate that RLs could be suggested as eventual biomarkers for AD diagnosis using saliva as biological fluid.

scholarly journals 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

2021 ◽  
pp. 1-9
Author(s):  
D. Kellar ◽  
S.N. Lockhart ◽  
P. Aisen ◽  
R. Raman ◽  
R.A. Rissman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
White Matter ◽  
Cerebral Spinal Fluid ◽  
Spinal Fluid ◽  
White Matter Hyperintensity ◽  
Intranasal Insulin ◽  
Fluid Biomarker

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: 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: A randomized (1:1) double-blind clinical trial. Setting: Twelve sites across the United States. Participants: Adults with mild cognitive impairment or Alzheimer’s disease. Intervention: 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: 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: 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: 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.

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