Publications by authors named "Walter Kukull"
Introduction: Alzheimer's disease (AD) co-pathology with Lewy bodies (LB) is frequent and influences clinical manifestations and outcomes. Its significance in primary age-related tauopathy (PART) is unknown. We investigated the influence of LB on cognition and brain atrophy in AD and PART.
View Article and Find Full Text PDFIntroduction: The effects of sex and apolipoprotein E (APOE)-Alzheimer's disease (AD) risk factors-on white matter microstructure are not well characterized.
Methods: Diffusion magnetic resonance imaging data from nine well-established longitudinal cohorts of aging were free water (FW)-corrected and harmonized. This dataset included 4741 participants (age = 73.
Article Synopsis
- A study was conducted to investigate the X-chromosome's role in Alzheimer's Disease (AD), which had been overlooked in previous genome-wide association studies.
- The research included 115,841 AD cases and 613,671 controls, considering different X-chromosome inactivation (XCI) states in females.
- While no strong genetic risk factors for AD were found on the X-chromosome, seven significant loci were identified, suggesting areas for future research.
The presence of multiple pathologies is the largest predictor of dementia. A major gap in the field is the in vivo detection of mixed pathologies and their antecedents. The Alzheimer's Disease Research Centers (ADRCs) are uniquely positioned to address this gap.
View Article and Find Full Text PDFCerebral amyloid angiopathy commonly co-occurs with amyloid β plaques and neurofibrillary degeneration and is proposed to contribute to cognitive impairment. However, the interplay among these pathologic changes of Alzheimer disease is not well understood. Here we replicate and extend findings of a recent study that suggested the association of cerebral amyloid angiopathy and cognitive impairment is mediated by neurofibrillary degeneration.
View Article and Find Full Text PDFArticle Synopsis
- Scientists studied the genes related to Alzheimer's disease and found over 80 gene locations that might be linked to this disease.
- They looked at data from nearly 8,000 people who had their brains examined after they died to better understand different brain changes connected to Alzheimer's.
- In their research, they discovered 8 important new gene locations, including some that were previously unknown, which helps us learn more about how genetics can affect the risk of Alzheimer's disease.
Background: Brain vascular pathology is an important comorbidity in Alzheimer's disease (AD), with white matter damage independently predicting cognitive impairment. However, it is still unknown how vascular pathology differentially impacts primary age-related tauopathy (PART) compared to AD. Therefore, our objectives were to compare the brain microangiopathic burden in patients with PART and AD, evaluated by MRI, while assessing its relation with neuropathological findings, patterns of brain atrophy and degree of clinical impairment.
View Article and Find Full Text PDFField-of-view extension for brain diffusion MRI via deep generative models.
J Med Imaging (Bellingham)
July 2024
Purpose: In brain diffusion magnetic resonance imaging (dMRI), the volumetric and bundle analyses of whole-brain tissue microstructure and connectivity can be severely impeded by an incomplete field of view (FOV). We aim to develop a method for imputing the missing slices directly from existing dMRI scans with an incomplete FOV. We hypothesize that the imputed image with a complete FOV can improve whole-brain tractography for corrupted data with an incomplete FOV.
View Article and Find Full Text PDFArticle Synopsis
- - This systematic review investigates white matter hyperintensity (WMH) research from 2000 to 2022, focusing on prevalence, mechanisms, and characteristics of studied cohorts while following PRISMA guidelines.
- - The analysis revealed 1007 visual rating scales, 118 pipeline development articles, and 509 implementation articles, with a significant focus on aging, dementia, and psychiatric disorders, and indicated that deep learning is the leading segmentation technique developed.
- - Despite advancements in quantitative techniques, traditional visual rating scales remain popular, with SPM being the most commonly used method; the review emphasizes the need for future standards in WMH segmentation and offers recommendations accordingly.
Introduction: The effects of sex, race, and Apolipoprotein E () - Alzheimer's disease (AD) risk factors - on white matter integrity are not well characterized.
Methods: Diffusion MRI data from nine well-established longitudinal cohorts of aging were free-water (FW)-corrected and harmonized. This dataset included 4,702 participants (age=73.
Psychosis in Alzheimer's Disease (AD) is prevalent and indicates poor prognosis. However, the neuropathological, cognitive and brain atrophy patterns underlying these symptoms have not been fully elucidated. In this study, we evaluated 178 patients with AD neuropathological change (ADNC) and ante-mortem volumetric brain magnetic resonance imaging (MRI).
View Article and Find Full Text PDFIntroduction: Although dementia-related proteinopathy has a strong negative impact on public health, and is highly heritable, understanding of the related genetic architecture is incomplete.
Methods: We applied multidimensional generalized partial credit modeling (GPCM) to test genetic associations with dementia-related proteinopathies. Data were analyzed to identify candidate single nucleotide variants for the following proteinopathies: Aβ, tau, α-synuclein, and TDP-43.
Introduction: Clinical research in Alzheimer's disease (AD) lacks cohort diversity despite being a global health crisis. The Asian Cohort for Alzheimer's Disease (ACAD) was formed to address underrepresentation of Asians in research, and limited understanding of how genetics and non-genetic/lifestyle factors impact this multi-ethnic population.
Methods: The ACAD started fully recruiting in October 2021 with one central coordination site, eight recruitment sites, and two analysis sites.
We aimed to prospectively assess the change in neuropsychiatric symptoms among people who develop cognitive impairment and have a history of post-traumatic stress disorder (PTSD). We analyzed longitudinal data from the National Alzheimer's Coordinating Center Unified Data Set (March 2015 to December 2021). Analyses included individuals who were cognitively normal and who had nonmissing assessment of PTSD at the initial visit and had at least 1 follow-up visit with cognitive impairment.
View Article and Find Full Text PDFIntroduction: Although large-scale genome-wide association studies (GWAS) have been conducted on AD, few have been conducted on continuous measures of memory performance and memory decline.
Methods: We conducted a cross-ancestry GWAS on memory performance (in 27,633 participants) and memory decline (in 22,365 participants; 129,201 observations) by leveraging harmonized cognitive data from four aging cohorts.
Results: We found high heritability for two ancestry backgrounds.
Background: Women demonstrate a memory advantage when cognitively healthy yet lose this advantage to men in Alzheimer's disease. However, the genetic underpinnings of this sex difference in memory performance remain unclear.
Methods: We conducted the largest sex-aware genetic study on late-life memory to date (N = 11,942; N = 15,641).
Article Synopsis
- Researchers developed an MRI-based signature to identify brain atrophy linked to sporadic early-onset Alzheimer's disease (EOAD) using two patient samples, one small (n=25) and another larger (n=211).
- The study found consistent atrophy patterns in specific brain regions, like the caudal lateral temporal cortex and inferior parietal lobule, while the medial temporal lobe was relatively spared.
- The EOAD-signature atrophy correlates with cognitive impairment severity, suggesting it's a reliable biomarker for Alzheimer’s-related neurodegeneration in clinical trials.
Article Synopsis
- The LEADS study focuses on understanding the genetic causes of early-onset Alzheimer's Disease (EOAD), specifically in individuals aged 40-64, by screening for known pathogenic variants.
- *Whole exome sequencing of 299 participants found pathogenic variants in 1.35% of EOAD cases and 6.58% of early-onset non-Alzheimer's disease cases, but no gene showed a significant enrichment for rare functional variants.
- *The findings suggest that LEADS may include new genetic variants related to early-onset cognitive impairment, making it an important resource for ongoing Alzheimer's research.*
Importance: The Clinical Dementia Rating (CDR) is a well-validated instrument widely used to detect and stage dementia due to Alzheimer disease. The digital Electronic Clinical Dementia Rating (eCDR) can be remotely self-administered and automatically scored, with potential to facilitate efficient dementia screening and staging.
Objective: To evaluate the association of the eCDR with the CDR and other in-clinic assessments for screening older adults for cognitive impairment.
Article Synopsis
- The study focuses on analyzing baseline amyloid-beta and tau-PET scans in participants with early-onset Alzheimer's disease (EOAD) to improve diagnostic understanding.* -
- Out of the 321 cognitively impaired participants, 75.7% were classified as having EOAD based on amyloid-PET, with 95.1% of them also showing elevated tau-PET signals, particularly in younger and female subjects.* -
- The findings highlight the significance of using these biomarkers for more accurate EOAD diagnoses and suggest potential implications for treatment strategies based on tau-PET levels.*
Introduction: Biomarkers remain mostly unavailable for non-Alzheimer's disease neuropathological changes (non-ADNC) such as transactive response DNA-binding protein 43 (TDP-43) proteinopathy, Lewy body disease (LBD), and cerebral amyloid angiopathy (CAA).
Methods: A multilabel non-ADNC classifier using magnetic resonance imaging (MRI) signatures was developed for TDP-43, LBD, and CAA in an autopsy-confirmed cohort (N = 214).
Results: A model using demographic, genetic, clinical, MRI, and ADNC variables (amyloid positive [Aβ+] and tau+) in autopsy-confirmed participants showed accuracies of 84% for TDP-43, 81% for LBD, and 81% to 93% for CAA, outperforming reference models without MRI and ADNC biomarkers.
Article Synopsis
- The study examines the Rey Auditory Verbal Learning Test (RAVLT) as a tool for assessing memory impairment in early-onset Alzheimer's disease (EOAD), focusing on the effects of amyloid presence and diagnostic syndrome.
- RAVLT recordings from 303 participants were analyzed, revealing that amyloid-positive individuals showed significant differences in memory performance compared to amyloid-negative individuals, including effects on raw scores and timing measures.
- The findings suggest that RAVLT is sensitive to variations in memory impairment linked to amyloid and syndrome types in EOAD, highlighting the need for further research to understand the predictive capabilities of these memory scores.
Article Synopsis
- Research autopsy cohorts offer valuable information about dementia, but their findings can differ due to recruitment biases.
- A study analyzed data from 7,178 autopsied participants across 28 centers, focusing on those cognitively normal at the start.
- Results showed that cohorts with more cognitively normal individuals had unique demographic and pathology profiles, indicating that the proportion of normal cognition at recruitment can predict differences in research outcomes.
Introduction: We used sex and apolipoprotein E ε4 (APOE ε4) carrier status as predictors of pathologic burden in early-onset Alzheimer's disease (EOAD).
Methods: We included baseline data from 77 cognitively normal (CN), 230 EOAD, and 70 EO non-Alzheimer's disease (EOnonAD) participants from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS). We stratified each diagnostic group by males and females, then further subdivided each sex by APOE ε4 carrier status and compared imaging biomarkers in each stratification.