David J Libon

Drexel University College of Medicine, Filadelfia, Pennsylvania, United States

Are you David J Libon?

Claim your profile

Publications (168)620.98 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We investigated whether midlife pulse pressure is associated with brain atrophy and cognitive decline, and whether the association was modified by apolipoprotein-E [epsilon]4 (APOE-[epsilon]4) and hypertension. Participants (549 stroke-free and dementia-free Framingham Offspring Cohort Study participants, age range=55.0 to 64.9 y) underwent baseline neuropsychological and magnetic resonance imaging (subset, n=454) evaluations with 5- to 7-year follow-up. Regression analyses investigated associations between baseline pulse pressure (systolic-diastolic pressure) and cognition, total cerebral volume and temporal horn ventricular volume (as an index of smaller hippocampal volume) at follow-up, and longitudinal change in these measures. Interactions with APOE-[epsilon]4 and hypertension were assessed. Covariates included age, sex, education, assessment interval, and interim stroke. In the total sample, baseline pulse pressure was associated with worse executive ability, lower total cerebral volume, and greater temporal horn ventricular volume 5 to 7 years later, and longitudinal decline in executive ability and increase in temporal horn ventricular volume. Among APOE-[epsilon]4 carriers only, baseline pulse pressure was associated with longitudinal decline in visuospatial organization. Findings indicate arterial stiffening, indexed by pulse pressure, may play a role in early cognitive decline and brain atrophy in mid to late life, particularly among APOE-[epsilon]4 carriers. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved
    No preview · Article · Nov 2015 · Alzheimer Disease and Associated Disorders
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The Clock Drawing Test—a simple pencil and paper test—has been used for more than 50 years as a screening tool to differentiate normal individuals from those with cognitive impairment, and has proven useful in helping to diagnose cognitive dysfunction associated with neurological disorders such as Alzheimer’s disease, Parkinson’s disease, and other dementias and conditions. We have been administering the test using a digitizing ballpoint pen that reports its position with considerable spatial and temporal precision, making available far more detailed data about the subject’s performance. Using pen stroke data from these drawings categorized by our software, we designed and computed a large collection of features, then explored the tradeoffs in performance and interpretability in classifiers built using a number of different subsets of these features and a variety of different machine learning techniques. We used traditional machine learning methods to build prediction models that achieve high accuracy. We operationalized widely used manual scoring systems so that we could use them as benchmarks for our models. We worked with clinicians to define guidelines for model interpretability, and constructed sparse linear models and rule lists designed to be as easy to use as scoring systems currently used by clinicians, but more accurate. While our models will require additional testing for validation, they offer the possibility of substantial improvement in detecting cognitive impairment earlier than currently possible, a development with considerable potential impact in practice.
    Full-text · Article · Oct 2015 · Machine Learning
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: There is remarkable heterogeneity in clinical Alzheimer's disease (AD) or vascular dementia (VaD). Objectives: 1) To statistically exam neuropsychological data to determine dementia subgroups for individuals clinically diagnosed with AD or VaD and then 2) examine group differences in specific gray/white matter regions of interest. Methods: A k-means cluster analysis requested a 3-group solution from neuropsychological data acquired from individuals diagnosed clinically with AD/VaD. MRI measures of hippocampal, caudate, ventricular, subcortical lacunar infarction, whole brain volume, and leukoaraiosis (LA) were analyzed. Three regions of LA volumes were quantified and these included the periventricular (5 mm around the ventricles), infracortical (5 mm beneath the gray matter), and deep (between periventricular and infracortical) regions. Results: Cluster analysis sorted AD/VaD patients into single domain amnestic (n = 41), single-domain dysexecutive (n = 26), and multi-domain (n = 26) phenotypes. Multi-domain patients exhibited worst performance on language tests; however, multi-domain patients were equally impaired on memory tests when compared to amnestic patients. Statistically-determined groups dissociated using neuroradiological parameters: amnestic and multi-domain groups presented with smaller hippocampal volume while the dysexecutive group presented with greater deep, periventricular, and whole brain LA. Neither caudate nor lacunae volume differed by group. Caudate nucleus volume negatively correlated with total LA in the dysexecutive and multi-domain groups. Conclusions: There are at least three distinct subtypes embedded within patients diagnosed clinically with AD/VaD spectrum dementia. We encourage future research to assess a) the neuroradiological substrates underlying statistically-determined AD/VaD spectrum dementia and b) how statistical modeling can be integrated into existing diagnostic criteria.
    No preview · Article · Sep 2015 · Journal of Alzheimer's disease: JAD
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: The current investigation examined verbal memory in idiopathic non-dementia Parkinson's disease and the significance of the left entorhinal cortex and left entorhinal-retrosplenial region connections (via temporal cingulum) on memory impairment in Parkinson's disease. Methods: Forty non-demented Parkinson's disease patients and forty non-Parkinson's disease controls completed two verbal memory tests - a wordlist measure (Philadelphia repeatable Verbal Memory Test) and a story measure (Logical Memory). All participants received T1-weighted and diffusion magnetic resonance imaging (3T; Siemens) sequences. Left entorhinal volume and left entorhinal-retrosplenial connectivity (temporal cingulum edge weight) were the primary imaging variables of interest with frontal lobe thickness and subcortical structure volumes as dissociating variables. Results: Individuals with Parkinson's disease showed worse verbal memory, smaller entorhinal volumes, but did not differ in entorhinal-retrosplenial connectivity. For Parkinson's disease entorhinal-retrosplenial edge weight had the strongest associations with verbal memory. A subset of Parkinson's disease patients (23%) had deficits (z-scores < -1.5) across both memory measures. Relative to non-impaired Parkinson's peers, this memory-impaired group had smaller entorhinal volumes. Discussion: Although entorhinal cortex volume was significantly reduced in Parkinson's disease patients relative to non-Parkinson's peers, only white matter connections associated with the entorhinal cortex were significantly associated with verbal memory performance in our sample. There was also no suggestion of contribution from frontal-subcortical gray or frontal white matter regions. These findings argue for additional investigation into medial temporal lobe gray and white matter connectivity for understanding memory in Parkinson's disease.
    Full-text · Article · Jul 2015 · PLoS ONE

  • No preview · Article · Jul 2015
  • Source

    Full-text · Dataset · May 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Analysis sought to determine whether Wechsler Memory Scale-Logical Memory (LM)-correct responses and errors were related to magnetic resonance imaging (MRI) brain volume measurements. The LM immediate (LM-I) and LM delay (LM-D) free recall correct responses and related and unrelated errors were scored. Principal components analysis yielded a 3-factor solution: LM-I and LM-D correct responses, LM-I and LM-D-unrelated errors, and LM-I/-D-related errors. The MRI total cerebral brain volume, frontal brain volume, temporal horn volume (THV), and white matter hyperintensities volume (WMHIV) were obtained. Increasing THV (suggesting greater regional atrophy) was associated with lower scores on the LM-correct responses factor. Extensive WMHIV was associated with higher scores on the LM-related errors factor. These results suggest that LM-correct responses could relate to emerging brain alterations. Longitudinal research might enhance the sensitivity of this test to identify preclinical impairment and persons at risk of mild cognitive impairment and dementia. © The Author(s) 2015.
    No preview · Article · Mar 2015 · American Journal of Alzheimer s Disease and Other Dementias
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Prior research has shown that individuals with Parkinson's disease dementia (PDD) show a different pattern of error types on everyday tasks compared with individuals with Alzheimer's disease (AD). This study evaluated whether these groups would respond differently to cues designed to remind participants of task goals and improve performance of everyday tasks (i.e., goal cues). Method: Participants with PDD (n = 20) and AD (n = 20), and a comparison group of individuals with Parkinson's disease and no dementia (n = 20), were administered performance-based tasks of everyday functioning that allowed for the quantification of errors before and after the presentation of goal cues. Results: AD participants showed a significantly greater response to the goal cues as compared with individuals with PDD. The goal cues facilitated the completion of task goals but did not promote error correction (i.e., the undoing of errors that had been made earlier during the task). Conclusions: Not all dementia patients respond similarly to cues designed to improve everyday functioning. Understanding patients' specific form of everyday action impairment is crucial for developing individualized interventions that target specific functional deficits.
    Full-text · Article · Dec 2014 · Neuropsychology
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the present study was to assess the validity of a 12-word Czech version of the Philadelphia (repeatable) Verbal Learning Test [czP(r)VLT-12]. The construction of the czP(r)VLT-12 was modeled after the California Verbal Learning Test (CVLT) and the nine-word Philadelphia (repeatable) Verbal Learning Test [P(r)VLT]. The czP(r)VLT-12 was constructed from a large corpus of old (60-74) and very old (75-96) Czech adults (n = 540). Participants met strict inclusion criteria for the absence of any active or past neurodegenerative disorders and performed within normal limits on other neuropsychological measures. Principal component analysis (PCA) and correlations between czP(r)VLT-12 factor structure and other memory tests were conducted. The czP(r)VLT-12 produced a four-factor solution, accounting for 70.90% of variance, with factors related to: (1) recall, (2) extra-list intrusion errors/recognition foils, (3) interference, and (4) acquisition rate; a solution similar to the CVLT and P(r)VLT. Increasing age resulted in a decline in most czP(r)VLT-12 indices, women outperformed men, and higher education led to higher scores. Memory performance in normal aging did not correlate with instrumental activities of daily living. Low, but significant, correlations were seen with other tests of cognitive performance (divergent validity). Appendices are available that provide normed percentile estimates of individual czP(r)VLT-12 performance stratified by age, education, and gender. In accordance with previous studies, these results demonstrate the usefulness of czP(r)VLT-12 in assessing declarative memory in older adults.
    No preview · Article · Sep 2014 · The Clinical Neuropsychologist
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Psychomotor slowing has been documented in depression. The digital Clock Drawing Test (dCDT) provides: (i) a novel technique to assess both cognitive and motor aspects of psychomotor speed within the same task and (ii) the potential to uncover subtleties of behavior not previously detected with non-digitized modes of data collection. Using digitized pen technology in 106 participants grouped by Age (younger/older) and Affect (euthymic/unmedicated depressed), we recorded cognitive and motor output by capturing how the clock is drawn rather than focusing on the final product. We divided time to completion (TTC) for Command and Copy conditions of the dCDT into metrics of percent of drawing (%Ink) versus non-drawing (%Think) time. We also obtained composite Z-scores of cognition, including attention/information processing (AIP), to explore associations of %Ink and %Think times to cognitive and motor performance. Despite equivalent TTC, %Ink and %Think Command times (Copy n.s.) were significant (AgeXAffect interaction: p=.03)-younger depressed spent a smaller proportion of time drawing relative to thinking compared to the older depressed group. Command %Think time negatively correlated with AIP in the older depressed group (r=-.46; p=.02). Copy %Think time negatively correlated with AIP in the younger depressed (r=-.47; p=.03) and older euthymic groups (r=-.51; p=.01). The dCDT differentiated aspects of psychomotor slowing in depression regardless of age, while dCDT/cognitive associates for younger adults with depression mimicked patterns of older euthymics. (JINS, 2014, 20, 1-9).
    Full-text · Article · Sep 2014 · Journal of the International Neuropsychological Society
  • Source

    Full-text · Article · Jul 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Epidemiologic autopsy studies show mixed Alzheimer's disease (AD)/vascular pathology in many patients. Moreover, clinical research shows that it is not uncommon for AD and vascular dementia (VaD) patients to be equally impaired on memory, executive, or other neurocognitive tests. However, this clinical heterogeneity has not been incorporated into the new diagnostic criteria for AD (Dubois et al., 2010; McKhann et al., 2011). Objective: The current research applied Latent Class Analysis (LCA) to a protocol of six neuropsychological parameters to identify phenotypic subtypes from a large group of AD/VaD participants. Follow-up analyses examined difference between groups on neuroradiological parameters and neuropsychological measures of process and errors. Methods: 223 AD/VaD patients were administered a comprehensive neuropsychological protocol. Measures of whole brain and hippocampal volume were available for a portion of the sample (n = 76). Results: LCA identified four distinct groups: moderate/mixed dementia (n = 54; 24.21%), mild/mixed dementia (n = 91; 40.80%); dysexecutive (n = 49, 21.97%), and amnestic (n = 29, 13.00%). Follow-up analyses comparing the groups on neuropsychological process and error scores showed that the dysexecutive group exhibited difficulty sustaining mental set. The moderate/mixed group evidenced pronounced impairment on tests of lexical retrieval/naming along with significant amnesia. Amnestic patients also presented with gross amnesia, but showed relative sparing on other neuropsychological measures. Mild/mixed patients exhibited milder memory deficits that were intermediary between the amnestic and moderate/mixed groups. Conclusions: There are distinct neuropsychological profiles in patients independent of clinical diagnosis, suggesting that the two are not wholly separate and that this information should be integrated into new AD diagnostic paradigms.
    No preview · Article · Jul 2014 · Journal of Alzheimer's disease: JAD
  • Source

    Full-text · Article · Jul 2014 · Alzheimer's and Dementia
  • Source

    Full-text · Article · Jul 2014 · Alzheimer's and Dementia
  • Source

    Preview · Article · Jul 2014 · Alzheimer's and Dementia
  • Source

    Full-text · Article · Jul 2014 · Alzheimer's and Dementia
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Clock Drawing Test performance was examined alongside other neuropsychological tests in mild cognitive impairment (MCI). We tested the hypothesis that clock-drawing errors are related to executive impairment. The current research examined 86 patients with MCI for whom, in prior research, cluster analysis was used to sort patients into dysexecutive (dMCI, n = 22), amnestic (aMCI, n = 13), and multidomain (mMCI, n = 51) subtypes. First, principal components analysis (PCA) and linear regression examined relations between clock-drawing errors and neuropsychological test performance independent of MCI subtype. Second, between-group differences were assessed with analysis of variance (ANOVA) where MCI subgroups were compared to normal controls (NC). PCA yielded a 3-group solution. Contrary to expectations, clock-drawing errors loaded with lower performance on naming/lexical retrieval, rather than with executive tests. Regression analyses found increasing clock-drawing errors to command were associated with worse performance only on naming/lexical retrieval tests. ANOVAs revealed no differences in clock-drawing errors between dMCI versus mMCI or aMCI versus NCs. Both the dMCI and mMCI groups generated more clock-drawing errors than the aMCI and NC groups in the command condition. In MCI, language-related skills contribute to clock-drawing impairment.
    Full-text · Article · Jul 2014 · Alzheimer's and Dementia
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We compared two methods of diagnosing mild cognitive impairment (MCI): conventional Petersen/Winblad criteria as operationalized by the Alzheimer's Disease Neuroimaging Initiative (ADNI) and an actuarial neuropsychological method put forward by Jak and Bondi designed to balance sensitivity and reliability. 1,150 ADNI participants were diagnosed at baseline as cognitively normal (CN) or MCI via ADNI criteria (MCI: n = 846; CN: n = 304) or Jak/Bondi criteria (MCI: n = 401; CN: n = 749), and the two MCI samples were submitted to cluster and discriminant function analyses. Resulting cluster groups were then compared and further examined for APOE allelic frequencies, cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarker levels, and clinical outcomes. Results revealed that both criteria produced a mildly impaired Amnestic subtype and a more severely impaired Dysexecutive/Mixed subtype. The neuropsychological Jak/Bondi criteria uniquely yielded a third Impaired Language subtype, whereas conventional Petersen/Winblad ADNI criteria produced a third subtype comprising nearly one-third of the sample that performed within normal limits across the cognitive measures, suggesting this method's susceptibility to false positive diagnoses. MCI participants diagnosed via neuropsychological criteria yielded dissociable cognitive phenotypes, significant CSF AD biomarker associations, more stable diagnoses, and identified greater percentages of participants who progressed to dementia than conventional MCI diagnostic criteria. Importantly, the actuarial neuropsychological method did not produce a subtype that performed within normal limits on the cognitive testing, unlike the conventional diagnostic method. Findings support the need for refinement of MCI diagnoses to incorporate more comprehensive neuropsychological methods, with resulting gains in empirical characterization of specific cognitive phenotypes, biomarker associations, stability of diagnoses, and prediction of progression. Refinement of MCI diagnostic methods may also yield gains in biomarker and clinical trial study findings because of improvements in sample compositions of 'true positive' cases and removal of 'false positive' cases.
    Full-text · Article · May 2014 · Journal of Alzheimer's disease: JAD
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background We assessed whether mild cognitive impairment (MCI) subtypes could be empirically derived within the Alzheimer's Disease Neuroimaging Initiative (ADNI) MCI cohort and examined associated biomarkers and clinical outcomes. Methods Cluster analysis was performed on neuropsychological data from 825 MCI ADNI participants. Results Four subtypes emerged: (1) dysnomic (n = 153), (2) dysexecutive (n = 102), (3) amnestic (n = 288), and (4) cluster-derived normal (n = 282) who performed within normal limits on cognitive testing. The cluster-derived normal group had significantly fewer APOE ε4 carriers and fewer who progressed to dementia compared with the other subtypes; they also evidenced cerebrospinal fluid Alzheimer's disease biomarker profiles that did not differ from the normative reference group. Conclusions Identification of empirically derived MCI subtypes demonstrates heterogeneity in MCI cognitive profiles that is not captured by conventional criteria. The large cluster-derived normal group suggests that conventional diagnostic criteria are susceptible to false-positive errors, with the result that prior MCI studies may be diluting important biomarker relationships.
    Full-text · Article · May 2014 · Alzheimer's and Dementia
  • [Show abstract] [Hide abstract]
    ABSTRACT: Total knee arthroplasty improves quality of life but is associated with postoperative cognitive dysfunction in older adults. This prospective longitudinal pilot study with a parallel control group tested the hypotheses that (1) nondemented adults would exhibit primary memory and executive difficulties after total knee arthroplasty, and (2) reduced preoperative hippocampus/entorhinal volume would predict postoperative memory change, whereas preoperative leukoaraiosis and lacunae volumes would predict postoperative executive dysfunction. Surgery (n = 40) and age-education-matched controls with osteoarthritis (n = 15) completed pre- and postoperative (3 weeks, 3 months, and 1 yr) memory and cognitive testing. Hypothesized brain regions of interest were measured in patients completing preoperative magnetic resonance scans (surgery, n = 31; control, n = 12). Analyses used reliable change methods to identify the frequency of cognitive change at each time point. The incidence of postoperative memory difficulties was shown with delay test indices (i.e., story memory test: 3 weeks = 17%, 3 months = 25%, 1 yr = 9%). Postoperative executive difficulty with measures of inhibitory function (i.e., Stroop Color Word: 3 weeks = 21%, 3 months = 22%, 1 yr = 9%). Hierarchical regression analysis assessing the predictive interaction of group (surgery, control) and preoperative neuroanatomical structures on decline showed that greater preoperative volumes of leukoaraiosis/lacunae were significantly contributed to postoperative executive (inhibitory) declines. This pilot study suggests that executive and memory declines occur in nondemented adults undergoing orthopedic surgery. Severity of preoperative cerebrovascular disease may be relevant for understanding executive decline, in particular.
    No preview · Article · Mar 2014 · Anesthesiology

Publication Stats

3k Citations
620.98 Total Impact Points

Institutions

  • 2008-2015
    • Drexel University College of Medicine
      • Department of Neurology
      Filadelfia, Pennsylvania, United States
  • 1993-2015
    • Drexel University
      • • Department of Neurology
      • • Department of Psychology
      Filadelfia, Pennsylvania, United States
  • 2012
    • William Penn University
      Filadelfia, Pennsylvania, United States
  • 2011
    • Temple University
      • Department of Psychology
      Philadelphia, Pennsylvania, United States
  • 2005-2006
    • Stratford University
      Стратфорд, Connecticut, United States
  • 2004
    • Hospital of the University of Pennsylvania
      • Department of Neurology
      Philadelphia, Pennsylvania, United States
  • 2002
    • Boston University
      • Department of Psychiatry
      Boston, Massachusetts, United States
  • 1991-2002
    • Crozer Chester Medical Center
      Upland, Pennsylvania, United States
  • 1990
    • The Philadelphia Center
      Filadelfia, Pennsylvania, United States