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Bradford C Dickerson

Publications and source records attributed to Bradford C Dickerson.

10 recordsLinked to original sources
PubMed2025

Comprehensive cross-sectional and longitudinal comparisons of plasma glial fibrillary acidic protein and neurofilament light across FTD spectrum disorders.

BACKGROUND: Therapeutic development for frontotemporal dementia (FTD) is hindered by the lack of biomarkers that inform susceptibility/risk, prognosis, and the underlying causative pathology. Blood glial fibrillary acidic protein (GFAP) has garnered attention as a FTD biomarker. However, investigations of GFAP in FTD have been hampered by symptomatic and histopathologic heterogeneity and small cohort sizes contributing to inconsistent findings. Therefore, we evaluated plasma GFAP as a FTD biomarker and compared its performance to that of neurofilament light (NfL) protein, a leading FTD biomarker. METHODS: We availed ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study resources to conduct a comprehensive cross-sectional and longitudinal examination of the susceptibility/risk, prognostic, and predictive performance of GFAP and NfL in the largest series of well-characterized presymptomatic FTD mutation carriers and participants with sporadic or familial FTD syndromes. Utilizing single molecule array technology, we measured GFAP and NfL in plasma from 161 controls, 127 presymptomatic mutation carriers, 702 participants with a FTD syndrome, and 67 participants with mild behavioral and/or cognitive changes. We used multivariable linear regression and Cox proportional hazard models adjusted for co-variates to examine the biomarker utility of baseline GFAP and NfL concentrations or their rates of change. RESULTS: Compared to controls, GFAP and NfL were elevated in each FTD syndrome but GFAP, unlike NfL, poorly discriminated controls from participants with mild symptoms. Similarly, both baseline GFAP and NfL were higher in presymptomatic mutation carriers who later phenoconverted, but NfL better distinguished non-converters from phenoconverters. We additionally observed that GFAP and NfL were associated with disease severity indicators and survival, but NfL far outperformed GFAP. Nevertheless, we validated findings that the GFAP/NfL ratio may discriminate frontotemporal lobar degeneration with tau versus TDP-43 pathology. CONCLUSIONS: Our head-to-head comparison of plasma GFAP and NfL as biomarkers for FTD indicate that NfL consistently outmatched GFAP as a prognostic and predictive biomarker for participants with a FTD syndrome, and as a susceptibility/risk biomarker for people at genetic risk of FTD. Our findings underscore the need to include leading biomarkers in investigations evaluating new biomarkers if the field is to fully ascertain their performance and clinical value.

Humans↗
PubMed2025

The Consortium for Clarity in ADRD Research Through Imaging (CLARiTI): Overview of consortium sites and anticipated enrollment.

INTRODUCTION: The Consortium for Clarity in Alzheimer's disease related dementias (ADRD) Research Through Imaging (CLARiTI) is a study that aims to collect standardized imaging and plasma biomarkers on 2000 Clinical Core participants enrolled across all Alzheimer's Disease Research Centers (ADRC) sites. We sought to summarize the known heterogeneity across centers regarding scientific focus and initial enrollment plans for CLARiTI. METHODS: We developed and distributed a survey capturing information on the 36 CLARiTI site's theme/expertise, recruitment plans, and the intersection of CLARiTI with other ADRC imaging efforts. RESULTS: Anticipated CLARiTI enrollees spanned 11 different categories of suspected etiologies underlying impairment. A wide range of risk factors were endorsed across sites regarding the enrollment of unimpaired individuals. Variability also existed regarding site-level strategies in enrollment into CLARiTI versus other imaging efforts. DISCUSSION: We anticipate that the 2000 individuals that will enroll into CLARiTI will reflect the clinical heterogeneity already in place across the ADRC network. HIGHLIGHTS: The ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI) will leverage and contribute to the existing Alzheimer's Disease Research Centers (ADRC) program by supporting standardized imaging and plasma collection across all centers. We summarize the variation in scientific focus and enrollment plans across ADRC sites participating in CLARiTI. The anticipated CLARiTI cohort will reflect the clinical heterogeneity that already exists across the ADRC network. CLARiTI will contribute to scientific goals related to the detection of multi-etiological signatures relevant for Alzheimer's disease and related disorders (ADRDs).

Humans↗
PubMed2006

Alterations in memory networks in mild cognitive impairment and Alzheimer's disease: an independent component analysis.

Memory function is likely subserved by multiple distributed neural networks, which are disrupted by the pathophysiological process of Alzheimer's disease (AD). In this study, we used multivariate analytic techniques to investigate memory-related functional magnetic resonance imaging (fMRI) activity in 52 individuals across the continuum of normal aging, mild cognitive impairment (MCI), and mild AD. Independent component analyses revealed specific memory-related networks that activated or deactivated during an associative memory paradigm. Across all subjects, hippocampal activation and parietal deactivation demonstrated a strong reciprocal relationship. Furthermore, we found evidence of a nonlinear trajectory of fMRI activation across the continuum of impairment. Less impaired MCI subjects showed paradoxical hyperactivation in the hippocampus compared with controls, whereas more impaired MCI subjects demonstrated significant hypoactivation, similar to the levels observed in the mild AD subjects. We found a remarkably parallel curve in the pattern of memory-related deactivation in medial and lateral parietal regions with greater deactivation in less-impaired MCI and loss of deactivation in more impaired MCI and mild AD subjects. Interestingly, the failure of deactivation in these regions was also associated with increased positive activity in a neocortical attentional network in MCI and AD. Our findings suggest that loss of functional integrity of the hippocampal-based memory systems is directly related to alterations of neural activity in parietal regions seen over the course of MCI and AD. These data may also provide functional evidence of the interaction between neocortical and medial temporal lobe pathology in early AD.

Aged↗
PubMed2006

An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest.

In this study, we have assessed the validity and reliability of an automated labeling system that we have developed for subdividing the human cerebral cortex on magnetic resonance images into gyral based regions of interest (ROIs). Using a dataset of 40 MRI scans we manually identified 34 cortical ROIs in each of the individual hemispheres. This information was then encoded in the form of an atlas that was utilized to automatically label ROIs. To examine the validity, as well as the intra- and inter-rater reliability of the automated system, we used both intraclass correlation coefficients (ICC), and a new method known as mean distance maps, to assess the degree of mismatch between the manual and the automated sets of ROIs. When compared with the manual ROIs, the automated ROIs were highly accurate, with an average ICC of 0.835 across all of the ROIs, and a mean distance error of less than 1 mm. Intra- and inter-rater comparisons yielded little to no difference between the sets of ROIs. These findings suggest that the automated method we have developed for subdividing the human cerebral cortex into standard gyral-based neuroanatomical regions is both anatomically valid and reliable. This method may be useful for both morphometric and functional studies of the cerebral cortex as well as for clinical investigations aimed at tracking the evolution of disease-induced changes over time, including clinical trials in which MRI-based measures are used to examine response to treatment.

Adult↗
PubMed2006

Neuroanatomical correlates of extraversion and neuroticism.

Introversion/extraversion and neuroticism are 2 important and frequently studied dimensions of human personality. These dimensions describe individual differences in emotional responding across a range of situations and may contribute to a predisposition for psychiatric disorders. Recent neuroimaging research has begun to provide evidence that neuroticism and introversion/extraversion have specific functional and structural neural correlates. Previous studies in healthy adults have reported an association between neuroticism, introversion/extraversion, and the activity of the prefrontal cortex and amygdala. Studies of individuals with psychopathological states have also indicated that anatomic variations in these brain areas may relate to extraversion and neuroticism. The purpose of the present study was to examine selected structural correlates of neuroticism and extraversion in healthy subjects (n = 28) using neuroanatomic measures of the cerebral cortex and amygdala. We observed that the thickness of specific prefrontal cortex regions correlates with measures of extraversion and neuroticism. In contrast, no such correlations were observed for the volume of the amygdala. The results suggest that specific aspects of regional prefrontal anatomy are associated with specific personality traits.

Adult↗
PubMed2006

Functional magnetic resonance imaging of cholinergic modulation in mild cognitive impairment.

PURPOSE OF REVIEW: Mild cognitive impairment often represents the earliest clinical phase of Alzheimer's disease and is thought to involve synaptic dysfunction. Functional neuroimaging methods may be sensitive to these early physiologic changes and may be useful in early detection, therapeutic monitoring, and prediction of treatment response and other clinical outcomes. This review will focus on functional magnetic resonance imaging and its use in measuring the effects of cholinergic modulation in mild cognitive impairment. RECENT FINDINGS: Functional magnetic resonance imaging has begun to be applied to measure changes in regional brain activation during cognitive task performance after pharmacologic manipulation. In mild cognitive impairment, recent reports have appeared demonstrating alterations in neocortical activation after acute and prolonged administration of acetylcholinesterase inhibitors. These functional changes may relate to both behavioral performance and measures of brain structure (e.g., hippocampal volume). SUMMARY: Pharmacologic functional magnetic resonance imaging is a rapidly emerging field, with applications in both basic human neuroscience and clinical psychiatry and neurology. Its use in mild cognitive impairment and Alzheimer's disease may provide novel insights into the cholinergic system, memory, and neurodegenerative disease.

Acetylcholine↗
PubMed2005

Prevalence and effects of lobar microhemorrhages in early-stage dementia.

BACKGROUND: 80-100% of patients with Alzheimer's disease have vascular pathology related to cerebral amyloid angiopathy (CAA), and 5-7% have CAA-related lobar microhemorrhages (LMH) at autopsy. The prevalence and effects of LMH detectable by gradient echo MRI (GE-MRI) in early-stage dementia are unknown. OBJECTIVE: To obtain, using GE-MRI, a prevalence estimate for LMH in patients with early-stage dementia and to assess the effects of LMH on dementia severity. METHODS: Eighty-four subjects aged >or=55 years (range 58-89; mean 76) underwent cognitive and GE-MRI evaluation. The 84 subjects consisted of 61 consecutive subjects evaluated as part of an initial clinical evaluation for dementia and 23 consecutively evaluated healthy older subjects (controls). Data were analyzed for presence and number of LMH on GE-MRI and the effect of number of LMH on dementia severity. RESULTS: Nine (15%) of the 61 dementia patients versus 1 (4%) of the 23 control subjects demonstrated LMH on GE-MRI. Multiple (>or=2) LMH were found in 7 of the 9 (88%) dementia subjects with LMH (range of LMH counts 1-330) and no (0%) control subjects. Multivariable causal modeling indicated that number of LMH (p < 0.02), age (p < 0.01) and duration of symptoms (p < 0.001) significantly increased dementia severity while higher educational level (p < 0.001) was protective. CONCLUSIONS: LMH were detected by GE-MRI in 15% of patients with early-stage dementia and may contribute to dementia severity.

Aged↗
PubMed2005

Neuroimaging biomarkers for clinical trials of disease-modifying therapies in Alzheimer's disease.

The pathophysiologic process leading to neurodegeneration in Alzheimer's disease (AD) is thought to begin long before clinical symptoms develop. Existing therapeutics for AD improve symptoms, but increasing efforts are being directed toward the development of therapies to impede the pathologic progression of the disease. Although these medications must ultimately demonstrate efficacy in slowing clinical decline, there is a critical need for biomarkers that will indicate whether a candidate disease-modifying therapeutic agent is actually altering the underlying degenerative process. A number of in vivo neuroimaging techniques, which can reliably and noninvasively assess aspects of neuroanatomy, chemistry, physiology, and pathology, hold promise as biomarkers. These neuroimaging measures appear to relate closely to neuropathological and clinical data, such as rate of cognitive decline and risk of future decline. As this work has matured, it has become clear that neuroimaging measures may serve a variety of potential roles in clinical trials of candidate neurotherapeutic agents for AD, depending in part on the question of interest and phase of drug development. In this article, we review data related to the range of neuroimaging biomarkers of Alzheimer's disease and consider potential applications of these techniques to clinical trials, particularly with respect to the monitoring of disease progression in trials of disease-modifying therapies.

Alzheimer Disease↗
PubMed2004

Medial temporal lobe function and structure in mild cognitive impairment.

Functional magnetic resonance imaging (fMRI) was used to study memory-associated activation of medial temporal lobe (MTL) regions in 32 nondemented elderly individuals with mild cognitive impairment (MCI). Subjects performed a visual encoding task during fMRI scanning and were tested for recognition of stimuli afterward. MTL regions of interest were identified from each individual's structural MRI, and activation was quantified within each region. Greater extent of activation within the hippocampal formation and parahippocampal gyrus (PHG) was correlated with better memory performance. There was, however, a paradoxical relationship between extent of activation and clinical status at both baseline and follow-up evaluations. Subjects with greater clinical impairment, based on the Clinical Dementia Rating Sum of Boxes, recruited a larger extent of the right PHG during encoding, even after accounting for atrophy. Moreover, those who subsequently declined over the 2.5 years of clinical follow-up (44% of the subjects) activated a significantly greater extent of the right PHG during encoding, despite equivalent memory performance. We hypothesize that increased activation in MTL regions reflects a compensatory response to accumulating AD pathology and may serve as a marker for impending clinical decline.

Aged↗