Robyn A Honea | University of Kansas Medical Center (original) (raw)

Papers by Robyn A Honea

Alzheimer's & Dementia, 2021

Introduction: Fasting glucose increases with age and is linked to modifiable Alzheimer's disease ... more Introduction: Fasting glucose increases with age and is linked to modifiable Alzheimer's disease risk factors such as cardiovascular disease and Type 2 diabetes (T2D). Methods: We leveraged available biospecimens and neuroimaging measures collected during the Alzheimer's Prevention Through Exercise (APEx) trial (n = 105) to examine the longitudinal relationship between change in blood glucose metabolism and change in regional cerebral amyloid deposition and gray and white matter (WM) neurodegeneration in older adults over 1 year of follow-up. Results: Individuals with improving fasting glucose (n = 61) exhibited less atrophy and regional amyloid accumulation compared to those whose fasting glucose worsened over 1 year (n = 44). Specifically, while individuals with increasing fasting glucose did not yet show cognitive decline, they did have regional atrophy in the hippocampus and inferior parietal cortex, and increased amyloid accumulation in the precuneus cortex. Signs of early dementia pathology occurred in the absence of significant group differences in insulin or body composition, and was not modified by apolipoprotein E ε4 carrier status. Discussion: Dysregulation of glucose in late life may signal preclinical brain change prior to clinically relevant cognitive decline. Additional work is needed to determine whether treatments specifically targeting fasting glucose levels may impact change in brain structure or cerebral amyloid in older adults.

Journal of Alzheimer's Disease, 2023

Background: First-degree relatives of individuals with late-onset Alzheimer's disease (AD) have i... more Background: First-degree relatives of individuals with late-onset Alzheimer's disease (AD) have increased risk for AD, with children of affected parents at an especially high risk. Objective: We aimed to investigate default mode network connectivity, medial temporal cortex volume, and cognition in cognitively healthy (CH) individuals with (FH+) and without (FH-) a family history of AD, alongside amnestic mild cognitive impairment (aMCI) and AD individuals, to determine the context and directionality of dysfunction in at-risk individuals. Our primary hypothesis was that there would be a linear decline (CH FH-> CH FH+ > aMCI > AD) within the risk groups on all measures of AD risk. Methods: We used MRI and fMRI to study cognitively healthy individuals (n = 28) with and without AD family history (FH+ and FH-, respectively), those with aMCI (n = 31) and early-stage AD (n = 25). We tested connectivity within the default mode network, as well as measures of volume and thickness within the medial temporal cortex and selected seed regions. Results: As expected, we identified decreased medial temporal cortex volumes in the aMCI and AD groups compared to cognitively healthy groups. We also observed patterns of connectivity across risk groups that suggest a nonlinear relationship of change, such that the FH+ group showed increased connectivity compared to the FH-and AD groups (CH FH+ > CH FH-> aMCI > AD). This pattern emerged primarily in connectivity between the precuneus and frontal regions. Conclusion: These results add to a growing literature that suggests compensatory brain function in otherwise cognitively healthy individuals with a family history of AD.

This paper was submitted directly (Track II) to the PNAS office.

The International journal of neuroscience, 2010

We compared white matter integrity with brain atrophy in healthy controls and participants with v... more We compared white matter integrity with brain atrophy in healthy controls and participants with very mild dementia (Clinical Dementia Rating 0 vs. 0.5) from the Brain Aging Project, a longitudinal study of aging and memory at the University of Kansas Medical Center. Structural magnetic resonance imaging and diffusion tensor imaging (DTI) including fractional anisotropy and mean diffusivity were performed on 27 patients with very mild dementia (Clinical Dementia Rating = 0.5) of the Alzheimer's type (DAT), and 32 cognitively normal subjects. Patient groups were compared across 6 volumetric measures and 14 DTI regions of interest. Very mildly demented patients showed expected disease-related patterns of brain atrophy with reductions in whole-brain and hippocampal volumes most prominent. DTI indices of white matter integrity were mixed. Right parahippocampus showed significant but small disease-related reductions in fractional anisotropy. Right parahippocampus and left internal cap...

Journal of Neuroscience, 2007

Regulator of G-protein signaling 4 (RGS4) modulates postsynaptic signal transduction by affecting... more Regulator of G-protein signaling 4 (RGS4) modulates postsynaptic signal transduction by affecting the kinetics of G alpha-GTP binding. Linkage, association, and postmortem studies have implicated the gene encoding RGS4 (RGS4) as a schizophrenia susceptibility factor. Using a multimodal neuroimaging approach, we demonstrate that genetic variation in RGS4 is associated with functional activation and connectivity during working memory in the absence of overt behavioral differences, with regional gray and white matter volume and with gray matter structural connectivity in healthy human subjects. Specifically, variation at one RGS4 single nucleotide polymorphism that has been associated previously with psychosis (rs951436) impacts frontoparietal and frontotemporal blood oxygenation level-dependent response and network coupling during working memory and results in regionally specific reductions in gray and white matter structural volume in individuals carrying the A allele. These findings suggest mechanisms in brain for the association of RGS4 with risk for psychiatric illness.

Psychiatry Research: Neuroimaging, 2006

The characterization of measurement error is critical in assessing the significance of diffusion ... more The characterization of measurement error is critical in assessing the significance of diffusion tensor imaging (DTI) findings in longitudinal and cohort studies of psychiatric disorders. We studied 20 healthy volunteers each one scanned twice (average interval between scans of 51 ± 46.8 days) with a single shot echo planar DTI technique. Inter-session variability for fractional anisotropy (FA) and Trace (D) was represented as absolute variation (standard deviation within subjects: SDw), percent coefficient of variation (CV) and intra-class correlation coefficient (ICC). The values from the two sessions were compared for statistical significance with repeated measures ANOVA or a nonparametric equivalent of a paired t-test. The results show good reproducibility for both FA and Trace (CVs below 10% and ICCs at or above 0.70 in most regions of interest) and evidence of systematic global changes in Trace between scans. The regional distribution of reproducibility described here has implications for interpretation of regional findings and for rigorous pre-processing. The regional distribution of reproducibility measures was different for SDw, CV and ICC. Each one of these measures reveals complementary information that needs to be taken into consideration when performing statistical operations on groups of DTI images.

Proceedings of the National Academy of Sciences, 2008

performed research; M.M. and A. Miyake contributed new reagents/analytic tools; M.M., R.E.S., S.

Journal of the American Dietetic Association, 1993

Journal of Public Health, 2006

The question as to whether fitness should be assessed in a European health monitoring system, per... more The question as to whether fitness should be assessed in a European health monitoring system, perhaps from the early stages of life onwards, remains to be answered. We aimed to examine the associations between cardiorespiratory fitness and metabolic risk factors in children. A total of 873 healthy children from Sweden and Estonia aged 9–10 years (444 girls and 429 boys)

Journal of Clinical Investigation, 2008

AKT1-dependent molecular pathways control diverse aspects of cellular development and adaptation,... more AKT1-dependent molecular pathways control diverse aspects of cellular development and adaptation, including interactions with neuronal dopaminergic signaling. If AKT1 has an impact on dopaminergic signaling, then genetic variation in AKT1 would be associated with brain phenotypes related to cortical dopaminergic function. Here, we provide evidence that a coding variation in AKT1 that affects protein expression in human B lymphoblasts influenced several brain measures related to dopaminergic function. Cognitive performance linked to frontostriatal circuitry, prefrontal physiology during executive function, and frontostriatal graymatter volume on MRI were altered in subjects with the AKT1 variation. Moreover, on neuroimaging measures with a main effect of the AKT1 genotype, there was significant epistasis with a functional polymorphism (Val158Met) in catechol-O-methyltransferase [COMT], a gene that indexes cortical synaptic dopamine. This genetic interaction was consistent with the putative role of AKT1 in dopaminergic signaling. Supportive of an earlier tentative association of AKT1 with schizophrenia, we also found that this AKT1 variant was associated with risk for schizophrenia. These data implicate AKT1 in modulating human prefrontal-striatal structure and function and suggest that the mechanism of this effect may be coupled to dopaminergic signaling and relevant to the expression of psychosis.

Biological Psychiatry, 2008

Background: Shared neuropathological characteristics of patients with schizophrenia and their sib... more Background: Shared neuropathological characteristics of patients with schizophrenia and their siblings might represent intermediate phenotypes that could be used to investigate genetic susceptibility to the illness. We sought to discover previously unidentified gray matter volume differences in patients with schizophrenia and their siblings with optimized voxel-based morphometry.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2012

We assessed the relationship of insulin resistance with cognitive decline and brain atrophy over ... more We assessed the relationship of insulin resistance with cognitive decline and brain atrophy over two years in early Alzheimer's disease (AD, n=48) and nondemented controls (n=61). Intravenous glucose tolerance tests were conducted at baseline to determine insulin area-under-the-curve (AUC). A standard battery of cognitive tasks and MRI were conducted at baseline and 2-year follow-up. In nondemented controls, higher baseline insulin AUC was associated with 2-year decline in global cognitive performance (beta=−0.36, p=0.005). In early AD, however, higher insulin AUC was associated with less decline in global cognitive performance (beta=0.26, p=0.06), slower global brain atrophy (beta=0.40, p=0.01) and less regional atrophy in the bilateral hippocampi and cingulate cortices. While insulin resistance is associated with cognitive decline in nondemented aging, higher peripheral insulin may have AD-specific benefits or insulin signaling may be affected by systemic physiologic changes associated with AD.

Archives of Physical Medicine and Rehabilitation, 2011

To examine exercise testing response in Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp... more To examine exercise testing response in Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD) and possible disease-related change over time. Retrospective assessment of a 2-year observational study. University medical center. Individuals without dementia (n=50) and with AD (n=31). Not applicable. Participants underwent a clinical dementia evaluation and performed an incremental exercise test using a treadmill and the modified Bruce protocol at baseline and at a 2-year follow-up. We examined oxygen consumption, minute ventilation, heart rate, and ventilatory equivalents for oxygen and carbon dioxide at submaximal and peak exercise intensities to determine whether the measures were different between groups or over time. Participants with AD and those without dementia performed similarly at submaximal effort, and both groups showed similar changes in exercise response over 2 years. However, nondemented individuals had consistently higher values of oxygen consumption (P≤.02) and minute ventilation at peak effort at baseline (P=.003). Individuals with AD demonstrate physiologic responses to submaximal exercise effort that are not significantly different than individuals without dementia. However, differences are apparent at the extreme of effort.

American Journal of Psychiatry, 2005

Voxel-based morphometry is a method for detecting group differences in the density or volume of b... more Voxel-based morphometry is a method for detecting group differences in the density or volume of brain matter. The authors reviewed the literature on use of voxel-based morphometry in schizophrenia imaging research to examine the capabilities of this method for clearly identifying specific structural differences in patients with schizophrenia, compared with healthy subjects. The authors looked for consistently reported results of relative deficits in gray and white matter in schizophrenia and evaluated voxel-based morphometry methods in order to propose a future strategy for using voxel-based morphometry in schizophrenia research. The authors reviewed all voxel-based morphometry studies of schizophrenia that were published to May 2004 (15 studies). The studies included a total of 390 patients with a diagnosis of schizophrenia and 364 healthy volunteers. Gray and white matter deficits in patients with schizophrenia, relative to healthy comparison subjects, were reported in a total of 50 brain regions. Deficits were reported in two of the 50 regions in more than 50% of the studies and in nine of the 50 regions in one study only. The most consistent findings were of relative deficits in the left superior temporal gyrus and the left medial temporal lobe. Use of a smaller smoothing kernel (4-8 mm) led to detection of a greater number of regions implicated in schizophrenia. This review implicates the left superior temporal gyrus and the left medial temporal lobe as key regions of structural difference in patients with schizophrenia, compared to healthy subjects. The diversity of regions reported in voxel-based morphometry studies is in part related to the choice of variables in the automated process, such as smoothing kernel size and linear versus affine transformation, as well as to differences in patient groups. Voxel-based morphometry can be used as an exploratory whole-brain approach to identify abnormal brain regions in schizophrenia, which should then be validated by using region-of-interest analyses.

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2012

Objective-Despite behavioral differences between genetic subtypes of Prader-Willi syndrome, no st... more Objective-Despite behavioral differences between genetic subtypes of Prader-Willi syndrome, no studies have been published characterizing brain structure in these subgroups. Our goal was to examine differences in the brain structure phenotype of common subtypes of Prader-Willi syndrome (PWS) [chromosome 15q deletions and maternal uniparental disomy 15 (UPD)].

Alzheimer's & Dementia, 2012

Alzheimer's & Dementia, 2013

lower brain volumes in the frontal and occipital lobes 2. We examined the influence of the obesit... more lower brain volumes in the frontal and occipital lobes 2. We examined the influence of the obesity associated SNP rs17817449 in FTO on longitudinal changes in brain volume in non-demented older individuals within the Baltimore Longitudinal Study of Aging (BLSA). We hypothesized that obesityassociated risk allele carriers of the FTO gene would show faster rates of brain atrophy relative to non-carriers. Methods: Non-demented individuals (N¼120; mean baseline age 70.5 years) received annual volumetric MRI (826 MRI scans in total) over a mean six-year interval and underwent genome-wide genotyping. Linear mixed effects models were used in a region of interest approach to examine differences in longitudinal rates of change in brain volumes between obesity-associated risk allele carriers and non-carriers of rs17817449. The analyses were adjusted for sex, age, APOE genotype and average body mass index (BMI) over the follow-up interval. Results: There were 72 individuals in the risk group and 48 in the nonrisk group. The minor allele frequency was 0.41. There were no differences between the two groups in APOE ε 4 carrier status and average BMI. We did not observe any differences in global, lobar or regional brain volumes at baseline. Risk allele carriers showed significantly greater rates of decline in volume in the cuneus (one-tailed p¼0.001; Bonferroni corrected p¼0.038) relative to the non-risk group. Conclusions: Non-demented older individuals carrying one or more copies of the obesity-related SNP rs17817449 in the FTO gene show greater rates of brain atrophy within the cuneus of the occipital lobe. Together with previous cross-sectional findings of reduced occipital lobe volume in risk allele carriers, these results suggest that the FTO gene influences regional vulnerability to rates of brain atrophy during aging.1.

Alzheimer's & Dementia, 2011