Timely and accurate diagnosis of Alzheimer’s disease (AD) in clinical practice is a great challenge, especially during early disease stages with subtle or mild symptoms of cognitive decline. Moreover, robust and more accessible blood-based screening tests for early diagnosis are needed. In this study, we investigated the core AD blood biomarkers — amyloid beta 42 (Aβ42) and 40 (Aβ40) peptides, phosphorylated tau 181 (p-Tau181), neurofilament light chain (NfL), and total tau (t-Tau) — and extracellular vesicle (EVs) size and concentration in individuals characterized by different stages of cognitive decline to identify biochemical markers of dementia for early diagnosis. A total of n = 800 human plasma samples were analyzed. Plasma levels of NfL, t-Tau, p-Tau181, Aβ42, Aβ40 and plasma EVs were evaluated in n = 217 elderly healthy subjects (CTRL), in individuals with subjective cognitive complaints (SCC, n = 48), pre-mild cognitive impairment (pre-MCI, n = 58) and mild cognitive impairment (MCI, n = 426), and in n = 51 probable AD dementia patients (AD-dem), using ultrasensitive Single Molecule Array technology (Simoa®) and nanoparticle tracking analysis (NTA). Logistic regression and Receiver Operating Characteristic (ROC) analyses were employed. Plasma NfL displayed increased levels in AD-dem and MCI patients, while p-Tau181, Aβ42/Aβ40 ratio, Aβ42/p-Tau181 ratio, and EVs plasma levels were altered since the early stages of the pathology: in particular, p-Tau181 levels increased as cognitive symptoms worsened, already in the SCC and pre-MCI groups compared to CTRL, while the ratio of EVs concentration and size (EVs ratio) was decreased in all groups compared to CTRL. Plasma p-Tau181 best classified AD-dem patients from CTRL with an area under the curve (AUC) equal to 0.87, while EVs ratio best differentiated SCC from CTRL (AUC = 0.78). Combining p-Tau181 and EVs ratio with Aβ42/Aβ40 ratio and NfL, respectively, significantly improved the classification of pre-MCI and MCI from CTRL (AUCcomb = 0.79 and AUCcomb = 0.85). Combining biomarkers did not improve accuracy in discriminating MCI from SCC, pre-MCI and AD-dem. p-Tau181 and EVs ratio are promising biomarkers for the identification of individuals at risk of degenerative dementia. Combining the core AD plasma biomarkers with EVs ratio can aid in diagnosing the early stages of AD dementia.
This dataset includes raw and processed data collected using a single lower-back-mounted inertial measurement unit (IMU) during a standardized 6-Minute Walk Test (6MWT) in a sample of sixty healthy adults (age range: 21-75 years; 50% female). Accelerometer and gyroscope signals were analyzed for metrological quality under static and dynamic conditions. A set of digital gait metrics was derived from the IMU data, including spatiotemporal parameters and measures of gait intensity, instability, symmetry, and regularity. These metrics are provided in the dataset alongside demographic, anthropometric, and physiological data. The dataset offers a practical, clinically relevant resource to support the development, validation, and benchmarking of novel algorithms for digital mobility assessments. Its structure enables comparisons across age and sex groups and provides normative data for future analyses on pathologic populations, supporting applications in aging studies, rehabilitation, and digital biomarker development. Raw signals, processed metrics and software codes are included in the dataset to support effective data reusability.
BACKGROUND:Motor and cognitive dysfunctions are common and disabling features in multiple sclerosis (MS) that remain challenging to treat. Here, we aimed to explore the effect of exergames as a stand-alone approach for people with MS and impaired processing speed. METHODS:This was a three-arm, randomised, rater-blinded, sham-controlled trial. People with MS and impaired processing speed were randomised in a 1:1:1 ratio to an 8-week home-based training with exergames (intervention of interest), adaptive Cognitive Training Kit (COGNI-TRAcK) (working memory training as comparator intervention) or sham intervention. A postintervention assessment was scheduled at week 16 postrandomisation. Statistical analyses were conducted to test the hypotheses that exergames were superior to sham intervention and non-inferior to adaptive COGNI-TRAcK on the symbol digit modalities test (SDMT). RESULTS:We screened 165 people with MS, of whom 102 were randomised (34 per arm). At week 8, both exergames and adaptive COGNI-TRAcK yielded improvements in SDMT, with adjusted mean differences versus sham intervention of 4.3 (95% CI 0.1 to 8.5) and 5.7 (95% CI 1.3 to 10.1) points, respectively. The non-inferiority analysis was inconclusive, as the mean between-arm difference (adaptive COGNI-TRAcK versus exergames) was 1.3 points (90% CI -1.7 to 4.3), crossing the predefined non-inferiority margin of 4 SDMT points. Exergames additionally demonstrated benefits on executive function, dynamic balance, fatigue and reduced work absenteeism. None of these benefits was retained at week 16. CONCLUSION:This study provides evidence that home-based exergames are suitable as a standalone approach to improve some specific MS-related cognitive and motor dysfunctions, but there is no evidence about their non-inferiority to working memory training. TRIAL REGISTRATION NUMBER:NCT04169750.
Timely intensive rehabilitation is crucial to contrast the negative escalation of events that follow a stroke injury, to promote tissue regeneration, and to restore the physiological function. This study aimed to identify measurable blood biomarkers that could be predictive of functional recovery in stroke survivors. 30 sub-acute stroke subjects were enrolled at Fondazione Don Gnocchi (Italy) during the observation prospective study EXO4STROKE (NCT05370105). Following clinical assessment, cytokines, neurofilaments and circulating Extracellular Vesicles (EVs) were evaluated in the serum of patients at admission (T0) and at discharge (T1) in intensive rehabilitation unit. Multiplexed SPRi analysis of circulating EVs allowed detection of brain (neurons, astrocytes, microglia) and non-brain (endothelium, skeletal muscle, and platelets) derived EVs, and the relative quantification of markers of pathological or regenerative processes. Machine learning-based analysis complemented the study by integrating statistically significant features in a cross-validated prediction model targeting functional recovery at T1 from T0 data. The results of the present study demonstrate that high serum levels of IL-6 and Neurofilament Light Chain at T0 were associated with higher residual disability at T1. In contrast, elevated circulating levels of EVs from neurons (CD171+) and microglia (CD11b+) were associated with better recovery after rehabilitation. Moreover, the overexpression of the VEGF receptor on microglial EVs was associated with higher functional improvement. Alternatively, the overexpression of TGF-β receptor on IB4 + EVs post-stroke was found associated with increased stroke severity. In conclusion, this study identifies a panel of few circulating biomarkers able to objectively assess post-stroke status and potentially predict functional recovery after rehabilitation.
Slacklining is a highly demanding dynamic balance discipline that induces task-specific neuromotor and kinematic adaptations. While previous studies have documented improvements in postural control following slackline training, little is known about how motor strategies differ between slackliners, athletes from other sports, and sedentary individuals during non-slackline balance tasks. The purpose of this study was to characterize differences in dynamic and kinematic motor strategies among professional slackliners, non-slackliner athletes, and sedentary individuals during a set of balance tasks. Thirty-two adults, including professional slackliners, athletes from other sports, and sedentary individuals, performed four balance tasks of increasing complexity. Dynamic and kinematic data were collected using a force-platform–based system combined with marker-less three-dimensional motion analysis. Group differences in center-of-pressure displacement and joint kinematics were analyzed using non-parametric statistical tests. Sedentary individuals exhibited greater trunk extension and larger antero-posterior center-of-pressure displacement compared with both slackliners and athletes. Slackliners demonstrated reduced postural sway and greater shoulder abduction and hip flexion across multiple tasks. In more demanding balance conditions, slackliners showed distinct upper- and lower-limb kinematic strategies compared with the other groups, particularly at the shoulder, hip, and knee joints. Individuals with different motor backgrounds adopt distinct motor control strategies during balance tasks. Long-term slackline practice is associated with joint-specific kinematic adaptations involving the shoulders, hips, and knees, which may partially extend beyond slackline-specific contexts. Key Terms : Slacklining; Dynamic balance; Postural control; Kinematic analysis; Motor strategies.
