Publications by authors named "David G. Clark"

Frontotemporal Dementia.

Continuum (Minneap Minn)

December 2024

Article Synopsis
  • - The article outlines frontotemporal dementia (FTD) by focusing on three core syndromes: behavioral variant FTD and two types of progressive aphasia (nonfluent and semantic variants), which are linked to specific protein abnormalities in the brain.
  • - It highlights that FTD is more heritable than Alzheimer's and indicates genetic variations, such as in C9orf72 and MAPT, are found in over 10% of cases, which help understand its pathology through clinical presentations and imaging.
  • - Although there are no FDA-approved treatments for FTD yet, ongoing clinical trials aim to find disease-modifying therapies, while current management strategies address behavioral and language issues through non-drug methods or off-label medication use. *
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Background: Predictors have not been determined of serum brain-derived neurotrophic factor (BDNF) levels among patients with heart failure (HF).

Objective: The primary purpose was to evaluate history of atrial fibrillation, age, gender, and left ventricular ejection fraction as predictors of serum BDNF levels at baseline, 10 weeks, and 4 and 8 months after baseline among patients with HF.

Methods: This study was a retrospective cohort analyses of 241 patients with HF.

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Objective: To compare verbal fluency scores derived from manual transcriptions to those obtained using automatic speech recognition enhanced with machine learning classifiers.

Methods: Using Amazon Web Services, we automatically transcribed verbal fluency recordings from 1400 individuals who performed both animal and letter F verbal fluency tasks. We manually adjusted timings and contents of the automatic transcriptions to obtain "gold standard" transcriptions.

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Neural circuits are composed of multiple regions, each with rich dynamics and engaging in communication with other regions. The combination of local, within-region dynamics and global, network-level dynamics is thought to provide computational flexibility. However, the nature of such multiregion dynamics and the underlying synaptic connectivity patterns remain poorly understood.

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Amyloid-β (Aβ) and tau proteins accumulate within distinct neuronal systems in Alzheimer's disease (AD). Although it is not clear why certain brain regions are more vulnerable to Aβ and tau pathologies than others, gene expression may play a role. We study the association between brain-wide gene expression profiles and regional vulnerability to Aβ (gene-to-Aβ associations) and tau (gene-to-tau associations) pathologies by leveraging two large independent AD cohorts.

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The BrainAGE method is used to estimate biological brain age using structural neuroimaging. However, the stability of the model across different scan parameters and races/ethnicities has not been thoroughly investigated. Estimated brain age was compared within- and across- MRI field strength and across voxel sizes.

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Neural networks are high-dimensional nonlinear dynamical systems that process information through the coordinated activity of many connected units. Understanding how biological and machine-learning networks function and learn requires knowledge of the structure of this coordinated activity, information contained, for example, in cross covariances between units. Self-consistent dynamical mean field theory (DMFT) has elucidated several features of random neural networks-in particular, that they can generate chaotic activity-however, a calculation of cross covariances using this approach has not been provided.

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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.
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Unlabelled: Amyloid-β (Aβ) and tau proteins accumulate within distinct neuronal systems in Alzheimer's disease (AD). Although it is not clear why certain brain regions are more vulnerable to Aβ and tau pathologies than others, gene expression may play a role. We studied the association between brain-wide gene expression profiles and regional vulnerability to Aβ (gene-to-Aβ associations) and tau (gene-to-tau associations) pathologies leveraging two large independent cohorts (n = 715) of participants along the AD continuum.

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Article Synopsis
  • - Identifying early biomarkers for Alzheimer's disease (AD) is crucial for effective treatments, with cerebral blood flow (CBF) being a potential indicator as it typically decreases in older adults with AD compared to healthy peers.
  • - A study involving 77 older adults investigated the relationship between CBF, hypertension, and AD-related factors like the APOEε4 gene and tau and amyloid levels using advanced imaging techniques.
  • - Results showed that changes in CBF are linked to tau and amyloid aggregation, with some relationships influenced by hypertension or APOEε4 status, highlighting the need for more research on CBF as an early biomarker for AD.
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Background: Cognitive dysfunction predicts mortality in heart failure (HF). Computerized cognitive training (CCT) has shown preliminary efficacy in improving cognitive function. However, the relationship between CCT and mortality is unclear.

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Background: Depressive symptoms, brain-derived neurotrophic factor (BDNF) Val66Met, and apolipoprotein (APOE)-ε4 may moderate response to computerized cognitive training (CCT) interventions among patients with heart failure (HF).

Objectives: The purpose of this study was to examine moderators of intervention response to CCT over 8 months among patients with HF enrolled in a 3-arm randomized controlled trial. Outcomes were memory, serum BDNF, working memory, instrumental activities of daily living (IADLs), and health-related quality of life (HRQL).

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Powdery mildew (PM) is a common fungal disease in many important crops. The PM caused by has been the most challenging problem in commercial () production globally, often leading to severe losses of crop yield and quality. A small number of PM-resistant breeding lines and cultivars have been reported in , but the underlying genetics for PM resistance in is largely unknown.

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Objective: To compare techniques for computing clustering and switching scores in terms of agreement, correlation, and empirical value as predictors of incident cognitive impairment (ICI).

Methods: We transcribed animal and letter F fluency recordings on 640 cases of ICI and matched controls from a national epidemiological study, amending each transcription with word timings. We then calculated clustering and switching scores, as well as scores indexing speed of responses, using techniques described in the literature.

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Background: The cardiac manifestations of Fabry disease are the leading cause of death, but risk stratification remains inadequate. Identifying patients who are at risk of adverse cardiac outcome may facilitate more evidence-based treatment guidance. Contemporary cardiovascular cardiac magnetic resonance biomarkers have become widely adopted, but their prognostic value remains unclear.

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Like angiosperms from several other families, the leguminous shrub Gastrolobium bilobum R.Br. produces and accumulates fluoroacetate, indicating that it performs the difficult chemistry needed to make a C-F bond.

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Introduction: In recent decades, researchers have defined novel methods for scoring verbal fluency tasks. In this work, we evaluate novel scores based on speed of word responses.

Methods: We transcribed verbal fluency recordings from 641 cases of incident cognitive impairment (ICI) and matched controls, all participants in a large national epidemiological study.

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Background: The objective of this 3-arm randomized controlled trial was to evaluate the efficacy of computerized cognitive training (CCT) in improving primary outcomes of delayed-recall memory and serum brain-derived neurotrophic factor (BDNF) levels; and the secondary outcomes were working memory, instrumental activities of daily living (IADLs) and health-related quality of life (HRQL) in patients with heart failure (HF).

Methods And Results: Patients (n = 256) were randomly assigned to 8 weeks of CCT using BrainHQ, computerized crossword puzzles active control intervention, and usual care. All patients received weekly nurse-enhancement interventions.

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The convergence of internal path integration and external sensory landmarks generates a cognitive spatial map in the hippocampus. We studied how localized odor cues are recognized as landmarks by recording the activity of neurons in CA1 during a virtual navigation task. We found that odor cues enriched place cell representations, dramatically improving navigation.

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Article Synopsis
  • - The study focuses on improving functional connectivity estimates from resting state fMRI to link brain function with cognitive outcomes, especially in Alzheimer's disease.
  • - It highlights issues with the current clinical use of functional connectivity biomarkers, such as their unreliability and lack of general applicability for predicting cognition.
  • - By combining connectome predictive modeling and differential identifiability, researchers enhance individual brain connectivity profiles, leading to better identification of networks influencing cognitive deficits in Alzheimer's patients.
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Background: RNA sequencing has been widely used to profile genome-wide gene expression and identify candidate genes controlling disease resistance and other important traits in plants. Gerbera daisy is one of the most important flowers in the global floricultural trade, and powdery mildew (PM) is the most important disease of gerbera. Genetic improvement of gerbera PM resistance has become a crucial goal in gerbera breeding.

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Petunia × hybrida cv 'Mitchell Diploid' floral volatile benzenoid/phenylpropanoid (FVBP) biosynthesis ultimately produces floral volatiles derived sequentially from phenylalanine, cinnamic acid, and p-coumaric acid. In an attempt to better understand biochemical steps after p-coumaric acid production, we cloned and characterized three petunia transcripts with high similarity to p-coumarate 3-hydroxylase (C3H), hydroxycinnamoyl-CoA:shikimate/quinate hydroxycinnamoyl transferase (HCT), and caffeoyl shikimate esterase (CSE). Transcript accumulation of PhC3H and PhHCT was highest in flower limb tissue during open flower stages.

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Introduction: Few studies to date have explored patient and caregiver views on the clinical use of amyloid positron emission tomography (PET).

Methods: A 7-item questionnaire assessing patient and caregiver views (510 total respondents) toward amyloid PET imaging was advertised broadly through alz.org/trialmatch.

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Article Synopsis
  • * Our research uncovered three significant variants: a protective variant in the PLCG2 gene and risk variants in ABI3 and TREM2, known for their roles in Alzheimer's susceptibility.
  • * The findings emphasize the importance of microglia, immune cells in the brain, suggesting that their genetic variations may contribute directly to the progression of Alzheimer's disease.
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