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Articles by Vernon S. Pankratz
Total Records ( 2 ) for Vernon S. Pankratz
  Stephen D. Weigand , Prashanthi Vemuri , Heather J. Wiste , Matthew L. Senjem , Vernon S. Pankratz , Paul S. Aisen , Michael W. Weiner , Ronald C. Petersen , Leslie M. Shaw , John Q. Trojanowski , David S. Knopman and Clifford R. Jack
  Background Positron-emission tomography (PET) imaging of amyloid with Pittsburgh Compound B (PIB) and Aβ42 levels in the cerebrospinal fluid (CSF Aβ42) demonstrate a highly significant inverse correlation. Both these techniques are presumed to measure brain Aβ amyloid load. The objectives of this study were to develop a method to transform CSF Aβ42 measures into calculated PIB measures (PIBcalc) of Aβ amyloid load, and to partially validate the method in an independent sample of subjects. Methods In all, 41 subjects from the Alzheimer‘s Disease Neuroimaging Initiative (ADNI) underwent PIB PET imaging and lumbar puncture (LP) at the same time. This sample, referred to as the ”training“ sample (nine cognitively normal subjects, 22 subjects with mild cognitive impairment, and 10 subjects with Alzheimer‘s disease), was used to develop a regression model by which CSF Aβ42 (with apolipoprotein E ɛ4 carrier status as a covariate) was transformed into units of PIB PET (PIBcalc). An independent ”supporting“ sample of 362 ADNI subjects (105 cognitively normal subjects, 164 subjects with mild cognitive impairment, and 93 subjects with Alzheime‘s disease) who underwent LP but not PIB PET imaging had their CSF Aβ42 values converted to PIBcalc. These values were compared with the overall PIB PET distribution found in the ADNI subjects (n = 102). Results A linear regression model demonstrates good prediction of actual PIB PET from CSF Aβ42 measures obtained in the training sample (R2 = 0.77, P < .001). PIBcalc data (derived from CSF Aβ42) in the supporting sample of 362 ADNI subjects who underwent LP but not PIB PET imaging demonstrate group-wise distributions that are highly consistent with the larger ADNI PIB PET distribution and with published PIB PET imaging studies. Conclusion Although the precise parameters of this model are specific for the ADNI sample, we conclude that CSF Aβ42 can be transformed into PIBcalc measures of Aβ amyloid load. Brain Aβ amyloid load can be ascertained at baseline in therapeutic or observational studies by either CSF or amyloid PET imaging and the data can be pooled using well-established multiple imputation techniques that account for the uncertainty in a CSF-based PIBcalc value.
  David S. Knopman , Sandra Weintraub and Vernon S. Pankratz
  Background The six domain standard Clinical Dementia Rating Scale (CDRstd) has been successful for staging patients with the clinical syndrome of probable Alzheimer‘s disease (AD). The CDRstd does not specifically address language dysfunction or alteration in personality and social behaviors which are prominent in behavioral variant frontotemporal dementia (bvFTD) and primary progressive aphasia (PPA). Objective To determine the value of adding domains of Language (LANG), and Behavior, Comportment, and Personality (BEHAV) to the CDRstd for the evaluation of patients with bvFTD and PPA. Methods Two new domains, LANG and BEHAV, were constructed to parallel the six domains sampled in the CDRstd. Clinical and neuropsychological test data were obtained from the National Alzheimer‘s Coordinating Center. The dataset contained information on 2550 probable AD, 88 vascular dementia, 281 dementia with Lewy body, 234 bvFTD, and 137 PPA patients. Results There were 76.5% of bvFTD and 99.3% of PPA patients with abnormal ratings (>0) on the LANG domain; 90.2% of bvFTD and 63.5% of PPA had abnormal ratings on the BEHAV domain. In patients with a CDRstd sum of boxes score of <4, 53.7% of bvFTD had BEHAV domain and 78.6% of PPA patients had LANG domain scores >1. Among probable AD patients, 3.7% had LANG ratings that were ≥1 and 3.8% had BEHAV ratings that were ≥1. Logistic regression analyses showed that adding either the LANG or BEHAV domains to the CDRstd sum of boxes score significantly improved the discrimination between probable AD, bvFTD, and PPA. Conclusions The new LANG and BEHAV domains add value to the CDRstd for the characterization of the nonamnestic symptoms that are prominent in patients with bvFTD and PPA but that also occur in those with probable AD.
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