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Introduction
My work has been in the field of Health Behavior Disease Prevention Research Methodology for over 30 years. I am a biostatistician engaged in the application of longitudinal modeling using a structural equation modeling framework investigating age-related cognitive decline. For the past 15 years I have also been engaged as an Autism epidemiologist investigating environmental exposure and individual susceptibility as contributors to the development of autism spectrum disorder.
Current institution
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January 2000 - December 2012
Publications
Publications (208)
INTRODUCTION
Alzheimer's disease (AD) biomarkers of Amyloid(A), Tau(T), and Neurodegeneration(N) have been increasingly studied to fill the gap in our understanding of racial and ethnic differences. This study aimed to examine the relationship between plasma AT(N) biomarkers and (1) AT(N) neuroimaging biomarkers, (2) demographics, (3) medical comor...
Aim
The goals of this investigation were to 1) identify and measure exposures inside homes of individuals with chemical intolerance (CI), 2) provide guidance for reducing these exposures, and 3) determine whether our environmental house calls (EHCs) intervention could reduce both symptoms and measured levels of indoor air contaminants.
Background...
Neuritic plaque (NP) formation can be dated in vivo. This analysis attempts to “date” the progression of neurofibrillary tangles (NFT) using the spatial distribution of NP as a reference. Autopsy data from 471 participants in the Honolulu-Asia Aging Study (HAAS) were combined into latent factor measures of NFT and NP counts. The variance in “early”...
Background: We sought to replicate our 2015 findings linking chemical intolerance in parents with the risk of their children developing autism and/or ADHD. Drawing upon our 2021 discovery of a strong association between chemical intolerance and mast cells, we propose an explanation for this link. Methods: In a population-based survey of U.S. adults...
Thank you for the opportunity to respond to the concerns raised by Ayoub-Charette et al [...]
Objectives
The impact of diabetes on quality of life (QoL) includes deficits in physical functioning and emotional and mental health. Individuals with diabetes can experience significant distress related to diabetes management and burden. Comorbid conditions can contribute to QoL among individuals with diabetes. Chemical Intolerance (CI) has receiv...
Chemical intolerance (CI) is characterized by multi-system symptoms initiated by a one-time high dose or persistent low-dose exposure to environmental toxicants. Symptoms of this “medically unexplained illness” often include fatigue, headache, weakness, rash, mood changes, musculoskeletal pain, gastrointestinal, difficulties with memory, concentrat...
INTRODUCTION
We tested the effect of statins on C‐reactive protein (CRP) and apolipoprotein E (APOE)'s associations with dementia severity.
METHODS
A total of 1725 participants of the Alzheimer's Disease Neuroimaging Initiative (ADNI) were assigned from 12‐month follow‐up data into the following groups: (1) ε4 (–)/statin (–), (2) ε4 (–)/statin (+)...
Background: Chemical Intolerance (CI) is characterized by intolerances for chemicals, foods, and drugs with multi-system symptoms. As yet, the biomechanism remains unclear. One study reported converging lines of evidence supporting a substantive association between mast cell activation syndrome (MCAS) and CI. The purpose of this study is to (1) con...
The Health and Aging Brain Study–Health Disparities (HABS–HD) project seeks to understand the biological, social, and environmental factors that impact brain aging among diverse communities. A common issue for HABS–HD is missing data. It is impossible to achieve accurate machine learning (ML) if data contain missing values. Therefore, developing a...
Background
Impairments in executive function (EF) are often attributed to ischemic cerebrovascular disease (ICVD) and frontal circuit pathology. However, EF can be distinguished from general intelligence and the latter is likely to manifest in “executive” measures. We aimed to distinguish the effects of imaging biomarkers on these constructs.
Meth...
Since its introduction, aspartame—the leading sweetener in U.S. diet sodas (DS)—has been reported to cause neurological problems in some users. In prospective studies, the offspring of mothers who consumed diet sodas/beverages (DSB) daily during pregnancy experienced increased health problems. We hypothesized that gestational/early-life exposure to...
Background
Worldwide observations point to a two-stage theory of disease called Toxicant-Induced Loss of Tolerance (TILT): Stage I, Initiation by an acute high-level or repeated lower-level chemical exposures, followed by Stage II, Triggering of multisystem symptoms by previously tolerated, structurally diverse chemical inhalants, foods/food additi...
Limited ancestral diversity has impaired our ability to detect risk variants more prevalent in non-European ancestry groups in genome-wide association studies (GWAS). We constructed and analyzed a multi-ancestry GWAS dataset in the Alzheimer Disease (AD) Genetics Consortium (ADGC) to test for novel shared and ancestry-specific AD susceptibility loc...
Background
In ageing adults, the most common form of dementia is Alzheimer’s disease (AD). AD pathogenesis involves the accumulation of beta‐amyloid (Aβ) protein aggregation in plaques and tau proteins in neurofibrillary tangles that are associated with a decreased number of synapses in the brain, altered neuronal function and cell death via neurot...
Background
Worldwide observations point to a two-stage theory of disease called Toxicant-Induced Loss of Tolerance (TILT): Stage I, Initiation by an acute high-level or repeated lower-level chemical exposures, followed by Stage II, Triggering of multisystem symptoms by previously tolerated, structurally diverse chemical inhalants, foods/food additi...
Aim
The goal of this investigation was to 1) identify exposure sources in the home, 2) teach occupants how to remove or replace them, and 3) determine whether measured levels and reported symptoms could be reduced by these changes.
Background
Chemical intolerance (CI) is an international public health and clinical concern, but few resources are ava...
Background
We have explored dementia’s blood-based protein biomarkers in the Texas Alzheimer’s Research and Care Consortium (TARCC) study. Among them are adipokines, i.e., proteins secreted by adipose tissue some of which have been associated with cognitive impairment.
Objective
To associate adipokines with dementia severity and replicate their as...
Atypical regulation of inflammation has been proposed in the etiology of autism spectrum disorder (ASD); however, measuring the temporal profile of fetal inflammation associated with future ASD diagnosis has not been possible. Here, we present a method to generate approximately daily profiles of prenatal and early childhood inflammation as measured...
Background
Chemical intolerance (CI) is a condition that may result in multisystem symptoms triggered by low levels of exposure to xenobiotics such as chemical inhalants, foods, and/or drugs. The population prevalence of self-reported chemical intolerance is estimated to be between 4 and 25% across several countries. Clinicians and researchers requ...
Type 2 diabetes mellitus (T2DM) at midlife increases dementia risk. Metabolic factors contribute more to Alzheimer’s disease (AD) risk in Mexican Americans (MA) than in non‐Hispanic Whites (NHW). However, most work relating T2DM to brain structure in older adults has been performed in NHWs. We evaluated how T2DM related to regional cortical thickne...
Neurodevelopmental regression (NDR) is an enigmatic event associated with autism spectrum disorder (ASD) during which a child loses previously acquired skills and develops ASD symptoms. In some, a trigger which precedes the NDR event, such as a fever, can be identified, but in many cases no trigger is obvious. We hypothesize that air pollution (PM2...
Purpose:
Improving patients' self-care for chronic disease is often elusive in the context of social deprivation. We evaluated whether a practice-integrated community health worker (CHW) intervention could encourage effective long-term self-management of type 2 diabetes mellitus (T2DM).
Methods:
This cohort study, in a safety-net primary care pr...
Background
Chemical Intolerance (CI) is characterized by multi-system symptoms initiated by exposures to environmental toxins. Symptoms include fatigue, headache, mood changes, musculoskeletal pain, gastro-intestinal issues, difficulties with memory/concentration. With mixed results, researchers have used targeted genetic approaches to understand t...
We reviewed published manuscripts from toxicology and epidemiology reporting harmful health effects and doses of persistent organic pollutants (POPs), published between 2000 and 2021. We found 42 in vitro , 32 in vivo , and 74 epidemiological studies and abstracted the dose associated with harm in a common Molar unit. We hypothesized that the dose...
Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 ris...
Aim
To determine whether environmental house calls that improved indoor air quality (IAQ) is effective in reducing symptoms of chemical intolerance (CI).
Background
Prevalence of CI is increasing worldwide. Those affected typically report symptoms such as headaches, fatigue, ‘brain fog’, and gastrointestinal problems – common primary care complain...
Background
This paper explores the relationship between chemical intolerance (CI) and mast cell activation syndrome (MCAS). Worldwide observations provide evidence for a two-stage disease process called toxicant-induced loss of tolerance (TILT) as a mechanism for CI. TILT is initiated by a major exposure event or a series of lower-level exposures....
Background
Chemical intolerance is a condition that may result in multisystem symptoms triggered by low levels of exposure to xenobiotics such as chemicals, foods, and drugs. The prevalence of chemical intolerance is estimated to be between 8% and 33% across several countries. Clinicians and researchers require a brief, practical tool for identifyi...
Background:
Chemical intolerance (CI) is characterized by multisystem symptoms triggered by low levels of exposure to xenobiotics including chemicals, foods/food additives, and drugs/medications. Prior prevalence estimates vary from 8-33% worldwide. Clinicians and researchers need a brief, practical screening tool for identifying possible chemical...
Recent research has pointed to the importance of the prenatal environment in the etiology of autism spectrum disorder (ASD) but the biological mechanisms which mitigate these environmental factors are not clear. Mitochondrial metabolism abnormalities, inflammation and oxidative stress as common physiological disturbances associated with ASD. Networ...
Keywords: Chemical Intolerance, Drug Intolerance, Food Intolerance, QEESI, BREESI, Multiple Chemical Sensitivity, Toxicant-induced Loss of Tolerance, Prevalence
Introduction:
Mexican Americans remain severely underrepresented in Alzheimer's disease (AD) research. The Health & Aging Brain among Latino Elders (HABLE) study was created to fill important gaps in the existing literature.
Methods:
Community-dwelling Mexican Americans and non-Hispanic White adults and elders (age 50 and above) were recruited....
Background
Despite 15–36% of the U.S. population reporting Chemical Intolerances (CI) or sensitivity, the condition has been overlooked in medicine and public health. CI is characterized by multisystem symptoms and new-onset intolerances that develop in a subset of individuals following a major chemical exposure event or repeated low-level exposure...
Background
Worldwide observations provide evidence for a two-stage disease process called Toxicant-Induced Loss of Tolerance (TILT), described in this journal in the first of two related papers. The disease process is initiated by a major exposure event, or a series of lower level exposures (Stage I, Initiation). Subsequently, affected individuals...
We investigate the role of the mitochondrion, an organelle highly sensitive to environmental agents, in the influence of prenatal air pollution exposure on neurodevelopment and behavior in 96 children with autism spectrum disorder (ASD) [45 with neurodevelopmental regression (NDR); 76% Male; mean (SD) age 10 y 9 m (3 y 9 m)]. Mitochondrial function...
We propose that the mitochondrion, an essential cellular organelle, mediates the long-term prenatal environmental effects of disease in autism spectrum disorder (ASD). Many prenatal environmental factors which increase the risk of developing ASD influence mitochondria physiology, including toxicant exposures, immune activation, and nutritional fact...
Background
The latent variable δ homolog (dEQ) has been established as a reliable indicator of cognitive performance and a predictor of future dementia. Here, we sought to identify genetic variants underlying dEQ in both non‐Hispanic White (NWH) and Mexican American (MA) populations, hypothesizing that novel genomic risk loci for dementia will be i...
The Quick Environmental Exposure and Sensitivity Inventory (QEESI) is a validated questionnaire used worldwide to assess intolerances to chemicals, foods, and drugs, and has emerged as the gold standard for assessing chemical intolerance (CI). Despite a reported prevalence of 8–33%, epidemiological studies and routine primary care clinics rarely as...
Neurodevelopmental regression (NDR) is a subtype of autism spectrum disorder (ASD) that manifests as loss of previously acquired developmental milestones. Early life dysregulation of nutritional metals and/or exposure to toxic metals have been associated with ASD, but the underlying biological mechanisms by which metals influence neurodevelopment r...
Objectives
Dementia severity is strongly related to Spearman's general intelligence factor “g ”, via the latent dementia phenotype “δ” and is distinct from domain‐specific cognitive impairments arising from disease‐specific regional pathologies. It is an empiric question whether Behavioral and Psychological Symptoms of Dementia (BPSD) are associate...
Background: The 50-item Quick Environmental Exposure and Sensitivity Inventory (QEESI) is a validated questionnaire used worldwide to assess intolerances to chemicals, foods, and/or drugs and has become the gold standard for assessing chemical intolerance (CI). Despite a reported prevalence of 8-33%, CI often goes undiagnosed in epidemiological stu...
Introduction:
Dementia severity can be empirically described by the latent dementia phenotype "δ" and its various composite "homologs". We have explored δ's blood-based protein biomarkers in the Texas Alzheimer's Research and Care Consortium (TARCC) study. However, it would be convenient to replicate those associations in the Alzheimer's Disease N...
Dementia severity can be quantitatively described by the latent dementia phenotype “δ” and its various composite “homologs”. We have explored δ’s blood-based protein biomarkers in the Texas Alzheimer’s Research and Care Consortium. However, it would be convenient to replicate them in the Alzheimer’s Disease Neuroimaging Initiative. To that end, we...
“δ” is a transdiagnostic omnibus dementia severity measure derived from general intelligence (i.e., Spearman’s “g”). It can be estimated in any cognitive battery that contains a measure of Instrumental Activities of Daily Living (IADL). As dementia’s essential cognitive impairment, δ may also explain the appearance of Behavioral and Psychological S...
The latent construct “d” (for “dementia”) offers a continuously distributed transdiagnostic dementia severity metric. Age is significantly associated with “d”. We test whether frailty mediates age’s effect on 6 year prospective change in dementia severity in Mexican-Americans (MA), using data from the Hispanic Established Population for Epidemiolog...
Purpose:
This study's purpose was to examine the processes and the potential for dental practitioners to address environmental health exposure risks to their patients through dental practice-based research participation. To explore this, the South Texas Oral Health Network (STOHN) initiated a collaboration with The Tooth Fairy National Study inves...
Background
We tested certain serum proteins’ ability to mediate the effects of demographic variables on prospective 5yr conversion to clinical “Alzheimer’s Disease” (AD) from non-demented states [i.e., Normal Control (NC) and Mild Cognitive Impairment (MCI)]. The proteins were rationally selected from among previously published mediators of those s...
Objective: Global factors have been identified in measures of cognitive performance (i.e., Spearman's g) and psychopathology (i.e., "General Psychopathology", "p"). Dementia is also strongly determined by the latent phenotype "δ", derived from g. We wondered if the Behavior and Psychological Symptoms of Dementia (BPSD) might arise from an associati...
The latent variable “δ” (for “dementia”) provides an etiologically “agnostic” omnibus dementia severity metric capable of recognizing the dementing potential of any condition. Depressive symptoms are independent predictors of δ and are thereby implicated as “dementing”. Serum resistin levels partially mediate the association between depressive symp...
Background
The latent variable “δ” (for “dementia) is a transdiagnostic measure of dementia severity. δ can be reified and applied to individuals as a composite “d-score”. Like Spearman’s general intelligence factor “g”, δ can be constructed from almost any cognitive battery. So many are available that we must further distinguish each composite as...
BACKGROUND
The adipokine adiponectin (APN)’s role in Alzheimer’s disease (AD) is controversial. Some studies suggest APN is neuroprotective while others propose it has harmful effects. We have used Multiple Indicators Multiple Causes (MIMIC) models to evaluate the effects of serum protein biomarkers on cognitive performance in the Texas Alzheimer's...
Dementia can be empirically described by the latent dementia phenotype “δ” and its various composite “homologs”. We have explored δ’s blood-based protein biomarkers in the Texas Alzheimer’s Research and Care Consortium (TARCC) study. However, it would be convenient to replicate those associations in the Alzheimer’s Disease Neuroimaging Initiative (...
Metals are critical to neurodevelopment, and dysregulation in early life has been documented in autism spectrum disorder (ASD). However, underlying mechanisms and biochemical assays to distinguish ASD cases from controls remain elusive. In a nationwide study of twins in Sweden, we tested whether zinc-copper cycles, which regulate metal metabolism,...
The "δ" (for "dementia") is a latent dementia phenotype that can be constructed by a unique confirmatory bifactor model in a structural equation model framework. Because it is derived from Spearman's general intelligence factor, "g," δ can be constructed from any cognitive battery. This may allow for accurate dementia case-finding by telephone and...
Background
Attending rounds remain the primary venue for formal teaching and learning at academic medical centers. Little is known about the effect of increasing clinical demands on teaching during attending rounds.Objective
To explore the relationships among teaching time, teaching topics, clinical workload, and patient complexity variables.Design...
Mitoplasticity occurs when mitochondria adapt to tolerate stressors. Previously we hypothesized that a subset of lymphoblastoid cell lines (LCLs) from children with autistic disorder (AD) show mitoplasticity (AD-A), presumably due to previous environmental exposures; another subset of AD LCLs demonstrated normal mitochondrial activity (AD-N). To be...
Describes data from the collaboration of STOHN and The Tooth Fairy project.
The purpose of this new collaboration between the South Texas Oral Health Network (STOHN), the national Tooth Fairy Study, and the Hoffman Tilt Program was to collect deciduous control teeth as controls and increase knowledge and awareness of practitioners to grow their c...
The latent variable “δ” (for “dementia”) uniquely explains dementia severity. Depressive symptoms are independent predictors of δ. We explored 115 serum proteins as potential causal mediators of the effect of depressive symptoms on δ in a large, ethnically diverse, longitudinal cohort. All models were adjusted for age, apolipoprotein E, education,...
The latent variable “δ” (for “dementia”) appears to be uniquely responsible for the dementing aspects of cognitive impairment. Age, depression, gender and the apolipoprotein E (APOE) e4 allele are independently associated with δ. In this analysis, we explore serum proteins as potential mediators of APOE’s specific association with δ in a large, eth...
Introduction
We tested the latent variable ??? (for ?dementia?)'s ability to predict conversion to ?mild cognitive impairment? (MCI) and Alzheimer's disease (AD).
Methods
An ethnicity equivalent d homolog (?dEQ?) was constructed in n = 1113 Mexican- American (MA) and n = 1958 non-Hispanic white (NHW) participants in the Texas Alzheimer's Research...
Introduction: We tested the latent variable " d " (for " dementia ")'s ability to predict conversion to " mild cognitive impairment " (MCI) and Alzheimer's disease (AD). Methods: An ethnicity equivalent d homolog (" dEQ ") was constructed in n 5 1113 Mexican-American (MA) and n 5 1958 non-Hispanic white (NHW) participants in the Texas Alzheimer's R...
The latent variable "δ" (for "dementia") appears to be uniquely responsible for the dementing aspects of cognitive impairment. Age, depressive symptoms, gender and the apolipoprotein E (APOE) ε4 allele are independently associated with δ. In this analysis, we explore serum proteins as potential mediators of age's specific association with δ in a la...
Background:
The latent variable “δ” has been validated as a dementia phenotype. δ can be extracted from Spearman’s general intelligence factor “g” in any data set that contains measures of cognition and instrumental activities of daily living (IADL). We used δ composites (“d-scores”) to estimate the prevalence of dementia in the Hispanic Establishe...
Although interactions within veterans' families may support or inhibit resilient coping to stress and trauma across the deployment cycle, research on family resilience has been hampered by the lack of a brief assessment. Using a three-stage mixed-method study, we developed and conducted preliminary validation of a measure of family resilience tailo...
Structural Equation Models (SEM) can explicitly distinguish "dementia-relevant" variance in cognitive task performance (i.e., "δ" for dementia). In prior work, δ appears to uniquely account for dementia severity regardless of the cognitive measures used to construct it. In this study, we test δ as a mediator of age's prospective association with fu...
Purpose:
Current strategies for improving diet and activity patterns focus on encouraging patients to make better choices, but they meet with limited success. Because the choices people make depend on the choices they have, we examined how practical opportunities for diet and physical activity shape behavioral intentions and achieved behaviors.
M...
Introduction:
Serum thrombopoietin (THPO) is a biomarker of Alzheimer's disease (AD) and the latent dementia phenotype, "δ". Both associations may be specific to non-Hispanic whites (NHW), not Mexican-Americans (MA). In this analysis, we examine ethnicity's effect on THPO's association with change in δ scores, in the Texas Alzheimer's Research and...
Objective:
To test a conceptual model of relationships, reflection, sensemaking, and learning in primary care practices transitioning to patient-centered medical homes (PCMH).
Data sources/study setting:
Primary data were collected as part of the American Academy of Family Physicians' National Demonstration Project of the PCMH.
Study design:
W...
“δ”, a latent variable constructed from cognitive performance and functional status measures, can accurately diagnose dementia. The minimal assessment needed is unknown. We have constructed a δ homolog, “dTEXAS”, from Telephone Executive Assessment Scale (TEXAS) items, and validated it in a convenience sample of Japanese persons (n = 176). dTEXAS s...
The latent variable “δ”, can accurately diagnose dementia. Its generalizability across populations is unknown. We constructed a δ homolog (“dT2J”) in data collected by the Texas Alzheimer’s Research and Care Consortium (TARCC). From this, we calculated a composite d-score “d”. We then tested d’s generalizability across random subsets of TARCC parti...
Background
Structural equation models (SEM) can explicitly distinguish dementia-relevant variance in cognitive task performance. The resulting latent construct “δ” (for dementia) provides a relatively “error free” continuously varying dementia-specific phenotype.
Objective
To estimate δ’s change over time (Δδ) and determine Δδ’s predictive validit...
Biological samples are an important part of investigating toxic exposures and disease outcomes. However, blood, urine, saliva, or hair can only reflect relatively recent exposures. Alternatively, deciduous teeth have served as a biomarker of early developmental exposure to heavy metals, but little has been done to assess organic toxic exposures suc...
The aim of this study was to assess whether chemically intolerant women are at greater risk for having a child with autism spectrum disorders (ASD) or attention deficit hyperactivity disorder (ADHD).
We conducted a case-control study of chemical intolerance among mothers of children with ASD (n = 282) or ADHD (n = 258) and children without these di...
Sensemaking is the social act of assigning meaning to ambiguous events. It is recognized as a means to achieve high reliability. We sought to assess sensemaking in daily patient care through examining how inpatient teams round and discuss patients.
Our purpose was to assess the association between inpatient physician team sensemaking and hospitaliz...
We have used structural equation models to explicitly distinguish functional status and therefore "dementia-relevant" variance in cognitive task performance (i.e., "δ" for dementia). Our approach is modular and can be directed to other targets. In this analysis, we construct a δ ortholog representing the "cognitive correlates of age" (cAGE). cAGE l...
Interleukin (IL-15), a pro-inflammatory cytokine has been studied as a possible marker of Alzheimer's disease (AD); however its exact role in neuro-inflammation or the pathogenesis AD is not well understood yet. A Multiple Indicators Multiple Causes (MIMIC) approach was used to examine the relationship between serum IL-15 levels and AD in a well ch...
Objective: “δ”, a latent variable constructed from batteries that contain both cognitive and functional status measures, can accurately diagnose dementia relative to expert clinicians. The minimal assessment needed is unknown. Methods: We validated 2 δ homologs in a convenience sample of elderly Japanese persons with normal cognition (NC), mild cog...
Background:
Screening, brief intervention, and referral to treatment (SBIRT) is an efficacious and cost-effective skill set when implemented in primary care settings regarding hazardous alcohol use. This study assesses the impact of medical resident SBIRT training across 3 specialties and identifies predictors of change in trainee behavior, attitu...
IMPORTANCEImproving inpatient care delivery has historically focused on improving individual components of the system. Applying the complexity science framework to clinical systems highlights the important role of relationships among providers in influencing system function and clinical outcomes.OBJECTIVE
To understand whether inpatient medical phy...
Vitamin D binding protein (VDBP), a multifunctional protein, has been found to be elevated in the cerebrospinal fluid (CSF) of neurodegenerative disorder cases, implicating it in the pathogenesis of Alzheimer's disease (AD). However, the contribution of VDBP to AD has not been fully explored. We used a Multiple Indicators Multiple Causes (MIMIC) ap...
We have employed structural equation models to explicitly distinguish functional status, and therefore “dementia-relevant” variance in cognitive task performance (i.e., “δ”). We previously associated δ with cytokines and other serum biomarkers in a well characterized Alzheimer's disease cohort, the Texas Alzheimer's Research and Care Consortium. Ho...
The empirical foundation of executive control function (ECF) remains controversial. We have employed structural equation models (SEM) to explicitly distinguish domain-specific variance in executive function (EF) performance from memory (MEM) and shared cognitive performance variance, i.e., Spearman's "g." EF does not survive adjustment for both MEM...