Predicting Conversion Time from Mild Cognitive Impairment to Dementia with Interval-Censored Models.

Background: Mild cognitive impairment (MCI) patients are at a high risk of developing Alzheimer's disease and related dementias (ADRD) at an estimated annual rate above 10%. It is clinically and practically important to accurately predict MCI-to-dementia conversion time. Objective: It is clinically and practically important to accurately predict MCI-to-dementia conversion time by using easily available clinical data. Methods: The dementia diagnosis often falls between two clinical visits, and such survival outcome is known as interval-censored data. We utilized the semi-parametric model and the random forest model for interval-censored data in conjunction with a variable selection approach to select important measures for predicting the conversion time from MCI to dementia. Two large AD cohort data sets were used to build, validate, and test the predictive model. Results: We found that the semi-parametric model can improve the prediction of the conversion time for patients with MCI-to-dementia conversion, and it also has good predictive performance for all patients. Conclusions: Interval-censored data should be analyzed by using the models that were developed for interval- censored data to improve the model performance.

A systematic review and meta-analysis on the effectiveness of bivalent mRNA booster vaccines against Omicron variants.

BACKGROUND: A global shift to bivalent mRNA vaccines is ongoing to counterbalance the diminishing effectiveness of the original monovalent vaccines due to the evolution of SARS-CoV-2 variants, yet substantial variation in the bivalent vaccine effectiveness (VE) exists across studies and a complete picture is lacking. METHODS: We searched papers evaluating absolute or relative effectiveness of SARS-CoV-2 BA.1 type or BA.4/5 type bivalent mRNA vaccines on eight publication databases published from September 1st, 2022, to November 8th, 2023. Pooled VE against Omicron-associated infection and severe events (hospitalization and/or death) was estimated in reference to unvaccinated, ≥2 original monovalent doses, and ≥ 3 original monovalent doses. RESULTS: From 630 citations identified, 28 studies were included, involving 55,393,303 individuals. Bivalent boosters demonstrated higher effectiveness against symptomatic or any infection for all ages combined, with an absolute VE of 53.5 % (95 % CI: -22.2-82.3 %) when compared to unvaccinated and relative VE of 30.8 % (95 % CI: 22.5-38.2 %) and 28.4 % (95 % CI: 10.2-42.9 %) when compared to ≥ 2 and ≥ 3 original monovalent doses, respectively. The corresponding VE estimates for adults ≥ 60 years old were 22.5 % (95 % CI: 16.8-39.8 %), 31.4 % (95 % CI: 27.7-35.0 %), and 30.6 % (95 % CI: -13.2-57.5 %). Pooled bivalent VE estimates against severe events were higher, 72.9 % (95 % CI: 60.5-82.4 %), 57.6 % (95 % CI: 42.4-68.8 %), and 62.1 % (95 % CI: 54.6-68.3 %) for all ages, and 72.0 % (95 % CI: 51.4-83.9 %), 63.4 % (95 % CI: 41.0-77.3 %), and 60.7 % (95 % CI: 52.4-67.6 %) for adults ≥ 60 years old, compared to unvaccinated, ≥2 original monovalent doses, and ≥ 3 original monovalent doses, respectively. CONCLUSIONS: The bivalent boosters demonstrated superior protection against severe outcomes than the original monovalent boosters across age groups, highlighting the critical need for improving vaccine coverage, especially among the vulnerable older subpopulation.

Predicting Progression to Clinical Alzheimer's Disease Dementia Using the Random Survival Forest.

BACKGROUND: Assessing the risk of developing clinical Alzheimer's disease (AD) dementia, by machine learning survival analysis approaches, among participants registered in Alzheimer's Disease Centers is important for AD dementia management. OBJECTIVE: To construct a prediction model for the onset time of clinical AD dementia using the National Alzheimer Coordinating Center (NACC) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) registered cohorts. METHODS: A model was constructed using the Random Survival Forest (RSF) approach and internally and externally validated on the NACC cohort and the ADNI cohort. An R package and a Shiny app were provided for accessing the model. RESULTS: We built a predictive model having the six predictors: delayed logical memory score (story recall), CDR® Dementia Staging Instrument - Sum of Boxes, general orientation in CDR®, ability to remember dates and ability to pay bills in the Functional Activities Questionnaire, and patient age. The C indices of the model were 90.82% (SE = 0.71%) and 86.51% (SE = 0.75%) in NACC and ADNI respectively. The time-dependent AUC and accuracy at 48 months were 92.48% (SE = 1.12%) and 88.66% (SE = 1.00%) respectively in NACC, and 90.16% (SE = 1.12%) and 85.00% (SE = 1.14%) respectively in ADNI. CONCLUSION: The model showed good prediction performance and the six predictors were easy to obtain, cost-effective, and non-invasive. The model could be used to inform clinicians and patients on the probability of developing clinical AD dementia in 4 years with high accuracy.

Effectiveness of SARS-CoV-2 vaccines against Omicron infection and severe events: a systematic review and meta-analysis of test-negative design studies.

Background: A rapidly growing body was observed of literature evaluating the vaccine effectiveness (VE) against Omicron in test-negative design studies. Methods: We systematically searched papers that evaluated VE of SARS-CoV-2 vaccines on PubMed, Web of Science, Cochrane Library, Google Scholar, Embase, Scopus, bioRxiv, and medRxiv published from November 26th, 2021, to June 27th, 2022 (full doses and the first booster), and to January 8th, 2023 (the second booster). The pooled VE against Omicron-associated infection and severe events were estimated. Results: From 2,552 citations identified, 42 articles were included. The first booster provided stronger protection against Omicron than full doses alone, shown by VE estimates of 53.1% (95% CI: 48.0-57.8) vs. 28.6% (95% CI: 18.5-37.4) against infection and 82.5% (95% CI: 77.8-86.2) vs. 57.3% (95% CI: 48.5-64.7) against severe events. The second booster offered strong protection among adults within 60 days of vaccination against infection (VE=53.1%, 95% CI: 48.0-57.8) and severe events (VE=87.3% (95% CI: 75.5-93.4), comparable to the first booster with corresponding VE estimates of 59.9% against infection and 84.8% against severe events. The VE estimates of booster doses against severe events among adults sustained beyond 60 days, 77.6% (95% CI: 69.4-83.6) for first and 85.9% (95% CI: 80.3-89.9) for the second booster. The VE estimates against infection were less sustainable regardless of dose type. Pure mRNA vaccines provided comparable protection to partial mRNA vaccines, but both provided higher protection than non-mRNA vaccines. Conclusions: One or two SARS-CoV-2 booster doses provide considerable protection against Omicron infection and substantial and sustainable protection against Omicron-induced severe clinical outcomes.

Predictors of Mortality in Individuals with Dementia in the National Alzheimer's Coordinating Center.

BACKGROUND: Dementia is one of the top causes of death worldwide, but individuals with dementia and their caregivers report that knowing what to expect, including regarding approaching end of life, is an unmet need. OBJECTIVE: To identify predictors of death in individuals with Alzheimer disease (AD) dementia, Lewy body dementia (LBD), vascular dementia, and frontotemporal dementia. METHODS: The study used data from National Alzheimer's Coordinating Center participants with dementia and an etiologic diagnosis of AD, Lewy body disease, frontotemporal lobar degeneration (FTLD, with or without motor neuron disease), or vascular dementia. Analyses included median survival across dementia types and predictors of death at 5 years based on baseline demographics and clinical measure performance. Five-year survival probability tables were stratified by predictor values. RESULTS: Individuals with AD had the longest survival (median 6 years), followed by FTLD (5 years), and vascular dementia and LBD (each 4 years). The strongest predictors of death for the full cohort were dementia type (higher risk with non-AD dementias), sex (higher risk with male sex), and race and ethnicity (higher risk with white and non-Hispanic participants). Age was associated with higher mortality risk across the non-Alzheimer dementias; other significant associations included worse cognitive status (FTLD, LBD) and more depression (LBD). CONCLUSION: Results can help clinicians counsel individuals with dementia and families regarding average dementia trajectories; findings regarding individual risk factors can aid individualizing expectations. Further research is needed to investigate drivers of mortality in the non-AD dementias to improve counseling and help identify potentially modifiable factors.