Anja Soldan

• Ph.D.
• Johns Hopkins University

Aging is associated with disruptions in circadian rhythms, lower brain white matter integrity, and cognitive changes. However, whether white matter integrity serves as a potential mechanism linking circadian dysfunction to age-related cognitive abilities in older adults is unclear. We investigated cross-sectional associations of actigraphic circadi...

Brain atrophy over time, as measured by magnetic resonance imaging (MRI), has been shown to predict subsequent cognitive impairment among individuals who were cognitively normal when first evaluated, indicating that subtle brain atrophy associated with Alzheimer's disease (AD) may begin years before clinical symptoms appear. Traditionally, atrophy...

BACKGROUND Alzheimer's disease (AD) is characterized by the abnormal accumulation of amyloid‐beta (Aβ) and tau that can be quantified in vivo through cerebrospinal fluid (CSF) sampling. Physical activity has emerged as a possible modifier of AD risk; however, its impact on CSF biomarkers and cognitive function is not yet fully understood. We examin...

INTRODUCTION We examined long‐term plasma biomarker trajectories among participants who were cognitively unimpaired and primarily middle aged at baseline and whether trajectories differed by Alzheimer's disease (AD) genetic risk and among those who developed cognitive impairment. METHODS Plasma amyloid beta (Aβ)42/Aβ40, phosphorylated tau (p‐tau)1...

Background Cerebral metabolic rate of oxygen (CMRO2) denotes the amount of O2 that the brain consumes. Changes in CMRO2 during aging and neurodegeneration have not been fully characterized. Using a non‐invasive, non‐contrast MRI CMRO2 technique, the present study reports CMRO2 changes in older adults from a total of 526 measurements, the largest CM...

Background Few studies have examined how a range of potential modifiers may influence the trajectories of Alzheimer’s disease (AD) blood biomarkers in those who were cognitively unimpaired when first assessed. This study examined potential modifiers of longitudinal changes in plasma biomarkers, including genetic factors (i.e., APOE e4 allele and AD...

Background Blood‐based biomarkers of amyloid and tau have been shown to predict AD‐dementia risk. Much less is known about their ability to predict risk of Mild Cognitive Impairment (MCI) among cognitively normal individuals. It is also unclear how AD non‐specific blood markers of neurodegeneration and neuroinflammation predict MCI and whether they...

Background Adverse social exposome (indexed by national Area Deprivation Index [ADI] 80‐100 or ‘high ADI’) is linked to structural inequities and increased risk of Alzheimer’s disease neuropathology. Twenty percent of the US population resides within high ADI areas, predominantly in inner cities, tribal reservations and rural areas. The percentage...

Background Cerebral metabolic rate of oxygen (CMRO2) denotes the amount of O2 that the brain consumes. Changes in CMRO2 during aging and neurodegeneration have not been fully characterized. Using a non‐invasive, non‐contrast MRI CMRO2 technique, the present study reports CMRO2 changes in older adults from a total of 526 measurements, the largest CM...

Background Previous studies have shown that higher levels of the synaptic protein NPTX2, measured in cerebrospinal fluid (CSF), are associated with lower risk of progression from normal cognition to Mild Cognitive Impairment (MCI) and dementia. Among those with MCI or dementia, higher NPTX2 levels have been associated with decreased atrophy in AD‐v...

There is large inter-individual variability in cognitive and brain aging trajectories, which have been related to differences in cognitive reserve (CR), brain mainenance, and the influence of genetic and environmental factors across the lifespan. This presentation will discuss recent evidence regarding CR using data from the BIOCARD study, which in...

Alzheimer’s disease (AD) genetic risk factors impact cognitive and brain health, but the extent to which these effects are mitigated by cognitive reserve (CR) is less well understood. This study examined whether higher levels of CR (measured by education and reading ability) were associated with a reduced impact of AD genetic risk on both longitudi...

Hearing loss is associated with cognitive decline and mood disorders, potentially through functional changes in the brain, as auditory deprivation affects higher-order sensory, attentional, and emotional processing. This study examined the cross-sectional association between hearing loss and functional connectivity, in 141 dementia-free participant...

Alzheimer’s disease (AD) is characterized by the abnormal accumulation of amyloid-β (plaques), and tau (neurofibrillary tangles) that can be quantified in vivo through cerebrospinal fluid (CSF) sampling. Physical activity has emerged as a possible modifier of AD risk; however, the influence of physical activity on CSF biomarkers and cognitive funct...

Background and objectives: Blood-based biomarkers of amyloid and tau have been shown to predict Alzheimer disease (AD) dementia. Much less is known about their ability to predict risk of mild cognitive impairment (MCI), an earlier disease stage. This study examined whether levels of blood biomarkers of amyloid (Aβ42/Aβ40 ratio), tau (p-tau181), ne...

Importance It remains unclear which risk factors accelerate brain atrophy along with a progression from normal cognition to mild cognitive impairment (MCI). Objective To examine risk factors associated with the acceleration of brain atrophy and progression from normal cognition to MCI based on long-term longitudinal data for middle-aged and older...

Reduced brain volumes and more prominent white matter hyperintensities on MRI scans are commonly observed among older adults without cognitive impairment. However, it remains unclear whether rates of change in these measures among cognitively normal adults differ as a function of genetic risk for late-onset Alzheimer’s disease, including APOE-ɛ4, A...

Greater physical activity and better sleep are associated with reduced risk of cognitive decline and dementia among older adults, but little is known about their combined associations with measures of brain function and neuropathology. This study investigated potential independent and interactive cross-sectional relationships between actigraphy-est...

Background Remembering names of people and places is a common problem in aging that is exacerbated in Alzheimer’s disease (AD). Because retrieval of proper names (PNs) has been associated with brain regions affected by AD (anterior and medial temporal lobe), PN retrieval may be an especially sensitive measure of early AD pathology. Extending result...

Background Neuronal pentraxin 2 (NPTX2) is a synaptic protein involved in the homeostatic regulation of cortical network dynamics and synaptic plasticity. Prior cross‐sectional studies suggest that NPTX2 levels decline across the spectrum of Alzheimer’s disease (AD), and that NPTX2 levels can distinguish individuals with normal cognition vs. mild c...

Background Mounting evidence indicates that tau accumulation in the entorhinal cortex (EC) occurs early in the course of Alzheimer’s disease (AD). Recent advances in automated segmentation methods allow for the investigation of smaller regions of the medial temporal lobes (MTL), including subregions of the EC. This study examined tau deposition in...

Background Individual differences in brain connectivity have been associated with cognitive variability in older adults, making them ideal markers of early changes that may predict subsequent cognitive decline. Using MRI measures, we previously demonstrated that cross‐sectionally, both structural and functional connectivity each uniquely contribute...

Introduction The accumulation of neurofibrillary tau tangles, a neuropathological hallmark of Alzheimer’s disease (AD), occurs in medial temporal lobe (MTL) regions early in the disease process, with some of the earliest deposits localized to subregions of the entorhinal cortex. Although functional specialization of entorhinal cortex subregions has...

Background Cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) are altered many years before the onset of clinical symptoms of mild cognitive impairment (MCI). Incorporating clinical symptom onset time into biomarker modeling may enhance our understanding of changes preceding MCI. Objective Using a new analytical approach, we examined...

Objective: This study examined whether cerebrospinal fluid (CSF) baseline levels of the synaptic protein NPTX2 predict time to onset of symptoms of Mild Cognitive Impairment (MCI), both alone and when accounting for traditional CSF Alzheimer's disease (AD) biomarker levels. Longitudinal NPTX2 levels were also examined. Methods: CSF was collected...

Background Prior findings indicate that both genetic factors and indices of cognitive reserve (CR) influence risk of cognitive decline, with APOE4 genetic status increasing risk, and APOE2 genetic status and higher CR indices decreasing risk. However, it remains unclear whether these genetic and lifestyle variables interact to influence long‐term c...

Background Both Alzheimer’s disease (AD) genetic risk factors and indices of cognitive reserve (CR) influence risk of cognitive decline, but it remains unclear whether they interact. This study examined whether a CR index score modifies the relationship between AD genetic risk factors and long-term cognitive trajectories in a large sample of indivi...

Velocity-selective inversion (VSI) based velocity-selective arterial spin labeling (VSASL) has been developed to measure cerebral blood flow (CBF) with low susceptibility to the prolonged arterial transit time and high sensitivity to brain perfusion signal. The purpose of this magnetic resonance imaging study is to evaluate the test-retest reliabil...

Background Alzheimer’s disease (AD) frequently co-occurs with other brain pathologies. Recent studies suggest there may be a mechanistic link between AD and small vessel cerebrovascular disease (CVD), as opposed to simply the overlap of two disorders. Objective We investigated the cross-sectional relationship between white matter hyperintensity (W...

Current cerebrospinal fluid (CSF) biomarker data of preclinical AD are based largely on cross‐sectional studies across the disease spectrum and short‐term longitudinal studies, with most studies conducted among older adults. However, neuropathological studies indicate that AD pathology is present in midlife. To better understand within‐person bioma...

Studies focused on understanding cerebrospinal fluid (CSF) biomarkers of presymptomatic disease processes in Alzheimer’s disease (AD) are restricted by sample sizes that lack statistical power to investigate subtle effects of interest pertaining to risk. Pooling data across cohorts may be effective to identify early trends in CSF biomarkers to subs...

Introduction: We examined longitudinal cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarker changes among cognitively normal individuals with 10.7 years follow-up, on average. Methods: Analyses included 278 participants (M age = 57.5 years); 94 have progressed from normal cognition to mild cognitive impairment (MCI). Amyloid beta (Aβ)42/...

Background and objectives: This study aimed to examine whether baseline CSF measures of Alzheimer disease (AD)-related pathology are associated with the time to onset of mild cognitive impairment (MCI) and whether these associations differ by age, sex, Apolipoprotein E (ApoE4) status, and proximal (≤7 years) vs distal (>7 years) time to symptom on...

Introduction: Oxygen extraction fraction (OEF) reflects the balance between oxygen delivery and consumption. We longitudinally measured OEF in older adults to examine the relationship with markers of Alzheimer's disease (AD) and vascular pathology. Methods: One hundred thirty-seven participants were studied at two time-points at an interval of 2...

In this study, we examined the independent contributions of structural and functional connectivity markers to individual differences in episodic memory performance in 107 cognitively normal older adults from the BIOCARD study. Structural connectivity, defined by the diffusion tensor imaging (DTI) measure of radial diffusivity (RD), was obtained fro...

Objective This study examined the association of lifetime experiences, measured by a cognitive reserve (CR) composite score composed of years of education, literacy, and vocabulary measures, to level and rate of change in white matter microstructure, as assessed by diffusion tensor imaging (DTI) measures. We also examined whether the relationship b...

The data show an association between measured and predicted changes in cognitive performance in older adults who are cognitively normal. Changes in cognitive performance over two years were assessed using the Cognitive Composite Score. The prediction of change in cognitive function was based on changes in pairwise functional connectivity between 80...

This cross-sectional study examined whether performance on the computerized Paired Associate Learning (PAL) task from the Cambridge Neuropsychological Test Automated Battery is associated with amyloid positivity as measured by Positron Emission Tomography, regional volume composites as measured by Magnetic Resonance Imaging, and cognitive impairmen...

Neurobiological substrates of cognitive decline in cognitively normal older individuals have been investigated by resting-state functional magnetic resonance imaging, but little is known about the relationship between longitudinal changes in the whole brain. In this study, we examined two-year changes in functional connectivity among 80 gray matter...

Higher physical activity levels are associated with reduced cognitive decline among older adults; however, current understanding of underlying brain mechanisms is limited. This cross-sectional study investigated the relationship between actigraphy-estimated total volume of physical activity (TVPA) and magnetic resonance imaging (MRI) measures of wh...

Background Neuropsychiatric symptoms (NPS) among cognitively normal older adults are increasingly recognized as risk factors for cognitive decline and impairment. However, the underlying mechanisms remain unclear. Objective To examine whether biomarkers of Alzheimer’s disease (amyloid burden) and cerebrovascular disease (white matter hyperintensit...

Background: Characterization of blood supply changes in older individuals is important in understanding brain aging and diseases. However, prior studies largely focused on cross-sectional design, thus change in cerebral blood flow (CBF) could not be assessed on an individual level. Purpose: To evaluate longitudinal short-term changes in global C...

Background Given mounting evidence that AD‐related neuropathological changes may be present in cognitively normal individuals, there is a need to examine brain biomarkers related to variability in cognition that may precede cognitive decline. Although prior studies demonstrate age‐related changes in structural connectivity (SC) and functional conne...

Background It is well documented that amyloid pathology accumulates many years prior to the emergence of clinical symptoms of Alzheimer’s disease (AD), when individuals are cognitively normal. Few prior studies have investigated the impact of AD pathology on brain connectivity among cognitively normal individuals. We investigated the impact of AD b...

Background The increased focus on preclinical Alzheimer’s disease (AD) necessitates an understanding of how general biomarkers of neuronal injury and AD‐specific biomarkers differentially contribute to the cognitive performance in cognitively normal individuals. It has been suggested that alterations in limbic white matter (WM) tracts may precede b...

Introduction: Motoric cognitive risk (MCR), a clinical syndrome characterized by slow gait speed and subjective cognitive complaints, has been associated with dementia risk. The neuropathological features underlying MCR remain poorly understood. Methods: The Atherosclerosis Risk in Communities (ARIC) community-based cohort study classified parti...

This study examines the relationship of engagement in different lifestyle activities to connectivity in large-scale functional brain networks, and whether network connectivity modifies cognitive decline, independent of brain amyloid levels. Participants (N = 153, mean age = 69 years, including N = 126 with amyloid imaging) were cognitively normal w...

Introduction Alterations in sleep and circadian rhythms are common in persons with Alzheimer’s disease (AD) dementia, but the nature of such changes in the early phases of AD remains unclear. This study compared sleep and circadian rest/activity rhythms (RARs), measured by standard and novel actigraphic indices, between participants with normal cog...

The brain signature concept aims to characterize brain regions most strongly associated with an outcome of interest. Brain signatures derive their power from data-driven searches that select features based solely on performance metrics of prediction or classification. This approach has important potential to delineate biologically relevant brain su...

Study Objectives To compare sleep and circadian rest/activity rhythms (RARs), quantified by standard and novel actigraphic metrics, between controls and participants with mild cognitive impairment (MCI), and to examine the cross-sectional relationships between these measures and cognition. Methods Actigraphy data were collected in 179 older indivi...

Abstract Quantitative susceptibility mapping in MRI and PET indicated that elevated brain iron was related to lower cognitive performance independent of β-amyloid in cognitively normal older adults. Background For individuals with mild cognitive impairment (MCI) or dementia, elevated brain iron together with β-amyloid is associated with lower cogn...

Objective: To determine whether vascular risk and AD biomarkers have independent or synergistic effects on cognitive decline, and whether vascular risk is associated with the accumulation of AD pathology, as measured by change in biomarkers over time. Methods: At baseline, participants (N = 168) were cognitively normal and primarily middle-aged...

Introduction: We sought to examine whether depressive symptoms and level of Alzheimer's disease (AD) pathology are independently or interactively associated with the risk of progression to mild cognitive impairment (MCI). Methods: The study included a total of 216 participants from the Biomarkers for Older Controls at Risk for Alzheimer's Diseas...

Objective Examine whether cognitive reserve moderates the association of 1) vascular risk factors and 2) white matter hyperintensity burden with risk of clinical progression and longitudinal cognitive decline. Methods BIOCARD Study participants were cognitively normal and primarily middle‐aged (M = 57 years) at baseline and have been followed with...

Introduction: Identifying cognitively normal individuals at high risk for progression to symptomatic Alzheimer's disease (AD) is critical for early intervention. Methods: An AD risk score was derived using unsupervised machine learning. The score was developed using data from 226 cognitively normal individuals and included cerebrospinal fluid, m...

Background: Systemic inflammation has emerged as a risk factor for cognitive decline and Alzheimer's disease, but inflammation's effect on distributed brain networks is unclear. We examined the relationship between peripheral inflammatory markers and subsequent functional connectivity within five large-scale cognitive networks and evaluated the mo...

Objective: Recent studies suggest that white matter hyperintensities (WMH) on MRI, which primarily reflect small vessel cerebrovascular disease, may play a role in the evolution of Alzheimer disease (AD). In a longitudinal study, we investigated whether WMH promote the progression of AD pathology, or alter the association between AD pathology and...

We examined whether cognitive reserve (CR) impacts level of, or rate of change in, biomarkers of Alzheimer's disease (AD) and small-vessel cerebrovascular disease in >250 individuals who were cognitively normal and middle-aged and older at the baseline. The four primary biomarker categories commonly examined in studies of AD were measured longitudi...

Significant evidence demonstrates that aging is associated with variability in cognitive performance, even among individuals who are cognitively normal. In this study, we examined measures from magnetic resonance imaging and cerebrospinal fluid (CSF) to investigate which measures, alone or in combination, were associated with individual differences...

Objective To examine the prospective association between blood biomarkers of immune functioning (i.e., innate immune activation, adaptive immunity, and inflammation) and subsequent cognitive decline and clinical progression to mild cognitive impairment (MCI) in cognitively normal individuals.Methods The BIOCARD study is an observational cohort stud...

Introduction: Large longitudinal biomarkers database focusing on middle age is needed for Alzheimer's disease (AD) prevention. Methods: Data for cerebrospinal fluid analytes, molecular imaging of cerebral fibrillar β-amyloid with positron emission tomography, magnetic resonance imaging-based brain structures, and clinical/cognitive outcomes were...

Intrinsic functional connectivity of large-scale brain networks has been shown to change with aging and Alzheimer's disease (AD). These alterations are thought to reflect changes in synaptic function, but the underlying biological mechanisms are poorly understood. This study examined whether Neuronal Pentraxin 2 (NPTX2), a synaptic protein that med...

The current "one size fits all" approach to our cognitive aging population is not adequate to close the gap between cognitive health span and lifespan. In this review article, we present a novel model for understanding, preventing, and treating age-related cognitive impairment (ARCI) based on concepts borrowed from precision medicine. We will discu...

Background Apolipoprotein E4 (APOE4) is a major genetic risk factor for late-onset Alzheimer disease. However, the mechanisms by which APOE4 affects the brain, underpinning this risk, have not been fully elucidated. Purpose To investigate the influence of APOE4 on global cerebral oxygen extraction fraction (OEF) and possible mediation through amylo...

Objective: Several models have been proposed for the evolution of Alzheimer’s disease (AD) biomarkers. The aim of this study was to identify changepoints in a range of biomarkers during the preclinical phase of AD. Methods: We examined nine measures based on cerebrospinal fluid (CSF), magnetic resonance imaging (MRI) and cognitive testing, obtained...

Objective: To examine the long-term cognitive trajectories of individuals with normal cognition at baseline and distinct amyloid/tau/neurodegeneration (ATN) profiles. Methods: Pooling data across 4 cohort studies, 814 cognitively normal participants (mean baseline age = 59.6 years) were classified into 8 ATN groups using baseline CSF levels of β...

The extent and spatial location of white matter hyperintensities (WMH) on brain MRI may be relevant to the development of cognitive decline in older persons. Here, we introduce a new method, known as the Multi-atlas based Detection and Localization (MADL), to evaluate WMH on fluid-attenuated inversion recovery (FLAIR) data. This method simultaneous...

Purpose of Review The aim of this review is to summarize current conceptual models of cognitive reserve (CR) and related concepts and to discuss evidence for these concepts within the context of aging and Alzheimer’s disease. Recent Findings Evidence to date supports the notion that higher levels of CR, as measured by proxy variables reflective of...

Objective: Several models have been proposed for the evolution of Alzheimer's disease (AD) biomarkers. The aim of this study was to identify changepoints in a range of biomarkers during the preclinical phase of AD. Methods: We examined nine measures based on cerebrospinal fluid (CSF), magnetic resonance imaging (MRI) and cognitive testing, obtained...

Objective There is increasing evidence of an association between depressive symptoms and mild cognitive impairment (MCI) in cross-sectional studies, but the longitudinal association between depressive symptoms and risk of MCI onset is less clear. The authors investigated whether baseline symptom severity of depression was predictive of time to onse...

Background: Few studies have examined the relationship between lifestyle activity engagement and cognitive trajectories among individuals who were cognitively normal at baseline. Objective: To examine the relationship of current engagement in lifestyle activities to previous cognitive performance among individuals who were cognitively normal at...

Objective Our objectives were to characterize the inter‐relation of known dementia‐related neuropathologies in one comprehensive model and quantify the extent to which accumulation of neuropathologies accounts for the association between age and dementia. Methods We used data from 1,362 autopsied participants of three community‐based clinicopathol...

Recent evidence indicates that measures from cerebrospinal fluid, MRI scans and cognitive testing obtained from cognitively normal individuals can be used to predict likelihood of progression to mild cognitive impairment several years later, for groups of individuals. However, it remains unclear whether these measures are useful for predicting like...

The concept of cognitive reserve (CR) was proposed to account for the discrepancy between levels of brain pathologic features or damage and clinical and cognitive function. This article provides a detailed review of prospective longitudinal studies that have investigated the interaction between CR and Alzheimer's disease (AD) biomarkers on clinical...

We examined if baseline levels of cognitive reserve (CR) and of Alzheimer's disease (AD) biomarkers modify the rate of change in cognition among individuals with normal cognition at baseline (n = 303, mean baseline age = 57 years, mean follow-up = 12 years); 66 participants subsequently developed mild cognitive impairment (MCI) or dementia due to A...

This study examined whether longitudinal MRI trajectories in medial temporal lobe (MTL) brain regions differed among groups of cognitively normal individuals defined by their cerebrospinal fluid (CSF) levels when they were first enrolled (N = 207; mean clinical follow-up = 13.3 years (max = 20 years), mean MRI follow-up = 2.4 years (max = 8 years))...