Background: As global aging accelerates, routinely assessing the functional status and morbidity burden of older patients becomes paramount. The aim of this study is to assess the validity of the comprehensive clinical and functional Health Assessment Tool (HAT) based on four cohorts of older adults (60 + years) from the Swedish National study on Aging and Care (SNAC) spanning urban, suburban, and rural areas.
Methods: The HAT integrates five health indicators (gait speed, global cognition, number of chronic diseases, and basic and instrumental activities of daily living), providing an individual-level score between 0 and 10. The tool was constructed using nominal response models, first separately for each cohort and then in a harmonized dataset. Outcomes included all-cause mortality over a maximum follow-up of 16 years and unplanned hospital admissions over a maximum of 3 years of follow-up. The predictive capacity was assessed through the area under the curve (AUC) using logistic regressions. For time to death, Cox regressions were performed, and Harrell's C-indices were reported. Results from the four cohorts were pooled using individual participant data meta-analysis and compared with those from the harmonized dataset.
Results: The HAT demonstrated high predictive capacity across all cohorts as well as in the harmonized dataset. In the harmonized dataset, the AUC was 0.84 (95% CI 0.81-0.87) for 1-year mortality, 0.81 (95% CI 0.80-0.83) for 3-year mortality, 0.80 (95% CI 0.79-0.82) for 5-year mortality, 0.69 (95% CI 0.67-0.70) for 1-year unplanned admissions, and 0.69 (95% CI 0.68-0.70) for 3-year unplanned admissions. The Harrell's C for time-to-death throughout 16 years of follow-up was 0.75 (95% CI 0.74-0.75).
Conclusions: The HAT is a highly predictive, clinically intuitive, and externally valid instrument with potential for better addressing older adults' health needs and optimizing risk stratification at the population level.
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http://dx.doi.org/10.1186/s12916-024-03454-4 | DOI Listing |
Alzheimers Dement
December 2024
Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
Background: The Apolipoprotein E ε4 (APOE-ε4) allele is common in the population, but acts as the strongest genetic risk factor for late-onset Alzheimer's disease (AD). Despite the strength of the association, there is notable heterogeneity in the population including a strong modifying effect of genetic ancestry, with the APOE-ε4 allele showing a stronger association among individuals of European ancestry (EUR) compared to individuals of African ancestry (AFR). Given this heterogeneity, we sought to identify genetic modifiers of APOE-ε4 related to cognitive decline leveraging APOE-ε4 stratified and interaction genome-wide association analyses (GWAS).
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Alzheimers Dement
December 2024
Allen Institute for Brain Science, Seattle, WA, USA.
Background: Numerous studies have identified AD-associated molecular and cellular changes to the cortex using single nucleus RNA sequencing (snRNA-seq) and, to a lesser extent, single nucleus ATAC-seq (snATAC-seq), applied to millions of cells across hundreds of donors. It has proven challenging, however, to determine whether changes are consistent because of differences in cohort selection, reported clinical metadata, data pre-processing, cellular taxonomy construction/mapping, and analytical strategies across studies.
Method: We uniformly re-processed 10 publicly available datasets (Table 1) that had applied snRNA-seq to 4.
Alzheimers Dement
December 2024
Cleveland Clinic, Cleveland, OH, USA.
Background: Cell-type specific expression quantitative trait loci (eQTLs) can help dissect cellular heterogeneity in the impact of genetic variation on gene expression for Alzheimer's disease (AD) and AD-related dementia (ADRD). However, due to the high cost and stringent sample collection criteria, it is challenging to obtain large single-nuclei RNA sequencing (snRNA-seq) data with sufficient cohort size to match genotyping data to systematically identify human brain-specific eQTLs for AD/ADRD.
Method: In this study, we presented a deep learning-based deconvolution framework on large-scale bulk RNA sequencing (RNA-seq) data to infer cell-type specific eQTLs in the human brains with AD/ADRD.
Alzheimers Dement
December 2024
University of Washington, School of Medicine, Seattle, WA, USA.
Background: Previously, we developed a co-calibrated and harmonized brain pathology score (BPS) across prospective cohort studies with research brain donation that incorporates multiple forms of postmortem neuropathology, using confirmatory factor analysis. We sought to identify genetic loci associated with BPS using a systems-biology approach, combining data from participants in the Adult Changes in Thought (ACT), the Religious Orders Study, and Rush Memory and Aging Project (ROSMAP) autopsy cohorts.
Method: We used PLINK in each cohort separately for genome-wide association studies (GWAS) of BPS using HRC imputed data from European ancestry participants, adjusting for age at death, sex, and population substructure.
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