Karen M Rodrigue

• PhD
• Professor (Associate) at The University of Texas at Dallas

Importance Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology. Objective To examine the association between depressive symptoms...

High cardiorespiratory fitness may mitigate regional gray matter shrinkage across the adult lifespan.

Importance Baseline cerebral microbleeds (CMBs) and APOE ε4 allele copy number are important risk factors for amyloid-related imaging abnormalities in patients with Alzheimer disease (AD) receiving therapies to lower amyloid-β plaque levels. Objective To provide prevalence estimates of any, no more than 4, or fewer than 2 CMBs in association with...

The corpus callosum is composed of several subregions, distinct in cellular and functional organization. This organization scheme may render these subregions differentially vulnerable to the aging process. Callosal integrity may be further compromised by cardiovascular risk factors, which negatively influence white matter health. Here, we test for...

INTRODUCTION Understanding impact of environmental properties on Alzheimer's disease (AD) is paramount. Spatial complexity of one's routinely navigated environment is an important but understudied factor. METHODS A total of 660 older adults from National Alzheimer's Coordinating Center (NACC) dataset were geolocated and environmental complexity in...

Background Interpretations of brain and cognitive reserve were tested by assessing the parallel, longitudinal relationship between grey matter atrophy and cognitive decline in an adult lifespan sample. Method Cognitive battery and structural MRI images were assessed in 463 healthy participants of age 20‐89. Participants were assessed up to 3 times...

The corpus callosum is composed of several subregions, distinct in cellular and functional organization. This organization scheme may render these subregions differentially vulnerable to the aging process. Callosal integrity may be further compromised by vascular risk factors, which negatively influence white matter health. Here, we test for hetero...

The present study examines the association between gray matter volume and cognition. Studies that have examined this issue have focused primarily on older adults, whereas the present study examines the issue across the entire adult lifespan. A total of 463 adults, ages 20-88 at first assessment, were followed longitudinally across three assessments...

The impact of aerobic exercise training (AET) on cerebral blood flow (CBF) regulation remains inconclusive. This study investigated the effects of one-year progressive, moderate-to-vigorous AET on CBF, central arterial stiffness, and cognitive performance in cognitively normal older adults. Seventy-three older adults were randomly assigned to AET o...

Background: Current evidence is inconsistent on the benefits of aerobic exercise training for preventing or attenuating age-related cognitive decline in older adults. Objective: To investigate the effects of a 1-year progressive, moderate-to-high intensity aerobic exercise intervention on cognitive function, brain volume, and cortical thickness...

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...

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 densit...

Introduction: 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. Methods:...

Healthy aging is accompanied by degraded white matter connectivity, which has been suggested to contribute to cognitive dysfunction observed in aging, especially in relation to fluid measures of cognition. Prior research linking white matter microstructure and cognition, however, has largely been limited to major association and heteromodal white m...

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 d...

Objective: To test the hypothesis that the combination of both elevated global 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 co...

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 bot...

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 hypothesi...

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...

Working memory (WM) and its BOLD-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 heal...

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-oxyge...

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...

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) un...

Cerebrovascular reactivity (CVR) mapping using CO2-inhalation can provide important insight into vascular health. At present, blood-oxygenation-level-dependent (BOLD) MRI acquisition is the most commonly used CVR method due to its high sensitivity, high spatial resolution, and relatively straightforward processing. However, large variations in CVR...

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) unde...

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 resona...

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, a phenomenon termed "dedifferentiation". The current study tested the hypothesis that ag...

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) morphom...

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 (parahippocamp...

Introduction: Heterogeneity of segmentation protocols for medial temporal lobe regions and hippocampal subfields on in vivo 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, fun...

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 lifespan, we analyzed grey matter (GM) morphometry (...

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 MRI scanning in...

Arterial spin labeling (ASL) MRI is increasingly used in research and clinical settings. The purpose of this work is to develop a cloud‐based tool for ASL data processing, referred to as ASL‐MRICloud, which may be useful to the MRI community. In contrast to existing ASL toolboxes, which are based on software installation on the user's local compute...

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 th...

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, COM...

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-...

Introduction: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid β (Aβ) pathology. Methods: We included 3451 Aβ+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Gener...

Although cerebrovascular factors are the second leading cause of cognitive impairment and dementia in elderly, the precise spatial and temporal trajectories of vascular decline in aging have not been fully characterized. With an advanced cerebrovascular reactivity (CVR) MRI technique that specifically informs vascular stiffness and dilatory ability...

Introduction: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid β (Aβ) pathology. Methods: We included 3451 Aβ+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Ge...

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...

Background With the disappointing outcomes of clinical trials on patients with Alzheimer's disease or mild cognitive impairment (MCI), there is increasing attention to understanding cognitive decline in normal elderly individuals, with the goal of identifying subjects who are most susceptible to imminent cognitive impairment. Purpose/Hypothesis To...

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 a...

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 recru...

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 valu...

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 influe...

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...

Objective: To examine the relationship of β-amyloid (Aβ) deposition to episodic memory in younger (30-49 years), middle-older (50-69 years), and older adults (70-89 years). We hypothesized that subclinical levels of amyloid would be linked to memory in adults across the lifespan in a dose-dependent fashion. Of great interest was whether, within th...

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. Due to the many extant and highly discrepant segmentation protocols, comparing results across studies is difficult....

Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies. To use individual participant data meta-analysis to estimate th...

Importance Amyloid-β positron emission tomography (PET) imaging allows in vivo detection of fibrillar plaques, a core neuropathological feature of Alzheimer disease (AD). Its diagnostic utility is still unclear because amyloid plaques also occur in patients with non–AD dementia.Objective To use individual participant data meta-analysis to estimat...

The recent ability to measure in vivo beta-amyloid (Aβ), a marker of Alzheimer's disease (AD), has led to an increased focus on the significance of Aβ deposition in clinically normal adults. Evidence suggests that healthy adults with elevated cortical Aβ show differences in neural activity associated with memory encoding-specifically encoding of fa...

Executive functioning exhibits significant decline with increasing age across the lifespan. Previous investigations into the neuroanatomical correlates of executive functioning have been largely limited to measures of prefrontal cortex volume and revealed relatively modest age-related associations. In this study, we investigate the effects of age-r...

Working memory (WM) performance decreases with age and as WM load increases, these deficits are magnified. fMRI studies in young adults suggest that brain activation increases with increasing WM load. It is unclear how the aging brain responds to this increased mental challenge. fMRI studies comparing older to younger adults suggest modulation to i...

One of the main obstacles in quantitative interpretation of functional magnetic resonance imaging (fMRI) signal is that this signal is influenced by non-neural factors such as vascular properties of the brain, which effectively increases signal variability. One approach to account for non-neural components is to identify and measure these confoundi...

The brain shrinks with age, but the timing of this process and the extent of its malleability are unclear. We measured changes in regional brain volumes in younger (age 20–31) and older (age 65–80) adults twice over a six months period, and examined the association between changes in volume, history of hypertension, and cognitive training. Between...

Importance Identifying risk factors for increased β-amyloid (Aβ) deposition is important for targeting individuals most at risk for developing Alzheimer disease and informing clinical practice concerning prevention and early detection. Objective To investigate risk factors for Aβ deposition in cognitively healthy middle-aged and older adults. Speci...

Sporadic Alzheimer disease (AD) is a multifaceted neurodegenerative syndrome with complicated and unclear etiology that results in debilitating cognitive decline in old age. Although several decades of AD research resulted in major scientific advancements in identifying and tracking the disease, as well as discovering many salient genetic and envir...

Little is known about the neural correlates of within-person variability in cognitive performance. We investigated associations between regional brain volumes and trial-to-trial, block-to-block, and day-to-day variability in choice–reaction time, and episodic and working memory accuracy. Healthy younger (n = 25) and older (n = 18) adults underwent...

The goal of this study was to examine the relationships between 2 age-sensitive indices of brain integrity-volume and iron concentration-and the associated age differences in memory performance. In 113 healthy adults (age 19-83 years), we measured the volume and estimated iron concentration in the hippocampus (HC), caudate nucleus (Cd), and primary...

Limited functional imaging evidence suggests that increased beta-amyloid deposition is associated with alterations in brain function, even in healthy older adults. However, the majority of these findings report on resting-state activity or functional connectivity in adults over age 60. Much less is known about the impact of beta-amyloid on neural a...

Previous studies have found that cortical responses to different stimuli become less distinctive as people get older. This age-related dedifferentiation may reflect the broadening of the tuning curves of category-selective neurons (broadening hypothesis) or it may be due to decreased activation of category-selective neurons (attenuation hypothesis)...

Several lines of evidence suggest that pathologic changes underlying Alzheimer disease (AD) begin years prior to the clinical expression of the disease, underscoring the need for studies of cognitively healthy adults to capture these early changes. The overall goal of the current study was to map the cortical distribution of β-amyloid (Aβ) in a hea...

Aging and age-related diseases have negative impact on the hippocampus (HC), which is crucial for such age-sensitive functions as memory formation, maintenance, and retrieval. We examined age differences in hippocampal subfield volumes in 10 younger and 19 older adults, and association of those volumes with memory performance in the older participa...

Like all organs in the human body, the brain experiences wear and tear throughout the life span. Because the state of the brain ’ s structure affects the quality of its function, the study of changes in brain structure has proven fruitful in understanding cognitive aging. In this chapter we briefly review the history of the morphometric research (c...

The goal of the study was to examine the differences in trajectories of change in the volume of white matter hyperintensities (WMH) in healthy adults within a relatively short period. We measured volumes of periventricular and deep WMH in frontal, temporal, parietal, and occipital lobes of healthy volunteers (age 49-83) on 3 occasions, approximatel...

With age, the brain undergoes comprehensive changes in its function and physiology. Cerebral metabolism and blood supply are among the key physiologic processes supporting the daily function of the brain and may play an important role in age-related cognitive decline. Using MRI, it is now possible to make quantitative assessment of these parameters...

Aging affects various structural and metabolic properties of the brain. However, associations among various aspects of brain aging are unclear. Moreover, those properties and associations among them may be modified by age-associated increase in vascular risk. In this study, we measured volume of brain regions that vary in their vulnerability to agi...