Biomedical subjects

John Kornak

Publications and source records attributed to John Kornak.

8 recordsLinked to original sources

PubMed2025

Brain aging rejuvenation factors in adults with genetic and sporadic neurodegenerative disease.

The largest risk factor for dementia is age. Heterochronic blood exchange studies have uncovered age-related blood factors that demonstrate 'pro-aging' or 'pro-youthful' effects on the mouse brain. The clinical relevance and combined effects of these factors for humans is unclear. We examined five previously identified brain rejuvenation factors in cerebrospinal fluid of adults with autosomal dominant forms of frontotemporal dementia and sporadic Alzheimer's disease. Our frontotemporal dementia cohort included 100 observationally followed adults carrying autosomal dominant frontotemporal dementia mutations (Mage = 49.6; 50% female; 43% C9orf72, 24% GRN, 33% MAPT) and 62 non-carriers (Mage = 52.6; 45% female) with cerebrospinal fluid analysed on Somascan, and longitudinal (Mvisits = 3 years, range 1-7 years) neuropsychological and functional assessments and plasma neurofilament light chain. Our Alzheimer's disease cohort included 35 adults with sporadic Alzheimer's disease (Mage = 69.4; 60% female) and 56 controls (Mage = 68.8, 50% female) who completed the same cerebrospinal fluid and clinical outcome measures cross-sectionally. Levels of C-C motif chemokine ligand 11, C-C motif chemokine ligand 2, beta-2-micorglobulin, bone gamma-carboxyglutamate protein (aka Osteocalcin) and colony stimulating factor 2 in cerebrospinal fluid were linearly combined into a composite score, with higher values reflecting 'pro-youthful' levels. In genetic frontotemporal dementia, higher baseline cerebrospinal fluid rejuvenation proteins predicted slower decline across cognitive, functional, and neurofilament light chain trajectories; estimates were similar across genotypes. In transdiagnostic analyses, higher cerebrospinal fluid rejuvenation proteins associated with better functional, cognitive, and neurofilament light chain outcomes in adults with sporadic Alzheimer's disease. Proteins with pre-clinical evidence for brain rejuvenation show translational clinical relevance in adults with Alzheimer's disease and related dementias and warrant further investigation.

Alzheimer’s disease↗

PubMed2006

Longitudinal stability of MRI for mapping brain change using tensor-based morphometry.

Measures of brain change can be computed from sequential MRI scans, providing valuable information on disease progression, e.g., for patient monitoring and drug trials. Tensor-based morphometry (TBM) creates maps of these brain changes, visualizing the 3D profile and rates of tissue growth or atrophy, but its sensitivity depends on the contrast and geometric stability of the images. As part of the Alzheimer's Disease Neuroimaging Initiative (ADNI), 17 normal elderly subjects were scanned twice (at a 2-week interval) with several 3D 1.5 T MRI pulse sequences: high and low flip angle SPGR/FLASH (from which Synthetic T1 images were generated), MP-RAGE, IR-SPGR (N = 10) and MEDIC (N = 7) scans. For each subject and scan type, a 3D deformation map aligned baseline and follow-up scans, computed with a nonlinear, inverse-consistent elastic registration algorithm. Voxelwise statistics, in ICBM stereotaxic space, visualized the profile of mean absolute change and its cross-subject variance; these maps were then compared using permutation testing. Image stability depended on: (1) the pulse sequence; (2) the transmit/receive coil type (birdcage versus phased array); (3) spatial distortion corrections (using MEDIC sequence information); (4) B1-field intensity inhomogeneity correction (using N3). SPGR/FLASH images acquired using a birdcage coil had least overall deviation. N3 correction reduced coil type and pulse sequence differences and improved scan reproducibility, except for Synthetic T1 images (which were intrinsically corrected for B1-inhomogeneity). No strong evidence favored B0 correction. Although SPGR/FLASH images showed least deviation here, pulse sequence selection for the ADNI project was based on multiple additional image analyses, to be reported elsewhere.

Aged↗

PubMed2006

A non-parametric approach for co-analysis of multi-modal brain imaging data: application to Alzheimer's disease.

We developed a new flexible approach for a co-analysis of multi-modal brain imaging data using a non-parametric framework. In this approach, results from separate analyses on different modalities are combined using a combining function and assessed with a permutation test. This approach identifies several cross-modality relationships, such as concordance and dissociation, without explicitly modeling the correlation between modalities. We applied our approach to structural and perfusion MRI data from an Alzheimer's disease (AD) study. Our approach identified areas of concordance, where both gray matter (GM) density and perfusion decreased together, and areas of dissociation, where GM density and perfusion did not decrease together. In conclusion, these results demonstrate the utility of this new non-parametric method to quantitatively assess the relationships between multiple modalities.

Aged↗

PubMed2005

Age effects on atrophy rates of entorhinal cortex and hippocampus.

The effects of age, subcortical vascular disease, apolipoprotein E (APOE) epsilon4 allele and hypertension on entorhinal cortex (ERC) and hippocampal atrophy rates were explored in a longitudinal MRI study with 42 cognitively normal (CN) elderly subjects from 58 to 87 years old. The volumes of the ERC, hippocampus, and white matter hyperintensities (WMH) and the presence of lacunes were assessed on MR images. Age was significantly associated with increased atrophy rates of 0.04+/-0.02% per year for ERC and 0.05+/-0.02% per year for hippocampus. Atrophy rates of hippocampus, but not that of ERC increased with presence of lacunes, in addition to age. WMH, APOE epsilon4 and hypertension had no significant effect on atrophy rates. In conclusion, age and presence of lacunes should be taken into consideration in imaging studies of CN subjects and AD patients to predict AD progression and assess the response to treatment trials.

Aged↗

PubMed2005

Summarizing complexity in high dimensions.

High-dimensional, multispectral data on complex physical systems are increasingly common. As the amount of information in data sets increases, the difficulty of effectively utilizing it also increases. For such data, summary information is required for understanding and modeling the underlying dynamics. It is here proposed to use an extension of computational mechanics [C. R. Shalizi and J. P. Crutchfield, J. Stat. Phys. 104, 817 (2001)] to arbitrary spatiotemporal and spectral dimension, for providing such summary information. An example of the use of these tools to identify state evolution in the brain, an archetypal, complex biophysical system, serves as an illustration.

Alzheimer Disease↗

PubMed2005

White matter lesions are associated with cortical atrophy more than entorhinal and hippocampal atrophy.

The goal of this study was to examine the relationship between subcortical vascular disease and brain atrophy in patients with Alzheimer's disease (AD) and mixed dementia (i.e., AD and subcortical vascular disease together). MRI was performed on 77 cognitively normal (CN) subjects, 50 AD and 13 mixed dementia patients. Subcortical vascular disease was determined by white matter hyperintensities (WMH) volume and presence of subcortical lacunes. Brain atrophy was measured using total brain cortical gray matter (CGM), entorhinal cortex (ERC) and hippocampal volumes. CGM volume, but not ERC or hippocampal volume was inversely related to WMH volume in patients and controls. In contrast, no relationship was detected between CGM, ERC, or hippocampal volumes and subcortical lacunes. Furthermore, no interaction was found between WMH and diagnosis on cortical atrophy, implying that WMH affect cortical atrophy indifferently of group. These results suggest that subcortical vascular disease, manifested as WMH, may affect cortical atrophy more than ERC and hippocampal atrophy. Further, AD pathology and subcortical vascular disease may independently affect cortical atrophy.

Aged↗

PubMed2002

A method for determining venous contribution to BOLD contrast sensory activation.

While BOLD contrast reflects hemodynamic changes within capillaries serving neural tissue, it also has a venous component. Studies that have determined the relation of large blood vessels to the activation map indicate that veins are the source of the largest response, and the most delayed in time. It would be informative if the location of these large veins could be extracted from the properties of the functional responses, since vessels are not visible in BOLD contrast images. The present study describes a method for investigating whether measures taken from the functional response can reliably predict vein location, or at least be useful in down-weighting the venous contribution to the activation response, and illustrates this method using data from one subject. We combined fMRI at 3 Tesla with high-resolution anatomic imaging and MR venography to test whether the intrinsic properties of activation time courses corresponded to tissue type. Measures were taken from a gamma fit to the functional response. Mean magnitude showed a significant effect of tissue type (p < 0.001) where CSF > veins approximately gray matter > white matter. Mean delays displayed the same ranking across tissue types (p < 0.001), except that veins > gray matter. However, measures for all tissue types were distributed across an overlapping range. A logistic regression model correctly discriminated 72% of the veins from gray matter in the absence of independent information of macroscopic vessels (ROC = 0.72). While tissue classification was not perfect for this subject, weighting the T contrast by the predicted probabilities materially reduced the venous component to the activation map.

Adult↗

PubMedDate not supplied

Comparisons between global and focal brain atrophy rates in normal aging and Alzheimer disease: Boundary Shift Integral versus tracing of the entorhinal cortex and hippocampus.

The objectives of this study were to (1) compare atrophy rates associated with normal aging and Alzheimer disease (AD) using the semi-automated Boundary Shift Integral (BSI) method and manual tracing of the entorhinal cortex (ERC) and hippocampus and (2) calculate power of BSI vs. ERC and hippocampal volume changes for clinical trials in AD. We quantified whole brain and ventricular BSI atrophy rates and ERC and hippocampal atrophy rates from longitudinal MRI data in 20 AD patients and 22 age-matched healthy controls. All methods revealed significant brain atrophy in controls and AD patients. AD patients had approximately 2.5 times greater whole brain BSI atrophy rates and more than 5 times greater ERC and hippocampal atrophy rates than controls. ERC and hippocampal atrophy rates were higher in both groups than whole brain BSI atrophy rates, but lower than ventricular BSI atrophy rates. Effect size and power calculations suggest that ERC and hippocampal measurements may be more sensitive than ventricular or whole brain BSI for detecting AD progression and the potential effects of disease modifying agents. Logistic regression analysis revealed that combined rates of ERC and ventricular BSI were the best explanatory variables for classifying AD from controls.

Aged↗