INTRODUCTION: In patients with Alzheimer’s disease (AD) and mild cognitive impairment, structural changes in the retina (i.e., reduced thicknesses of the ganglion cell and retinal nerve fiber layers and inclusion bodies that appear to contain beta-amyloid protein [Ab]) have been previously reported. We sought to explore whether anatomic retinal changes are detectable in the preclinical […]
Feasibility of baseline neurocognitive assessment using Cogstate during the first month of therapy for childhood leukemia.
PURPOSE: Neurocognitive impairment is frequently observed among acute lymphoblastic leukemia (ALL) survivors within the domains of intelligence, attention, processing speed, working memory, learning, and memory. However, few have investigated treatment-induced changes in neurocognitive function during the first months of treatment. Additionally, dysfunction during treatment may be preceded by changes in biomarkers measured within cerebrospinal fluid […]
OBJECTIVE: To test whether plasma tau is altered in Alzheimer disease (AD) and whether it is related to changes in cognition, CSF biomarkers of AD pathology (including β-amyloid [Aβ] and tau), brain atrophy, and brain metabolism. METHODS: This was a study of plasma tau in prospectively followed patients with AD (n = 179), patients with […]
OBJECTIVE: We assessed a blood-based signature, which previously demonstrated high accuracy at stratifying individuals with high or low neocortical β-amyloid burden (NAB), to determine whether it could also identify individuals at risk of progression to Alzheimer disease (AD) within 54 months. METHODS: We generated the blood-based signature for 585 healthy controls (HCs) and 74 participants […]
Clinical and cognitive trajectories in cognitively healthy elderly individuals with suspected non-Alzheimer’s disease pathophysiology (SNAP) or Alzheimer’s disease pathology: a longitudinal study.
BACKGROUND: Brain amyloid β (Aβ) deposition and neurodegeneration have been documented in about 50-60% of cognitively healthy elderly individuals (aged 60 years or older). The long-term cognitive consequences of the presence of Alzheimer’s disease pathology and neurodegeneration, and whether they have an independent or synergistic effect on cognition, are unclear. We aimed to characterise the […]
Associations between Performance on an Abbreviated CogState Battery, Other Measures of Cognitive Function, and Biomarkers in People at Risk for Alzheimer’s Disease.
It is not known whether computerized cognitive assessments, like the CogState battery, are sensitive to preclinical cognitive changes or pathology in people at risk for Alzheimer’s disease(AD). In 469 late middle-aged participants from the Wisconsin Registry for Alzheimer’s Prevention(mean age 63.8±7 years at testing; 67% female; 39% APOE4+), we examined relationships between a CogState abbreviated […]
Disclosure of positron emission tomography amyloid imaging results: A preliminary study of safety and tolerability.
INTRODUCTION: Three 18F-labeled radiopharmaceuticals have been Food and Drug Administration-approved for the identification of cortical amyloidosis in clinical settings. Although there has been strong debate among professionals as to the ethical and social consequences of disclosing such information, increasing numbers of participants are being recruited into secondary prevention trials for which they are likely to, […]
Alzheimer’s disease cerebrospinal fluid biomarkers are not influenced by gravity drip or aspiration extraction methodology.
INTRODUCTION: Cerebrospinal fluid (CSF) biomarkers, although of established utility in the diagnostic evaluation of Alzheimer’s disease (AD), are known to be sensitive to variation based on pre-analytical sample processing. We assessed whether gravity droplet collection versus syringe aspiration was another factor influencing CSF biomarker analyte concentrations and reproducibility. METHODS: Standardized lumbar puncture using small calibre […]
BACKGROUND: Postoperative cognitive dysfunction (POCD) affects 16 to 21% of the elderly 3 months after anesthesia and surgery and is associated with adverse outcomes. The exact cause of POCD remains unknown. The authors hypothesized that elderly individuals with Alzheimer disease (AD) neuropathology, identified by cerebrospinal fluid (CSF) analysis, would have increased the risk for POCD. […]
Nonlinear Association Between Cerebrospinal Fluid and Florbetapir F-18 β-Amyloid Measures Across the Spectrum of Alzheimer Disease.
IMPORTANCE: Cerebrospinal fluid (CSF) and positron emission tomographic (PET) amyloid biomarkers have been proposed for the detection of Alzheimer disease (AD) pathology in living patients and for the tracking of longitudinal changes, but the relation between biomarkers needs further study. OBJECTIVE: To determine the association between CSF and PET amyloid biomarkers (cross-sectional and longitudinal measures) […]
The role of vascular endothelial growth factor in neurodegeneration and cognitive decline: exploring interactions with biomarkers of Alzheimer disease.
IMPORTANCE: A subset of older adults present post mortem with Alzheimer disease (AD) pathologic features but without any significant clinical manifestation of dementia. Vascular endothelial growth factor (VEGF) has been implicated in staving off AD-related neurodegeneration. OBJECTIVE: To evaluate whether VEGF levels are associated with brain aging outcomes (hippocampal volume and cognition) and to further […]
Assessing cognition and function in Alzheimer’s disease clinical trials: do we have the right tools?
Several lines of evidence from Alzheimer’s disease (AD) research continue to support the notion that the biological changes associated with AD are occurring possibly several decades before an individual will experience the cognitive and functional changes associated with the disease. The National Institute on Aging-Alzheimer’s Association revised criteria for AD provided a framework for this […]
OBJECTIVE: New preclinical Alzheimer disease (AD) diagnostic criteria have been developed using biomarkers in cognitively normal (CN) adults. We implemented these criteria using an MRI biomarker previously associated with AD dementia, testing the hypothesis that individuals at high risk for preclinical AD would be at elevated risk for cognitive decline. METHODS: The Alzheimer’s Disease Neuroimaging […]
Identifying disease sensitive and quantitative trait-relevant biomarkers from multidimensional heterogeneous imaging genetics data via sparse multimodal multitask learning.
MOTIVATION: Recent advances in brain imaging and high-throughput genotyping techniques enable new approaches to study the influence of genetic and anatomical variations on brain functions and disorders. Traditional association studies typically perform independent and pairwise analysis among neuroimaging measures, cognitive scores and disease status, and ignore the important underlying interacting relationships between these units. RESULTS: […]
OBJECTIVE: To investigate the vascular contribution to longitudinal changes in Alzheimer disease (AD) biomarkers. METHODS: The Alzheimer’s Disease Neuroimaging Initiative is a clinic based, longitudinal study with CSF, PET, and MRI biomarkers repeatedly measured in participants with normal cognition (NC), mild cognitive impairment (MCI), and mild AD. Participants with severe cerebrovascular risks were excluded. Cardiovascular […]