Neurologia Clinica Lange Pdf Download |TOP|
Neurologia Clinica Lange Pdf Download
the clustering of voxels into distinct sets (clusters) is known to reflect not only anatomical, but also functional and metabolic similarity among the voxels, and hence, to be useful to identify neuropsychiatric disorders [ 37 38 ]. thus, the four clusters of clusters identified in the ad dementia group (table 3) were predominantly located in temporal and parietal cortical regions, which is in agreement with previously described patterns of hypometabolism in ad [ 39 ]. in contrast, clusters that were identified in the prodromal ad group (table 4) were mainly located in frontal, temporal and parietal brain regions.
to date, there is no curative treatment for ad. while a variety of drugs are in development, none of them have been tested in large randomized trials to show a clinical benefit in ad, and none of them has been approved by the us food and drug administration or the european medicines agency.
however, the ncs-a did not distinguish between patients with typical and atypical ad. thus, nincds-adrda criteria for the clinical diagnosis of ad were applied. the nincds-adrda criteria were based on an assessment of the neurological examination and the medical history. cognitive tests were not included in the nincds-adrda classification. the nincds-adrda criteria for ad are therefore not based on a pathophysiological perspective, but rather on a clinical perspective. however, these criteria are also used by many clinicians for clinical diagnosis, and were thus considered as a reasonable reference standard in our study.
the intra-class correlation coefficient was above 0.76 for the primary and secondary outcomes (i.e. memory composite and mmse score, respectively), indicating a good level of test-retest reliability. for the neuropsychological battery, intra-class correlation coefficients were as follows: 0.74 for the memory composite (i. delayed recall of an anterograde word list); 0.83 for the visuo-spatial composite (i. delayed recall of an anterograde and retrograde word list); 0.
the elecsys -amyloid  csf immunoassay in use is not a commercially available ivd assay. it is an assay that is currently under development and for investigational use only. the measuring range of assay is 200 (lower technical limit)1700pg/ml (upper technical limit). the performance of the assay beyond the upper technical limit has not been formally established. therefore, the use of values above the upper technical limit, which are provided based on an extrapolation of the calibration curve, is restricted to exploratory research purposes and is excluded for clinical decision making or for the derivation of medical decision points.
for data pre-processing, individual fdg-pet scans were co-registered to individual t1-weighted mr images and were spatially normalized to the standard reference space defined by the colin27 standardization template in montreal neurological institute (mni)-space [ 17 ]. the obtained transformation matrix was applied to the fdg-pet scans, resampled to 3-mm isotropic voxels, and smoothed with a 3-mm full-width at half maximum kernel. data pre-processing and further analysis were performed using the spm5 software package ( www.fil.ion.ucl.ac.uk/spm ). for each subject the mean fdg-pet image was calculated and subjects were subsequently ranked based on the spm-based fdg-pet signal intensity. this was done to ensure a homogeneous data set, as fdg-pet data of low signal intensity may not be reliably registered to a global mean. subjects with a mean fdg-pet signal above the 75th percentile were labeled as showing ‘typical ad’ fdg-pet patterns, whereas those with a fdg-pet signal below the 25th percentile and those with fdg-pet signal levels between these two percentiles were labeled as showing ‘atypical ad’ patterns. in order to calculate a brain fdg-pet pattern index that reflects the distribution of patients across the three ad subtypes, each subject’s fdg-pet patterns were compared to the fdg-pet patterns of the other subjects with regard to the spatial distribution, and a subject-weighted fdg-pet pattern index was calculated. this resulting pattern index represents the patient’s similarity to the three ad subtype clusters as defined by the cortical-predominant, limbic-predominant and typical subtypes, respectively. each subtype is characterized by a different hypometabolic pattern in the posterior and anterior cingulate, hippocampus and medial temporal cortex ( figure 2 ). anterior temporal lobe hypometabolism corresponding to typical ad is most widespread among the typical subtype ( figure 2b ) and a posterior temporal lobe hypometabolism pattern corresponding to atypical ad is most widespread among the limbic-predominant subtype ( figure 2d ). accordingly, the subject-weighted fdg-pet pattern index is the largest for typical and limbic-predominant subtypes, whereas the index is intermediate for the cortical-predominant subtype ( figure 2e ).