Carol Van Hulle

• Ph.D.
• University of Wisconsin–Madison

Healthy human relationships incorporate empathy; yet empathy may sometimes be a risky strength. Here we examine whether links between parent and child depressive symptoms are moderated by child empathy in early school age children. Children's empathy (empathic concern and hypothesis testing) and empathy‐related responding (personal distress and pro...

INTRODUCTION This study examined the association of longitudinal atrophy with baseline cerebrospinal fluid (CSF) amyloid beta (Aβ, A) and phosphorylated tau (p‐tau, T) biomarkers (Aβ42/40, p‐tau181) in 406 cognitively unimpaired (CU) individuals (6.670 years of follow‐up on average, up to 13 imaging visits) to assess whether A+ is associated with A...

INTRODUCTION Specific features of subjective cognitive decline (SCD‐plus) have been proposed to indicate an increased risk of preclinical Alzheimer's disease (AD). However, few studies have examined how these features relate to AD biomarkers in cognitively unimpaired (CU) older adults. METHODS Meta‐analyses were performed using cross‐sectional dat...

INTRODUCTION Timely detection and tracking of Alzheimer's disease (AD) ‐related cognitive decline has become a public health priority. We investigated whether the NIH Toolbox for Assessment of Neurological and Behavioral Function—Cognition Battery (NIHTB‐CB) detects AD‐related cognitive decline. METHODS N = 171 participants (age 76.5 ± 8; 53% fema...

Background The National Institutes of Health Toolbox for Assessment of Neurological and Behavioral Function (NIHTB) was developed to address the need for a brief yet comprehensive instrument to facilitate more uniform assessment in large‐scale research studies. Here, we investigated whether the cognitive measures of the NIHTB detect cognitive decli...

Background The timing of neurodegeneration in relation to the onset of Alzheimer’s disease pathology is not fully known. This study examined the association of longitudinal atrophy derived from T1‐weighted MRI with 1) cerebrospinal fluid (CSF) amyloid‐tau (AT) groupings and 2) Pittsburgh compound B (PiB) PET‐derived estimates of amyloid duration am...

Background Prior research has highlighted the impact of neighborhood quality on health outcomes. Given veterans' unique experiences and challenges, exploring the association between neighborhood quality on cognitive measures and vascular risk scores is crucial for guiding targeted interventions, improving overall cognitive well‐being, promoting hea...

Background The omega‐3 fatty acid eicosapentaenoic acid (EPA) has positive benefits for cardiovascular risk, reducing inflammation and improving endothelial function. Evidence suggests that Icosapent ethyl, a purified form of EPA, can improve cardiovascular outcomes in at‐risk patients. Veterans are at higher risk for vascular dysfunction, a risk f...

Background The timing of neurodegeneration in relation to the onset of Alzheimer’s disease pathology is not fully known. This study examined the association of longitudinal atrophy derived from T1‐weighted MRI with 1) cerebrospinal fluid (CSF) amyloid‐tau (AT) groupings and 2) Pittsburgh compound B (PiB) PET‐derived estimates of amyloid duration am...

Background Individuals’ attitudes toward research predict recruitment, engagement, and retention. The Research Attitudes Questionnaire (RAQ), developed to predict individuals’ willingness to participate, is often used in AD research. It can be used to identify strategies to mitigate individuals’ reluctance to engage in research. To date, there are...

Background Alzheimer’s disease (AD) and related dementias can have long preclinical phases; thus, midlife intervention and prevention methods could prove efficacious. Multiple health‐related lifestyle factors have been associated with risk for AD. However, research on lifestyle factors has focused on clinical outcomes such as cognitive decline, mil...

Background Past research suggests that ethnoracialized groups differ in their willingness to engage in preclinical Alzheimer's disease (AD) research overall. Studies indicated that participation willingness was affected by attitudes toward research and perceived invasiveness of biomarker collection techniques. However, comparative quantitative stud...

Background In cognitively unimpaired (CU) older adults, the presence of a subjective cognitive decline (SCD) combined with evidence of abnormal b‐amyloid (Ab) is proposed as stage 2 of Alzheimer’s disease (AD) by the NIA‐AA framework (Jack et al., 2018). However, the associations found between SCD and preclinical AD are inconsistent across studies,...

Background Each year, millions of Americans experience mild traumatic brain injury (mTBI). Current research on the long‐term effects of mTBI vary considerably. Several mechanisms linking mTBI to dementia have been proposed including amyloid plaque formation and cerebrovascular injury following mTBI. Veterans have higher rates of mTBI than non‐Veter...

Background Mild behavioral impairment (MBI) is associated with all‐cause dementia. Little is known about MBI’s effects on cognitive function among individuals in earlier disease stages, particularly in racially diverse samples. We examined relationships between MBI and cognitive decline in a richly characterized sample of white and African American...

Background The National Institutes of Health Toolbox for Assessment of Neurological and Behavioral Function (NIHTB) was developed to address the need for a brief yet comprehensive instrument to facilitate more uniform assessment in large‐scale research studies. Here, we investigated whether the cognitive measures of the NIHTB detect cognitive decli...

Background The sensitivity of amyloid to pre-analytic factors complicates cerebrospinal fluid (CSF) diagnostics for Alzheimer disease. We report reliability and validity evidence for automated immunoassays from frozen and fresh CSF samples in an ongoing, single-site research program. Methods CSF samples were obtained from 2 Wisconsin cohorts (1256...

Breakdown of the neurovascular unit is associated with blood-brain barrier (BBB) leakiness contributing to cognitive decline and disease pathology in the early stages of Alzheimer’s disease (AD). Vascular stability depends on angiopoietin-1 (ANGPT-1) signalling, antagonised by angiopoietin-2 (ANGPT-2) expressed upon endothelial injury. We examined...

Background Data suggest that establishing trust supports willingness to participate in research studies; yet there is a shortage of standardized systematic studies testing the effectiveness of various methods of building trust. The Building Bridges pilot study examined ways of establishing trust in communities of color comparing two different inter...

Background Changes in connected speech (CS; language used in everyday conversations) have been documented throughout the Alzheimer’s disease (AD) spectrum, including the very early stages of disease. Our group identified four factors comprised of 10 measures of CS: fluency, semantic content, lexical diversity, and grammatical complexity. We demonst...

Background Changes in connected speech (CS; language used in everyday conversations) have been documented throughout the Alzheimer’s disease (AD) spectrum, including the very early stages of disease. Our group identified four factors comprised of 10 measures of CS: fluency, semantic content, lexical diversity, and grammatical complexity. We demonst...

Background The cerebrospinal fluid (CSF) amyloid β‐negative and tau‐positive (A‐T+) biomarker profile, as defined by normal amyloid β42/40 ratio (Aβ42/40) and increased phosphorylated tau (p‐tau), is sometimes seen in daily clinical practice. However, knowledge is lacking on its prevalence and whether patients with this profile are at risk for biol...

Background Research investigating underrepresented groups’ willingness to engage in research has largely relied on qualitative research and/or specialized samples (e.g., patients’ first‐degree relatives). Moreover, extant quantitative studies include disproportionately small numbers of these participants. This investigation is from an ongoing proje...

Background Lower measures of myelin have been associated with abnormal levels of AD biomarkers and APOE4 carriage. However, most human studies have been cross‐sectional, leaving the relationship between AD and myelin changes unclear. The purpose of this study was to determine the association between AD pathology, APOE4, glial activation, and longit...

Background Vascular dysfunction often occurs concurrently with Alzheimer’s disease (AD). Breakdown of the blood–brain barrier (BBB) and vascular injury may be related to amyloid and tau pathology. In preliminary analyses, we examined the relationship between cerebrospinal fluid (CSF) biomarkers of AD, neurodegeneration, and glial activation, and tw...

Background Alzheimer’s disease (AD) and related dementias are public health concerns often with long preclinical phases. Thus, intervention and prevention methods in midlife could prove efficacious. Cerebrospinal fluid (CSF) biomarkers can change early in the disease process and have been utilized for dementia diagnostics. Multiple health‐related l...

Background Postmortem brain tissue analysis suggests that apolipoprotein E ( APOE ) ε4 is associated with lower brain myelination (Blanchard et al. 2022). However, in vivo evidence for this association is lacking. Here, we examined the relationship between APOE genotype and myelin content in the brain using multicomponent relaxometry (mcDESPOT) ima...

Background Cerebral spinal fluid (CSF) as a biomarker of Alzheimer’s disease (AD) is a helpful tool in diagnosing preclinical disease. While blood‐based biomarkers are becoming increasingly used for early detection, CSF collection is still necessary for validation of AD blood‐based biomarkers and for identification of biomarkers for other types of...

Background There is a need to better understand the role of modifiable risk factors in the development of racial/ethnic health disparities in Alzheimer’s disease (AD). In particular, research is lacking on how clinical risk scores may interact with genetic liability for dementia in diverse populations. Here, we examined the influence of the Cardiov...

Background Epidemiological evidence suggests that excess risk for Alzheimer’s disease and related dementias (ADRD) in minoritized populations is preventable. Social connectedness associates with reduced ADRD risk: plausible mechanisms include (I) direct influence on AD pathology, and (II) indirect influence through cognitive reserve processes. Incl...

Background The prodrome of cognitive declines and/or dementia may include late‐life neuropsychiatric symptoms such as apathy. In primarily non‐Hispanic White samples, apathy associates with both cognition and amyloid deposition in cognitively intact patients and those with Alzheimer’s disease (AD). However, little is known about these relationships...

Background Lower measures of myelin have been associated with abnormal levels of AD biomarkers and APOE4 carriage. However, most human studies have been cross‐sectional, leaving the relationship between AD and myelin changes unclear. The purpose of this study was to determine the association between AD pathology, APOE4, glial activation, and longit...

Introduction Metabolomics technology facilitates studying associations between small molecules and disease processes. Correlating metabolites in cerebrospinal fluid (CSF) with Alzheimer’s disease (AD) CSF biomarkers may elucidate additional changes that are associated with early AD pathology and enhance our knowledge of the disease. Methods The re...

Importance: Knowledge is lacking on the prevalence and prognosis of individuals with a β-amyloid-negative, tau-positive (A-T+) cerebrospinal fluid (CSF) biomarker profile. Objective: To estimate the prevalence of a CSF A-T+ biomarker profile and investigate its clinical implications. Design, setting, and participants: This was a retrospective...

Background Genetic scores for late-onset Alzheimer’s disease (LOAD) have been associated with preclinical cognitive decline and biomarker variations. Compared with an overall polygenic risk score (PRS), a pathway-specific PRS (p-PRS) may be more appropriate in predicting a specific biomarker or cognitive component underlying LOAD pathology earlier...

Background The NIH Toolbox was designed to provide brief, reliable, and valid measures of neurological and behavioral functions. Emotion assessment using the NIH Toolbox Emotion Battery has recently received significant attention given emerging evidence that emotional health is predictive of physical health and overall well‐being. The purpose of th...

Background Cerebrospinal fluid (CSF) concentration of soluble TREM2 (sTREM2), a potential biomarker for microglial activation, is associated with attenuated longitudinal neurodegeneration and cognitive decline in Alzheimer’s disease (AD), but data in early disease are lacking. This study’s purpose was to use longitudinal volumetric imaging to asses...

Background The apolipoprotein E gene (APOE) is the predominant genetic risk factor for late‐onset Alzheimer disease (AD), with three alleles contributing to disease risk and strongly associated with many AD endophenotypes: ε2 (reduced risk), ε3 (reference), and ε4 (increased risk). Researchers often include APOE ε4 carrier status (ε4+/‐) in analyse...

Chronic systemic inflammation increases the risk of neurodegeneration, but the mechanisms remain unclear. Part of the challenge in reaching a nuanced understanding is the presence of multiple risk factors that interact to potentiate adverse consequences. To address modifiable risk factors and mitigate downstream effects, it is necessary, although d...

Introduction: A hallmark of Alzheimer's disease (AD) is the aggregation of proteins (amyloid beta [A] and hyperphosphorylated tau [T]) in the brain, making cerebrospinal fluid (CSF) proteins of particular interest. Methods: We conducted a CSF proteome-wide analysis among participants of varying AT pathology (n = 137 participants; 915 proteins) w...

Modifiable factors can influence the risk for Alzheimer's disease (AD) and serve as targets for intervention; however, the biological mechanisms linking these factors to AD are unknown. This study aims to identify plasma metabolites associated with modifiable factors for AD, including MIND diet, physical activity, smoking, and caffeine intake, and...

Breakdown of the neurovascular unit in early Alzheimer’s disease (AD) leads to leakiness of the blood-brain barrier (BBB), contributing to cognitive decline and disease pathology. Vascular stability depends on angiopoietin-1 (ANGPT1) signalling, antagonised by angiopoietin-2 (ANGPT2) upon endothelial injury. We have examined the relationship betwee...

Introduction: Apolipoprotein E (APOE) ε4-carrier status or ε4 allele count are included in analyses to account for the APOE genetic effect on Alzheimer's disease (AD); however, this does not account for protective effects of APOE ε2 or heterogeneous effect of ε2, ε3, and ε4 haplotypes. Methods: We leveraged results from an autopsy-confirmed AD s...

Background Metabolic syndrome (MetS) has been associated with increased risk for Alzheimer’s disease and related dementias (ADRD). Understanding the association of MetS risk factors to processing speed and executive function in the pre-clinical stages of ADRD in under-represented groups would offer insight on potential mechanisms through which MetS...

Background Our understanding of the pathophysiology underlying Alzheimer’s disease (AD) has benefited from genomic analyses, including those that leverage polygenic risk score (PRS) models of disease. The use of functional annotation has been able to improve the power of genomic models. Objective We sought to leverage genomic functional annotation...

Background: Genetic scores for late-onset Alzheimer's disease (LOAD) have been associated with preclinical cognitive decline and biomarker variations. Compared with an overall polygenic risk score (PRS), a pathway-specific PRS (p-PRS) may be more appropriate in predicting a specific biomarker or cognitive component underlying LOAD pathology earlier...

Social isolation and loneliness contribute to cognitive decline, and social isolation represents a key modifiable risk factor for dementia. Substantial interruptions in social engagement due to the COVID‐19 pandemic have heightened awareness of this issue, but common later‐life events may also reduce social connectedness. The neurocognitive impacts...

Difficulty recalling proper names (PNs; e.g., names of people/places) is a common complaint of individuals at risk for Alzheimer’s disease (AD). We recently reported that cognitively unimpaired (CU), positron emission tomography amyloid‐beta (Aβ) positive (A+) individuals recalled fewer PNs than Aβ negative individuals on the Logical Memory (LM) de...

Several studies have shown the importance of establishing trust in supporting an individual’s willingness to participate in research; yet evidence is limited regarding systematic studies testing the effectiveness of various methods used to build trust. Our pilot study examined two methods of building trust in communities of color by measuring willi...

Cerebrospinal fluid (CSF) levels of neurogranin, an index of synaptic degeneration, and neurofilament light chain (NfL), an index of neuroaxonal degradation, are both biomarkers of neurodegeneration in Alzheimer’s disease (AD). The presence of APOE is the strongest genetic risk factor for late onset AD and has also been associated with increased CS...

Subjective memory complaints (SMC) are common in middle‐aged adults. Associations between SMC and cognitive ability have been inconsistent perhaps because SMC measures rarely specifically match measured cognitive domains. We examined the relationship between objective and subjective evaluations of participants’ ability to recall proper names. N = 1...

The National Alzheimer’s Coordinating Center (NACC) maintains a national database of clinical and cognitive data collected under a standard protocol set by the National Institute on Aging (NIA) called the Uniform Data Set (UDS). Development of factor scores unbiased by race/ethnicity will allow for comparison of other lifestyle and psychosocial fac...

The prevalence of clinical Alzheimer’s disease (AD) and type 2 diabetes is higher in African Americans (AA) relative to non‐Hispanic White Americans. Although diabetes is a risk factor for Alzheimer’s clinical syndrome, it is unclear whether diabetes associates with amyloid‐β, a pathological hallmark of AD. We investigated whether diabetic status w...

Gut bacterial metabolites in circulation and postmortem brain tissue differ in abundance between cognitively unimpaired (CU) and Alzheimer’s disease (AD) individuals. Furthermore, in mice chronic injection of bacterial components exacerbates AD pathology. In CSF, we found the microbially‐produced trimethylamine‐N‐oxide was linked to AD and neurodeg...

African Americans (AA) are under‐represented in Alzheimer’s disease (AD) biomarker research. Blood‐based biomarkers for AD offer the promise of greater diversity in research studies, but little is known about the performance of these biomarkers within an AA cohort. We examined the association between modifiable and non‐modifiable risk factors on th...

In an emerging biomarker era, scientists, clinicians and patients must trust that Alzheimer’s disease (AD) biomarkers are broadly applicable across populations. However, biomarker studies inadequately include minoritized populations – largely because biomarker collection is invasive and centralized, and outreach wholly insufficient. The AA‐FAIM stu...

Alzheimer’s disease (AD) models of disease progression have been built largely on non‐Hispanic White samples. Availability of AD blood‐based biomarkers may improve screening for AD risk and facilitate greater diversity in research studies; little is known about these biomarkers within African Americans (AA). Here, we characterized associations betw...

Exposure to psychosocial stress empirically associates with risk of cognitive impairment and dementia. Plausible mechanisms include (I) direct influence on AD pathology, and (II) indirect influence through cognitive reserve processes. Current evidence for modifiable determinants of amyloid and tau deposition is mixed, and stress has rarely been stu...

INTRODUCTION APOE ε4 -carrier status or ε4 allele count are included in analyses to account for the APOE genetic effect on Alzheimer’s disease (AD); however, this does not account for protective effects of APOE ε2 or heterogeneous effect of ε2, ε3, ε4 haplotypes. METHODS We leveraged results from an autopsy-confirmed AD study to generate a weighte...

Background Sphingomyelin (SM) levels have been associated with Alzheimer’s disease (AD), but the association direction has been inconsistent and research on cerebrospinal fluid (CSF) SMs has been limited by sample size, breadth of SMs examined, and diversity of biomarkers available. Objective Here, we seek to build on our understanding of the role...

Person-centered typologies identified with latent profile analysis can clarify patterns of chronic and acute risk factors for suicidal ideation. We derived five profiles of individuals using cognitive, behavioral, and familial factors relating to suicidal ideation risk factors. Participants (n = 1,142) were assessed at age 8 using the Laboratory Te...

We use the highly structured Laboratory-Temperament Assessment Battery to measure behaviors that map onto the Research Domain Criteria (RDoC) positive and negative valence systems. Using a birth record-based sample (N = 1374 individual twins; mean age 7.7 years), we created composites of observed behavior reflecting the RDoC constructs Reward Respo...

Psychological well-being is associated with cognition in later life but has not been examined across diverse populations—including minoritized communities at disproportionately high risk of dementia. Further, most previous work has not been able to examine links between specific facets of psychological well-being and performance within distinct cog...

INTRODUCTION Metabolomics technology facilitates studying associations between small molecules and disease processes. Correlating metabolites in cerebrospinal fluid (CSF) with Alzheimer’s disease (AD) CSF biomarkers may elucidate additional changes that are associated with early AD pathology and enhance our knowledge of the disease. METHODS The re...

Background Modifiable factors can influence the risk for Alzheimer’s disease (AD) and serve as targets for intervention; however, the biological mechanisms linking these factors to AD are unknown. This study aims to identify plasma metabolites associated with modifiable factors for AD, including MIND diet, physical activity, smoking, and caffeine i...

Temperament is central to later emerging psychopathology and may have clinicalutility for predicting the occurrence of symptoms. Often, temperament traits are examined inrelation to single disorders, even though evidence suggests that temperament is a transdiagnosticrisk factor. We examine how three factors of temperament at age 2 predict latent cl...

INTRODUCTION Sphingomyelin (SM) levels have been associated with Alzheimer’s disease (AD), but the association direction has been inconsistent and research on cerebrospinal fluid (CSF) SMs has been limited by sample size, breadth of SMs examined, and diversity of biomarkers available. METHODS Leveraging two longitudinal AD cohorts with metabolome-...

Background High subjective well‐being is a hallmark of successful aging, and growing evidence demonstrates its associations with better cognitive function and slowed decline in aging adults. To date, predominantly white study cohorts preclude an understanding of well‐being as a protective factor in minoritized populations. Using validated NIH Toolb...

Background A lumbar puncture (LP) is required to study cerebrospinal fluid (CSF) based biomarkers in preclinical Alzheimer’s Disease (AD). However, participants are often reluctant to undergo an LP due to fear. Insufficient data on the experiences of participants from underrepresented groups may contribute to their greater reluctance to agree to LP...

Background Subjective memory complaints (SMC) in the absence of impaired performance on objective measures increases risk for dementia among some individuals. Connected Speech Language (CSL) is language produced in a continuous sequence as in conversations. Subtle, yet detectable, changes in CSL have been shown to predict cognitive decline, suggest...

Background Subtle changes in connected speech language (CSL) comprising fluency disruptions and limited semantic content are present in preclinical stages of Alzheimer’s disease (AD) and dementia. Our prior research suggests that individuals identified by PET imaging as amyloid‐positive experience more rapid decline of semantic content than those w...

Background Research on menopausal hormone therapy (MHT) for the reduction/prevention of cognitive decline or Alzheimer’s disease has been inconsistent. The Women’s Health Initiative Memory Study (WHIMS) revealed elevated incident cognitive impairment for women starting MHT after age > 65 with oral conjugated equine estrogens (o‐CEE) treatment, espe...

Background Quantifying the temporal progression of key pathophysiological events in Alzheimer’s disease is crucial for staging disease, dementia risk assessment, and informing clinical trials. This work extends a novel algorithm (sampled iterative local linear approximation; SILLA) developed for modeling PET trajectories to: 1) generate a unified C...

Background This work examined heterogeneity in cognitive trajectories between amyloid(A) and tau(T) cerebrospinal fluid (CSF) stratified biomarker groups in late‐middle‐aged, initially cognitively unimpaired individuals. Additionally, candidate biomarkers of neurodegeneration were investigated for potential added value in predicting cognitive decli...

Background Several Alzheimer’s disease (AD) metabolomics studies in cerebrospinal fluid (CSF) and plasma identified associations between sphingomyelin metabolites (SMs) and AD. However, the results were inconsistent, potentially due to small sample sizes. They were limited in the AD, neurodegeneration, and neuroinflammation biomarkers available for...

Background Asymmetric binding patterns in tau PET imaging are sometimes observed, but less is known about how this asymmetry might explain clinical phenotypes and AD variants, especially in a longitudinal context. Previous work has demonstrated that unilateral tau deposition in left frontal and temporal regions is common in logopenic progressive ap...

Previous research assessing consequences of interpregnancy intervals (IPIs) on child development is mixed. Utilizing a population-based US sample (n=5,339), we first estimated the associations between background characteristics (e.g., sociodemographic and maternal characteristics) and short (≤ 1 year) and long (> 3 years) IPI. Then, we estimated as...

A major hallmark of Alzheimer's disease (AD) is the aggregation of misfolded proteins (β-amyloid (A) and hyperphosphorylated tau (T)) in the brain. As these proteins can be monitored by cerebrospinal fluid (CSF) measures, the AD proteome in CSF has been of particular interest. Here, we conducted a proteome-wide assessment of the CSF in an AD cohort...

Introduction: We investigated whether insulin resistance (IR) was associated with longitudinal age-related change in cognition and biomarkers of Alzheimer's disease (AD) pathology and neurodegeneration in middle-aged and older adults who were non-demented at baseline. Methods: IR was measured with homeostatic model assessment of insulin resistan...

Background The brain is the most cholesterol-rich organ and myelin contains 70% of total brain cholesterol. Statins are potent cholesterol-lowing medications used by millions of adults for prevention of vascular disease, yet the effect of statins on cholesterol-rich brain white matter (WM) is largely unknown. Methods We used longitudinal neuroimag...

Introduction: Connected speech and language (CSL) decline has been associated with early cognitive decline, but associations between CSL and Alzheimer's disease (AD) biomarkers remain a gap in the literature. Our goal was to examine associations with amyloid beta (Aβ) and longitudinal CSL trajectories in cognitively unimpaired adults at increased...

Introduction: Batch differences in cerebrospinal fluid (CSF) biomarker measurement can introduce bias into analyses for Alzheimer's disease studies. We evaluated and adjusted for batch differences using statistical methods. Methods: A total of 792 CSF samples from 528 participants were assayed in three batches for 12 biomarkers and 3 biomarker r...

Although our understanding of Alzheimer's disease (AD) has greatly improved in recent years, the root cause remains unclear, making it difficult to find effective diagnosis and treatment options. Our understanding of the pathophysiology underlying AD has benefited from genomic analyses, including those that leverage polygenic risk score (PRS) model...

Introduction: Neurite orientation dispersion and density imaging (NODDI), a multi-compartment diffusion-weighted imaging (DWI) model, may be useful for detecting early cortical microstructural alterations in Alzheimer's disease prior to cognitive impairment. Methods: Using neuroimaging (NODDI and T1-weighted magnetic resonance imaging [MRI]) and...

Clarifying longitudinal, behavioral predictors for adolescent suicidality could enhance prediction and treatment efforts. We examined whether childhood attentional focusing, persistence, and problem-solving behavior are associated with risk for adolescent suicidal ideation. Participants were 116 twins, 40 of whom endorsed active suicidal ideation (...

Background Studies using cerebrospinal fluid (CSF) biomarkers often combine CSF samples collected at different centers or assayed in different laboratories or batches, creating a clustered data structure. Such clustering needs to be controlled in the analysis of the combined data. Intraclass correlation coefficient (ICC), i.e., the ratio of the bet...

Background Insulin resistance (IR) has been related to increased risk for Alzheimer’s clinical syndrome. While some cross‐sectional studies have linked IR to Alzheimer’s disease (AD) pathology, others have been negative. We examined the relationship of IR to longitudinal cerebrospinal fluid (CSF) biomarkers of AD pathology, cerebral amyloid chronic...

Background Metabolic syndrome (MetS) in mid‐life is a known risk factor for Alzheimer’s disease & related dementias (ADRD). Racial and ethnic minorities represent under‐represented groups (URGs) in ADRD research. Targeted outreach, recruitment and retention initiatives broaden the reach of Alzheimer Disease Research Centers (ADRC) within prioritize...

Background There is growing interest in using digital biomarkers, like recorded spontaneous speech, as indicators of Alzheimer’s disease progression. Several studies have shown that changes in connected speech and language (CSL), including speech fluency markers and linguistic content, are associated with preclinical cognitive decline. Little is kn...

Background Variants within the gene‐rich membrane‐spanning 4‐domains subfamily A ( MS4A ) gene region have been associated with increased or reduced risk for Alzheimer's disease (AD) by large genome‐wide association studies (GWAS). Although MS4A family members are known to be cell membrane proteins implicated in immunity, their role in AD pathogene...

Background Cognitive decline in Alzheimer’s disease (AD) may be explained by degeneration of long myelinated axons in brain white matter. Neurofilament Light Chain (NFL) protein is a cytoplasmic protein in large caliber myelinated axons, released when neurodegenerative processes occur, and elevated in AD [(Preische et al., 2019), (Skillbäck et al.,...

Background The brain is the most cholesterol‐rich organ and myelin contains 70% of total brain cholesterol. Statins are potent cholesterol‐lowing medications used by millions of adults for prevention of cerebrovascular disease, yet the effect of statins on cholesterol‐rich brain white matter (WM) is largely unknown. In this study, diffusion tensor...

Background Both MCI and AD dementia are associated with decreased cortical microstructure as measured by neurite orientation dispersion and density imaging (NODDI). Specifically, in MCI, neurite density index (NDI) – but not cortical thickness – is decreased in several key AD regions, suggesting NODDI may be more sensitive than conventional structu...

Background Characterizing longitudinal changes in AD and neurodegeneration related CSF biomarkers in cognitively unimpaired adults is critical to distinguishing typical aging from disease pathology, Yet longitudinal change in established and especially emerging CSF biomarkers are not well characterized. We examined linear age trends in CSF biomarke...