scholarly journals Sex and ApoE Genotype Differences in Treatment Response to Two Doses of Intranasal Insulin in Adults with Mild Cognitive Impairment or Alzheimer's Disease

2013 ◽  
Vol 35 (4) ◽  
pp. 789-797 ◽  
Author(s):  
Amy Claxton ◽  
Laura D. Baker ◽  
Charles W. Wilkinson ◽  
Emily H. Trittschuh ◽  
Darla Chapman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Treatment Response ◽  
Apoe Genotype ◽  
Intranasal Insulin

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 Influence of APOE Genotype on Alzheimer’s Disease CSF Biomarkers in a Spanish Population

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
J. A. Monge-Argilés ◽  
R. Gasparini-Berenguer ◽  
M. Gutierrez-Agulló ◽  
C. Muñoz-Ruiz ◽  
J. Sánchez-Payá ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Apoe Genotype ◽  
Amnestic Mild Cognitive Impairment ◽  
Spanish Population ◽  
Csf Biomarkers ◽  
Csf Levels

Objectives. To evaluate the association between apolipoprotein E (APOE) genotype and cerebrospinal fluid (CSF) levels of Alzheimer’s disease (AD) biomarkers and to study the influence of APOE genotype on the development of AD in a Spanish population.Material and Methods. The study comprised 29 amnestic mild cognitive impairment (MCI) patients and 27 control subjects. Using ELISA methodology, CSF biomarkers and tau/Aβratios were obtained. ANOVA and adjusted odds ratios were calculated.Results. We observed the effect of APOE genotype and age on CSF AD variables. The progression to AD was more clearly influenced by CSF AD variables than by age or APOE status.Conclusions. APOE status influences CSF AD variables. However, the presence of APOEε4 does not appear to be a deterministic factor for the development of AD, because CSF variables have a greater influence on progression to the disease. These results confirm previous observations and, to our knowledge, are the first published in a Spanish population.

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.

APOE ɛ4-TOMM40L Haplotype Increases the Risk of Mild Cognitive Impairment Conversion to Alzheimer’s Disease

2020 ◽  
Vol 78 (2) ◽  
pp. 587-601
Author(s):  
Remy Cardoso ◽  
Carolina Lemos ◽  
Bárbara Oliveiros ◽  
Maria Rosário Almeida ◽  
Inês Baldeiras ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Apoe Genotype ◽  
Csf Biomarkers ◽  
Cognitively Normal ◽  
Conversion Time ◽  
E4 Allele ◽  
Normal Controls

Background: Mild cognitive impairment (MCI) has been considered as a pre-dementia stage, although the factors leading to Alzheimer’s disease (AD) conversion remain controversial. Objective: Evaluate whether TOMM40 poly-T (TOMM40′ 523) polymorphism is associated with the risk and conversion time from MCI to AD and secondly with AD cerebrospinal fluid (CSF) biomarkers, disentangling the APOE genotype. Methods: 147 AD patients, 102 MCI patients, and 105 cognitively normal controls were genotyped for poly-T polymorphism. MCI patients were subdivided into two groups, the group of patients that converted to AD (MCI-AD) and the group of those that remained stable (MCI-S). Results: TOMM40′ 523 L allele was significantly more frequent in the MCI-AD group and having at least one L allele significantly increased the risk of conversion from MCI to AD (OR = 8.346, p < 0.001, 95% CI: 2.830 to 24.617). However, when adjusted for the presence of APOE ɛ4 allele, both the L allele and ɛ4 allele lost significance in the model (p > 0.05). We then analyzed the APOE ɛ4-TOMM40′ 523 L haplotype and observed that patients carrying this haplotype had significantly higher risk (OR = 5.83; 95% CI = 2.30–14.83) and mean lower times of conversion to AD (p = 0.003). This haplotype was also significantly associated with a biomarker profile compatible with AD (p = 0.007). Conclusion: This study shows that the APOE ɛ4-TOMM40′ 523 L haplotype is associated with a higher risk and shorter times of conversion from MCI to AD, possibly driven by CSF biomarkers and mitochondrial dysfunction.

Prevalence of Apolipoprotein E Polymorphisms in Alzheimer’s Disease, Mild Cognitive Impairment, and Healthy Elderly: A Northern Greece Study

2018 ◽  
Vol 18 (4) ◽  
pp. 216-224 ◽  
Author(s):  
Anthoula C. Tsolaki ◽  
Olympia Gatzima ◽  
Makrina Daniilidou ◽  
Eutuxia Lazarou ◽  
Panagiotis D. Bamidis ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Apolipoprotein E ◽  
Apoe Genotype ◽  
Dependent Manner ◽  
Apoe Ε4 ◽  
Healthy Elderly ◽  
Increased Risk

Background: Apolipoprotein E ε4 allele (APOEε4) is a major genetic risk factor for Alzheimer’s disease (AD). APOEε4 carriers have a higher risk of cognitive impairment and AD in a gene dose-dependent manner. The above notion is investigated in the Greek population. Methods: A sample of 1,703 subjects (967 AD patients, 576 mild cognitive impairment [MCI] and 160 Healthy Elderly), was genotyped for APOE from 2008 to 2017. DNA was extracted from peripheral blood using the QIAamp Blood DNA purification kit (Qiagen Inc., USA). Descriptive statistics, one-way analysis of variance with Bonferroni post hoc tests, Pearson chi-square test, and binary logistic regression models were used for the statistical analysis. Results: The APOE genotype and allele frequencies in AD group were significantly different from those in the Control and MCI groups. The frequencies of ε4/4 homozygotes were 1.9, 1.6, and 5.7%, while the ε4/– carriers’ distribution was 22.5, 24.1, and 37.4% in the Control, MCI, and AD groups respectively. The estimated odds of ε4/4 for AD was 5.731-fold higher compared to the estimated odds of ε3/3. The interaction between gender and APOE did not have a significant effect on the odds for MCI (p = 0.942) and AD (p = 0.984). Conclusion: In Greece, APOE ε4 presence is related to an increased risk for AD in a dose-related manner. Contrary to long-standing views, men and women with the APOE ε4 genotype have nearly the same odds of developing MCI and AD.

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