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1.  An Abbreviated Montreal Cognitive Assessment (MoCA) for Dementia Screening 
The Clinical neuropsychologist  2015;29(4):413-425.
The Montreal Cognitive Assessment (MoCA) is a cognitive screening instrument growing in popularity, but few studies have conducted psychometric item analyses or attempted to develop abbreviated forms. We sought to derive and validate a short form MoCA (SF;MoCA) and compare its classification accuracy to the standard MoCA and MMSE in mild cognitive impairment (MCI), Alzheimer disease (AD), and normal aging.
408 subjects (MCI n=169, AD n=87, normal n=152) were randomly divided into derivation and validation samples. Item analysis in the derivation sample identified most sensitive MoCA items. Receiver Operating Characteristic (ROC) analyses were used to develop cutoff scores and evaluate the classification accuracy of the SF;MoCA, standard MoCA, and MMSE. Net Reclassification Improvement (NRI) analyses and comparison of ROC curves were used to compare classification accuracy of the three measures.
Serial subtraction (Cramer's V=.408), delayed recall (Cramer's V=.702), and orientation items (Cramer's V=.832) were included in the SF;MoCA based on largest effect sizes in item analyses. Results revealed 72.6% classification accuracy of the SF; MoCA, compared with 71.9% for the standard MoCA and 67.4% for the MMSE. Results of NRI analyses and ROC curve comparisons revealed that classification accuracy of the SF;MoCA was comparable to the standard version and generally superior to the MMSE.
Findings suggest the SF;MoCA could be an effective brief tool in detecting cognitive impairment.
PMCID: PMC4501880  PMID: 25978540
short form; Alzheimer's disease; mild cognitive impairment; cognitive screening; Montreal Cognitive Assessment
2.  Teleneuropsychology: Evidence for Video Teleconference-Based Neuropsychological Assessment 
The use of videoconference technology to deliver health care diagnostics and treatment continues to grow at a rapid pace. Telepsychiatry and telepsychology applications are well-accepted by patients and providers, and both diagnostic and treatment outcomes have generally been similar to traditional face-to-face interactions. Preliminary applications of videoconference-based neuropsychological assessment (teleneuropsychology) have yielded promising results in the feasibility and reliability of several standard tests, although large-scale studies are lacking. This investigation was conducted to determine the reliability of video teleconference (VTC) - based neuropsychological assessment using a brief battery of standard neuropsychological tests commonly used in the evaluation of known or suspected dementia. Tests included the Mini-Mental State Examination (MMSE), Hopkins Verbal Learning Test-Revised, Digit Span forward and backward, short form Boston Naming Test, Letter and Category Fluency, and Clock Drawing. Tests were administered via VTC and in-person to subjects, counterbalanced using alternate test forms and standard instructions. Two hundred two adult subjects were tested in both rural and urban settings, including 83 with cognitive impairment and 119 healthy controls. We found highly similar results across VTC and in-person conditions, with significant intraclass correlations (mean = .74; range: 0.55–0.91) between test scores. Findings remained consistent in subjects with or without cognitive impairment and in persons with MMSE scores as low as 15. VTC-based neuropsychological testing is a valid and reliable alternative to traditional face-to-face assessment using selected measures. More VTC-based studies using additional tests in different populations are needed to fully explore the utility of this new testing medium.
PMCID: PMC4410096  PMID: 25343269
Telehealth; Telemedicine; Teleneuropsychology; Telepsychology; Dementia; VTC-testing; Rural and urban
3.  Subclinical atherosclerosis and subsequent cognitive function 
Atherosclerosis  2015;241(1):36-41.
To examine the relationship between measures of subclinical atherosclerosis and subsequent cognitive function.
Participants from the Dallas Heart Study (DHS), a population-based multiethnic study of cardiovascular disease pathogenesis, were re-examined 8 years later (DHS-2) with the Montreal Cognitive Assessment (MoCA); N = 1904, mean age = 42.9, range 8–65. Associations of baseline measures of subclinical atherosclerosis (coronary artery calcium, abdominal aortic plaque, and abdominal aortic wall thickness) with MoCA scores measured at follow-up were examined in the group as a whole and in relation to age and ApoE4 status.
A significant linear trend of successively lower MoCA scores with increasing numbers of atherosclerotic indicators was observed (F(3, 1150) = 5.918, p = .001). CAC was weakly correlated with MoCA scores (p = .047) and MoCA scores were significantly different between participants with and without CAC (M = 22.35 vs 23.69, p = 0.038). With the exception of a small association between abdominal AWT and MoCA in subjects over age 50, abdominal AWT and abdominal aortic plaque did not correlate with MoCA total score (p ≥.052). Cognitive scores and atherosclerosis measures were not impacted by ApoE4 status (p ≥.455).
In this ethnically diverse population-based sample, subclinical atherosclerosis was minimally associated with later cognitive function in middle-aged adults.
PMCID: PMC4722814  PMID: 25957568
Montreal Cognitive Assessment; MoCA; Cognition; Atherosclerosis; Dallas heart study
4.  Optimal neurocognitive, personality and behavioral measures for assessing impulsivity in cocaine dependence 
Impulsivity may underlie the poor treatment retention and high relapse rates observed in cocaine-dependent persons. However, observed differences in measures of impulsivity between cocaine-dependent and healthy control participants often do not reach clinical significance, suggesting that the clinical relevance of these differences may be limited.
To examine which measures of impulsivity (i.e. self-report impulsivity, self-report personality, neurocognitive testing) best distinguish cocaine-dependent and healthy control participants (i.e. showing differences at least 1.5 standard deviations [SD] from controls). Optimal measures were considered to demonstrate sufficient classification accuracy.
Sixty-five recently abstinent cocaine-dependent and 25 healthy control participants were assessed using select neurocognitive tests and self-report questionnaires including the NEO Personality Inventory-Revised (NEO-PI-R), Temperament and Character Inventory (TCI), Barratt Impulsiveness Scale (BIS-11a), and the Frontal Systems Behavior Scale (FrSBe).
When corrected for years of education and gender, neurocognitive measures did not demonstrate clinically significant differences between cocaine-dependent and control participants. The personality measures TCI Purposefulness and Congruent Second Nature and NEO-PI-R Impulsiveness, and the self-rating measures FrSBe Disinhibition and BIS-11 Motor Impulsivity and Total successfully identified clinically meaningful elevations in impulsivity within cocaine-dependent participants (>1.5 SDs from controls). Furthermore, these measures achieved 84–93% accuracy in discriminating cocaine-dependent from control participants.
Clinically significant neurocognitive impairment in cocaine-dependent participants was not observed in this sample. As the BIS-11 or FrSBe are brief to administer, accurate, and have been shown to predict treatment retention and relapse, these measures appear to be optimal, relative to the personality measures, for examining trait impulsivity in cocaine dependence.
PMCID: PMC4448965  PMID: 25083938
BIS-11; cocaine dependence; FrSBe; impulsivity; neurocognitive
5.  Simple Neuropsychological Test Scores Associated with Rate of Cognitive Decline in Early Alzheimer Disease 
The Clinical neuropsychologist  2014;28(6):926-940.
Alzheimer disease (AD) characteristically begins with episodic memory impairment followed by other cognitive deficits; however, the course of illness varies, with substantial differences in the rate of cognitive decline. For research and clinical purposes, it would be useful to distinguish between persons who will progress slowly from persons who will progress at an average or faster rate.
To use neurocognitive performance features and disease-specific and health information to determine a predictive model for the rate of cognitive decline in subjects with mild AD.
We reviewed the records of a series of ninety-six consecutive subjects with mild AD from 1995 to 2011who had been administered selected neurocognitive tests and clinical measures. Based on Clinical Dementia Rating (CDR) of functional and cognitive decline over two years, subjects were classified as Faster (n = 45) or Slower Progressors (n = 51). Stepwise logistic regression analyses using neurocognitive performance features, disease-specific, health, and demographic variables were performed.
Neuropsychological scores that distinguished Faster from Slower Progressors included Trail Making Test - A, Digit Symbol, and California Verbal Learning Test (CVLT) Total Learned and Primacy Recall. No disease-specific, health, or demographic variable predicted rate of progression; however, history of heart disease showed a trend. Among the neuropsychological variables, Trail Making Test - A best distinguished Faster from Slower Progressors, with an overall accuracy of 68%. In an omnibus model including neuropsychological, disease-specific, health, and demographic variables, only Trail Making Test - A distinguished between groups.
Several neuropsychological performance features were associated with the rate of cognitive decline in mild AD, with baseline Trail Making Test - A performance best separating those who declined at an average or faster rate from those who showed slower progression.
PMCID: PMC4406376  PMID: 25131004
Alzheimer Disease; Progression; Cognitive Decline
6.  Predictors of Performance on the MMSE and the DRS-2 Among American Indian Elders 
Little is known about factors that predict older American Indians’ performance on cognitive tests. This study examined 137 American Indian elders’ performance on the MMSE and the Dementia Rating Scale—Second Edition (DRS-2). Multivariate regression identified younger age, more education, not receiving Supplemental Security Income, and frequent receipt of needed health care as predictors of better performance on the MMSE. Better performance on the DRS-2 was predicted by more education, boarding school attendance, not receiving Supplemental Security Income, and frequent receipt of needed health care. This study points to the importance of economic and educational factors on cognitive test performance among American Indian elders.
PMCID: PMC4530971  PMID: 21037127
7.  Video teleconference-based neurocognitive screening in geropsychiatry 
Psychiatry research  2015;225(3):734-735.
Validation of remote video teleconference (VTC)-based procedures for geropsychiatry applications is essential to ensure validity and reliability of diagnostic procedures. The current study demonstrates the similarity of scores obtained from several brief neurocognitive screening measures in an outpatient VA geropsychiatry clinic population when participants were tested in-person and via VTC. Results revealed similar mean scores and moderate to good consistency among our mixed geropsychiatric sample on brief measures of global cognition, attention, and visuospatial function.
PMCID: PMC4410696  PMID: 25596957
Telemedicine; Neuropsychology; Assessment
8.  Point and Interval Estimates of Percentile Ranks for Scores on the Texas Functional Living Scale 
The Clinical neuropsychologist  2012;26(7):1154-1165.
Point and interval estimates of percentile ranks are useful tools in assisting with the interpretation of neurocognitive test results. We provide percentile ranks for raw subscale scores on the Texas Functional Living Scale (TFLS; Cullum, Weiner, & Saine, 2009) using the TFLS standardization sample data (N = 800). Percentile ranks with interval estimates are also provided for the overall TFLS T score. Conversion tables are provided a long with the option of obtaining the point and interval estimates using a computer program written to accompany this paper (TFLS_PRs. exe). The percentile ranks for the subscales offer an alternative to using the cumulative percentage tables in the test manual and provide a useful and quick way for neuropsychologists to assimilate information on the case’s profile of scores on the TFLS subscales. The provision of interval estimates for the percentile ranks is in keeping with the contemporary emphasis on the use of confidence intervals in psychological statistics
PMCID: PMC4410014  PMID: 22985303
IADLs; Percentile norms; Interval estimates; Bayesian methods; Computer scoring
Prior work on the link between blood-based biomarkers and cognitive status has largely been based on dichotomous classifications rather than detailed neuropsychological functioning. The current project was designed to create serum-based biomarker algorithms that predict neuropsychological test performance.
A battery of neuropsychological measures was administered. Random forest analyses were utilized to create neuropsychological test-specific biomarker risk scores in a training set that were entered into linear regression models predicting the respective test scores in the test set. Serum multiplex biomarker data were analyzed on 108 proteins from 395 participants (197 AD cases and 198 controls) from the Texas Alzheimer’s Research and Care Consortium.
The biomarker risk scores were significant predictors (p<0.05) of scores on all neuropsychological tests. With the exception of premorbid intellectual status (6.6%), the biomarker risk scores alone accounted for a minimum of 12.9% of the variance in neuropsychological scores. Biomarker algorithms (biomarker risk scores + demographics) accounted for substantially more variance in scores. Review of the variable importance plots indicated differential patterns of biomarker significance for each test, suggesting the possibility of domain-specific biomarker algorithms.
Our findings provide proof-of-concept for a novel area of scientific discovery, which we term “molecular neuropsychology.”
PMCID: PMC4400831  PMID: 24107792
Neuropsychology; Biomarkers; Algorithms; Molecular; Psychology
10.  Expanding the Ecological Validity of WAIS-IV and WMS-IV With the Texas Functional Living Scale 
Assessment  2010;18(2):141-155.
Assessment of functional status is an important aspect of clinical evaluation. As part of the standardization of the Wechsler Adult Intelligence Scale–Fourth Edition (WAIS-IV) and Wechsler Memory Scale–Fourth Edition (WMS-IV), participants completed the Texas Functional Living Scale (TFLS), a measure of Instrumental Activities of Daily Living. The relationships between TFLS and WAIS-IV and WMS-IV were examined in both normally developing and clinical samples. In general, the highest correlations were between TFLS and measures of general cognitive ability (WAIS-IV FSIQ [Full Scale IQ] and GAI [General Ability Index]) and working memory (WAIS-IV WMI [Working Memory Index] and WMS-IV VWMI [Visual Working Memory Index]). Across the clinical populations, working memory subtests were generally strongly related to TFLS performance, although this relationship was more consistent with WAIS-IV than WMS-IV. Contrast scaled scores are presented for the TFLS based on WAIS-IV or WMS-IV performance. These scores allow the evaluation of functional abilities within the context of cognitive and memory ability, enhancing and expanding the utility of the WAIS-IV and WMS-IV.
PMCID: PMC4389280  PMID: 20921288
IADL; WAIS-IV; WMS-IV; TFLS; functional assessment
11.  Global brain hypoperfusion and oxygenation in amnestic mild cognitive impairment 
To determine if global brain hypoperfusion and oxygen hypometabolism occur in patients with amnestic mild cognitive impairment (aMCI).
Thirty-two aMCI and 21 normal subjects participated. Total cerebral blood flow (TCBF), cerebral metabolic rate of oxygen (CMRO2) and brain tissue volume were measured using color-coded duplex ultrasonography (CDUS), near-infrared spectroscopy (NIRS), and MRI. TCBF was normalized by total brain tissue volume (TBV) for group comparisons (nTCBF). Cerebrovascular resistance (CVR) was calculated as mean arterial pressure divided by TCBF.
Reductions in nTCBF by 9%, CMRO2 by 11%, and increase in CVR by 13% were observed in aMCI relative to normal subjects. No group differences in TBV were observed. nTCBF was correlated with CMRO2 in normal controls, but not in aMCI.
Global brain hypoperfusion, oxygen hypometabolism and neurovascular decoupling observed in aMCI suggest that changes in cerebral hemodynamics occur early at prodromal stage of Alzheimer’s disease, which can be assessed using low cost and bed-side available CDUS and NIRS technology.
PMCID: PMC3859724  PMID: 23871763
mild cognitive impairment; cerebral blood flow; cerebral metabolic rate of oxygen; ultrasonography; near-infrared spectroscopy; MRI
12.  Masters Athletes Exhibit Larger Regional Brain Volume and Better Cognitive Performance than Sedentary Older Adults 
Journal of magnetic resonance imaging : JMRI  2013;38(5):10.1002/jmri.24085.
To investigate differences in the age-related decline in brain tissue concentration between Masters athletes and sedentary older adults.
Materials and Methods
Twelve Masters athletes (MA) (3 females, age=72.4±5.6yrs, endurance training>15yrs), 12 sedentary elderly (SE) similar in age and educational level (4 females, age=74.6±4.3yrs), and 9 young controls (YC)(4 females, age=27.2±3.6yrs) participated. T1-weighted-high-resolution (1×1×1mm3) images were acquired. Voxel-based analysis was conducted to identify clusters showing tissue concentration differences with t-tests. Cognitive function was assessed using a standard clinical battery focused on executive function and memory.
Two Masters athletes and 2 sedentary elderly were unable to complete MRI study. Both SE and MA showed lower GM concentrations than YC in the superior, inferior and middle frontal gyrus, superior temporal gyrus, postcentral gyrus and the cingulate gyrus (PFDR-corrected<0.001) and lower WM concentrations in the inferior frontal gyrus and precentral gyrus (PFDR-corrected<0.005). Notably, MA showed higher GM and WM concentrations than SE in the sub-gyral, cuneus, and precuneus regions related to visuospatial function, motor control, and working memory (PFDR-corrected<0.005). After controlling for estimated intelligence, MA outperformed SE on tasks of letter (p<0.01) and category (p<0.05) fluency.
Life-long exercise may confer benefits to some aspects of executive function and age-related brain tissue loss in the regions related to visuospatial function, motor control, and working memory in older adults.
PMCID: PMC3812419  PMID: 23908143
Aging; brain; cognition; exercise; MRI
13.  Older Adults with Amnestic Mild Cognitive Impairment Exhibit Exacerbated Gait Slowing under Dual-Task Challenges 
Current Alzheimer research  2014;11(5):494-500.
With age, performance of motor tasks becomes more reliant on cognitive resources to compensate for the structural and functional declines in the motor control regions in the brain. We hypothesized that participants with amnestic mild cognitive impairment (aMCI) are more prone to motor dysfunctions than cognitively normal older adults under dual-task conditions where competitive demands challenge cognitive functions while performing a motor task simultaneously.
Sixteen aMCI participants (females=9, age=64±5yrs, clinical dementia rating score=0.5) and 10 age- and education-matched cognitively normal adults (females=5, age=62±6yrs) participated. Using a 10-meter-walk test (10MW), gait velocity was recorded at baseline and under 4 different dual-task (DT) conditions designed to challenge working memory, executive function, and episodic memory. Specifically, DT1: verbal fluency; DT2: 5-digit backward span; DT3: serial-7 subtraction; and DT4: 3-item delayed recall. Physical function was measured by Timed Up-and-Go (TUG), simple reaction time (RT) to a free-falling yardstick, and functional reach (FR).
No difference was found in physical functions, aerobic fitness, and exercise cardiopulmonary responses between aMCI participants and controls. However, aMCI participants showed more pronounced gait slowing from baseline when compared to the controls (p<0.05; p=0.001; p<0.001; p<0.001, respectively).
Our finding supports the theory of shared resource of motor and cognitive control. Participants with aMCI manifested more gait slowing than cognitively-normal older adults under DT conditions, with the largest differences during tests of working and episodic memory. The outcome of dual-task assessment shows promise as a potential marker for detection of aMCI and early Alzheimer disease.
PMCID: PMC4082490  PMID: 24801217
Dual-task; early detection; gait; mild cognitive impairment; motor control
14.  Depressive symptoms and white matter dysfunction in retired NFL players with concussion history 
Neurology  2013;81(1):25-32.
To determine whether correlates of white matter integrity can provide general as well as specific insight into the chronic effects of head injury coupled with depression symptom expression in professional football players.
We studied 26 retired National Football League (NFL) athletes who underwent diffusion tensor imaging (DTI) scanning. Depressive symptom severity was measured using the Beck Depression Inventory II (BDI-II) including affective, cognitive, and somatic subfactor scores (Buckley 3-factor model). Fractional anisotropy (FA) maps were processed using tract-based spatial statistics from FSL. Correlations between FA and BDI-II scores were assessed using both voxel-wise and region of interest (ROI) techniques, with ROIs that corresponded to white matter tracts. Tracts demonstrating significant correlations were further evaluated using a receiver operating characteristic curve that utilized the mean FA to distinguish depressed from nondepressed subjects.
Voxel-wise analysis identified widely distributed voxels that negatively correlated with total BDI-II and cognitive and somatic subfactors, with voxels correlating with the affective component (p < 0.05 corrected) localized to frontal regions. Four tract ROIs negatively correlated (p < 0.01) with total BDI-II: forceps minor, right frontal aslant tract, right uncinate fasciculus, and left superior longitudinal fasciculus. FA of the forceps minor differentiated depressed from nondepressed athletes with 100% sensitivity and 95% specificity.
Depressive symptoms in retired NFL athletes correlate negatively with FA using either an unbiased voxel-wise or an ROI-based, tract-wise approach. DTI is a promising biomarker for depression in this population.
PMCID: PMC3770203  PMID: 23709590
15.  Neuroimaging of Cognitive Dysfunction and Depression in Aging Retired NFL Players: A cross-sectional study 
JAMA neurology  2013;70(3):326-335.
To assess for the presence of cognitive impairment and depression in aging former NFL players, and identify neuroimaging correlates of these dysfunctions.
Comparison of aging NFL players with cognitive impairment and depression to those without these dysfunctions and with matched healthy controls
Research center in the North Texas region of the United States.
We performed a cross-sectional study of retired professional football players with and without a history of concussion recruited from the North Texas region, along with age-, education-, and IQ-matched controls. We studied thirty-four retired NFL players (mean age 62) neurologically and neuropsychologically. A subset of 26 also underwent detailed neuroimaging; imaging data in this subset were compared to imaging data acquired in 26 healthy matched controls.
Main Outcome Measures
Neuropsychological measures, clinical diagnoses of depression, neuroimaging measures of white matter pathology, and a measure of cerebral blood flow (CBF).
Of the 34 participants, 20 were cognitively normal, 4 were diagnosed with a fixed cognitive deficit, 8 with Mild Cognitive Impairment, and 2 with dementia; 8 were diagnosed with depression. Of the subgroup in which neuroimaging data were acquired, cognitively impaired (CI) participants showed greatest deficits on tests of naming, word finding, and visual/verbal episodic memory. We found significant differences in white matter abnormalities in CI players and depressed players compared to their respective controls. Regional blood flow differences in the CI group (left temporal pole, inferior parietal lobule, superior temporal gyrus) corresponded to regions associated with impaired neurocognitive performance (problems with memory, naming and word finding).
Cognitive deficits and depression appear to be more common in aging NFL players compared to controls. These deficits are correlated with white matter abnormalities and changes in regional CBF.
PMCID: PMC4016798  PMID: 23303193
concussion; memory; depression; cognition; NFL; white matter; DTI; ASL; aging
16.  Predictive Pursuit Association with Deficits in Working Memory in Psychosis 
Biological psychiatry  2012;72(9):752-757.
Deficits in smooth pursuit eye movements (SPEM) are an established phenotype for schizophrenia (SZ) and are being investigated as a potential liability marker for bipolar disorder. While the molecular determinants of this deficit are still unclear, research has verified deficits in predictive pursuit mechanisms in SZ. Because predictive pursuit may depend on the working memory system, we have hypothesized a relationship between the two in healthy controls (HC) and SZ, and here examine whether it extends to psychotic bipolar disorder (BDP).
Volunteers with SZ (n = 38), BDP (n = 31), and HC (n = 32), performed a novel eye movement task to assess predictive pursuit as well as a standard visuospatial measure of working memory.
Individuals with SZ and BDP both showed reduced predictive pursuit gain compared with HC (p <.05). Moreover, each patient group showed worse performance in visuospatial working memory compared to controls (p <.05). A strong correlation (r = .53, p =.007) was found between predictive pursuit gain and working memory in HC, a relationship that showed a trend correlation within the BDP group but not among SZ.
Individuals with SZ and BDP showed similar deficits in predictive pursuit, suggesting that this alteration could be a characteristic trait of the psychosis domain. The correlation between predictive pursuit and working memory in HC supports the assumption that working memory is related to predictive pursuit eye movements; however, the degradation of working memory in people with psychosis disrupts its association with eye tracking behavior.
PMCID: PMC3427716  PMID: 22554452
psychosis; schizophrenia; bipolar disorder; smooth pursuit eye movement; predictive pursuit; working memory
17.  Motor Symptoms at Onset of Parkinson Disease and Risk for Cognitive Impairment and Depression 
To determine if side and type of initial motor symptoms in Parkinson disease predict risk for later development of cognitive impairment or depressive symptoms.
We recruited 124 nondemented patients with Parkinson disease to participate in a cohort study of cognitive function and depressive symptoms that used validated neuropsychological tests and a depressive symptom inventory. We first reviewed the patients’ charts to determine their initial motor symptom and side of onset, and then classified the patients into 4 groups: right-side onset tremor, right-side onset bradykinesia/rigidity, left-side onset tremor, and left-side onset bradykinesia/rigidity. We excluded patients with bilateral symptom onset. We used analysis of variance on neuropsychological test performance and depressive symptoms to determine if group classification affected risk of cognitive impairment or depressive symptoms. We controlled our analyses for disease duration and motor severity as measured by the Unified Parkinson Disease Rating Scale Part III motor score.
There were no differences in any cognitive measure by side and type of initial motor symptoms. The right-side onset tremor group had the lowest depressive symptom scores, and no patient in any group reported severe depressive symptoms.
Our findings suggest that patterns of nigral cell loss correlating to the initial side and type of motor symptoms in Parkinson disease are not related to the risk of later cognitive impairment. By contrast, patients with right-side onset of tremor appear to have a lower risk of depressive symptoms than patients with other presentations.
PMCID: PMC3477612  PMID: 22960435
18.  Donepezil effects on hippocampal and prefrontal functional connectivity in Alzheimer’s disease: Preliminary report 
Journal of Alzheimer's disease : JAD  2012;31(0 3):S221-S226.
We used functional connectivity magnetic resonance imaging (fcMRI) to investigate changes in interhemispheric brain connectivity in 11 patients with mild Alzheimer’s disease (AD) following eight weeks of treatment with the cholinesterase inhibitor donepezil. We examined functional connectivity between four homologous temporal, frontal, and occipital regions. These regions were selected to represent sites of AD neuropathology, sites of donepezil-related brain activation change in prior studies, and sites that are minimally affected by the pathologic changes of AD. Based on previous findings of selective, localized frontal responses to donepezil, we predicted that frontal connectivity would be most strongly impacted by treatment. Of the areas we examined, we found that treatment had a significant effect only on functional connectivity between right and left dorsolateral prefrontal cortices. Implications for understanding the impact of donepezil treatment on brain functioning and behavior in patients with AD are discussed. This preliminary report suggests that fcMRI may provide a useful index of treatment outcome in diseases affecting brain connectivity. Future research should investigate these treatment-related changes in larger samples of patients and age-matched controls.
PMCID: PMC3749074  PMID: 22886013
Alzheimer’s disease; donepezil; functional connectivity; dorsolateral prefrontal cortex; hippocampus
19.  Consumer Acceptability of Brief Videoconference-based Neuropsychological Assessment in Older Individuals with and without Cognitive Impairment 
The Clinical neuropsychologist  2013;27(5):808-817.
Growing evidence suggests that neuropsychological assessment via videoconference shows good agreement with traditional in-person assessment. However, there are few published studies regarding patient acceptability of this methodology, particularly in individuals with cognitive impairment. In this study we sought to evaluate patient preferences and acceptability of teleneuropsychology to further shed light on the viability of this cognitive assessment medium. We examined acceptability of videoconference-based neuropsychological assessment among healthy aging individuals and in subjects with mild cognitive impairment or early stage Alzheimer disease. We found that teleneuropsychology appears to be well accepted by consumers. Our results reflected 98% satisfaction, and roughly 2/3 of participants indicated no preference between traditional face-to-face testing and examination by teleneuropsychology. Furthermore, even participants with cognitive impairment showed good acceptability of teleneuropsychological assessment. In conjunction with the preliminary data on reliability and validity from this growing literature, these results support teleneuropsychology as a viable and acceptable method for assessing cognitive functioning, and show promise for the implementation and utilization of this cognitive assessment medium in clinical and research settings.
PMCID: PMC3692573  PMID: 23607729
20.  Assessment of cognition in early dementia 
Better tools for assessing cognitive impairment in the early stages of Alzheimer’s disease (AD) are required to enable diagnosis of the disease before substantial neurodegeneration has taken place and to allow detection of subtle changes in the early stages of progression of the disease. The National Institute on Aging and the Alzheimer’s Association convened a meeting to discuss state of the art methods for cognitive assessment, including computerized batteries, as well as new approaches in the pipeline. Speakers described research using novel tests of object recognition, spatial navigation, attentional control, semantic memory, semantic interference, prospective memory, false memory and executive function as among the tools that could provide earlier identification of individuals with AD. In addition to early detection, there is a need for assessments that reflect real-world situations in order to better assess functional disability. It is especially important to develop assessment tools that are useful in ethnically, culturally and linguistically diverse populations as well as in individuals with neurodegenerative disease other than AD.
PMCID: PMC3613863  PMID: 23559893
21.  A Blood-Based Algorithm for the Detection of Alzheimer's Disease 
We previously created a serum-based algorithm that yielded excellent diagnostic accuracy in Alzheimer's disease. The current project was designed to refine that algorithm by reducing the number of serum proteins and by including clinical labs. The link between the biomarker risk score and neuropsychological performance was also examined.
Serum-protein multiplex biomarker data from 197 patients diagnosed with Alzheimer's disease and 203 cognitively normal controls from the Texas Alzheimer's Research Consortium were analyzed. The 30 markers identified as the most important from our initial analyses and clinical labs were utilized to create the algorithm.
The 30-protein risk score yielded a sensitivity, specificity, and AUC of 0.88, 0.82, and 0.91, respectively. When combined with demographic data and clinical labs, the algorithm yielded a sensitivity, specificity, and AUC of 0.89, 0.85, and 0.94, respectively. In linear regression models, the biomarker risk score was most strongly related to neuropsychological tests of language and memory.
Our previously published diagnostic algorithm can be restricted to only 30 serum proteins and still retain excellent diagnostic accuracy. Additionally, the revised biomarker risk score is significantly related to neuropsychological test performance.
PMCID: PMC3169374  PMID: 21865746
Algorithm, blood-based; Alzheimer's disease; Diagnosis
22.  Staging Dementia Using Clinical Dementia Rating Scale Sum of Boxes Scores 
Archives of neurology  2008;65(8):1091-1095.
The Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) score is commonly used, although the utility regarding this score in staging dementia severity is not well established.
To investigate the effectiveness of CDRSOB scores in staging dementia severity compared with the global CDR score.
Retrospective study.
Texas Alzheimer's Research Consortium minimum data set cohort.
A total of 1577 participants (110 controls, 202 patients with mild cognitive impairment, and 1265 patients with probable Alzheimer disease) were available for analysis.
Main Outcome Measures
Receiver operating characteristic curves were generated from a derivation sample to determine optimal cutoff scores and ranges, which were then applied to the validation sample.
Optimal ranges of CDR-SOB scores corresponding to the global CDR scores were 0.5 to 4.0 for a global score of 0.5, 4.5 to 9.0 for a global score of 1.O, 9.5 to 15.5 for a global score of 2.0, and 16.0 to 18.0 for a global score of 3.0. When applied to the validation sample, κ scores ranged from 0.86 to 0.94 (P <.001 for all), with 93.0% of the participants falling within the new staging categories.
The CDR-SOB score compares well with the global CDR score for dementia staging. Owing to the increased range of values, the CDR-SOB score offers several advantages over the global score, including increased utility in tracking changes within and between stages of dementia severity. Interpretive guidelines for CDR-SOB scores are provided.
PMCID: PMC3409562  PMID: 18695059
23.  Diffusion Tensor Imaging Biomarkers for Traumatic Axonal Injury: Analysis of Three Analytic Methods 
Traumatic axonal injury (TAI) is a common mechanism of traumatic brain injury not readily identified using conventional neuroimaging modalities. Novel imaging modalities such as diffusion tensor imaging (DTI) can detect microstructural compromise in white matter (WM) in various clinical populations including TAI. DTI-derived data can be analyzed using global methods (i.e., WM histogram or voxel based approaches) or a regional approach (i.e., tractography). While each of these methods produce qualitatively comparable results, it is not clear which is most useful in clinical research and ultimately in clinical practice. This study compared three methods of analyzing DTI-derived data with regard to detection of WM injury and their association with clinical outcomes. Thirty patients with TAI and 19 demographically similar normal controls were scanned using a 3T magnet. Patients were scanned approximately eight months post-injury, and underwent an outcomes assessment at that time. Histogram analysis of FA and MD showed global WM integrity differences between patients and controls. Voxel-based and tractography analyses showed significant decreases in FA within centroaxial structures involved in TAI. All three techniques were associated with functional and cognitive outcomes. DTI measures of microstructural integrity appear robust, as the three analysis techniques studied showed adequate utility for detecting WM injury.
PMCID: PMC3097093  PMID: 21070694
DTI; DAI; Traumatic Brain Injury; memory; Tractography; cognitive outcomes
24.  Brain-Derived Neurotrophic Factor Levels in Alzheimer's Disease 
The current search for biomarkers that are diagnostic and/or prognostic of Alzheimer's disease (AD) is of vital importance given the rapidly aging population. It was recently reported that brain derived neurotrophic factor (BDNF) fluctuated according to AD severity, suggesting that BDNF might have utility for diagnostics and monitoring of therapeutic efficacy. The current study sought to examine whether BDNF levels varied according to AD severity, as previously reported.
There were 196 participants (Probable AD n = 98, Controls n = 98) in the Texas Alzheimer's Research Consortium (TARC) Longitudinal Research Cohort available for analysis. BDNF levels were assayed via multiplex immunoassay. Regression analyses were utilized to examine the relation between BDNF levels, MMSE, and CDR scores adjusting for age and gender.
In adjusted models, BDNF levels did not distinguish between AD patients and normal controls and did not significantly predict AD severity or global cognitive functioning.
These findings do not support the notion that BDNF serves as a diagnostic marker for AD or disease severity. It is likely that the most accurate approach to identifying biomarkers of AD will be through an algorithmic approach that combines multiple markers reflective of various pathways.
PMCID: PMC2787708  PMID: 19363274
Alzheimer's disease; Biomarkers; BDNF; Dementia Severity; Clinical Dementia Rating
NeuroRehabilitation  2009;24(1):75-85.
Neuropsychological evaluations conducted in the United States and abroad commonly include the use of tests translated from English to Spanish. The use of translated naming tests for evaluating predominately Spanish-speakers has recently been challenged on the grounds that translating test items may compromise a test’s construct validity. The Texas Spanish Naming Test (TNT) has been developed in Spanish specifically for use with Spanish-speakers; however, it is unlikely patients from diverse Spanish-speaking geographical regions will perform uniformly on a naming test. The present study evaluated and compared the internal consistency and patterns of item-difficulty and -discrimination for the TNT and two commonly used translated naming tests in three countries (i.e., United States, Colombia, Spain). Two hundred fifty two subjects (126 demented, 116 nondemented) across three countries were administered the TNT, Modified Boston Naming Test-Spanish, and the naming subtest from the CERAD. The TNT demonstrated superior internal consistency to its counterparts, a superior item difficulty pattern than the CERAD naming test, and a superior item discrimination pattern than the MBNT-S across countries. Overall, all three Spanish naming tests differentiated nondemented and moderately demented individuals, but the results suggest the items of the TNT are most appropriate to use with Spanish-speakers. Preliminary normative data for the three tests examined in each country are provided.
PMCID: PMC2666471  PMID: 19208960

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