28 research outputs found
QUANTITATIVE CLINICAL NEUROLOGICAL TESTING. I. A STUDY OF A BATTERY OF TESTS DESIGNED TO EVALUATE IN PART THE NEUROLOGICAL FUNCTION OF PATIENTS WITH MULTIPLE SCLEROSIS AND ITS USE IN A THERAPEUTIC TRIAL *
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73100/1/j.1749-6632.1965.tb20231.x.pd
An assessment of the reliability of three methods used in evaluating the status of multiple sclerosis patients
The reliability of three different evaluation methods used in a cooperative clinical trial of the efficacy of ACTH in multiple sclerosis patients was evaluated in a uniformity study that used an efficient statistical design requiring only 10 patients and 5 examiners. The methods were the standard neurologic examination, a scoring system for functional grades and disability status, and a 7-day symptom score. Each patient was examined only 3 times at the beginning of the study and 3 more times 6 days later. No significant differences among the 5 examiners were observed on 82 of the 87 items used to measure neurologic function. With the exception of 1 variable, there were no significant differences among the average values of the sequence of the 3 examinations, nor among the average increments of change in the numerical scores between the first and second trials.In an additional examination in which all 5 examiners simultaneously evaluated 3 patients 1 at a time, it was found that the 5 examiners observed uniformly in all of the neurologic tests.The results of this study indicate that, by and large, the three evaluation methods appear to be reliable in the evaluation of neurologic status when used in a cooperative clinical trial where several investigators contribute data. Furthermore, investigations of reliability in cooperative studies can be performed with the use of efficient statistical designs such as the incomplete Latin-square design.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32998/1/0000382.pd
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE Δ4 allele
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