scholarly journals P-tau and neurodegeneration mediate the effect of β-amyloid on cognition in non-demented elders

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Ling-Zhi Ma ◽  
Hao Hu ◽  
Zuo-Teng Wang ◽  
Ya-Nan Ou ◽  
Qiang Dong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Mediating Effect ◽  
Total Effect ◽  
Independent Effect ◽  
Carrier Status ◽  
Mediation Effects ◽  
Β Amyloid ◽  
The Impact

Abstract Background There are many pathological changes in the brains of Alzheimer’s disease (AD) patients. For many years, the mainstream view on the pathogenesis of AD believes that β-amyloid (Aβ) usually acts independently in addition to triggering functions. However, the evidence now accumulating indicates another case that these pathological types have synergies. The objective of this study was to investigate whether effects of Aβ pathology on cognition were mediated by AD pathologies, including tau-related pathology (p-tau), neurodegeneration (t-tau, MRI measurements), axonal injury (NFL), synaptic dysfunction (neurogranin), and neuroinflammation (sTREM2, YKL-40). Methods Three hundred seventy normal controls (CN) and 623 MCI patients from the ADNI (Alzheimer’s Disease Neuroimaging Initiative) database were recruited in this research. Linear mixed-effects models were used to evaluate the associations of baseline Aβ with cognitive decline and biomarkers of several pathophysiological pathways. Causal mediation analyses with 10,000 bootstrapped iterations were conducted to explore the mediation effects of AD pathologies on cognition. Results Tau-related pathology, neurodegeneration, neuroinflammation are correlated with the concentration of Aβ, even in CN participants. The results show that age, gender, and APOE ε4 carrier status have a moderating influence on some of these relationships. There is a stronger association of Aβ with biomarkers and cognitive changes in the elderly and females. In CN group, Aβ pathology is directly related to poor cognition and has no mediating effect (p < 0.05). In mild cognitive impairment, tau-related pathology (26.15% of total effect) and neurodegeneration (14.8% to 47.0% of total effect) mediate the impact of Aβ on cognition. Conclusions In conclusion, early Aβ accumulation has an independent effect on cognitive decline in CN and a tau, neurodegeneration-dependent effect in the subsequent cognitive decline in MCI patients.

scholarly journals Neuroticism alters the transcriptome of the frontal cortex to contribute to the cognitive decline and onset of Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Céline H. De Jager ◽  
Charles C. White ◽  
David A. Bennett ◽  
Yiyi Ma
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Brain Regions ◽  
Personality Characteristics ◽  
Tau Pathology ◽  
Postmortem Human Brain ◽  
Brain Transcriptome ◽  
Neo Five Factor Inventory ◽  
The Impact

AbstractAccumulating evidence has suggested that the molecular transcriptional mechanism contributes to Alzheimer’s disease (AD) and its endophenotypes of cognitive decline and neuropathological traits, β-amyloid (Aβ) and phosphorylated tangles (TAU). However, it is unknown what is the impact of the AD risk factors, personality characteristics assessed by the NEO Five-Factor Inventory, on the human brain’s transcriptome. Using postmortem human brain samples from 466 subjects, we found that neuroticism has a significant overall impact on the brain transcriptome (omnibus P = 0.005) but not the other four personality characteristics. Focused on those cognitive decline related gene co-expressed modules, neuroticism has nominally significant associations (P < 0.05) with four neuronal modules, which are more related to PHFtau than Aβ across all eight brain regions. Furthermore, the effect of neuroticism on cognitive decline and AD might be mediated through the expression of module 7 and TAU pathology (P = 0.008). To conclude, neuroticism has a broad impact on the transcriptome of human brains, and its effect on cognitive decline and AD may be mediated through gene transcription programs related to TAU pathology.

scholarly journals Association of naturally occurring antibodies to β-amyloid with cognitive decline and cerebral amyloidosis in Alzheimer’s disease

2021 ◽  
Vol 7 (1) ◽  
pp. eabb0457
Author(s):  
Yu-Hui Liu ◽  
Jun Wang ◽  
Qiao-Xin Li ◽  
Christopher J. Fowler ◽  
Fan Zeng ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Plasma Levels ◽  
Imaging Biomarkers ◽  
Amino Terminus ◽  
Cross Sectional ◽  
Naturally Occurring ◽  
Β Amyloid ◽  
Naturally Occurring Antibodies

The pathological relevance of naturally occurring antibodies to β-amyloid (NAbs-Aβ) in Alzheimer’s disease (AD) remains unclear. We aimed to investigate their levels and associations with Aβ burden and cognitive decline in AD in a cross-sectional cohort from China and a longitudinal cohort from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. NAbs-Aβ levels in plasma and cerebrospinal fluid (CSF) were tested according to their epitopes. Levels of NAbs targeting the amino terminus of Aβ increased, and those targeting the mid-domain of Aβ decreased in both CSF and plasma in AD patients. Higher plasma levels of NAbs targeting the amino terminus of Aβ and lower plasma levels of NAbs targeting the mid-domain of Aβ were associated with higher brain amyloidosis at baseline and faster cognitive decline during follow-up. Our findings suggest a dynamic response of the adaptive immune system in the progression of AD and are relevant to current passive immunotherapeutic strategies.

Cognitive Decline and the Changing Self in Relationship

2015 ◽  
pp. 61-75
Author(s):  
Darby Morhardt ◽  
Marcia Spira
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Family Member ◽  
Family Members ◽  
Well Being ◽  
Family Roles ◽  
The Family ◽  
Person With Dementia ◽  
The Impact

When a member of a family is diagnosed with Alzheimer's disease, the impact of the disease reverberates throughout the relationships within the family. This paper explores the challenges and strengths within one family as members manage and cope with Alzheimer's disease. The person with dementia and his family members are individually interviewed and each person explores the consequences of the disease on personal well-being as well as the relationships within the family. The family demonstrates how dementia in one family member demands flexibility in family roles as they navigate life through the challenges of living with dementia.

O2-06-04: DOES β-AMYLOID BURDEN PREDICT COGNITIVE DECLINE STATUS IN ADULTS AT RISK FOR ALZHEIMER'S DISEASE?

2006 ◽  
Vol 14 (7S_Part_11) ◽  
pp. P632-P634
Author(s):  
Heather L. Shouel ◽  
Rebecca L. Koscik ◽  
Lindsay R. Clark ◽  
Sara Elizabeth Berman ◽  
Brad T. Christian ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
At Risk ◽  
Cognitive Decline ◽  
Amyloid Burden ◽  
Β Amyloid

The Impact of Amyloid-β or Tau on Cognitive Change in the Presence of Severe Cerebrovascular Disease

2020 ◽  
Vol 78 (2) ◽  
pp. 573-585
Author(s):  
Hyemin Jang ◽  
Hee Jin Kim ◽  
Yeong Sim Choe ◽  
Soo-Jong Kim ◽  
Seongbeom Park ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Interaction Effect ◽  
Significant Interaction ◽  
Amyloid Β ◽  
Cognitive Change ◽  
Significant Interaction Effect ◽  
The Impact

Background: As Alzheimer’s disease (AD) and cerebral small vessel disease (CSVD) commonly coexist, the interaction between two has been of the considerable interest. Objective: We determined whether the association of Aβ and tau with cognitive decline differs by the presence of significant CSVD. Methods: We included 60 subcortical vascular cognitive impairment (SVCI) from Samsung Medical Center and 82 Alzheimer’s disease-related cognitive impairment (ADCI) from ADNI, who underwent Aβ (florbetaben or florbetapir) and tau (flortaucipir, FTP) PET imaging. They were retrospectively assessed for 5.0±3.9 and 5.6±1.9 years with Clinical Dementia Rating-sum of boxes (CDR-SB)/Mini-Mental State Examination (MMSE). Mixed effects models were used to investigate the interaction between Aβ/tau and group on CDR-SB/MMSE changes. Results: The frequency of Aβ positivity (45% versus 54.9%, p = 0.556) and mean global FTP SUVR (1.17±0.21 versus 1.16±0.17, p = 0.702) were not different between the two groups. We found a significant interaction effect of Aβ positivity and SVCI group on CDR-SB increase/MMSE decrease (p = 0.013/p < 0.001), and a significant interaction effect of global FTP uptake and SVCI group on CDR-SB increase/MMSE decrease (p < 0.001 and p = 0.030). Finally, the interaction effects of regional tau and group were prominent in the Braak III/IV (p = 0.001) and V/VI (p = 0.003) not in Braak I/II region (p = 0.398). Conclusion: The association between Aβ/tau and cognitive decline is stronger in SVCI than in ADCI. Therefore, our findings suggested that Aβ positivity or tau burden (particularly in the Braak III/IV or V/VI regions) and CSVD might synergistically affect cognitive decline.

scholarly journals The Apolipoprotein E Antagonistic Pleiotropy Hypothesis: Review and Recommendations

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Elizabeth R. Tuminello ◽  
S. Duke Han
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Apolipoprotein E ◽  
Evolutionary Biology ◽  
Future Research ◽  
Antagonistic Pleiotropy ◽  
Life Stages ◽  
New Research ◽  
The Impact

Research on apolipoprotein E (APOE) has consistently revealed a relationship between the gene'sε4 allele and risk for development of Alzheimer's disease (AD). However, research with younger populations ofε4 carriers has suggested that the APOEε4 allele may in fact be beneficial in earlier ages and may only confer risk of cognitive decline later in life. Accordingly, we and others have proposed that APOE may represent an example of antagonistic pleiotropy. Antagonistic pleiotropy is an evolutionary biology concept that proposes certain genes or alleles that may differentially impact fitness during different life stages. We critically review this hypothesis in light of new research of the impact of APOE on cognition and neural integrity across the lifespan. We provide recommendations for the revision of the antagonistic pleiotropy hypothesis of APOE and suggest important avenues for future research in this area.

scholarly journals Mild behavioral impairment correlates of cognitive impairments in older adults without dementia: mediation by amyloid pathology

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yan Sun ◽  
Wei Xu ◽  
Ke-Liang Chen ◽  
Xue-Ning Shen ◽  
Lan Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairments ◽  
Amyloid Pet ◽  
Amyloid Burden ◽  
Behavioral Impairment ◽  
Mediation Effects ◽  
Mediation Analyses ◽  
Language Functions ◽  
Β Amyloid

AbstractThe relationship between mild behavioral impairment (MBI) and Alzheimer’s disease (AD) is intricate and still not well investigated. The purpose of the study is to examine the roles of the AD imaging pathologies in modulating the associations of MBI with cognitive impairments. We analyzed 1129 participants (563 [49.86%] female), who had measures of Neuropsychiatric Inventory Questionnaire (NPI-Q), cognition, and amyloid PET AD biomarkers from the Alzheimer’s disease Neuroimaging Initiative (ADNI). We assess the longitudinal neuropathological and clinical correlates of baseline MBI via linear mixed effects and Cox proportional hazard models. The mediation analyses were used to test the mediation effects of AD pathologies on cognition. We found that MBI was associated with worse global cognition as represented by Mini-Mental State Examination (MMSE) (p < 0.001), and higher β-amyloid burden (p < 0.001). β-amyloid partially mediated the effects of MBI on cognition with the mediation percentage varied from 14.67 to 40.86% for general cognition, memory, executive, and language functions for non-dementia individuals. However, no significant associations were discovered between MBI and tau burden or neurodegeneration. Furthermore, longitudinal analyses revealed that individuals with MBI had a faster increase in brain amyloid burden (p < 0.001) and a higher risk of clinical conversion (HR = 2.42, 95% CI = 1.45 to 4.01 p < 0.001). In conclusion, MBI could be an imperative prediction indicator of clinical and pathological progression. In addition, amyloid pathologies might partially mediate the influences of MBI on cognitive impairments and AD risk.

scholarly journals Individual Differences and Features of Self-Reported Memory Lapses as Risk Factors for Alzheimer’s Disease: Protocol for a Coordinated Analysis Across Two Longitudinal Datasets (Preprint)

2020 ◽  
Author(s):  
Jacqueline Mogle ◽  
Nikki Hill ◽  
Jennifer Turner
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Cognitive Aging ◽  
Screening Tools ◽  
Accurate Identification ◽  
Age And Gender ◽  
Memory Problems ◽  
And Gender ◽  
The Impact

UNSTRUCTURED Increasing evidence promotes the clinical utility of self-reported memory problems for detecting early impairment associated with Alzheimer’s disease (AD). However, past work investigating memory problems often conflated the types of problems (i.e., retrospective and prospective) with their features (i.e., frequency and consequences). This bias limits the specificity of traditional measures of memory problems and minimizes their ability to detect differential trajectories associated with cognitive decline. In the present study, we use a novel measure of self-reported memory problems that uses daily reports of memory lapses to disentangle types from features to analyze the impact of each dimension in two longitudinal datasets. Further, this study explores the individual difference factors of age and gender as potential moderators of the relationships between self-reported memory lapses and objective cognitive decline. This study uses multilevel, coordinated analyses across two measurement burst datasets to examine the links between features and consequences of memory lapses (retrospective and prospective) and their association with objective cognitive decline. The current sample (n = 535; ages 50-85 years; 61% women) is drawn from two ongoing, nationally funded research studies: the Effects of Stress on Cognitive Aging, Physiology, and Emotion Study and the Einstein Aging Study. Both studies assess the daily experience of memory lapses, including the type as well as the emotional and functional outcomes, and objective measures of cognition such as processing speed and episodic memory. We will use multilevel modeling to test our conceptual model that differences in frequency and types of memory lapses show differential trends in their relationships with cognitive decline and that these relationships vary by age and gender of participant. The early and accurate identification of individuals most at risk for cognitive decline is of paramount importance. Previous research exploring self-reported memory problems and AD is promising, however limitations in measurement may explain prior reports of inconsistences. The current study addresses these concerns by examining daily reports of memory lapses, how these vary by age and gender, and their relationship with objective cognitive performance. Overall this study aims to identify key features of daily memory lapses and the differential trajectories that best predict cognitive decline to help inform future AD risk screening tools.

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