Serum Adiponectin in Alzheimer’s Disease (AD): Association with AD Biomarkers and Cognitive Outcome

2021 ◽  
pp. 1-10
Author(s):  
Heeyoung Kim ◽  
Sungmin Jun ◽  
Bum Soo Kim ◽  
In-Joo Kim ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Adiponectin Level ◽  
Cognitive Outcome ◽  
Serum Adiponectin ◽  
Carrier Status ◽  
Serum Adiponectin Level

Background: The association between dementia and serum adiponectin has been evaluated in many studies; however, conclusions remain mixed. Objective: We investigated the cross-sectional associations of adiponectin with cognitive function and Alzheimer’s disease (AD) biomarkers and whether serum adiponectin levels can predict cognitive outcomes. Methods: This study included 496 participants from the Alzheimer’s Disease Neuroimaging Initiative 1 (ADNI1) with available serum adiponectin levels at baseline and ≥65 years of age. Subjects were stratified based on sex and apolipoprotein ɛ4 (APOE4) carrier status to determine associations between adiponectin and cognitive function. The linear mixed model was used to analyze associations between adiponectin level and cognitive outcome in amnestic mild cognitive impairment (aMCI) patients. Results: Serum adiponectin levels were higher in aMCI and AD than in CN subjects among APOE4 non-carrier males (adiponectin in CN, aMCI, and AD: 0.54±0.24, 0.74±0.25, and 0.85±0.25, respectively, p < 0.001). In this group, serum adiponectin levels were associated with age (p = 0.001), ADAS13 (p < 0.001), memory function (p < 0.001), executive function (p < 0.001), total tau (p < 0.001), and phosphorylated tau (p < 0.001) measures in cerebrospinal fluid (CSF). Higher adiponectin level was not associated with cognitive outcome in aMCI patients in the linear mixed model analysis over 5.3±2.6 years of mean follow-up. Conclusion: Serum adiponectin level was associated with cognitive function and CSF AD biomarkers among APOE4 non-carrier males. However, serum adiponectin level was not associated with longitudinal cognitive function outcome in aMCI.

scholarly journals Steady-state cerebral autoregulation in older adults with amnestic mild cognitive impairment: linear mixed model analysis

2020 ◽  
Vol 129 (2) ◽  
pp. 377-385
Author(s):  
Li Zhang ◽  
Evan P. Pasha ◽  
Jie Liu ◽  
Chang-Yang Xing ◽  
Danilo Cardim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cerebral Autoregulation ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Amnestic Mild Cognitive Impairment ◽  
Pathophysiological Mechanism ◽  
Mixed Model Analysis

Cerebral autoregulation is a fundamental regulatory mechanism to protect brain perfusion against changes in blood pressure that, if impaired, may contribute to the development of Alzheimer’s disease. Using a linear mixed model, we demonstrated that the efficacy of cerebral autoregulation, assessed during stepwise changes in arterial pressure, was reduced in individuals with amnestic mild cognitive impairment, a prodromal stage of Alzheimer’s disease. These findings support the hypothesis that cerebrovascular dysfunction may be an important underlying pathophysiological mechanism for the development of clinical Alzheimer’s disease.

scholarly journals Segmented Linear Mixed Model Analysis Reveals Association of the APOE ɛ4 Allele with Faster Rate of Alzheimer’s Disease Dementia Progression

2021 ◽  
pp. 1-17
Author(s):  
X. Richard Chen ◽  
Yongzhao Shao ◽  
Martin J. Sadowski ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Late Onset ◽  
Apoe Genotype ◽  
Middle Temporal Gyrus ◽  
Mixed Model Analysis ◽  
Increased Risk ◽  
E4 Allele

Background: APOE ɛ4 allele carriers present with increased risk for late-onset Alzheimer’s disease (AD), show cognitive symptoms at earlier age, and are more likely to transition from mild cognitive impairment (MCI) to dementia but despite this, it remains unclear whether or not the ɛ4 allele controls the rate of disease progression. Objective: To determine effects of the ɛ4 allele on rates of cognitive decline and brain atrophy during MCI and dementia stages of AD. Methods: A segmented linear mixed model was chosen for longitudinal modeling of cognitive and brain volumetric data of 73 ɛ3/ɛ3, 99 ɛ3/ɛ4, and 39 ɛ4/ɛ4 Alzheimer’s Disease Neuroimaging Initiative participants who transitioned during the study from MCI to AD dementia. Results: ɛ4 carriers showed faster decline on MMSE, ADAS-11, CDR-SB, and MoCA scales, with the last two measures showing significant ɛ4 allele-dose effects after dementia transition but not during MCI. The ɛ4 effect was more prevalent in younger participants and in females. ɛ4 carriers also demonstrated faster rates of atrophy of the whole brain, the hippocampus, the entorhinal cortex, the middle temporal gyrus, and expansion of the ventricles after transitioning to dementia but not during MCI. Conclusion: Possession of the ɛ4 allele is associated with a faster progression of dementia due to AD. Our observations support the notion that APOE genotype not only controls AD risk but also differentially regulates mechanisms of neurodegeneration underlying disease advancement. Furthermore, our findings carry significance for AD clinical trial design.

scholarly journals APOE missense variant R145C is associated with increased Alzheimer's disease risk in African ancestry individuals with the APOE ϵ3/ϵ4 genotype

2021 ◽  
Author(s):  
Yann Le Guen ◽  
Michael E Belloy ◽  
Sarah J Eger ◽  
Annabel Chen ◽  
Gabriel Kennedy ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
African Ancestry ◽  
Age At Onset ◽  
Missense Variant ◽  
Competing Risk ◽  
Next Generation Sequencing Data ◽  
Increased Risk

BACKGROUND The APOE gene has two common missense variants that greatly impact the risk of late-onset Alzheimer's disease (AD). Here we examined the risk of a third APOE missense variant, R145C, that is rare in European-Americans but present in 4% of African-Americans and always in phase with APOE ϵ3. METHODS In this study, we included 11,790 individuals of African and Admixed-African ancestry (4,089 cases and 7,701 controls). The discovery sample was composed of next generation sequencing data (2,888 cases and 4,957 controls), and the replication was composed of microarray data imputed on the TOPMed reference panel (1,201 cases and 2,744 contols). To assess the effect of R145C independently of the ϵ2 and ϵ4 alleles, we performed stratified analyses in ϵ2/ϵ3, ϵ3/ϵ3, and ϵ3/ϵ4 subjects. In primary analyses, the AD risk associated with R145C was estimated using a linear mixed model regression on case-control diagnosis. In secondary analyses, we estimated the influence of R145C on age-at-onset using linear-mixed-model regression, and risk of conversion to AD using competing risk regression. RESULTS In ϵ3/ϵ4-stratified meta-analyses, R145C carriers had an almost three-fold increased risk compared to non-carriers (odds ratio, 2.75; 95% confidence interval [CI], 1.84 to 4.11; P = 8.3x10-7) and had a reported AD age-at-onset almost 6 years younger (β, -5.72; 95% CI, 7.87 to -3.56; P = 2.0x10-7). Competing risk regression showed that the cumulative incidence of AD grows faster with age in R145C carriers compared to non-carriers (hazard ratio, 2.42, 95% CI, 1.81 to 3.25; P = 3.7x10-9). CONCLUSION The R145C variant is a potent risk factor for AD among African ancestry individuals with the ϵ3/ϵ4 genotype. Our findings should enhance AD risk prediction in African ancestry individuals and help elucidate the mechanisms linking the apoE protein to AD pathogenesis. The findings also add to the growing body of evidence demonstrating the importance of including ancestrally-diverse populations in genetic studies.

Development and Evaluation of a Tactile Cognitive Function Test Device for Alzheimer’s Disease Early Detection

2015 ◽  
Vol 3 (2) ◽  
pp. 58-65 ◽  
Author(s):  
Jiajia Yang ◽  
Mohd Usairy Syafiq ◽  
Yinghua Yu ◽  
Satoshi Takahashi ◽  
Zhenxin Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Early Detection ◽  
Test Device ◽  
Function Test ◽  
Cognitive Function Test

scholarly journals Association of Cognitive Function Screening Results with Adherence and Performance in a Pedometer-Based Intervention

2021 ◽  
pp. 1-9
Author(s):  
Anoop Sheshadri ◽  
Piyawan Kittiskulnam ◽  
Cynthia Delgado ◽  
Rebecca L. Sudore ◽  
Jennifer C. Lai ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
Physical Performance ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Controlled Trial ◽  
Cognitive Status ◽  
Dialysis Patients ◽  
Exercise Interventions ◽  
And Performance

<b><i>Introduction:</i></b> A randomized, controlled trial of a pedometer-based walking intervention with weekly activity goals led to increased walking among dialysis patients. We examined whether impairment per cognitive function screening is associated with adherence and performance in the intervention. <b><i>Methods:</i></b> Thirty dialysis patients were randomly assigned to a 3-month pedometer-based intervention with weekly goals. Participants were administered the Telephone Interview of Cognitive Status (TICS), a test of global mental status. We examined the association of levels of impairment on the TICS (≥33: unimpaired, 26–32: ambiguous impairment, 21–25: mild cognitive impairment [MCI]) with adherence, achieving weekly goals, and increasing steps, physical performance (Short Physical Performance Battery, SPPB), and self-reported physical function (PF) through multivariable linear mixed-model and logistic regression analyses adjusted for age, sex, BMI, dialysis modality, baseline steps, baseline SPPB, and stroke status. <b><i>Results:</i></b> One-third of participants were unimpaired, and 13% had MCI. Participants with worse results on cognitive function screening missed more calls and completed fewer weekly goals than participants with better results. During the intervention, a worse result on cognitive function screening was associated with smaller increases in steps compared to those without impairment: (ambiguous: −620 [95% CI −174, −1,415], MCI: −1,653 [95% CI −120, −3,187]); less improvement in SPPB (ambiguous: −0.22 points [95% CI −0.08, −0.44], MCI: −0.45 [95% CI −0.13, −0.77]); and less improvement in PF (ambiguous: −4.0 points [95% CI −12.2, 4.1], MCI: −14.0 [95% CI −24.9, −3.1]). During the postintervention period, a worse result on cognitive function screening was associated with smaller increases in SPPB (ambiguous: −0.54 [95% CI −1.27, 0.19], MCI: −0.97 [95% CI −0.37, −1.58]) and PF (ambiguous: −3.3 [95% CI −6.5, −0.04], MCI: −10.5 [95% CI −18.7, −2.3]). <b><i>Discussion/Conclusion:</i></b> Participants with worse results on cognitive function screening had worse adherence and derived less benefit from this pedometer-based intervention. Future exercise interventions should be developed incorporating methods to address cognitive impairment, for example, by including caregivers when planning such interventions.

Sign in / Sign up

Export Citation Format

Share Document