William R. Shankle

The University of Western Ontario, London, Ontario, Canada

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Publications (62)378.04 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite increasing global prevalence, the precise pathogenesis and terms for objective diagnosis of neurodegenerative dementias remain controversial, and comprehensive understanding of the disease remains lacking. Here, we conducted metabolomic analysis of serum and saliva obtained from patients with neurodegenerative dementias (n = 10), including Alzheimer's disease, frontotemporal lobe dementia, and Lewy body disease, as well as from age-matched healthy controls (n = 9). Using CE-TOF-MS, six metabolites in serum (β-alanine, creatinine, hydroxyproline, glutamine, iso-citrate, and cytidine) and two in saliva (arginine and tyrosine) were significantly different between dementias and controls. Using multivariate analysis, serum was confirmed as a more efficient biological fluid for diagnosis compared to saliva; additionally, 45 metabolites in total were identified as candidate markers that could discriminate at least one pair of diagnostic groups from the healthy control group. These metabolites possibly provide an objective method for diagnosing dementia-type by multiphase screening. Moreover, diagnostic-type-dependent differences were observed in several tricarboxylic acid cycle compounds detected in serum, indicating that some pathways in glucose metabolism may be altered in dementia patients. This pilot study revealed novel alterations in metabolomic profiles between various neurodegenerative dementias, which would contribute to etiological investigations.
    Electrophoresis 10/2013; 34(19). · 3.16 Impact Factor
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    ABSTRACT: Identifying disease-modifying treatment effects in earlier stages of Alzheimer's disease (AD)-when changes are subtle-will require improved trial design and more sensitive analytical methods. We applied hierarchical Bayesian analysis with cognitive processing (HBCP) models to the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and MCI (mild cognitive impairment) Screen word list memory task data from 14 Alzheimer's disease AD patients of the Myriad Pharmaceuticals' phase III clinical trial of Flurizan (a γ-secretase modulator) versus placebo. The original analysis of 1649 patients found no treatment group differences. HBCP analysis and the original ADAS-Cog analysis were performed on the small sample. HBCP analysis detected impaired memory storage during delayed recall, whereas the original ADAS-Cog analytical method did not. The HBCP model identified a harmful treatment effect in a small sample, which has been independently confirmed from the results of other γ-secretase inhibitor. The original analytical method applied to the ADAS-Cog data did not detect this harmful treatment effect on either the full or the small sample. These findings suggest that HBCP models can detect treatment effects more sensitively than currently used analytical methods required by the Food and Drug Administration, and they do so using small patient samples.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 11/2012; · 14.48 Impact Factor
  • Archives of neurology 08/2012; 69(8):1084-5. · 7.58 Impact Factor
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    ABSTRACT: Determining how cognition affects functional abilities is important in Alzheimer disease and related disorders. A total of 280 patients (normal or Alzheimer disease and related disorders) received a total of 1514 assessments using the functional assessment staging test (FAST) procedure and the MCI Screen. A hierarchical Bayesian cognitive processing model was created by embedding a signal detection theory model of the MCI Screen-delayed recognition memory task into a hierarchical Bayesian framework. The signal detection theory model used latent parameters of discriminability (memory process) and response bias (executive function) to predict, simultaneously, recognition memory performance for each patient and each FAST severity group. The observed recognition memory data did not distinguish the 6 FAST severity stages, but the latent parameters completely separated them. The latent parameters were also used successfully to transform the ordinal FAST measure into a continuous measure reflecting the underlying continuum of functional severity. Hierarchical Bayesian cognitive processing models applied to recognition memory data from clinical practice settings accurately translated a latent measure of cognition into a continuous measure of functional severity for both individuals and FAST groups. Such a translation links 2 levels of brain information processing and may enable more accurate correlations with other levels, such as those characterized by biomarkers.
    Alzheimer disease and associated disorders 03/2012; · 2.88 Impact Factor
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    ABSTRACT: Vascular causes and factors remain the most significant preventable component of cognitive disorders of elderly individuals. The Hachinski Ischemic Score (HIS) is the questionnaire most commonly used for diagnosis of vascular dementia. To consolidate and further validate the HIS. The Canadian Study for Health and Aging was used for this study. It was a cohort study conducted in 3 waves in 1991, 1996-1997, and 2001-2002. The HIS containing 13 items was subjected to correspondence analysis to identify its optimal scaling of item scores and minimal set of items while maximizing the explainable variance. A community-based cohort study. For this analysis, we used 2968 of 3054 well-characterized and well-diagnosed cases with complete HIS data (86 cases had ≥1 item missing) from Canadian Study for Health and Aging phases 2 (1996-1997; n = 2431) and 3 (2001-2002; n = 623). Two optimized HIS versions were identified that classify patients with vascular dementia vs those with nonvascular dementia as well as or more accurately than the original HIS instrument. Assuming the HIS instrument measures only a single dimension, correspondence analysis identified the 7 most discriminative HIS items. Binary scoring (0, 1) of these items led to a 7-item HIS model that classified as well as the original 13-item HIS instrument. By merging highly similar HIS items and applying correspondence analysis, a 5-item composite HIS model was created that measures 2 meaningful dimensions of information and classified vascular vs nonvascular dementia better than the original HIS instrument. Each HIS version developed has specific advantages and disadvantages in terms of simplicity, scoring, generalizability, and accuracy. Depending on the specific setting, 2 reduced HIS versions consisting of 5 composite-question items or 7 single-question items classify as well as or better than the original HIS instrument.
    Archives of neurology 02/2012; 69(2):169-75. · 7.58 Impact Factor
  • Neurology 07/2011; 7(4). · 8.30 Impact Factor
  • Junko Hara, William Shankle
    Alzheimer's and Dementia 07/2011; 7(4). · 17.47 Impact Factor
  • Source
    James P. Pooley, Michael D. Lee, William R. Shankle
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    ABSTRACT: The study of human episodic memory is a topic that interests cognitive and mathematical psychologists as well as clinicians interested in the diagnosis and assessment of Alzheimer’s disease and related disorders (ADRD). In this paper, we use simple cognitive models for the recognition and recall tasks typically applied in clinical assessments of ADRD to study memory performance in ADRD patients. Our models make use of hierarchical Bayesian methods as a way to model individual differences in patient performance and to facilitate the modeling of performance changes that occur during multiple recall tasks. We show how the models are able to account for different aspects of patient performance, and also discuss some of the predictive capabilities of the model. We conclude with a discussion on the scope to improve on our results by discussing the link between memory theory in psychology and clinical practice.
    Journal of Mathematical Psychology 02/2011; · 1.81 Impact Factor
  • Alzheimer's and Dementia 07/2010; 6(4). · 17.47 Impact Factor
  • Junko Hara, Kaitlin Masatsugu, William R. Shankle
    Alzheimer's and Dementia 07/2010; 6(4). · 17.47 Impact Factor
  • William R. Shankle, Gus Alva, Michael D. Lee
    Alzheimer's and Dementia 07/2010; 6(4). · 17.47 Impact Factor
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    ABSTRACT: Among the major impediments to the design of clinical trials for the prevention of Alzheimer's disease (AD), the most critical is the lack of validated biomarkers, assessment tools, and algorithms that would facilitate identification of asymptomatic individuals with elevated risk who might be recruited as study volunteers. Thus, the Leon Thal Symposium 2009 (LTS'09), on October 27-28, 2009 in Las Vegas, Nevada, was convened to explore strategies to surmount the barriers in designing a multisite, comparative study to evaluate and validate various approaches for detecting and selecting asymptomatic people at risk for cognitive disorders/dementia. The deliberations of LTS'09 included presentations and reviews of different approaches (algorithms, biomarkers, or measures) for identifying asymptomatic individuals at elevated risk for AD who would be candidates for longitudinal or prevention studies. The key nested recommendations of LTS'09 included: (1) establishment of a National Database for Longitudinal Studies as a shared research core resource; (2) launch of a large collaborative study that will compare multiple screening approaches and biomarkers to determine the best method for identifying asymptomatic people at risk for AD; (3) initiation of a Global Database that extends the concept of the National Database for Longitudinal Studies for longitudinal studies beyond the United States; and (4) development of an educational campaign that will address public misconceptions about AD and promote healthy brain aging.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 03/2010; 6(2):89-97. · 14.48 Impact Factor
  • William R Shankle
    Alzheimer's & dementia: the journal of the Alzheimer's Association 03/2010; 6(2):145-6. · 14.48 Impact Factor
  • William R Shankle, Tushar Mangrola, Timothy Chan, Junko Hara
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    ABSTRACT: The Memory Performance Index (MPI) quantifies the pattern of recalled and nonrecalled words of the Consortium to Establish a Registry for Alzheimer's Disease Wordlist (CWL) onto a 0 to 100 scale and distinguishes normal from mild cognitive impairment with 96% to 97% accuracy. In group A, 121,481 independently living individuals, 18 to 106 years old, were assessed with the CWL and classified as cognitively impaired (N = 5,971) or normal (N = 115,510). The MPI and CWL immediate free recall (IFR), delayed free recall (DFR), and total free recall (TFR) scores (the outcome measures) were each regressed against predictors of age, gender, race, education, test administration method (in-person or telephone), and wordlist used. Predictor effect sizes (Cohen's f(2)) were computed for each outcome. In addition, CWL plus Functional Assessment Staging Tests (FAST) were administered to 441 normal to moderately severely demented (FAST stages 1 to 6) patients (group B). Median MPI scores were tested for significant differences across FAST stage. For group A, the variance explained by all predictors combined was MPI = 55.0%, IFR = 24.9%, DFR = 23.4%, and TFR = 26.9%. The age effect size on MPI score was large, but it was small on IFR, DFR, and TFR. The other predictors all had negligible (<0.02) or small effect sizes (0.02 to 0.15). For group B, median MPI scores progressively declined across all FAST stages (P < .0002). MPI score progressively declines with increasing dementia severity. Also, MPI score explains 2 to 3 times more variance than total scores, which improves ability to detect treatment effects.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 07/2009; 5(4):295-306. · 14.48 Impact Factor
  • Alzheimer's and Dementia 07/2009; 5(4). · 17.47 Impact Factor
  • William R. Shankle, Junko Hara
    Alzheimer's and Dementia 07/2009; 5(4). · 17.47 Impact Factor
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    ABSTRACT: Omentum transposition surgery (OT) applied to various neurodegenerative disorders has produced clinically significant improvement, which may be due to omentally-derived factors. To evaluate the clinical effect of left hemisphere OT in a primary progressive aphasia (PPA) patient, 3 year follow-up data were analysed. Left hemisphere OT was performed on a 68-year-old male with PPA, characterized by moderate dementia and severe expressive aphasia with relatively preserved comprehension, object recognition and visual-spatial abilities. He was longitudinally assessed with cognitive, functional, behavioral and brain HMPAO SPECT measures pre-OT, at baseline and every 3-6 months for 34 months. All measures improved above baseline for >20 months and persisted at or above baseline for 34 months. Cortical activity increased by a maximum of 21% underneath transposed omentum and in synaptically connected areas, and persisted in >50% of the cortex for at least 12 months. Subjectively, family members observed improved verbal and non-verbal communication. OT produced a sustained, beneficial treatment effect in PPA and warrants further clinical and basic research to identify explanatory factors.
    Neurological Research 02/2009; 31(7):766-9. · 1.45 Impact Factor
  • William Rodman Shankle
    Alzheimer's & dementia: the journal of the Alzheimer's Association 02/2009; 5(1):7-9. · 14.48 Impact Factor
  • Junko Hara, William R. Shankle
    Alzheimer's and Dementia 07/2008; 4(4). · 17.47 Impact Factor
  • William R. Shankle, Tushar Mangrola, Timothy Chan, Junko Hara
    Alzheimer's and Dementia 07/2008; 4(4). · 17.47 Impact Factor

Publication Stats

453 Citations
378.04 Total Impact Points

Institutions

  • 2012
    • The University of Western Ontario
      • Department of Clinical Neurological Sciences
      London, Ontario, Canada
    • The Neurosciences Institute
      La Jolla, California, United States
  • 2011
    • National Center for Geriatrics and Gerontology
      Ōfu, Aichi, Japan
  • 1993–2011
    • University of California, Irvine
      • • Department of Cognitive Sciences
      • • School of Social Sciences
      • • Division of Neurology
      Irvine, California, United States
    • Children's Hospital Los Angeles
      • Department of Pathology and Laboratory Medicine
      Los Angeles, California, United States
  • 2010
    • Swinburne University of Technology
      Melbourne, Victoria, Australia
  • 2007
    • UC Irvine Health
      Santa Ana, California, United States