scholarly journals Does Study Partner Type Impact the Rate of Alzheimer's Disease Progression?

2013 ◽  
Vol 38 (3) ◽  
pp. 507-514 ◽  
Author(s):  
Joshua D. Grill ◽  
Yan Zhou ◽  
Jason Karlawish ◽  
David Elashoff
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Partner Type ◽  
Study Partner

scholarly journals Recruitment and Retention of Participant and Study Partner Dyads in Two Multinational Alzheimer’s Disease Registration Trials

2020 ◽  
Author(s):  
Olivia M Bernstein ◽  
Joshua D. Grill ◽  
Daniel L. Gillen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Random Forest ◽  
Random Forest Model ◽  
P Value ◽  
Confounding Factors ◽  
Forest Model ◽  
Partner Type ◽  
Study Partner ◽  
The Relationship

Abstract Background: Early study exit is detrimental to statistical power and increases the risk for bias in Alzheimer’s disease clinical trials. Previous analyses in early phase academic trials demonstrated associations between rates of trial incompletion and participants’ study partner type, with participants enrolling with non-spouse study partners being at greater risk.Methods: We conducted secondary analyses of two multinational phase III trials of semagacestat, an oral gamma secretase inhibitor, for mild-to-moderate AD dementia. Cox’s proportional hazards regression model was used to estimate the relationship between study partner type and the risk of early exit from the trial after adjustment for a priori identified potential confounding factors. Additionally, we used a random forest model to identify top predictors of dropout.Results: Among participants with spousal, adult child, and other study partners, respectively, 35%, 38%, and 36% dropped out or died prior to protocol-defined study completion, respectively. In unadjusted models, the risk of trial incompletion differed by study partner type (unadjusted p-value=0.027 for test of differences by partner type), but in models adjusting for potential confounding factors the differences were not statistically significant (p-value=0.928). In exploratory modeling, participant age was identified as the primary characteristic to explain the relationship between study partner type and the risk of failing to complete the trial. Participant age was also the strongest predictor of trial incompletion in the random forest model.Conclusions: After adjustment for age, no qualitative differences in the risk of incompletion were observed when comparing participants with different study partner types in these trials. Differences between our findings and the findings of previous studies may be explained by differences in trial phase, size, geographic regions, or the composition of academic and non-academic sites.

scholarly journals Recruitment and retention of participant and study partner dyads in two multinational Alzheimer’s disease registration trials

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Olivia M. Bernstein ◽  
Joshua D. Grill ◽  
Daniel L. Gillen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Random Forest ◽  
Random Forest Model ◽  
Phase Iii ◽  
Confounding Factors ◽  
Forest Model ◽  
Partner Type ◽  
Study Partner ◽  
The Relationship

Abstract Background Early study exit is detrimental to statistical power and increases the risk for bias in Alzheimer’s disease clinical trials. Previous analyses in early phase academic trials demonstrated associations between rates of trial incompletion and participants’ study partner type, with participants enrolling with non-spouse study partners being at greater risk. Methods We conducted secondary analyses of two multinational phase III trials of semagacestat, an oral gamma secretase inhibitor, for mild-to-moderate AD dementia. Cox’s proportional hazards regression model was used to estimate the relationship between study partner type and the risk of early exit from the trial after adjustment for a priori identified potential confounding factors. Additionally, we used a random forest model to identify top predictors of dropout. Results Among participants with spousal, adult child, and other study partners, respectively, 35%, 38%, and 36% dropped out or died prior to protocol-defined study completion, respectively. In unadjusted models, the risk of trial incompletion differed by study partner type (unadjusted p value = 0.027 for test of differences by partner type), but in models adjusting for potential confounding factors, the differences were not statistically significant (p value = 0.928). In exploratory modeling, participant age was identified as the primary characteristic to explain the relationship between study partner type and the risk of failing to complete the trial. Participant age was also the strongest predictor of trial incompletion in the random forest model. Conclusions After adjustment for age, no differences in the risk of incompletion were observed when comparing participants with different study partner types in these trials. Differences between our findings and the findings of previous studies may be explained by differences in trial phase, size, geographic regions, or the composition of academic and non-academic sites.

scholarly journals Disease progression modelling from preclinical Alzheimer’s disease (AD) to AD dementia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Soo Hyun Cho ◽  
Sookyoung Woo ◽  
Changsoo Kim ◽  
Hee Jin Kim ◽  
Hyemin Jang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Disease Assessment ◽  
Time Interval ◽  
Disease Course ◽  
Preclinical Alzheimer’S Disease ◽  
Apoe Ε4 ◽  
Preclinical Ad ◽  
Cognitive Subscale

AbstractTo characterize the course of Alzheimer’s disease (AD) over a longer time interval, we aimed to construct a disease course model for the entire span of the disease using two separate cohorts ranging from preclinical AD to AD dementia. We modelled the progression course of 436 patients with AD continuum and investigated the effects of apolipoprotein E ε4 (APOE ε4) and sex on disease progression. To develop a model of progression from preclinical AD to AD dementia, we estimated Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 (ADAS-cog 13) scores. When calculated as the median of ADAS-cog 13 scores for each cohort, the estimated time from preclinical AD to MCI due to AD was 7.8 years and preclinical AD to AD dementia was 15.2 years. ADAS-cog 13 scores deteriorated most rapidly in women APOE ε4 carriers and most slowly in men APOE ε4 non-carriers (p < 0.001). Our results suggest that disease progression modelling from preclinical AD to AD dementia may help clinicians to estimate where patients are in the disease course and provide information on variation in the disease course by sex and APOE ε4 status.

scholarly journals The extracellular chaperone Clusterin enhances Tau aggregate seeding in a cellular model

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Patricia Yuste-Checa ◽  
Victoria A. Trinkaus ◽  
Irene Riera-Tur ◽  
Rahmi Imamoglu ◽  
Theresa F. Schaller ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Frontotemporal Dementia ◽  
Brain Regions ◽  
Model System ◽  
Cellular Model ◽  
Tau Pathology ◽  
Extracellular Chaperone ◽  
Tau Aggregate

AbstractSpreading of aggregate pathology across brain regions acts as a driver of disease progression in Tau-related neurodegeneration, including Alzheimer’s disease (AD) and frontotemporal dementia. Aggregate seeds released from affected cells are internalized by naïve cells and induce the prion-like templating of soluble Tau into neurotoxic aggregates. Here we show in a cellular model system and in neurons that Clusterin, an abundant extracellular chaperone, strongly enhances Tau aggregate seeding. Upon interaction with Tau aggregates, Clusterin stabilizes highly potent, soluble seed species. Tau/Clusterin complexes enter recipient cells via endocytosis and compromise the endolysosomal compartment, allowing transfer to the cytosol where they propagate aggregation of endogenous Tau. Thus, upregulation of Clusterin, as observed in AD patients, may enhance Tau seeding and possibly accelerate the spreading of Tau pathology.

Subjective Cognitive Decline and its Relation to Verbal Memory and Sex in Cognitively Unimpaired Individuals from a Colombian Cohort with Autosomal-Dominant Alzheimer’s Disease

2021 ◽  
pp. 1-9
Author(s):  
Jairo E. Martinez ◽  
Enmanuelle Pardilla-Delgado ◽  
Edmarie Guzmán-Vélez ◽  
Clara Vila-Castelar ◽  
Rebecca Amariglio ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Differences ◽  
Cognitive Decline ◽  
Verbal Memory ◽  
Autosomal Dominant ◽  
Memory Performance ◽  
Subjective Cognitive Decline ◽  
Mutation Carriers ◽  
Study Partner

Abstract Objective: Subjective Cognitive Decline (SCD) may be an early indicator of risk for Alzheimer’s disease (AD). Findings regarding sex differences in SCD are inconsistent. Studying sex differences in SCD within cognitively unimpaired individuals with autosomal-dominant AD (ADAD), who will develop dementia, may inform sex-related SCD variations in preclinical AD. We examined sex differences in SCD within cognitively unimpaired mutation carriers from the world’s largest ADAD kindred and sex differences in the relationship between SCD and memory performance. Methods: We included 310 cognitively unimpaired Presenilin-1 (PSEN-1) E280A mutation carriers (51% females) and 1998 noncarrier family members (56% females) in the study. Subjects and their study partners completed SCD questionnaires and the CERAD word list delayed recall test. ANCOVAs were conducted to examine group differences in SCD, sex, and memory performance. In carriers, partial correlations were used to examine associations between SCD and memory performance covarying for education. Results: Females in both groups had greater self-reported and study partner-reported SCD than males (all p < 0.001). In female mutation carriers, greater self-reported (p = 0.02) and study partner-reported SCD (p < 0.001) were associated with worse verbal memory. In male mutation carriers, greater self-reported (p = 0.03), but not study partner-reported SCD (p = 0.11) was associated with worse verbal memory. Conclusions: Study partner-reported SCD may be a stronger indicator of memory decline in females versus males in individuals at risk for developing dementia. Future studies with independent samples and preclinical trials should consider sex differences when recruiting based on SCD criteria.

scholarly journals Deep Recurrent Model for Individualized Prediction of Alzheimer’s Disease Progression

NeuroImage ◽  
2021 ◽  
pp. 118143
Author(s):  
Wonsik Jung ◽  
Eunji Jun ◽  
Heung-Il Suk ◽  
Alzheimer’s Disease Neuroimaging Initiative
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Individualized Prediction
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