A functional proportional hazard cure rate model for interval-censored data

2021 ◽  
pp. 096228022110529
Author(s):  
Haolun Shi ◽  
Da Ma ◽  
Mirza Faisal Beg ◽  
Jiguo Cao

Existing survival models involving functional covariates typically rely on the Cox proportional hazards structure and the assumption of right censorship. Motivated by the aim of predicting the time of conversion to Alzheimer’s disease from sparse biomarker trajectories in patients with mild cognitive impairment, we propose a functional mixture cure rate model with both functional and scalar covariates for interval censoring and sparsely sampled functional data. To estimate the nonparametric coefficient function that depicts the effect of the shape of the trajectories on the survival outcome and cure probability, we utilize the functional principal component analysis to extract the functional features from the sparsely and irregularly sampled trajectories. To obtain parameter estimates from the mixture cure rate model with interval censoring, we apply the expectation-maximization algorithm based on Poisson data augmentation. The estimation accuracy of our method is assessed via a simulation study and we apply our model on Alzheimer’s disease Neuroimaging Initiative data set.

2016 ◽  
Vol 44 (7) ◽  
pp. 1153-1164 ◽  
Author(s):  
Diego I. Gallardo ◽  
Héctor W. Gómez ◽  
Heleno Bolfarine

2019 ◽  
Vol 29 (7) ◽  
pp. 1831-1845
Author(s):  
Diego I Gallardo ◽  
Yolanda M Gómez ◽  
Héctor W Gómez ◽  
Mário de Castro

In this paper, we propose a generalization of the power series cure rate model for the number of competing causes related to the occurrence of the event of interest. The model includes distributions not yet used in the cure rate models context, such as the Borel, Haight and Restricted Generalized Poisson distributions. The model is conveniently parameterized in terms of the cure rate. Maximum likelihood estimation based on the Expectation Maximization algorithm is discussed. A simulation study designed to assess some properties of the estimators is carried out, showing the good performance of the proposed estimation procedure in finite samples. Finally, an application to a bone marrow transplant data set is presented.


2021 ◽  
pp. 1-12
Author(s):  
Fang Yu ◽  
David M. Vock ◽  
Lin Zhang ◽  
Dereck Salisbury ◽  
Nathaniel W. Nelson ◽  
...  

Background: Aerobic exercise has shown inconsistent cognitive effects in older adults with Alzheimer’s disease (AD) dementia. Objective: To examine the immediate and longitudinal effects of 6-month cycling on cognition in older adults with AD dementia. Methods: This randomized controlled trial randomized 96 participants (64 to cycling and 32 to stretching for six months) and followed them for another six months. The intervention was supervised, moderate-intensity cycling for 20–50 minutes, 3 times a week for six months. The control was light-intensity stretching. Cognition was assessed at baseline, 3, 6, 9, and 12 months using the AD Assessment Scale-Cognition (ADAS-Cog). Discrete cognitive domains were measured using the AD Uniform Data Set battery. Results: The participants were 77.4±6.8 years old with 15.6±2.9 years of education, and 55%were male. The 6-month change in ADAS-Cog was 1.0±4.6 (cycling) and 0.1±4.1 (stretching), which were both significantly less than the natural 3.2±6.3-point increase observed naturally with disease progression. The 12-month change was 2.4±5.2 (cycling) and 2.2±5.7 (control). ADAS-Cog did not differ between groups at 6 (p = 0.386) and 12 months (p = 0.856). There were no differences in the 12-month rate of change in ADAS-Cog (0.192 versus 0.197, p = 0.967), memory (–0.012 versus –0.019, p = 0.373), executive function (–0.020 versus –0.012, p = 0.383), attention (–0.035 versus –0.033, p = 0.908), or language (–0.028 versus –0.026, p = 0.756). Conclusion: Exercise may reduce decline in global cognition in older adults with mild-to-moderate AD dementia. Aerobic exercise did not show superior cognitive effects to stretching in our pilot trial, possibly due to the lack of power.


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S641-S641
Author(s):  
Shanna L Burke

Abstract Little is known about how resting heart rate moderates the relationship between neuropsychiatric symptoms and cognitive status. This study examined the relative risk of NPS on increasingly severe cognitive statuses and examined the extent to which resting heart rate moderates this relationship. A secondary analysis of the National Alzheimer’s Coordinating Center Uniform Data Set was undertaken, using observations from participants with normal cognition at baseline (13,470). The relative risk of diagnosis with a more severe cognitive status at a future visit was examined using log-binomial regression for each neuropsychiatric symptom. The moderating effect of resting heart rate among those who are later diagnosed with mild cognitive impairment (MCI) or Alzheimer’s disease (AD) was assessed. Delusions, hallucinations, agitation, depression, anxiety, elation, apathy, disinhibition, irritability, motor disturbance, nighttime behaviors, and appetite disturbance were all significantly associated (p<.001) with an increased risk of AD, and a reduced risk of MCI. Resting heart rate increased the risk of AD but reduced the relative risk of MCI. Depression significantly interacted with resting heart rate to increase the relative risk of MCI (RR: 1.07 (95% CI: 1.00-1.01), p<.001), but not AD. Neuropsychiatric symptoms increase the relative risk of AD but not MCI, which may mean that the deleterious effect of NPS is delayed until later and more severe stages of the disease course. Resting heart rate increases the relative risk of MCI among those with depression. Practitioners considering early intervention in neuropsychiatric symptomology may consider the downstream benefits of treatment considering the long-term effects of NPS.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tadeja Gracner ◽  
Patricia W. Stone ◽  
Mansi Agarwal ◽  
Mark Sorbero ◽  
Susan L Mitchell ◽  
...  

Abstract Background Though work has been done studying nursing home (NH) residents with either advanced Alzheimer’s disease (AD) or Alzheimer’s disease related dementia (ADRD), none have distinguished between them; even though their clinical features affecting survival are different. In this study, we compared mortality risk factors and survival between NH residents with advanced AD and those with advanced ADRD. Methods This is a retrospective observational study, in which we examined a sample of 34,493 U.S. NH residents aged 65 and over in the Minimum Data Set (2011–2013). Incident assessment of advanced disease was defined as the first MDS assessment with severe cognitive impairment (Cognitive Functional Score equals to 4) and diagnoses of AD or ADRD. Demographics, functional limitations, and comorbidities were evaluated as mortality risk factors using Cox models. Survival was characterized with Kaplan-Maier functions. Results Of those with advanced cognitive impairment, 35 % had AD and 65 % ADRD. At the incident assessment of advanced disease, those with AD had better health compared to those with ADRD. Mortality risk factors were similar between groups (shortness of breath, difficulties eating, substantial weight-loss, diabetes mellitus, heart failure, chronic obstructive pulmonary disease, and pneumonia; all p < 0.01). However, stroke and difficulty with transfer (for women) were significant mortality risk factors only for those with advanced AD. Urinary tract infection, and hypertension (for women) only were mortality risk factors for those with advanced ADRD. Median survival was significantly shorter for the advanced ADRD group (194 days) compared to the advanced AD group (300 days). Conclusions There were distinct mortality and survival patterns of NH residents with advanced AD and ADRD. This may help with care planning decisions regarding therapeutic and palliative care.


2021 ◽  
Author(s):  
Louise Bloch ◽  
Christoph M. Friedrich

Abstract Background: The prediction of whether Mild Cognitive Impaired (MCI) subjects will prospectively develop Alzheimer's Disease (AD) is important for the recruitment and monitoring of subjects for therapy studies. Machine Learning (ML) is suitable to improve early AD prediction. The etiology of AD is heterogeneous, which leads to noisy data sets. Additional noise is introduced by multicentric study designs and varying acquisition protocols. This article examines whether an automatic and fair data valuation method based on Shapley values can identify subjects with noisy data. Methods: An ML-workow was developed and trained for a subset of the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. The validation was executed for an independent ADNI test data set and for the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) cohort. The workow included volumetric Magnetic Resonance Imaging (MRI) feature extraction, subject sample selection using data Shapley, Random Forest (RF) and eXtreme Gradient Boosting (XGBoost) for model training and Kernel SHapley Additive exPlanations (SHAP) values for model interpretation. This model interpretation enables clinically relevant explanation of individual predictions. Results: The XGBoost models which excluded 116 of the 467 subjects from the training data set based on their Logistic Regression (LR) data Shapley values outperformed the models which were trained on the entire training data set and which reached a mean classification accuracy of 58.54 % by 14.13 % (8.27 percentage points) on the independent ADNI test data set. The XGBoost models, which were trained on the entire training data set reached a mean accuracy of 60.35 % for the AIBL data set. An improvement of 24.86 % (15.00 percentage points) could be reached for the XGBoost models if those 72 subjects with the smallest RF data Shapley values were excluded from the training data set. Conclusion: The data Shapley method was able to improve the classification accuracies for the test data sets. Noisy data was associated with the number of ApoEϵ4 alleles and volumetric MRI measurements. Kernel SHAP showed that the black-box models learned biologically plausible associations.


2015 ◽  
Vol 16 (17) ◽  
pp. 7923-7927 ◽  
Author(s):  
Ahmad Reza Baghestani ◽  
Farid Zayeri ◽  
Mohammad Esmaeil Akbari ◽  
Leyla Shojaee ◽  
Naghmeh Khadembashi ◽  
...  

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