ABSTRACT
BACKGROUND AND OBJECTIVES: There is no disease-modifying treatment of corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), 2 disorders characterized by their striking phenotypic, and, in CBS, pathologic heterogeneity. Seed amplification assays (SAAs) could enable the detection of neuropathologic processes, such as α-synuclein (αSyn) copathology, that affect the success of future disease-modifying treatment strategies. The primary objective was to assess possible αSyn copathology in CBS and PSP, as detected in CSF using an αSyn SAA (αSyn-SAA). Secondary objectives were to evaluate the association of αSyn-SAA positivity with other biomarkers including of Alzheimer disease (AD), and with clinical presentation. We hypothesized that αSyn-SAA positivity would be detectable in CBS and PSP and that it would be associated with AD biomarker positivity and ß-amyloid (Aß) 42 levels, neurodegeneration as assessed by neurofilament light chain (NfL) levels, and symptoms associated with synucleinopathies. METHODS: This cross-sectional observational study included patients clinically diagnosed with CBS and PSP who underwent a lumbar puncture between 2012 and 2021 (Toronto Western Hospital, Canada). CSF was tested for αSyn-SAA positivity, AD biomarkers, and NfL levels. Clinical data were derived from medical records. RESULTS: We tested the CSF of 40 patients with CBS (19 female patients, 65.9 ± 8.6 years) and 28 with PSP (13 female patients, 72.5 ± 8.7 years old), mostly White (n = 50) or Asian (n = 14). αSyn-SAA positivity was observed in 35.9% patients with CBS and 28.6% with PSP. In young-onset, but not late-onset patients, αSyn-SAA positivity and AD positivity were associated (odds ratio [OR] 8.8, 95% CI 1.2-82.6, p < 0.05). A multivariable linear regression analysis showed a significant interaction of αSyn-SAA status by age at onset on CSF Aß42 levels (ß = 0.3 ± 0.1, p < 0.05). Indeed, age at onset was positively related to Aß42 levels only in αSyn-SAA-positive patients, as shown by slope comparison. A logistic regression analysis also suggested that REM sleep behavior disorder was associated with αSyn-SAA positivity (OR 60.2, 95% CI 5.2-1,965.8; p < 0.01). DISCUSSION: We detected a frequency of αSyn-SAA positivity in CBS and PSP in line with pathologic studies, highlighting the usefulness of SAAs for in vivo detection of otherwise undetectable neuropathologic processes. Our results also suggest that AD status (specifically low Aß42) and older age at onset may contribute to αSyn-SAA positivity. This opens new perspectives for the stratification of patients in clinical trials.
Subject(s)
Amyloid beta-Peptides , Biomarkers , alpha-Synuclein , Humans , alpha-Synuclein/cerebrospinal fluid , Female , Male , Aged , Middle Aged , Biomarkers/cerebrospinal fluid , Cross-Sectional Studies , Amyloid beta-Peptides/cerebrospinal fluid , Parkinsonian Disorders/cerebrospinal fluid , Parkinsonian Disorders/diagnosis , Supranuclear Palsy, Progressive/cerebrospinal fluid , Supranuclear Palsy, Progressive/diagnosis , Peptide Fragments/cerebrospinal fluid , Neurofilament Proteins/cerebrospinal fluid , Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/diagnosis , Aged, 80 and overABSTRACT
BACKGROUND: Acute effects of continuous exercise on the markers of blood fluidity have been addressed in different populations and the changes are intensity related. However, the effect of different high intensity interval exercise (HIIE) on these variables is unclear. OBJECTIVE: This study is designed to determine the effects of two different HIIE with different work/rest ratios but the same energy expenditure on the main determinants of blood fluidity. METHODS: Ten overweight men (age, 26.3±1.7 yrs) completed two HIIE protocols on two separate occasions with one week intervening. The two HIIE encompassed performing: 1) 6 intervals of 2âmin activity at 85% of VO2max interspersed by 2âmin active recovery at 30% of VO2max (ratio 1 to 1, HIIE1/1), and 2) 6 intervals of 30âs activity at 110% of VO2max interspersed by 4âmin active recovery at 40% of VO2max (ratio 1 to 8, HIIE1/8). Each exercise trial was followed by 30âmin rest. Venous blood samples were obtained before exercise, immediately after exercise and after recovery and analyzed for blood and plasma viscosity, fibrinogen and red blood cell indices. RESULTS: The HIIE1/1 protocol led to higher reduction (Pâ<â0.01) in plasma volume changes compared to HIIE1/8 (9.9% vs 5.7%). Moreover, increases in blood viscosity, plasma viscosity, hematocrit, RBC count and mean arterial blood pressure observed following HIIE1/1 were significantly (Pâ<â0.05) higher than HIIE1/8 ; whereas, the changes in fibrinogen concentration neither were significant in response to both trials nor were significantly different between two protocols (Pâ>â0.05). However, the changes in all variables during exercise were transient and returned to the baseline levels after 30âmin recovery. CONCLUSIONS: It is concluded that the HIIE protocol with lower intensity and shorter rest intervals (higher work to rest ratio) clearly results in more physiological strain than HIIE with higher intensity but longer rest intervals (lower work to rest ratio) in overweight individuals, and that the work to rest ratio could be as important as exercise intensity when considering the hemorheological variables during HIIE.