A cross-sectional comparison of performance, neurophysiological and MRI outcomes of responders and non-responders to fampridine treatment in multiple sclerosis - An explorative study

OBJECTIVE: To compare baseline physical and cognitive performance, neurophysiological, and magnetic resonance imaging (MRI) outcomes and examinetheir interrelationship inparticipants with Multiple Sclerosis (MS), already established aseither responder or non-responder to Fampridine treatment, andto examine associationswiththe expanded disability status scale (EDSS) and 12-item MS walking scale (MSWS-12). METHODS: Baseline data from an explorative longitudinal observational study were analyzed. Participants underwent the Timed 25-Foot Walk Test (T25FW), Six Spot Step Test (SSST), Nine-Hole Peg Test, Five Times Sit-to-Stand Test, Symbol Digit Modalities Test (SDMT), neurophysiological testing, including central motor conduction time (CMCT), peripheral motor conduction time (PMCT), motor evoked potential (MEP) amplitudesand electroneuronographyof the lower extremities, and brain MRI (brain volume, number and volume of T2-weighted lesions and lesion load normalized to brain volume). RESULTS: 41 responders and 8 non-responders were examined. There were no intergroup differences inphysical performance, cognitive, neurophysiological, andMRI outcomes (p > 0.05).CMCT was associated withT25FW, SSST, EDSS, and MSWS-12,(p < 0.05). SDMT was associated with the number and volume of T2-weighted lesions, and lesion load normalized to brain volume (p < 0.05). CONCLUSION: No differences were identified between responders and non-responders to Fampridine treatment regarding physical and cognitive performance, neurophysiological or MRI outcomes. The results call for cautious interpretation and further large-scale studies are needed to expand ourunderstanding of underlying mechanisms discriminating Fampridine responders and non-responders.CMCT may be used as a marker of disability and walking impairment, while SDMT was associated with white matter lesions estimated by MRI. ClinicalTrials.gov identifier: NCT03401307

Dynamic amyloid and metabolic signatures of delayed recall performance within the clinical spectrum of Alzheimer’s disease

Associations between pathophysiological events and cognitive measures provide insights regarding brain networks affected during the clinical progression of Alzheimer’s disease (AD). In this study, we assessed patients’ scores in two delayed episodic memory tests, and investigated their associations with regional amyloid deposition and brain metabolism across the clinical spectrum of AD. We assessed the clinical, neuropsychological, structural, and positron emission tomography (PET) baseline measures of participants from the Alzheimer’s Disease Neuroimaging Initiative. Subjects were classified as cognitively normal (CN), or with early (EMCI) or late (LMCI) mild cognitive impairment, or AD dementia. The memory outcome measures of interest were logical memory 30 min delayed recall (LM30) and Rey Auditory Verbal Learning Test 30 min delayed recall (RAVLT30). Voxel-based [18F]florbetapir and [18F]FDG uptake-ratio maps were constructed and correlations between PET images and cognitive scores were calculated. We found that EMCI individuals had LM30 scores negatively correlated with [18F]florbetapir uptake on the right parieto-occipital region. LMCI individuals had LM30 scores positively associated with left lateral temporal lobe [18F]FDG uptake, and RAVLT30 scores positively associated with [18F]FDG uptake in the left parietal lobe and in the right enthorhinal cortex. Additionally, LMCI individuals had LM30 scores negatively correlated with [18F]florbetapir uptake in the right frontal lobe. For the AD group, [18F]FDG uptake was positively correlated with LM30 in the left temporal lobe and with RAVLT30 in the right frontal lobe, and [18F]florbetapir uptake was negatively correlated with LM30 scores in the right parietal and left frontal lobes. The results show that the association between regional brain metabolism and the severity of episodic memory deficits is dependent on the clinical disease stage, suggesting a dynamic relationship between verbal episodic memory deficits, AD pathophysiology, and clinical disease stages