Publications by authors named "Kristen M Kennedy"

75 Publications

The effect of vascular health factors on white matter microstructure mediates age-related differences in executive function performance.

Cortex 2021 08 25;141:403-420. Epub 2021 May 25.

The University of Texas at Dallas, School of Behavioral and Brain Sciences, Center for Vital Longevity, Dallas, TX, USA. Electronic address:

Even within healthy aging, vascular risk factors can detrimentally influence cognition, with executive functions (EF) particularly vulnerable. Fronto-parietal white matter (WM) connectivity in part, supports EF and may be particularly sensitive to vascular risk. Here, we utilized structural equation modeling in 184 healthy adults (aged 20-94 years of age) to test the hypotheses that: 1) fronto-parietal WM microstructure mediates age effects on EF; 2) higher blood pressure (BP) and white matter hyperintensity (WMH) burden influences this association. All participants underwent comprehensive cognitive and neuropsychological testing including tests of processing speed, executive function (with a focus on tasks that require switching and inhibition) and completed an MRI scanning session that included FLAIR imaging for semi-automated quantification of white matter hyperintensity burden and diffusion-weighted imaging for tractography. Structural equation models were specified with age (as a continuous variable) and blood pressure predicting within-tract WMH burden and fractional anisotropy predicting executive function and processing speed. Results indicated that fronto-parietal white matter of the genu of the corpus collosum, superior longitudinal fasciculus, and the inferior frontal occipital fasciculus (but not cortico-spinal tract) mediated the association between age and EF. Additionally, increased systolic blood pressure and white matter hyperintensity burden within these white matter tracts contribute to worsening white matter health and are important factors underlying age-brain-behavior associations. These findings suggest that aging brings about increases in both BP and WMH burden, which may be involved in the degradation of white matter connectivity and in turn, negatively impact executive functions as we age.
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http://dx.doi.org/10.1016/j.cortex.2021.04.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319097PMC
August 2021

Functional Connectivity Within and Between -Back Modulated Regions: An Adult Lifespan Psychophysiological Interaction Investigation.

Brain Connect 2021 03 10;11(2):103-118. Epub 2021 Feb 10.

Center for Vital Longevity, School of Behavioral and Brain Science, The University of Texas at Dallas, Dallas, Texas, USA.

Working memory (WM) and its blood-oxygen-level-dependent-related parametric modulation under load decrease with age. Functional connectivity (FC) generally increases with WM load; however, how aging impacts connectivity and whether this is load-dependent, region-dependent, or associated with cognitive performance is unclear. This study examines these questions in 170 healthy adults (mean = 52.99 ± 19.18) who completed functional magnetic resonance imaging scanning during an -back task (0-, 2-, 3-, and 4-back). The FC was estimated by utilizing a modified generalized psychophysiological interaction approach with seeds from fronto-parietal (FP) and default mode (DM) regions that modulated to -back difficulty. The FC analyses focused on both connectivity during WM engagement (task vs. control) and connectivity in response to increased WM load (linear slope across conditions). Each analysis utilized within- and between-region FC, predicted by age (linear or quadratic), and its associations with in- and out-of-scanner task performance. Engaging in WM either generally (task vs. control) or as a function of difficulty strengthened integration within- and between-FP and DM regions. Notably, these task-sensitive functional connections were robust to the effects of age. Stronger negative FC between FP and DM regions was also associated with better WM performance in an age-dependent manner, occurring selectively in middle-aged and older adults. These results suggest that FC is critical for engaging in cognitively demanding tasks, and its lack of sensitivity to healthy aging may provide a means to maintain cognition across the adult lifespan. Thus, this study highlights the contribution of maintenance in brain function to support working memory processing with aging.
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http://dx.doi.org/10.1089/brain.2020.0791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984940PMC
March 2021

Cortical thickness mediates the relationship between DRD2 C957T polymorphism and executive function across the adult lifespan.

Brain Struct Funct 2021 Jan 11;226(1):121-136. Epub 2020 Nov 11.

Center for Vital Longevity, School of Behavioral and Brain Science, The University of Texas At Dallas, Dallas, TX, USA.

Dopamine (DA) signaling is critical for optimal cognitive performance. Aging is accompanied by a change in the strength of this signaling, with a loss of striatal and extrastriatal D2 binding potential. The reduction in dopamine modulation with age negatively influences various aspects of cognition. DRD2 C957T (rs6277) impacts DA D2 receptor density and availability, with C homozygotes linked to lower striatal DA availability and reduced executive functioning (EF), but also high extrastriatal binding potential. Here, we investigated in 176 participants aged 20-94 years whether: (1) DRD2 C carriers differ from T carriers in cortical thickness or subcortical volume in areas of high concentrations of D2 receptors that receive projections from mesocortical or nigrostriatal dopaminergic pathways; (2) whether the DRD2*COMT relationship has any synergistic effects on cortical thickness; (3) whether the effect of DRD2 on brain structure depends upon age; and (4) whether DRD2-related regional thinning affects executive function performance. We show that DRD2 impacts cortical thickness in the superior parietal lobule, precuneus, and anterior cingulate (marginal after FDR correction), while statistically controlling sex, age, and COMT genotype. Specifically, C homozygotes demonstrated thinner cortices than both heterozygotes and/or T homozygotes in an age-invariant manner. Additionally, DRD2 predicted executive function performance via cortical thickness. The results highlight that genetic influences on dopamine availability impact cognitive performance via the contribution of brain structure in cortical regions influenced by DRD2.
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http://dx.doi.org/10.1007/s00429-020-02169-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855542PMC
January 2021

Influence of sample size and analytic approach on stability and interpretation of brain-behavior correlations in task-related fMRI data.

Hum Brain Mapp 2021 01 30;42(1):204-219. Epub 2020 Sep 30.

Center for Vital Longevity, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, Texas, USA.

Limited statistical power due to small sample sizes is a problem in fMRI research. Most of the work to date has examined the impact of sample size on task-related activation, with less attention paid to the influence of sample size on brain-behavior correlations, especially in actual experimental fMRI data. We addressed this issue using two large data sets (a working memory task, N = 171, and a relational processing task, N = 865) and both univariate and multivariate approaches to voxel-wise correlations. We created subsamples of different sizes and calculated correlations between task-related activity at each voxel and task performance. Across both data sets the magnitude of the brain-behavior correlations decreased and similarity across spatial maps increased with larger sample sizes. The multivariate technique identified more extensive correlated areas and more similarity across spatial maps, suggesting that a multivariate approach would provide a consistent advantage over univariate approaches in the stability of brain-behavior correlations. In addition, the multivariate analyses showed that a sample size of roughly 80 or more participants would be needed for stable estimates of correlation magnitude in these data sets. Importantly, a number of additional factors would likely influence the choice of sample size for assessing such correlations in any given experiment, including the cognitive task of interest and the amount of data collected per participant. Our results provide novel experimental evidence in two independent data sets that the sample size commonly used in fMRI studies of 20-30 participants is very unlikely to be sufficient for obtaining reproducible brain-behavior correlations, regardless of analytic approach.
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http://dx.doi.org/10.1002/hbm.25217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721240PMC
January 2021

Contribution of iron and Aβ to age differences in entorhinal and hippocampal subfield volume.

Neurology 2020 11 16;95(18):e2586-e2594. Epub 2020 Sep 16.

From the School of Behavioral and Brain Sciences (C.M.F., K.M.K., K.M.R.), Center for Vital Longevity, University of Texas at Dallas; and Department of Psychology (A.M.D.) and Department of Psychiatry and Behavioral Neurosciences, Institute of Gerontology, Wayne State University, Detroit, MI.

Objective: To test the hypothesis that the combination of elevated global β-AMYLOID (Aβ) burden and greater striatal iron content would be associated with smaller entorhinal cortex (ERC) volume, but not hippocampal subfield volumes, we measured volume and iron content using high-resolution MRI and Aβ using PET imaging in a cross-sectional sample of 70 cognitively normal older adults.

Methods: Participants were scanned with florbetapir F PET to obtain Aβ standardized uptake value ratios. Susceptibility-weighted MRI was collected and processed to yield R2* images, and striatal regions of interest (ROIs) were manually placed to obtain a measure of striatal iron burden. Ultra-high resolution T2/PD-weighted MRIs were segmented to measure medial temporal lobe (MTL) volumes. Analyses were conducted using mixed-effects models with MTL ROI as a within-participant factor; age, iron content, and Aβ as between-participant factors; and MTL volumes (ERC and 3 hippocampal subfield regions) as the dependent variable.

Results: The model indicated a significant 4-way interaction among age, iron, Aβ, and MTL region. Post hoc analyses indicated that the 3-way interaction among age, Aβ, and iron content was selective to the ERC (β = -3.34, standard error = 1.33, 95% confidence interval -5.95 to -0.72), whereas a significant negative association between age and ERC volume was present only in individuals with both elevated iron content and Aβ.

Conclusions: These findings highlight the importance of studying Aβ in the context of other, potentially synergistic age-related brain factors such as iron accumulation and the potential role for iron as an important contributor to the earliest, preclinical stages of pathologic aging.
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http://dx.doi.org/10.1212/WNL.0000000000010868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682827PMC
November 2020

Greater BOLD Variability is Associated With Poorer Cognitive Function in an Adult Lifespan Sample.

Cereb Cortex 2021 Jan;31(1):562-574

Center for Vital Longevity, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, TX 75235, USA.

Moment-to-moment fluctuations in brain signal assessed by functional magnetic resonance imaging blood oxygenation level dependent (BOLD) variability is increasingly thought to represent important "signal" rather than measurement-related "noise." Efforts to characterize BOLD variability in healthy aging have yielded mixed outcomes, demonstrating both age-related increases and decreases in BOLD variability and both detrimental and beneficial associations. Utilizing BOLD mean-squared-successive-differences (MSSD) during a digit n-back working memory (WM) task in a sample of healthy adults (aged 20-94 years; n = 171), we examined effects of aging on whole-brain 1) BOLD variability during task (mean condition MSSD across 0-2-3-4 back conditions), 2) BOLD variability modulation to incrementally increasing WM difficulty (linear slope from 0-2-3-4 back), and 3) the association of age-related differences in variability with in- and out-of-scanner WM performance. Widespread cortical and subcortical regions evidenced increased mean variability with increasing age, with no regions evidencing age-related decrease in variability. Additionally, posterior cingulate/precuneus exhibited increased variability to WM difficulty. Notably, both age-related increases in BOLD variability were associated with significantly poorer WM performance in all but the oldest adults. These findings lend support to the growing corpus suggesting that brain-signal variability is altered in healthy aging; specifically, in this adult lifespan sample, BOLD-variability increased with age and was detrimental to cognitive performance.
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http://dx.doi.org/10.1093/cercor/bhaa243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727366PMC
January 2021

Beta-amyloid burden predicts poorer mnemonic discrimination in cognitively normal older adults.

Neuroimage 2020 11 29;221:117199. Epub 2020 Jul 29.

Center for Vital Longevity, School of Behavioral and Brain Sciences, The University of Texas at Dallas, 1600 Viceroy Dr., Suite 800, Dallas, TX 75235, USA. Electronic address:

One of the earliest indicators of Alzheimer's disease pathology is the presence of beta-amyloid (Αβ) protein deposition. Significant amyloid deposition is evident even in older adults who exhibit little or no overt cognitive or memory impairment. Hippocampal-based processes that help distinguish between highly similar memory representations may be the most susceptible to early disease pathology. Amyloid associations with memory have been difficult to establish, possibly because typical memory assessments do not tax hippocampal operations sufficiently. Thus, the present study utilized a spatial mnemonic discrimination task designed to tax hippocampal pattern separation/completion processes in a sample of cognitively normal middle-aged and older adults (53-98 years old) who underwent PET F-Florbetapir Αβ scanning. The degree of interference between studied and new information varied, allowing for an examination of mnemonic discrimination as a function of mnemonic similarity. Results indicated that greater beta-amyloid burden was associated with poorer discrimination across decreasing levels of interference, suggesting that even subtle elevation of beta-amyloid in cognitively normal adults is associated with impoverished performance on a hippocampally demanding memory task. The present study demonstrates that degree of amyloid burden negatively impacts the ability of aging adults to accurately distinguish old from increasingly distinct new information, providing novel insight into the cognitive expression of beta-amyloid neuropathology.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813158PMC
November 2020

Frontostriatal white matter connectivity: age differences and associations with cognition and BOLD modulation.

Neurobiol Aging 2020 10 7;94:154-163. Epub 2020 Jun 7.

Center for Vital Longevity, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, TX, USA. Electronic address:

Despite the importance of cortico-striatal circuits to cognition, investigation of age effects on the structural circuitry connecting these regions is limited. The current study examined age effects on frontostriatal white matter connectivity, and identified associations with both executive function performance and dynamic modulation of blood-oxygen-level-dependent (BOLD) activation to task difficulty in a lifespan sample of 169 healthy humans aged 20-94 years. Greater frontostriatal diffusivity was associated with poorer executive function and this negative association strengthened with increasing age. Whole-brain functional magnetic resonance imaging (fMRI) analyses additionally indicated an association between frontostriatal mean diffusivity and BOLD modulation to difficulty selectively in the striatum across 2 independent fMRI tasks. This association was moderated by age, such that younger- and middle-aged individuals showed reduced dynamic range of difficulty modulation as a function of increasing frontostriatal diffusivity. Together these results demonstrate the importance of age-related degradation of frontostriatal circuitry on executive functioning across the lifespan, and highlight the need to capture brain changes occurring in early-to middle-adulthood.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.05.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483315PMC
October 2020

White Matter Microstructure Predicts Focal and Broad Functional Brain Dedifferentiation in Normal Aging.

J Cogn Neurosci 2020 08 14;32(8):1536-1549. Epub 2020 Apr 14.

The University of Texas at Dallas.

Ventral visual cortex exhibits highly organized and selective patterns of functional activity associated with visual processing. However, this specialization decreases in normal aging, with functional responses to different visual stimuli becoming more similar with age, a phenomenon termed "dedifferentiation." The current study tested the hypothesis that age-related degradation of the inferior longitudinal fasciculus (ILF), a white matter pathway involved in visual perception, could account for dedifferentiation of both localized and distributed brain activity in ventral visual cortex. Participants included 281 adults, ages 20-89 years, from the Dallas Lifespan Brain Study who underwent diffusion-weighted imaging to measure white matter diffusivity, as well as fMRI to measure functional selectivity to viewing photographs from different categories (e.g., faces, houses). In general, decreased ILF anisotropy significantly predicted both focal and broad functional dedifferentiation. Specifically, there was a localized effect of structure on function, such that decreased anisotropy in a smaller mid-fusiform region of ILF predicted less selective (i.e., more dedifferentiated) response to viewing faces in a proximal face-responsive region of fusiform. On the other hand, the whole ILF predicted less selective response across broader ventral visual cortex for viewing animate (e.g., human faces, animals) versus inanimate (e.g., houses, chairs) images. This structure-function relationship became weaker with age and was no longer significant after the age of 70 years. These findings indicate that decreased white matter anisotropy is associated with maladaptive differences in proximal brain function and is an important variable to consider when interpreting age differences in functional selectivity.
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http://dx.doi.org/10.1162/jocn_a_01562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098673PMC
August 2020

Striatal iron content is linked to reduced fronto-striatal brain function under working memory load.

Neuroimage 2020 04 20;210:116544. Epub 2020 Jan 20.

Center for Vital Longevity, School of Behavioral and Brain Science, The University of Texas at Dallas, Dallas, TX, USA.

Non-heme iron accumulation contributes to age-related decline in brain structure and cognition via a cascade of oxidative stress and inflammation, although its effect on brain function is largely unexplored. Thus, we examine the impact of striatal iron on dynamic range of BOLD modulation to working memory load. N ​= ​166 healthy adults (age 20-94) underwent cognitive testing and an imaging session including n-back (0-, 2-, 3-, and 4-back fMRI), R2*-weighted imaging, and pcASL to measure cerebral blood flow. A statistical model was constructed to predict voxelwise BOLD modulation by age, striatal iron content and an age ​× ​iron interaction, controlling for cerebral blood flow, sex, and task response time. A significant interaction between age and striatal iron content on BOLD modulation was found selectively in the putamen, caudate, and inferior frontal gyrus. Greater iron was associated with reduced modulation to difficulty, particularly in middle-aged and younger adults with greater iron content. Further, iron-related decreases in modulation were associated with poorer executive function in an age-dependent manner. These results suggest that iron may contribute to differences in functional brain activation prior to older adulthood, highlighting the potential role of iron as an early factor contributing to trajectories of functional brain aging.
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http://dx.doi.org/10.1016/j.neuroimage.2020.116544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054151PMC
April 2020

Contributions of White Matter Connectivity and BOLD Modulation to Cognitive Aging: A Lifespan Structure-Function Association Study.

Cereb Cortex 2020 03;30(3):1649-1661

Center for Vital Longevity, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, TX 75235, USA.

The ability to flexibly modulate brain activation to increasing cognitive challenge decreases with aging. This age-related decrease in dynamic range of function of regional gray matter may be, in part, due to age-related degradation of regional white matter tracts. Here, a lifespan sample of 171 healthy adults (aged 20-94) underwent magnetic resonance imaging (MRI) scanning including diffusion-weighted imaging (for tractography) and functional imaging (a digit n-back task). We utilized structural equation modeling to test the hypothesis that age-related decrements in white matter microstructure are associated with altered blood-oxygen-level-dependent (BOLD) modulation, and both in turn, are associated with scanner-task accuracy and executive function performance. Specified structural equation model evidenced good fit, demonstrating that increased age negatively affects n-back task accuracy and executive function performance in part due to both degraded white matter tract microstructure and reduced task-difficulty-related BOLD modulation. We further demonstrated that poorer white matter microstructure integrity was associated with weakened BOLD modulation, particularly in regions showing positive modulation effects, as opposed to negative modulation effects. This structure-function association study provides further evidence that structural connectivity influences functional activation, and the two mechanisms in tandem are predictive of cognitive performance, both during the task, and for cognition measured outside the scanner environment.
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http://dx.doi.org/10.1093/cercor/bhz193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132902PMC
March 2020

Joint contributions of cortical morphometry and white matter microstructure in healthy brain aging: A partial least squares correlation analysis.

Hum Brain Mapp 2019 12 26;40(18):5315-5329. Epub 2019 Aug 26.

Center for Vital Longevity, The University of Texas at Dallas, School of Behavioral and Brain Sciences, Dallas, Texas.

Cortical atrophy and degraded axonal health have been shown to coincide during normal aging; however, few studies have examined these measures together. To lend insight into both the regional specificity and the relative timecourse of structural degradation of these tissue compartments across the adult lifespan, we analyzed gray matter (GM) morphometry (cortical thickness, surface area, volume) and estimates of white matter (WM) microstructure (fractional anisotropy, mean diffusivity) using traditional univariate and more robust multivariate techniques to examine age associations in 186 healthy adults aged 20-94 years old. Univariate analysis of each tissue type revealed that negative age associations were largest in frontal GM and WM tissue and weaker in temporal, cingulate, and occipital regions, representative of not only an anterior-to-posterior gradient, but also a medial-to-lateral gradient. Multivariate partial least squares correlation (PLSC) found the greatest covariance between GM and WM was driven by the relationship between WM metrics in the anterior corpus callosum and projections of the genu, anterior cingulum, and fornix; and with GM thickness in parietal and frontal regions. Surface area was far less susceptible to age effects and displayed less covariance with WM metrics, while regional volume covariance patterns largely mirrored those of cortical thickness. Results support a retrogenesis-like model of aging, revealing a coupled relationship between frontal and parietal GM and the underlying WM, which evidence the most protracted development and the most vulnerability during healthy aging.
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http://dx.doi.org/10.1002/hbm.24774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864896PMC
December 2019

Current themes and issues in neuroimaging of aging processes: Editorial overview to the special issue on imaging the nonpathological aging brain.

Neuroimage 2019 11 31;201:116046. Epub 2019 Jul 31.

School of Behavioral and Brain Sciences, Center for Vital Longevity, The University of Texas at Dallas, USA. Electronic address:

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http://dx.doi.org/10.1016/j.neuroimage.2019.116046DOI Listing
November 2019

The role of hippocampal subfield volume and fornix microstructure in episodic memory across the lifespan.

Hippocampus 2019 12 23;29(12):1206-1223. Epub 2019 Jul 23.

Center for Vital Longevity, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, Texas.

Advancing age is associated with both declines in episodic memory and degradation of medial temporal lobe (MTL) structure. The contribution of MTL to episodic memory is complex and depends upon the interplay among hippocampal subfields and surrounding structures that participate in anatomical connectivity to the cortex through inputs (parahippocampal and entorhinal cortices) and outputs (fornix). However, the differential contributions of MTL system components in mediating age effects on memory remain unclear. In a sample of 177 healthy individuals aged 20-94 we collected high-resolution T1-weighted, ultrahigh-resolution T2/PD, and diffusion tensor imaging (DTI) MRI sequences on a 3T Phillips Achieva scanner. Hippocampal subfield and entorhinal cortex (ERC) volumes were measured from T2/PD scans using a combination of manual tracings and training of a semiautomated pipeline. Parahippocampal gyrus volume was estimated using Freesurfer and DTI scans were used to obtain diffusion metrics from tractography of the fornix. Item and associative episodic memory constructs were formed from multiple tests. Competing structural equation models estimating differential association among these structural variables were specified and tested to investigate whether and how fornix diffusion and volume of parahippocampal gyrus, ERC, and hippocampal subfields mediate age effects on associative and/or item memory. The most parsimonious, best-fitting model included an anatomically based path through the MTL as well as a single hippocampal construct which combined all subfields. Results indicated that fornix microstructure independently mediated the effect of age on associative memory, but not item memory. Additionally, all regions and estimated paths (including fornix) combined to significantly mediate the age-associative memory relationship. These findings suggest that preservation of fornix connectivity and MTL structure with aging is important for maintenance of associative memory performance across the lifespan.
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http://dx.doi.org/10.1002/hipo.23133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082831PMC
December 2019

Age moderates the relationship between cortical thickness and cognitive performance.

Neuropsychologia 2019 09 6;132:107136. Epub 2019 Jul 6.

Center for Vital Longevity and School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, TX, 75235, USA.

Findings from cross-sectional and longitudinal magnetic resonance imaging (MRI) studies indicate that cortical thickness declines across the adult lifespan, with regional differences in rate of decline. Global and regional thickness have also been found to co-vary with cognitive performance. Here we examined the relationships between age, mean cortical thickness, and associative recognition performance across three age groups (younger, middle-aged and older adults; total n = 133). Measures of cortical thickness were obtained using a semi-automated method. Older age was associated with decreased memory performance and a reduction in mean cortical thickness. After controlling for the potentially confounding effects of head motion, mean cortical thickness was negatively associated with associative memory performance in the younger participants, but was positively correlated with performance in older participants. A similar but weaker pattern was evident in the relationships between cortical thickness and scores on four cognitive constructs derived from a neuropsychological test battery. This pattern is consistent with prior findings indicating that the direction of the association between cortical thickness and cognitive performance reverses between early and later adulthood. In addition, head motion was independently and negatively correlated with associative recognition performance in younger and middle-aged, but not older, participants, suggesting that variance in head motion is determined by multiple factors that vary in their relative influences with age.
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http://dx.doi.org/10.1016/j.neuropsychologia.2019.107136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702041PMC
September 2019

Progress update from the hippocampal subfields group.

Alzheimers Dement (Amst) 2019 Dec 13;11:439-449. Epub 2019 Jun 13.

Department of Psychology, Florida State University, Tallahassee, FL, USA.

Introduction: Heterogeneity of segmentation protocols for medial temporal lobe regions and hippocampal subfields on magnetic resonance imaging hinders the ability to integrate findings across studies. We aim to develop a harmonized protocol based on expert consensus and histological evidence.

Methods: Our international working group, funded by the EU Joint Programme-Neurodegenerative Disease Research (JPND), is working toward the production of a reliable, validated, harmonized protocol for segmentation of medial temporal lobe regions. The working group uses a novel data set and online consensus procedures to ensure validity and facilitate adoption.

Results: This progress report describes the initial results and milestones that we have achieved to date, including the development of a draft protocol and results from the initial reliability tests and consensus procedures.

Discussion: A harmonized protocol will enable the standardization of segmentation methods across laboratories interested in medial temporal lobe research worldwide.
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http://dx.doi.org/10.1016/j.dadm.2019.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581847PMC
December 2019

Cortisol relates to regional limbic system structure in older but not younger adults.

Psychoneuroendocrinology 2019 03 14;101:111-120. Epub 2018 Sep 14.

School of Psychology, Georgia Institute of Technology, 654 Cherry Street, Atlanta, GA 30332-0170, United states. Electronic address:

We investigated if the relationship between age and regional limbic system brain structure would be moderated by diurnal cortisol output and diurnal cortisol slope. Participants aged 23-83 years collected seven salivary cortisol samples each day for 10 consecutive days and underwent magnetic resonance imaging. Age, sex, cortisol, and an age x cortisol interaction were tested as predictors of hippocampal and amygdalar volume and caudal and rostral anterior cingulate cortex (ACC) thickness. We found significant interactions between age and cortisol on left and right amygdalar volumes and right caudal ACC thickness. Older adults with higher cortisol output had smaller left and right amygdalar volumes than older adults with lower cortisol output and younger adults with higher cortisol output. Older and younger adults with lower cortisol output had similar amygdalar volumes. Older adults with a steeper decline in diurnal cortisol had a thicker right caudal ACC than younger adults with a similarly shaped cortisol slope. Hippocampal volume was not related to either cortisol slope or output, nor was pallidum volume which was assessed as an extra-limbic control region. Results suggest that subtle differences in cortisol output are related to differences in limbic system structure in older but not younger adults.
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http://dx.doi.org/10.1016/j.psyneuen.2018.09.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074622PMC
March 2019

Genetic predisposition for inflammation exacerbates effects of striatal iron content on cognitive switching ability in healthy aging.

Neuroimage 2019 01 25;185:471-478. Epub 2018 Oct 25.

Center for Vital Longevity, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, TX, USA. Electronic address:

Non-heme iron homeostasis interacts with inflammation bidirectionally, and both contribute to age-related decline in brain structure and function via oxidative stress. Thus, individuals with genetic predisposition for inflammation may be at greater risk for brain iron accumulation during aging and more vulnerable to cognitive decline. We examine this hypothesis in a lifespan sample of healthy adults (N = 183, age 20-94 years) who underwent R2*-weighted magnetic resonance imaging to estimate regional iron content and genotyping of interleukin-1beta (IL-1β), a pro-inflammatory cytokine for which the T allelle of the single nucleotide polymorphism increases risk for chronic neuroinflammation. Older age was associated with greater striatal iron content that in turn accounted for poorer cognitive switching performance. Heterozygote IL-1β T-carriers demonstrated poorer switching performance in relation to striatal iron content as compared to IL-1β C/C counterparts, despite the two groups being of similar age. With increasing genetic inflammation risk, homozygote IL-1β T/T carriers had lesser age-related variance in striatal iron content as compared to the other groups but showed a similar association of greater striatal iron content predicting poorer cognitive switching. Non-heme iron and inflammation, although necessary for normal neuronal function, both promote oxidative stress that when accumulated in excess, drives a complex mechanism of neural and cognitive decline in aging.
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http://dx.doi.org/10.1016/j.neuroimage.2018.10.064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6301022PMC
January 2019

Frontoparietal cortical thickness mediates the effect of COMT ValMet polymorphism on age-associated executive function.

Neurobiol Aging 2019 01 21;73:104-114. Epub 2018 Sep 21.

Center for Vital Longevity, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, TX, USA. Electronic address:

Proper dopamine (DA) signaling is likely necessary for maintaining optimal cognitive performance as we age, particularly in prefrontal-parietal networks and in fronto-striatal networks. Thus, reduced DA availability is a salient risk factor for accelerated cognitive aging. A common polymorphism that affects DA D1 receptor dopamine availability, COMT ValMet (rs4680), influences enzymatic breakdown of DA, with COMT Val carriers having a 3- to 4-fold reduction in synaptic DA compared to COMT Met carriers. Furthermore, dopamine receptors and postsynaptic availability are drastically reduced with aging, as is executive function performance that ostensibly relies on these pathways. Here, we investigated in 176 individuals aged 20-94 years whether: (1) COMT Val carriers differ from their Met counterparts in thickness of regional cortices receiving D1 receptor pathways: prefrontal, parietal, cingulate cortices; (2) this gene-brain association differs across the adult lifespan; and (3) COMT-related regional thinning evidences cognitive consequences. We found that COMT Val carriers evidenced thinner cortex in prefrontal, parietal, and posterior cingulate cortices than COMT Met carriers and this effect was not age-dependent. Further, we demonstrate that thickness of these regions significantly mediates the effect of COMT genotype on an executive function composite measure. These results suggest that poorer executive function performance is due partly to thinner association cortex in dopaminergic-rich regions, and particularly so in individuals who are genetically predisposed to lower postsynaptic dopamine availability, regardless of age.
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http://dx.doi.org/10.1016/j.neurobiolaging.2018.08.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251730PMC
January 2019

Increasing beta-amyloid deposition in cognitively healthy aging predicts nonlinear change in BOLD modulation to difficulty.

Neuroimage 2018 12 11;183:142-149. Epub 2018 Aug 11.

Center for Vital Longevity, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, TX, 75235, USA.

Recent evidence indicates that the relationship between increased beta-amyloid (Aβ) deposition and functional task-activation can be characterized by a non-linear trajectory of change in functional activation (Foster et al., 2017), explaining mixed results in prior literature showing both increases and decreases in activation as a function of beta-amyloid burden in cognitively normal adults. Here we sought to replicate this nonlinear effect in the same sample using a different functional paradigm to test the generalizability of this phenomenon. Participants (N = 68 healthy adults aged 49-94) underwent fMRI (0-, 2-, 3-, 4-back working memory task; WM) and F-Florbetapir PET scanning. A parametric WM load contrast was used as the dependent variable in a model with age, mean cortical Aβ, and Aβ as predictors. Results revealed that nonlinear amyloid (Aβ) was a significant negative predictor of modulation of activation to WM load in two large inferior clusters: bilateral subcortical nuclei and bilateral lateral cerebellum. Individuals with slightly elevated Aβ burden evidenced greater modulation as compared to individuals with little or no Aβ burden, whereas individuals with the greatest Aβ burden evidenced lesser modulation as compared to individuals with slightly elevated Aβ. Increased modulation to WM load predicted better task accuracy and executive function measured outside the scanner. The current study provides further evidence for a dose-response, nonlinear relationship between increasing Aβ burden and alteration in brain activation in cognitively healthy adults, extending the existing evidence to dynamic range of activation to task difficulty, and reconciling seemingly discrepant effects of amyloid on brain function.
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http://dx.doi.org/10.1016/j.neuroimage.2018.08.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197922PMC
December 2018

Association between subjective memory assessment and associative memory performance: Role of ad risk factors.

Psychol Aging 2018 02;33(1):109-118

Center for Vital Longevity, School of Behavioral and Brain Sciences, The University of Texas at Dallas.

Decline in associative memory abilities is a common cognitive complaint among older adults and is detectable in both normal aging and in prodromal Alzheimer's disease (AD). Subjective memory (SM) complaints may serve as an earlier marker of these mnemonic changes; however, previous research examining the predictive utility of SM to observed memory performance yielded inconsistent results. This inconsistency is likely due to other sources of variance that occur with memory decline such as mood/depression issues, presence of apolipoprotein E (APOE ε4) genotype, or beta-amyloid deposition. Here we examine the relationship between SM and associative memory ability in the context of factors that increase susceptibility to AD in 195 healthy adults (79 men) aged 20-94 years. Participants completed an SM questionnaire, a mood/depression scale, two associative memory tests (a word-pair and a name-face test), and were genotyped for APOE ε4. PET-amyloid imaging data were collected for a subset of those over 50 years of age (N = 74). We found that SM predicted performance on both associative memory tests even after covarying for age, sex, mood, and APOE ε4 status. Interestingly, for the name-face associative task, increased SM concerns predicted memory performance selectively in participants over the age of 60, with the APOEε4 risk group showing the strongest effect. Finally, men with higher beta-amyloid deposition reported more memory complaints. Our findings suggest that SM reliably tracks memory performance, even in cognitively healthy adults, and may reflect an increased risk for AD. (PsycINFO Database Record
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http://dx.doi.org/10.1037/pag0000217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836750PMC
February 2018

Both hyper- and hypo-activation to cognitive challenge are associated with increased beta-amyloid deposition in healthy aging: A nonlinear effect.

Neuroimage 2018 02;166:285-292

Center for Vital Longevity, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, TX 75235, USA. Electronic address:

Beta-amyloid (Aβ) positive individuals hyper-activate brain regions compared to those not at-risk; however, hyperactivation is then thought to diminish as Alzheimer's disease symptomatology begins, evidencing eventual hypoactivation. It remains unclear when in the disease staging this transition occurs. We hypothesized that differential levels of amyloid burden would be associated with both increased and decreased activation (i.e., a quadratic trajectory) in cognitively-normal adults. Participants (N = 62; aged 51-94) underwent an fMRI spatial distance-judgment task and Amyvid-PET scanning. Voxelwise regression modeled age, linear-Aβ, and quadratic-Aβ as predictors of BOLD activation to difficult spatial distance-judgments. A significant quadratic-Aβ effect on BOLD response explained differential activation in bilateral angular/temporal and medial prefrontal cortices, such that individuals with slightly elevated Aβ burden exhibited hyperactivation whereas even higher Aβ burden was then associated with hypoactivation. Importantly, in high-Aβ individuals, Aβ load moderated the effect of BOLD activation on behavioral task performance, where in lower-elevation, greater deactivation was associated with better accuracy, but in higher-elevation, greater deactivation was associated with poorer accuracy during the task. This study reveals a dose-response, quadratic relationship between increasing Aβ burden and alterations in BOLD activation to cognitive challenge in cognitively-normal individuals that suggests 1) the shift from hyper-to hypo-activation may begin early in disease staging, 2) depends, in part, on degree of Aβ burden, and 3) tracks cognitive performance.
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http://dx.doi.org/10.1016/j.neuroimage.2017.10.068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747976PMC
February 2018

Dynamic range in BOLD modulation: lifespan aging trajectories and association with performance.

Neurobiol Aging 2017 12 5;60:153-163. Epub 2017 Sep 5.

Center for Vital Longevity, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, TX, USA.

Alteration of dynamic range of modulation to cognitive difficulty has been proposed as a salient predictor of cognitive aging. Here, we examine in 171 adults (aged 20-94 years) the effects of age on dynamic modulation of blood oxygenation-level dependent activation to difficulty in parametrically increasing working memory (WM) load (0-, 2-, 3-, and 4-back conditions). First, we examined parametric increases and decreases in activation to increasing WM load (positive modulation effect and negative modulation effect). Second, we examined the effect of age on modulation to difficulty (WM load) to identify regions that differed with age as difficulty increased (age-related positive and negative modulation effects). Weakened modulation to difficulty with age was found in both the positive modulation (middle frontal, superior/inferior parietal) and negative modulation effect (deactivated) regions (insula, cingulate, medial superior frontal, fusiform, and parahippocampal gyri, hippocampus, and lateral occipital cortex). Age-related alterations to positive modulation emerged later in the lifespan than negative modulation. Furthermore, these effects were significantly coupled in that greater upmodulation was associated with lesser downmodulation. Importantly, greater fronto-parietal upmodulation to difficulty and greater downmodulation of deactivated regions were associated with better task accuracy and upmodulation with better WM span measured outside the scanner. These findings suggest that greater dynamic range of modulation of activation to cognitive challenge is in service of current task performance, as well as generalizing to cognitive ability beyond the scanner task, lending support to its utility as a marker of successful cognitive aging.
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http://dx.doi.org/10.1016/j.neurobiolaging.2017.08.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5653406PMC
December 2017

White Matter Degradation is Associated with Reduced Financial Capacity in Mild Cognitive Impairment and Alzheimer's Disease.

J Alzheimers Dis 2017 ;60(2):537-547

The University of Texas at Dallas, School of Behavioral and Brain Sciences, Center for Vital Longevity, Dallas, TX, USA.

Financial capacity (FC) is a cognitively complex activity of daily living that declines in mild cognitive impairment (MCI) and Alzheimer's disease (AD), limiting an individual's ability to manage one's finances and function independently. The neural underpinnings of this decline in function are poorly understood but likely involve age-related and disease-related degradation across structural networks. The purpose of the current study was to determine if altered white matter integrity is associated with declining FC in persons with MCI and AD compared to older controls. Individuals with MCI due to AD (n = 31), mild dementia (n = 39), and cognitively healthy older adults (n = 60) were administered a neuropsychological battery including the FC Instrument, a performance-based measure of FC. All 130 participants also underwent diffusion tensor imaging (DTI) upon which tract-based spatial statistics were performed. Both FC and white matter integrity decreased in accordance with disease severity with little to no effect in healthy elderly, significant effects in MCI, and greater effects in AD. Regional white matter degradation (increased diffusivities and decreased fractional anisotropy) was associated with reduced FC in both MCI and AD groups even after controlling for age, education, and gender. Specifically, in MCI, decreased fractional anisotropy, but not increased diffusivities, was associated with poorer FC in widespread cingulo-parietal-frontal and temporo-occipital areas. In AD, rather than anisotropy, increased mean and axial diffusivities in anterior cingulate, callosum, and frontal areas associated with poorer FC. These findings suggest a severity gradient of white matter degradation across DTI metrics and AD stages that predict declining financial skill and knowledge.
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http://dx.doi.org/10.3233/JAD-170341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642279PMC
April 2018

Differential Aging Trajectories of Modulation of Activation to Cognitive Challenge in APOE ε4 Groups: Reduced Modulation Predicts Poorer Cognitive Performance.

J Neurosci 2017 07 26;37(29):6894-6901. Epub 2017 Jun 26.

Center for Vital Longevity, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, Texas 75235

The present study was designed to investigate the effect of a genetic risk factor for Alzheimer's disease (AD), ApolipoproteinE ε4 (APOEε4), on the ability of the brain to modulate activation in response to cognitive challenge in a lifespan sample of healthy human adults. A community-based sample of 181 cognitively intact, healthy adults were recruited from the Dallas-Fort Worth metroplex. Thirty-one APOEε4+ individuals (48% women), derived from the parent sample, were matched based on sex, age, and years of education to 31 individuals who were APOEε4-negative (APOEε4-). Ages ranged from 20 to 86 years of age. Blood oxygen level-dependent functional magnetic resonance imaging was collected during the performance of a visuospatial distance judgment task with three parametric levels of difficulty. Multiple regression was used in a whole-brain analysis with age, APOE group, and their interaction predicting functional brain modulation in response to difficulty. Results revealed an interaction between age and APOE in a large cluster localized primarily to the bilateral precuneus. APOEε4- individuals exhibited age-invariant modulation in response to task difficulty, whereas APOEε4+ individuals showed age-related reduction of modulation in response to increasing task difficulty compared with ε4- individuals. Decreased modulation in response to cognitive challenge was associated with reduced task accuracy as well as poorer name-face associative memory performance. Findings suggest that APOEε4 is associated with a reduction in the ability of the brain to dynamically modulate in response to cognitive challenge. Coupled with a significant genetic risk factor for AD, changes in modulation may provide additional information toward identifying individuals potentially at risk for cognitive decline associated with preclinical AD. Understanding how risk factors for Alzheimer's disease (AD) affect brain function and cognition in healthy adult samples may help to identify the biomarkers needed to detect nonsymptomatic, preclinical phases of the disease. Findings from the current study show that ApolipoproteinE ε4-positive (APOEε4+) individuals exhibit an altered lifespan trajectory in the ability of the brain to dynamically modulate function to cognitive challenge compared with APOEε4- individuals. This effect manifests in otherwise healthy individuals who are at increased risk for AD in the precuneus, a salient region for early AD changes. Notably, these functional alterations are detrimental to performance, and thus, the combination of a genetic risk factor and altered modulation may provide important information for identifying individuals who are at increased risk for AD.
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http://dx.doi.org/10.1523/JNEUROSCI.3900-16.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518419PMC
July 2017

Association of Longitudinal Cognitive Decline With Amyloid Burden in Middle-aged and Older Adults: Evidence for a Dose-Response Relationship.

JAMA Neurol 2017 07;74(7):830-838

Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas6Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas.

Importance: Presently, the clinical standard for reporting the results of an amyloid positron emission tomography scan is to assign a dichotomous rating of positive or negative for the presence of amyloid. In a 4-year longitudinal study, we investigated whether using a continuous measure of the magnitude of baseline amyloid burden would provide valuable information about the rate of future cognitive decline over the subsequent 4 years compared with a dichotomous measure in middle-aged and older adults.

Objective: To examine whether a continuous, dose-response relationship between amyloid burden and cognitive decline was present among middle-aged and older adults.

Design, Setting, And Participants: This cohort study included 174 participants from the Dallas Lifespan Brain Study who were 40 to 89 years old at the beginning of the study, were cognitively normal at baseline (a Mini-Mental State Examination score of 26 or higher) with no history of neurological or psychiatric disorders, and had completed amyloid imaging ([18F]-florbetapir) at baseline and cognitive assessments at baseline and a 4-year follow-up. Continuous amyloid burden was measured as the mean cortical standardized uptake value ratio (SUVR) at baseline.

Main Outcomes And Measures: Linear mixed models assessed the effect of increasing baseline amyloid over time (SUVR × time interaction) on episodic memory, reasoning, processing speed, vocabulary, and Mini-Mental State Examination performance. Age, sex, education, apolipoprotein ε4, and the random effect of intercepts were included as covariates.

Results: The mean (SD) age for all participants (n = 174) was 66.44 (11.74) years, and 65 participants (37%) were men. The primary analyses yielded significant SUVR × time interactions in episodic memory, processing speed, vocabulary, and Mini-Mental State Examination performance, but not in reasoning performance. Higher baseline SUVR projected greater cognitive decline over 4 years. When controlling for variance related to a dichotomized positive/negative classification, most effects on cognition remained. Dichotomized amyloid status alone yielded fewer significant effects of amyloid on cognitive decline than continuous SUVR. Among amyloid-positive participants, increasing baseline SUVR predicted an increasing decline in episodic memory, but other effects on cognition were more limited. Finally, higher baseline amyloid burden among middle-aged adults was related to changes in vocabulary, with the effect driven by 3 apolipoprotein ε4 homozygotes.

Conclusions And Relevance: These results suggest that the magnitude of amyloid burden at baseline is associated with the rate of cognitive decline over 4 years and potentially provides important information about the rate of future cognitive decline that is not available from a dichotomous positive/negative categorization.
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http://dx.doi.org/10.1001/jamaneurol.2017.0892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710531PMC
July 2017

APOEε4 Genotype and Hypertension Modify 8-year Cortical Thinning: Five Occasion Evidence from the Seattle Longitudinal Study.

Cereb Cortex 2018 06;28(6):1934-1945

Department of Radiology, Integrated Brain Imaging Center (IBIC), University of Washington, 1959 NE Pacific St, Seattle, WA 98195, USA.

We investigated individual differences in longitudinal trajectories of brain aging in cognitively normal healthy adults from the Seattle Longitudinal Study covering 8 years of longitudinal change (across 5 occasions) in cortical thickness in 249 midlife and older adults (52-95 years old). We aimed to understand true brain change; examine the influence of salient risk factors that modify an individual's rate of cortical thinning; and compare cross-sectional age-related differences in cortical thickness to longitudinal within-person cortical thinning. We used Multivariate Multilevel Modeling to simultaneously model dependencies among 5 lobar composites (Frontal, Parietal, Temporal, Occipital, and Cingulate [CING]) and account for the longitudinal nature of the data. Results indicate (1) all 5 lobar composites significantly atrophied across 8 years, showing nonlinear longitudinal rate of cortical thinning decelerated over time, (2) longitudinal thinning was significantly altered by hypertension and Apolipoprotein-E ε4 (APOEε4), varying by location: Frontal and CING thinned more rapidly in APOEε4 carriers. Notably, thinning of parietal and occipital cortex showed synergistic effect of combined risk factors, where individuals who were both APOEε4 carriers and hypertensive had significantly greater 8-year thinning than those with either risk factor alone or neither risk factor, (3) longitudinal thinning was 3 times greater than cross-sectional estimates of age-related differences in thickness in parietal and occipital cortices.
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http://dx.doi.org/10.1093/cercor/bhx099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019039PMC
June 2018

Functional magnetic resonance imaging data of incremental increases in visuo-spatial difficulty in an adult lifespan sample.

Data Brief 2017 Apr 11;11:54-60. Epub 2017 Jan 11.

Center for Vital Longevity, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, TX 75235, USA.

These data provide coordinates generated from a large healthy adult lifespan sample undergoing functional Magnetic Resonance Imaging (fMRI) while completing a spatial judgment task with varying levels of difficulty, as well as a control categorical condition. The data presented here include the average blood-oxygen-dependent (BOLD) response to the spatial judgment vs. the control task, as well as the BOLD response to incremental increasing difficulty; see also "Age-related Reduction of BOLD Modulation to Cognitive Difficulty Predicts Poorer Task Accuracy and Poorer Fluid Reasoning Ability" (Rieck et al., 2017) [1].
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http://dx.doi.org/10.1016/j.dib.2017.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5256670PMC
April 2017

Age-related reduction of BOLD modulation to cognitive difficulty predicts poorer task accuracy and poorer fluid reasoning ability.

Neuroimage 2017 02 13;147:262-271. Epub 2016 Dec 13.

Center for Vital Longevity, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, TX 75235, USA. Electronic address:

Aging is associated with reduced resources needed to perform difficult cognitive tasks, but the neural underpinnings are not well understood, especially as there is scant evidence linking functional brain differences to aging cognition. Therefore, the current study examined modulation of fMRI activation from easier to harder spatial distance judgments across a large lifespan sample (N=161; ages 20-94) to identify when in the lifespan modulation to difficulty begins to show deficits and if age-related modulation predicts cognition. Analyses revealed two sets of regions in which modulation increased with difficulty due to either more activation (positive modulation) or more deactivation (negative modulation) to difficulty. These two networks evidenced differential aging trajectories: a right-lateralized fronto-parietal network that decreased in modulation to difficulty between middle- and older-age, and a network of regions in ventromedial prefrontal cortex, posterior cingulate, left angular and middle frontal gyri that showed decreased modulation at the transition from younger to middle-age. Critically, older adults who maintained negative modulation to difficulty showed higher task accuracy. Further, individuals who showed greater coupling between positive and negative modulation performed better on a fluid reasoning task. Age-related preservation of coupled modulation in both cognitive control regions and regions typically associated with default network may be a salient marker of how the brain adapts to maintain cognitive function as we age.
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http://dx.doi.org/10.1016/j.neuroimage.2016.12.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5303662PMC
February 2017

A harmonized segmentation protocol for hippocampal and parahippocampal subregions: Why do we need one and what are the key goals?

Hippocampus 2017 01 15;27(1):3-11. Epub 2016 Nov 15.

VA Boston Healthcare System, Boston, USA.

The advent of high-resolution magnetic resonance imaging (MRI) has enabled in vivo research in a variety of populations and diseases on the structure and function of hippocampal subfields and subdivisions of the parahippocampal gyrus. Because of the many extant and highly discrepant segmentation protocols, comparing results across studies is difficult. To overcome this barrier, the Hippocampal Subfields Group was formed as an international collaboration with the aim of developing a harmonized protocol for manual segmentation of hippocampal and parahippocampal subregions on high-resolution MRI. In this commentary we discuss the goals for this protocol and the associated key challenges involved in its development. These include differences among existing anatomical reference materials, striking the right balance between reliability of measurements and anatomical validity, and the development of a versatile protocol that can be adopted for the study of populations varying in age and health. The commentary outlines these key challenges, as well as the proposed solution of each, with concrete examples from our working plan. Finally, with two examples, we illustrate how the harmonized protocol, once completed, is expected to impact the field by producing measurements that are quantitatively comparable across labs and by facilitating the synthesis of findings across different studies. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/hipo.22671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5167633PMC
January 2017
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