scholarly journals Disentangling independent and mediated causal relationships between blood metabolites, cognitive factors, and Alzheimer’s Disease

2021 ◽  
Author(s):  
Jodie Lord ◽  
Rebecca Green ◽  
Shing Wan Choi ◽  
Christopher Hübel ◽  
Dag Aarsland ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Factors ◽  
Blood Metabolites ◽  
Causal Relationships

scholarly journals Disentangling independent and mediated causal relationships between blood metabolites, cognitive factors, and Alzheimer’s Disease

2021 ◽  
Author(s):  
Jodie Lord ◽  
Rebbeca Green ◽  
Shing Wan Choi ◽  
Christopher Hübel ◽  
Dag Aarsland ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genome Wide Association Study ◽  
Causal Effect ◽  
Cognitive Factors ◽  
High Density Lipoproteins ◽  
Blood Metabolites ◽  
Causal Relationships ◽  
Polygenic Scores ◽  
Causal Pathway

AbstractBackgroundEducation and cognition demonstrate consistent inverse associations with Alzheimer’s Disease (AD). The biological underpinnings, however, remain unclear. Blood metabolites can reflect the endpoint of biological processes and are accessible and malleable. Identifying metabolites with aetiological relevance to AD and disentangling how these relate to cognitive factors along the AD causal pathway could, therefore, offer unique insights into underlying causal mechanisms.MethodsUsing data from the largest metabolomics genome-wide association study (N≈24,925) and three independent AD cohorts (N=4,725), cross-trait polygenic scores were generated and meta-analyzed. Metabolites genetically associated with AD were taken forward for causal analyses. Bidirectional two-sample Mendelian randomization (MR) interrogated univariable causal relationships between (i) metabolites and AD, (ii) metabolites, education and cognition (iii) education, cognition and AD, and (iv) education and cognition. Mediating relationships were computed using multivariable MR.ResultsThirty-four metabolites were genetically associated with AD at p<0.05. Of these, glutamine and free cholesterol in extra-large high-density lipoproteins (XL.HDL.FC) demonstrated a protective causal effect (Glutamine: 95% CI=0.70-0.92; XL.HDL.FC: 95% CI=0.75-0.92). An AD-protective effect was also observed for education (95% CI=0.61-0.85) and cognition (95% CI=0.60-0.89), with bidirectional mediation evident. Cognition as a mediator of the education-AD relationship was stronger than vice-versa, however. No evidence of mediation via any metabolite was found.ConclusionsGlutamine and XL.HDL.FC show protective causal effects on AD. Education and cognition also demonstrate protection, though education’s effect is almost entirely mediated by cognition. These insights provide key pieces of the AD causal puzzle, important for informing future multi-modal work and progressing towards effective intervention strategies.

scholarly journals Causal Association Between Heart Failure and Alzheimer’s Disease: A Two-Sample Bidirectional Mendelian Randomization Study

2022 ◽  
Vol 12 ◽  
Author(s):  
Chenglin Duan ◽  
Jingjing Shi ◽  
Guozhen Yuan ◽  
Xintian Shou ◽  
Ting Chen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sensitivity Analysis ◽  
Causal Relationship ◽  
Observational Studies ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Causal Relationships ◽  
Simple Mode

Background: Traditional observational studies have demonstrated an association between heart failure and Alzheimer’s disease. The strengths of observational studies lie in their speed of implementation, cost, and applicability to rare diseases. However, observational studies have several limitations, such as uncontrollable confounders. Therefore, we employed Mendelian randomization of genetic variants to evaluate the causal relationships existing between AD and HF, which can avoid these limitations.Materials and Methods: A two-sample bidirectional MR analysis was employed. All datasets were results from the UK’s Medical Research Council Integrative Epidemiology Unit genome-wide association study database, and we conducted a series of control steps to select the most suitable single-nucleotide polymorphisms for MR analysis, for which five primary methods are offered. We reversed the functions of exposure and outcomes to explore the causal direction of HF and AD. Sensitivity analysis was used to conduct several tests to avoid heterogeneity and pleiotropic bias in the MR results.Results: Our MR studies did not support a meaningful causal relationship between AD on HF (MR-Egger, p = 0.634 &gt; 0.05; weighted median (WM), p = 0.337 &gt; 0.05; inverse variance weighted (IVW), p = 0.471 &gt; 0.05; simple mode, p = 0.454 &gt; 0.05; weighted mode, p = 0.401 &gt; 0.05). At the same time, we did not find a significant causal relationship between HF and AD with four of the methods (MR-Egger, p = 0.195 &gt; 0.05; IVW, p = 0.0879 &gt; 0.05; simple mode, p = 0.170 &gt; 0.05; weighted mode, p = 0.110 &gt; 0.05), but the WM method indicated a significant effect of HF on AD (p = 0.025 &lt; 0.05). Because the statistical powers of IVW and MR-Egger are more than that of WM, we think that there is no causal effect of HF on AD. Sensitivity analysis and horizontal pleiotropy were not detected in the MR analysis.Conclusion: Our results did not provide significant evidence indicating any causal relationships between HF and AD in the European population. Therefore, more large-scale datasets or datasets related to similar factors are expected for further MR analysis.

Quality of life in dementia: the role of non-cognitive factors in the ratings of people with dementia and family caregivers

2013 ◽  
Vol 25 (7) ◽  
pp. 1097-1105 ◽  
Author(s):  
Maria Fernanda Barroso Sousa ◽  
Raquel Luiza Santos ◽  
Cynthia Arcoverde ◽  
Pedro Simões ◽  
Tatiana Belfort ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Depressive Symptoms ◽  
Family Caregivers ◽  
Linear Regression Analysis ◽  
Cognitive Factors ◽  
People With Dementia ◽  
Significant Difference

ABSTRACTBackground: The validity of self-reported quality-of-life (QoL) assessments of people with dementia (PWD) is a critical issue. We designed this study to determine the non-cognitive factors that are associated with self-reported QoL and PWD QoL as rated by family caregivers.Methods: Using a cross-sectional study, we assessed QoL of 41 people with mild Alzheimer's disease (AD). The individuals with AD and their family caregivers completed the Quality of Life in Alzheimer's Disease Scale (QoL-AD), the Assessment Scale of Psychosocial Impact of the Diagnosis of Dementia (ASPIDD), the Mini-Mental State Examination (MMSE), the Clinical Dementia Rating (CDR) scale, the Cornell Scale for Depression in Dementia (CSDD), the Pfeffer Functional Activities Questionnaire (FAQ), and the Zarit Burden Interview (ZBI). Univariate and multivariate regression analyses were conducted to examine the contribution of the various cofactors.Results: We observed a significant difference (t = 3.292, p < 0.01, d = 0.727) in the QoL measures of PWD after comparing self-reported assessments with the assessments of family caregivers. Linear regression analysis demonstrated that awareness of disease was related to PWD QoL-AD scores. Both the education levels of family caregivers and the depressive symptoms in PWD were related to the family caregivers’ ratings of PWD QoL.Conclusions: The difference between self-reported QoL and family caregivers’ ratings of QoL in people with mild dementia indicated that cognitive impairment was not the primary factor that accounted for the differences in the QoL assessments. Our findings suggested that non-cognitive factors, such as awareness of disease and depressive symptoms, played an important role in the differences between the self-reported AD QoL ratings and the caregivers’ AD QoL ratings. A major implication is that discrete measures such as cognition or level of function are likely to miss important factors that influence QoL.

Daily oscillation of cognitive factors is modified in the temporal cortex of an amyloid β(1-42)-induced rat model of Alzheimer’s disease

2021 ◽  
Vol 170 ◽  
pp. 106-114
Author(s):  
Cinthia Coria-Lucero ◽  
Carina Ledezma ◽  
Andrea Castro ◽  
Silvia Delgado ◽  
Ana Cecilia Anzulovich ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rat Model ◽  
Temporal Cortex ◽  
Amyloid Β ◽  
Cognitive Factors ◽  
Model Of Alzheimer’S Disease ◽  
Daily Oscillation

scholarly journals Deciphering the causal relationship between blood metabolites and Alzheimer’s Disease: a Mendelian Randomization study

2020 ◽  
Author(s):  
Jodie Lord ◽  
Bradley Jermy ◽  
Rebecca Green ◽  
Andrew Wong ◽  
Jin Xu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Causal Relationship ◽  
Bayesian Model Averaging ◽  
Association Studies ◽  
High Density Lipoproteins ◽  
Mendelian Randomisation ◽  
Blood Metabolites ◽  
Genome Wide Association Studies ◽  
Causal Pathway

AbstractThere are currently no disease modifying treatments for Alzheimer’s Disease (AD). Epidemiological studies have highlighted blood metabolites as potential biomarkers, but possible confounding and reverse causation prevent causal conclusions. Here, we investigated whether nineteen metabolites previously associated with midlife cognitive function, are on the causal pathway to AD.Summary statistics from the largest Genome-Wide Association Studies (GWAS) for AD and for metabolites were used to perform bi-directional univariable Mendelian Randomisation (MR). Bayesian model averaging MR (MR-BMA) was additionally performed to address high correlation between metabolites and to identify metabolite combinations which may be on the AD causal pathway.Univariable MR indicated three Extra-Large High-Density Lipoproteins (XL.HDL) to be on the causal pathway to AD: Free Cholesterol (XL.HDL.FC: OR=0.86, 95% CI=0.78-0.94), Total Lipids (XL.HDL.L: OR=0.88, 95% CI=0.80-0.97), and Phospholipids (XL.HDL.PL: OR=0.87, 95% CI=0.81-0.97); significant at an adjusted threshold of p<0.009. MR-BMA corroborated XL.HDL.FC to be amongst the top three causal metabolites, additionally to Total Cholesterol in XL.HDL (XL.HDL.C) and Glycoprotein Acetyls (GP) (posterior probabilities=0.112, 0.113, 0.287 respectively). Both XL.HDL.C and GP also demonstrated suggestive evidence of univariable causal associations (XL.HDL.C:OR=0.88, 95% CI=0.79-0.99; GP:OR=1.2, 95% CI=1.05-1.38); significant at the 5% level.This study offers insight into the causal relationship between metabolites previously demonstrating association with mid-life cognition, and AD. It highlights GP in addition to several XL.HDLs as causal candidates which warrant further investigation. As the pathological changes underpinning AD are thought to develop decades prior to symptom onset, progressing these findings could hold special value in informing future risk reduction strategies.

P3-447: Cognitive factors associated with longitudinal decline in driving skill in patients with Alzheimer's disease

2008 ◽  
Vol 4 ◽  
pp. T652-T652 ◽  
Author(s):  
Elena K. Festa ◽  
George D. Papandonatos ◽  
Brian R. Ott ◽  
William C. Heindel
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Factors ◽  
Factors Associated ◽  
Driving Skill

scholarly journals The Influence of Psychosocial and Cognitive Factors on Perceived Threat of Alzheimer’s Disease

2017 ◽  
Vol 32 (5) ◽  
pp. 289-299 ◽  
Author(s):  
Jenny E. Ostergren ◽  
Steven G. Heeringa ◽  
Carlos F. Mendes de Leon ◽  
Cathleen M Connell ◽  
J. Scott Roberts
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Personal Experience ◽  
Cognitive Factors ◽  
Perceived Threat ◽  
Cognitive Predictors ◽  
History Of ◽  
Nationally Representative ◽  
The Relationship ◽  
Retirement Study

This study explored psychosocial and cognitive predictors of perceived threat of Alzheimer’s disease (AD). Respondents were 1641 adults (mean age: 64.4; 54% female; 82% white) who completed a module in the Health and Retirement Study, a nationally representative survey of adults aged ≥50. Findings show that perceived threat was significantly higher for those aged 50 to 64 ( P < .001) and 65 to 74 ( P < .05) than for those ≥75. Respondents with a family history of AD had significantly greater perceived threat ( P < .001) than those with no experience. Stronger endorsement of the beliefs that stress ( P < .01) or genetics ( P < .01) are important AD risk factors was significantly associated with greater perceived threat, as was having more depressive symptoms ( P < .01), poorer self-rated memory ( P < .01), and lower cognitive function ( P < .01). Personal experience moderated the relationship between perceived threat and 2 variables: age and self-rated memory. Understanding perceived AD threat may inform practice and policies centered on early and accurate diagnosis.

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