Danielle Harvey

University of California, Davis, Davis, California, United States

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Publications (108)620.71 Total impact

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    ABSTRACT: It is recognized that individuals with mild cognitive impairment (MCI) already demonstrate difficulty in aspects of daily functioning, which predicts disease progression. This study examined the relationship between self- versus informant-report of functional ability, and how those reports relate to objective disease measures across the disease spectrum (i.e. cognitively normal, MCI, Alzheimer's disease). A total of 1080 subjects with self- and/or informant-rated Everyday Cognition questionnaires were included. Objective measures included cognitive functioning, structural brain atrophy, cerebrospinal fluid abnormalities, and a marker of amyloid deposition using positron emission tomography with [18F]AV45 (florbetapir). Overall, informant-report was consistently more associated with objective markers of disease than self-report although self-reported functional status may still have some utility in early disease.
    Alzheimer's & Dementia. 11/2014;
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    ABSTRACT: Both traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are common problems resulting from military service, and both have been associated with increased risk of cognitive decline and dementia resulting from Alzheimer's disease (AD) or other causes. This study aims to use imaging techniques and biomarker analysis to determine whether traumatic brain injury (TBI) and/or PTSD resulting from combat or other traumas increase the risk for AD and decrease cognitive reserve in Veteran subjects, after accounting for age. Using military and Department of Veterans Affairs records, 65 Vietnam War veterans with a history of moderate or severe TBI with or without PTSD, 65 with ongoing PTSD without TBI, and 65 control subjects are being enrolled in this study at 19 sites. The study aims to select subject groups that are comparable in age, gender, ethnicity, and education. Subjects with mild cognitive impairment (MCI) or dementia are being excluded. However, a new study just beginning, and similar in size, will study subjects with TBI, subjects with PTSD, and control subjects with MCI. Baseline measurements of cognition, function, blood, and cerebrospinal fluid biomarkers; magnetic resonance images (structural, diffusion tensor, and resting state blood-level oxygen dependent (BOLD) functional magnetic resonance imaging); and amyloid positron emission tomographic (PET) images with florbetapir are being obtained. One-year follow-up measurements will be collected for most of the baseline procedures, with the exception of the lumbar puncture, the PET imaging, and apolipoprotein E genotyping. To date, 19 subjects with TBI only, 46 with PTSD only, and 15 with TBI and PTSD have been recruited and referred to 13 clinics to undergo the study protocol. It is expected that cohorts will be fully recruited by October 2014. This study is a first step toward the design and statistical powering of an AD prevention trial using at-risk veterans as subjects, and provides the basis for a larger, more comprehensive study of dementia risk factors in veterans.
    Alzheimer's and Dementia 06/2014; 10(3):S226–S235. · 17.47 Impact Factor
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    ABSTRACT: Chromosome 22q11.2 deletion syndrome (22q11.2DS), fragile X syndrome (FXS), and Turner syndrome (TS) are complex and variable developmental syndromes caused by different genetic abnormalities; yet, they share similar cognitive impairments in the domains of numbers, space, and time. The atypical development of foundational neural networks that underpin the attentional system is thought to result in further impairments in higher-order cognitive functions. The current study investigates whether children with similar higher-order cognitive impairments but different genetic disorders also show similar impairments in alerting, orienting and executive control of attention. Girls with 22q11.2DS, FXS, or TS and typically developing (TD) girls, aged 7 to 15 years, completed an attention network test, a flanker task with alerting and orienting cues. Exploration of reaction times and accuracy allowed us to test for potential commonalities in attentional functioning in alerting, orienting and executive control. Linear regression models were used to test whether the predictors of group and chronological age were able to predict differences in attention indices. Girls with 22q11.2DS, FXS, or TS demonstrated unimpaired function of the alerting system and impaired function of the executive control system. Diagnosis-specific impairments were found such that girls with FXS made more errors and had a reduced orienting index, while girls with 22q11.2DS showed specific age-related deficits in the executive control system. These results suggest that the control but not the implementation of attention is selectively impaired in girls with 22q11.2DS, TS or FXS. Additionally, the age effect on executive control in girls with 22q11.2DS implies a possible altered developmental trajectory.
    Journal of Neurodevelopmental Disorders 03/2014; 6(1):5. · 3.45 Impact Factor
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    ABSTRACT: Abstract Individuals with chromosome 22q11.2 deletion syndrome (22q11.2DS) have been shown to have impairments in processing spatiotemporal information. The authors examined whether children with 22q11.2DS exhibit impairments in spatial working memory performance due to these weaknesses, even when controlling for maintenance of attention. Children with 22q11.2DS (n = 47) and typically developing controls (n = 49) ages 6-15 years saw images within a grid and after a delay, then indicated the positions of the images in the correct temporal order. Children with 22q11.2DS made more spatial and temporal errors than controls. Females with 22q11.2DS made more spatial and temporal errors than males. These results extend findings of impaired spatiotemporal processing into the memory domain in 22q11.2DS by documenting their influence on working memory performance.
    American Journal on Intellectual and Developmental Disabilities 03/2014; 119(2):115-132. · 2.08 Impact Factor
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    ABSTRACT: Fragile X premutation carriers (fXPC) are characterized by 55-200 CGG trinucleotide repeats in the 5' untranslated region on the Xq27.3 site of the X chromosome. Clinically, they are associated with the fragile X-Associated Tremor/Ataxia Syndrome, a late-onset neurodegenerative disorder with diffuse white matter neuropathology. Here, we conducted first-ever graph theoretical network analyses in fXPCs using 30-direction diffusion-weighted magnetic resonance images acquired from 42 healthy controls aged 18-44 years (HC; 22 male and 20 female) and 46 fXPCs (16 male and 30 female). Globally, we found no differences between the fXPCs and HCs within each gender for all global graph theoretical measures. In male fXPCs, global efficiency was significantly negatively associated with the number of CGG repeats. For nodal measures, significant group differences were found between male fXPCs and male HCs in the right fusiform and the right ventral diencephalon (for nodal efficiency), and in the left hippocampus [for nodal clustering coefficient (CC)]. In female fXPCs, CC in the left superior parietal cortex correlated with counting performance in an enumeration task. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Human Brain Mapping 02/2014; · 6.88 Impact Factor
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    ABSTRACT: The everyday functional capacities of older adults are determined by multiple factors. The primary goal of the present study was to evaluate whether apathy and depression have unique influences on degree of functional impairment, independent of the effects of specific cognitive impairments. Participants included 344 older adults (199 normal, 87 with MCI, 58 with dementia). The Everyday Cognition (ECog) scales were used to measure both global and domain-specific functional abilities. Neuropsychiatric symptoms of depression and apathy were measured by the Neuropsychiatric Inventory (NPI), and specific neuropsychological domains measured included episodic memory and executive functioning. Results indicated that worse memory and executive function, as well as greater depression and apathy, were all independent and additive determinants of poorer functional abilities. Apathy had a slightly more restricted effect than the other variables across the specific functional domains assessed. Secondary analysis suggested that neuropsychiatric symptoms may be more strongly associated with everyday function within cognitively normal and MCI groups, while cognitive impairment is more strongly associated with everyday function in dementia. Thus, a somewhat different set of factors may be associated with functional status across various clinical groups.
    The Clinical Neuropsychologist 02/2014; · 1.68 Impact Factor
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    ABSTRACT: Background It is unknown which commonly used Alzheimer disease (AD) biomarker values—baseline or progression—best predict longitudinal cognitive decline. Methods 526 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). ADNI composite memory and executive scores were the primary outcomes. Individual-specific slope of the longitudinal trajectory of each biomarker was first estimated. These estimates and observed baseline biomarker values were used as predictors of cognitive declines. Variability in cognitive declines explained by baseline biomarker values was compared with variability explained by biomarker progression values. Results About 40% of variability in memory and executive function declines was explained by ventricular volume progression among mild cognitive impairment patients. A total of 84% of memory and 65% of executive function declines were explained by fluorodeoxyglucose positron emission tomography (FDG-PET) score progression and ventricular volume progression, respectively, among AD patients. Conclusions For most biomarkers, biomarker progressions explained higher variability in cognitive decline than biomarker baseline values. This has important implications for clinical trials targeted to modify AD biomarkers.
    Alzheimer's & Dementia. 01/2014;
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    ABSTRACT: Generalized linear mixed models were used to examine longitudinal trajectories of everyday functional limitations by diagnostic stability/progression. Older adults (N = 384) were followed an average 3.6 years; participants were grouped by diagnosis at study baseline and last follow-up (normal cognition, Mild Cognitive Impairment, or dementia at each time point). At study baseline there were clear group differences; most notably among participants initially characterized as cognitively normal, those who developed Mild Cognitive Impairment or dementia over follow-up already demonstrated greater functional impairment compared with those who remained cognitively normal. Change in functional impairment progressed slowly in the early disease groups, but showed an accelerated worsening in those converting to dementia. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
    Psychology and Aging 12/2013; 28(4):1070-5. · 2.73 Impact Factor
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    ABSTRACT: Patients with multiple sclerosis (MS) demonstrate thinning of peripapillary retinal nerve fiber layer (RNFL) and decreased macular volume as measured by optical coherence tomography (OCT). To our knowledge, there are no previous reports from a large MS OCT database with strict quality control measures that quantitate RNFL and macula in patients with relapsing-remitting multiple sclerosis. The University of California Davis OCT Reading Center gathered OCT data at baseline as part of the North American phase 3 trial of fingolimod (Gilenya). Average RNFL thickness (RNFLT) and macular volume (TMV) were measured using time domain OCT (TD-OCT). RNFL quadrants, clock hours, and macular subfields were included. With strict quality control and accounting for signal strength differences, scans were categorized as "reduced" or "not reduced" for each field, based on being less than 5th percentile for age-matched controls derived from the normative database in the scanner software. Patients were deemed "abnormal" if at least 1 eye had reduced values for a given parameter. Patients with abnormalities in corresponding RNFL and macular subfields were compared by cross-tabulation. The TD-OCT data were prospectively collected from 939 of the 1,083 trial patients, 712 of whom met all final quality and data inclusion criteria. Of the final cohort, 242 (34.0%) demonstrated reduced (less than 5th percentile) average RNFLT in at least 1 eye. One hundred seventy-eight (25.0%) patients had reduced TMV. One hundred twenty-eight (18.0%) demonstrated both reduced TMV and RNFLT in the same eye, whereas 42 (5.8%) had reduced TMV and RNFLT in both eyes. Of the 242 patients with reduced average RNFL thickness, 128 (52.9%) also had reduced TMV. Fifty patients had reduced TMV in the absence of reduced RNFLT in at least 1 eye, a cohort prevalence of 7.0%. Quadrant and subfield analysis showed a predominance of temporal and inferior RNFL thinning, with inferior macular thinning corresponding best to RNFL thinning. RNFL and macular thinning/volume loss is common at baseline in relapsing-remitting multiple sclerosis, as measured by TD-OCT. When the RNFL is thin, the macular volume is reduced in more than half of the patients. There is a population of reduced TMV without any reduction in RNFLT. Documenting the prevalence and distribution of these structural abnormalities supports recent reports and suggests new retinal areas to probe for functional vision changes in MS.
    Journal of neuro-ophthalmology: the official journal of the North American Neuro-Ophthalmology Society 09/2013; · 1.09 Impact Factor
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    ABSTRACT: To compare the quality of care delivered to critically ill and injured children receiving telemedicine, telephone, or no consultation in rural emergency departments. Retrospective chart review with concurrent surveys. Three hundred twenty patients presenting in the highest triage category to five rural emergency departments with access to pediatric critical care consultations from an academic children's hospital. Quality of care was independently rated by two pediatric emergency medicine physicians applying a previously validated 7-point implicit quality review tool to the medical records. Quality was compared using multivariable linear regression adjusting for age, severity of illness, and temporal trend. Referring physicians were surveyed to evaluate consultation-related changes in their care. Parents were also surveyed to evaluate their satisfaction and perceived quality of care. In the multivariable analysis, with the no-consultation cohort as the reference, overall quality was highest among patients who received telemedicine consultations (n = 58; β = 0.50 [95% CI, 0.17-0.84]), intermediate among patients receiving telephone consultation (n = 63; β = 0.12 [95% CI, -0.14 to 0.39]), and lowest among patients receiving no consultation (n = 199). Referring emergency department physicians reported changing their diagnosis (47.8% vs 13.3%; p < 0.01) and therapeutic interventions (55.2% vs 7.1%; p < 0.01) more frequently when consultations were provided using telemedicine than telephone. Parent satisfaction and perceived quality were significantly higher when telemedicine was used, compared with telephone, for six of the seven measures. Physician-rated quality of care was higher for patients who received consultations with telemedicine than for patients who received either telephone or no consultation. Telemedicine consultations were associated with more frequent changes in diagnostic and therapeutic interventions, and higher parent satisfaction, than telephone consultations.
    Critical care medicine 08/2013; · 6.37 Impact Factor
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    ABSTRACT: The purpose of this study was to evaluate how demographic variables relate to cognitive change and address whether cross-sectional demographic effects on cognitive tests are mirrored in differences in longitudinal trajectories of cognitive decline. We hypothesized that race and ethnicity, education, and language of test administration would relate to cross-sectional status and that the rate of cognitive decline would differ among African Americans, Hispanics, and Caucasians, across levels of educational attainment, and according to linguistic background. Participants were 404 educationally, ethnically, and cognitively diverse older adults enrolled in an ongoing longitudinal study of cognition. Mixed-effects regression analysis was used to measure baseline status and longitudinal change in episodic memory, executive functioning, and semantic memory. Results showed that ethnicity and education were strongly associated with baseline scores, but were, at most, weakly associated with change in cognition over time after accounting for confounding variables. There was evidence that the episodic-memory scores of Spanish-speaking Hispanic participants with limited education underestimated their true abilities in the initial evaluation, which may reflect lack of familiarity with the testing environment. These results-consistent with other reports in the literature-suggest that cross-sectional effects of demographic variables on cognitive-test scores result from differences in life experiences that directly influence test performance and do not indicate greater disease effects on cognition in minorities and those with limited education. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
    Psychology and Aging 02/2013; · 2.73 Impact Factor
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    ABSTRACT: The recently developed Everyday Cognition scales (ECog) measure multiple cognitively relevant functional domains (e.g., Everyday Memory, Everyday Language, Everyday Visuospatial abilities, and three everyday executive domains). The present study further evaluated the validity of the ECog by examining its relationship with objective measures of neuropsychological function, and neurobiological markers of disease as reflected by structural neuroimaging. Participants included 474 older adults (244 normals, 142 with MCI, 88 with dementia). The neuropsychological domains measured were episodic memory, semantic memory, spatial ability, and executive functioning. Brain MRI volumes included total brain (BV), hippocampus (HC) and dorsolateral prefrontal cortex (DLPFC). Neuropsychological measures of episodic memory and executive function were most consistently related to the ECog domains; spatial abilities had a specific relationship to the Everyday Visuospatial ECog domain. HC and BV volumes were related to most ECog domains, while DLPFC volume was independently related to two everyday executive domains (Everyday Planning and Everyday Organization). The pattern of associations varied somewhat as a function of diagnosis. Episodic memory and HC had more consistent associations with the ECog domains in older adults with MCI/dementia than in cognitively normal elderly. (JINS, 2013, 19, 1-12).
    Journal of the International Neuropsychological Society 02/2013; · 2.70 Impact Factor
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    ABSTRACT: BACKGROUND: A previous study reported enhanced psychomotor speed, and subtle but significant cognitive impairments, modulated by age and by mutations in the fragile X mental retardation 1 (FMR1) gene in adult female fragile X premutation carriers (fXPCs). Because male carriers, unlike females, do not have a second, unaffected FMR1 allele, male fXPCs should exhibit similar, if not worse, impairments. Understanding male fXPCs is of particular significance because of their increased risk of developing Fragile X-associated tremor/ataxia syndrome (FXTAS). METHODS: Male fXPCs (n = 18) and healthy control (HC) adults (n = 26) aged less than 45 years performed two psychomotor speed tasks (manual and oral) and two visuospatial tasks (magnitude comparison and enumeration). In the magnitude comparison task, participants were asked to compare and judge which of two bars was larger. In the enumeration task, participants were shown between one and eight green bars in the center of the screen, and asked to state the total number displayed. Enumeration typically proceeds in one of two modes: subitizing, a fast and accurate process that works only with a small set of items, and counting, which requires accurate serial-object detection and individuation during visual search. We examined the associations between the performance on all tasks and the age, full-scale intelligent quotient, and CGG repeat length of participants. RESULTS: We found that in the magnitude comparison and enumeration tasks, male fXPCs exhibited slower reaction times relative to HCs, even after controlling for simple reaction time. CONCLUSIONS: Our results indicate that male fXPCs as a group show impairments (slower reaction times) in numerical visuospatial tasks, which are consistent with previous findings. This adds to a growing body of literature characterizing the phenotype in fXPCs who are asymptomatic for FXTAS. Future longitudinal studies are needed to determine how these impairments relate to risk of developing FXTAS.
    Journal of Neurodevelopmental Disorders 11/2012; 4(1):26. · 3.45 Impact Factor
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    ABSTRACT: Various neuroimaging measures are being evaluated for tracking Alzheimer's disease progression in therapeutic trials, including measures of structural brain change based on repeated scanning of patients with magnetic resonance imaging (MRI). Methods to compute brain change must be robust to scan quality. Biases may arise if any scans are thrown out, as this can lead to the true changes being overestimated or underestimated. Here we analyzed the full ADNI-1 MRI dataset and assessed several sources of bias that can arise when tracking brain changes with structural brain imaging methods, as part of a pipeline for tensor-based morphometry (TBM). In all healthy subjects who completed MRI scanning at screening, 6, 12, and 24months, brain atrophy was essentially linear with no detectable bias in longitudinal measures. In power analyses for clinical trials based on these change measures, only 39AD and 95 MCI subjects were needed for a 24-month trial to detect a 25% reduction in the average rate of change using a two-sided test (α=0.05, power=80%). Further sample size reductions were achieved by stratifying the data into Apolipoprotein E (ApoE) ε4 carriers vs. non-carriers. We show how selective data exclusion affects sample size estimates, motivating an objective comparison of different analysis techniques based on statistical power and robustness. TBM is an unbiased, robust, high-throughput imaging surrogate marker for large, multi-site neuroimaging studies and clinical trials of AD and MCI.
    NeuroImage 11/2012; · 6.25 Impact Factor
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    ABSTRACT: The Alzheimer's Disease Neuroimaging Initiative (ADNI) three-dimensional T(1)-weighted magnetic resonance imaging (MRI) acquisitions provide a rich data set for developing and testing analysis techniques for extracting structural endpoints. To promote greater rigor in analysis and meaningful comparison of different algorithms, the ADNI MRI Core has created standardized analysis sets of data comprising scans that met minimum quality control requirements. We encourage researchers to test and report their techniques against these data. Standard analysis sets of volumetric scans from ADNI-1 have been created, comprising screening visits, 1-year completers (subjects who all have screening, 6- and 12-month scans), 2-year annual completers (screening, 1-year and 2-year scans), 2-year completers (screening, 6-months, 1-year, 18-months [mild cognitive impaired (MCI) only], and 2-year scans), and complete visits (screening, 6-month, 1-year, 18-month [MCI only], 2-year, and 3-year [normal and MCI only] scans). As the ADNI-GO/ADNI-2 data become available, updated standard analysis sets will be posted regularly.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 10/2012; · 14.48 Impact Factor
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    ABSTRACT: Alzheimer disease (AD) and dementia with Lewy bodies (DLB) are common etiologies of dementia with overlapping clinical features. Our objective was to determine which extrapyramidal signs (EPSs) are most helpful in identifying DLB. We analyzed data from the National Alzheimer's Coordinating Center, including demographics, Unified Parkinson's Disease Rating Scale (UPDRS) scores, Mini-Mental State Examination (MMSE) scores, and clinical diagnosis. The subjects were divided into 3 groups: AD, DLB, or Lewy body variant (LBV). The UPDRS motor scores were totaled and analyzed within and across the MMSE strata using regression techniques. Further, we divided UPDRS subscores into 9 EPSs, dichotomized as either present or absent. Logistic regression analysis was used to compare each of the EPS in the AD and Lewy body (DLB+LBV) groups. DLB subjects (n=130) were more likely to be male individuals, younger, and have higher MMSE scores (P<0.001) compared with that in AD (n=1826) or LBV (n=105) subjects. Differences were found for total UPDRS score and number of EPSs (P<0.001), after controlling for age, sex, and MMSE. Logistic regression models demonstrated that masked facies best differentiated AD from Lewy body (odds ratio=6.5, P<0.001, 95% confidence interval, 3.8-11.1). If these findings are neuropathologically validated, then the presence of specific EPS may help clinicians better differentiate AD and DLB.
    Alzheimer disease and associated disorders 09/2012; · 2.88 Impact Factor
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    ABSTRACT: We present a method that significantly improves magnetic resonance imaging (MRI) based brain tissue segmentation by modeling the topography of boundaries between tissue compartments. Edge operators are used to identify tissue interfaces and thereby more realistically model tissue label dependencies between adjacent voxels on opposite sides of an interface. When applied to a synthetic MRI template corrupted by additive noise, it provided more consistent tissue labeling across noise levels than two commonly used methods (FAST and SPM5). When applied to longitudinal MRI series it provided lesser variability in individual trajectories of tissue change, suggesting superior ability to discriminate real tissue change from noise. These results suggest that this method may be useful for robust longitudinal brain tissue change estimation.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 08/2012; 2012:5319-22.
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    ABSTRACT: We sought to develop and evaluate a composite memory score from the neuropsychological battery used in the Alzheimer's Disease (AD) Neuroimaging Initiative (ADNI). We used modern psychometric approaches to analyze longitudinal Rey Auditory Verbal Learning Test (RAVLT, 2 versions), AD Assessment Schedule - Cognition (ADAS-Cog, 3 versions), Mini-Mental State Examination (MMSE), and Logical Memory data to develop ADNI-Mem, a composite memory score. We compared RAVLT and ADAS-Cog versions, and compared ADNI-Mem to RAVLT recall sum scores, four ADAS-Cog-derived scores, the MMSE, and the Clinical Dementia Rating Sum of Boxes. We evaluated rates of decline in normal cognition, mild cognitive impairment (MCI), and AD, ability to predict conversion from MCI to AD, strength of association with selected imaging parameters, and ability to differentiate rates of decline between participants with and without AD cerebrospinal fluid (CSF) signatures. The second version of the RAVLT was harder than the first. The ADAS-Cog versions were of similar difficulty. ADNI-Mem was slightly better at detecting change than total RAVLT recall scores. It was as good as or better than all of the other scores at predicting conversion from MCI to AD. It was associated with all our selected imaging parameters for people with MCI and AD. Participants with MCI with an AD CSF signature had somewhat more rapid decline than did those without. This paper illustrates appropriate methods for addressing the different versions of word lists, and demonstrates the additional power to be gleaned with a psychometrically sound composite memory score.
    Brain Imaging and Behavior 07/2012; · 2.67 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE:WMH, associated with cognitive decline and cardiovascular risk factors, may represent only the extreme end of a more widespread continuous WM injury process that progresses during aging and is poorly understood. We investigated the ability of FLAIR and DTI to characterize the longitudinal course of WMH development.MATERIALS AND METHODS:One hundred nineteen participants (mean age, 74.5 ± 7.4), including cognitively healthy elders and subjects diagnosed with Alzheimer disease and mild cognitive impairment, received a comprehensive clinical evaluation and brain MR imaging, including FLAIR and DTI on 2 dates. The risk for each baseline normal-appearing WM voxel to convert into WMH was modeled as a function of baseline FA (model M1) and both baseline FA and standardized FLAIR (M2). Sensitivity, specificity, accuracy, and AUC for predicting conversion to WMH were compared between models.RESULTS:Independent of clinical diagnosis, lower baseline FA (P < .001, both models) and higher baseline FLAIR intensity (P < .001, M2) were independently associated with increased risk for conversion from normal WM to WMH. M1 exhibited higher sensitivity but lower specificity, accuracy, and AUC compared with M2.CONCLUSIONS:These findings provide further evidence that WMH result from a continuous process of WM degeneration with time. Stepwise decreases in WM integrity as measured by both DTI and FLAIR were independently associated with stepwise increases in WMH risk, emphasizing that these modalities may provide complementary information for understanding the time course of aging-associated WM degeneration.
    American Journal of Neuroradiology 06/2012; · 3.17 Impact Factor
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    ABSTRACT: The Alzheimer's Disease Neuroimaging Initiative (ADNI) measures abilities broadly related to executive function (EF), including WAIS-R Digit Symbol Substitution, Digit Span Backwards, Trails A and B, Category Fluency, and Clock Drawing. This study investigates whether a composite executive function measure based on these multiple indicators has better psychometric characteristics than the widely used individual components. We applied item response theory methods to 800 ADNI participants to derive an EF composite score (ADNI-EF) from the above measures. We then compared ADNI-EF with component measures in 390 longitudinally-followed participants with mild cognitive impairment (MCI) with respect to: (1) Ability to detect change over time; (2) Ability to predict conversion to dementia; (3) Strength of cross-sectional association with MRI-derived measures of structures involved in frontal systems, and (4) Strength of baseline association with cerebrospinal fluid (CSF) levels of amyloid β(1-42), total tau, and phosphorylated tau(181P). ADNI-EF showed the greatest change over time, followed closely by Category Fluency. ADNI-EF needed a 40 % smaller sample size to detect change. ADNI-EF was the strongest predictor of AD conversion. ADNI-EF was the only measure significantly associated with all the MRI regions, though other measures were more strongly associated in a few of the regions. ADNI-EF was associated with all the CSF measures. ADNI-EF appears to be a useful composite measure of EF in MCI, as good as or better than any of its composite parts. This study demonstrates an approach to developing a psychometrically sophisticated composite score from commonly-used tests.
    Brain Imaging and Behavior 05/2012; · 2.67 Impact Factor

Publication Stats

5k Citations
620.71 Total Impact Points

Institutions

  • 2003–2014
    • University of California, Davis
      • • Department of Neurology
      • • UC Davis Medical Center
      • • School of Medicine
      Davis, California, United States
  • 2006–2012
    • University of California, Los Angeles
      • • Department of Neurology
      • • Laboratory of Neuro Imaging
      Los Angeles, CA, United States
  • 2010–2011
    • Fairbanks Memorial Hospital
      Fairbanks, Alaska, United States
    • Beijing Normal University
      • School of Information Science and Technology
      Beijing, Beijing Shi, China
    • California State University, Sacramento
      Sacramento, California, United States
  • 2009–2010
    • Davis School District
      Davis, California, United States
    • University of California, San Diego
      • Department of Medicine
      San Diego, CA, United States
    • University of California, Berkeley
      • School of Public Health
      Berkeley, California, United States
  • 2008
    • VU University Medical Center
      Amsterdamo, North Holland, Netherlands