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BACKGROUND: MRI is an important tool for disease diagnosis of Creutzfeldt-Jakob disease (CJD), yet its role in identifying preclinical stages of disease remains unclear. Here, we explored subtle white matter (WM) alterations in genetic CJD (gCJD) patients and in asymptomatic E200K mutation carriers using MRI, depending on total tau protein (t-tau) levels in CSF. METHODS: Six symptomatic gCJD patients and N=60 healthy relatives of gCJD patients were included. Participants underwent genetic testing for the E200K mutation, MRI scans at 3T and a lumbar puncture (LP) for t-tau. Diffusion tensor imaging (DTI) metrics were calculated along WM tracts. RESULTS: gCJD patients demonstrated higher mean diffusivity (MD), radial diffusivity (RD) and lower fractional anisotropy (FA) values compared with healthy relatives in several WM tracts (p<0.05). Out of the healthy relatives, 50% (N=30) were found to be carriers of the E200K mutation. T-tau levels in cerebrospinal fluid (CSF) were above the normal range (>290 pg/mL) in N=8 out of 23 carriers who underwent an LP. No significant differences in FA, MD, axial diffusivity (AD) and RD were detected between healthy mutation carriers (HMC) and healthy non-carriers within the WM tracts. Finally, significantly higher FA and lower MD, RD and AD along several WM tracts were found in HMC with elevated t-tau compared with HMC with normal t-tau (p<0.05). CONCLUSIONS: DTI abnormalities along WM tracts were found in healthy E200K mutation carriers with elevated t-tau in CSF. Longer follow-up is required to determine whether these subtle WM alterations are predictive of future conversion to symptomatic gCJD. TRIAL REGISTRATION NUMBER: NCT05746715.
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Background: Current evidence suggest that 25%-33% of stroke-survivors develop post-stroke cognitive impairment (PSCI). The licensed drug Maraviroc, a CCR5-antagonist, is postulated to act via a neuroprotective mechanism that may offer the potential of preventing progression to vascular dementia. Our hypothesis: Maraviroc may have the potential to augment learning skills and cognitive performance by affecting synaptic plasticity, along with neuro-inflammatory modulation in patients with cerebral small vessel disease (SVD) and PSCI. Design: MARCH is a multi-center, double-blind randomized-control Phase-II trial of Maraviroc 150 or 600 mg/day versus placebo for 12-months in five stroke centers in Israel. Included are patients diagnosed with recent (1-24 months) subcortical stroke who experience mild PSCI and have evidence of white matter lesions and SVD on neuroimaging. Outcomes: Primary outcomes: 1. Change in cognitive scores. 2. Drug related adverse events. Secondary outcomes: change in functional and affective scores, MRI-derived measures, inflammatory markers, carotid atherosclerosis, cerebrospinal-fluid biomarkers in a sub-study. A sample size of 60 in each treatment group and 30 in the placebo group (total - 150 participants) provides 80% power between the treatment and the placebo groups. Conclusions: The results of this work could lead to a novel, readily available, therapeutic avenue to reduce PSCI, and possibly other pathologies. This study will test safety and effectiveness of Maraviroc in limiting cognitive deterioration and/or post stroke cognitive impairment in patients with cerebral small vessel disease. Schedule: First-patient first-visit was May 2021. Recruitment to complete in 2023, follow-up to complete in 2024.
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BACKGROUND: Most of the research on primary care workload has focused on the number of visits or the average duration of visits to a primary care physician (PCP) and their effect on the quality of medical care. However, the accumulated annual visit duration has yet to be examined. This measure could also have implications for the allocation of resources among health plans and across regions. In this study we aimed to define and characterize the concept of "Accumulated Annual Duration of Time" (AADT) spent with a PCP. METHOD: A cross-sectional study based on a national random sample of 77,247 adults aged 20 and over. The study's variables included annual number of visits and AADT with a PCP, demographic characteristics and chronic diseases. The time period was the entire year of 2012. RESULTS: For patients older than 20 years, the average annual number of visits to a PCP was 8.8 ± 9.1, and the median 6 ± 10 IQR (Interquartile Range). The mean AADT was 65.8 ± 75.7 min, and the median AADT was 43 ± 75 IQR minutes. The main characteristics of patients with a higher annual number of visits and a higher AADT with a PCP were: female, older in age, a higher Charlson index and a low socio-economic status. Chronic diseases were also found to increase the number of annual visits to a PCP as well as the AADT, patients with chronic heart failure had highest AADT in comparison to others (23.1 ± 15.5 vs. 8.6 ± 8.9 visits; and 165.3 ± 128.8 vs. 64.5 ± 74 min). It was also found that the relationship between AADT and age was very similar to the relationship between visits and age. CONCLUSION: While facing the ongoing increase in a PCP's work load and shortening of visit length, the concept of AADT provides a new measure to compare between different healthcare systems that allocate different time frames for a single primary care visit. For Israel, the analysis of the AADT data provides support for continued use of the number of visits in the capitation formula, as a reliable and readily-accessible indicator of primary care usage.