Timing of Biomarker Changes in Sporadic Alzheimer's Disease in Estimated Years from Symptom Onset.

OBJECTIVE: A clock relating amyloid positron emission tomography (PET) to time was used to estimate the timing of biomarker changes in sporadic Alzheimer disease (AD). METHODS: Research participants were included who underwent cerebrospinal fluid (CSF) collection within 2 years of amyloid PET. The ages at amyloid onset and AD symptom onset were estimated for each individual. The timing of change for plasma, CSF, imaging, and cognitive measures was calculated by comparing restricted cubic splines of cross-sectional data from the amyloid PET positive and negative groups. RESULTS: The amyloid PET positive sub-cohort (n = 118) had an average age of 70.4 ± 7.4 years (mean ± standard deviation) and 16% were cognitively impaired. The amyloid PET negative sub-cohort (n = 277) included individuals with low levels of amyloid plaque burden at all scans who were cognitively unimpaired at the time of the scans. Biomarker changes were detected 15-19 years before estimated symptom onset for CSF Aß42/Aß40, plasma Aß42/Aß40, CSF pT217/T217, and amyloid PET; 12-14 years before estimated symptom onset for plasma pT217/T217, CSF neurogranin, CSF SNAP-25, CSF sTREM2, plasma GFAP, and plasma NfL; and 7-9 years before estimated symptom onset for CSF pT205/T205, CSF YKL-40, hippocampal volumes, and cognitive measures. INTERPRETATION: The use of an amyloid clock enabled visualization and analysis of biomarker changes as a function of estimated years from symptom onset in sporadic AD. This study demonstrates that estimated years from symptom onset based on an amyloid clock can be used as a continuous staging measure for sporadic AD and aligns with findings in autosomal dominant AD. ANN NEUROL 2024;95:951-965.

Motor, cognitive and mobility deficits in 1000 geriatric patients: protocol of a quantitative observational study before and after routine clinical geriatric treatment - the ComOn-study.

BACKGROUND: Motor and cognitive deficits and consequently mobility problems are common in geriatric patients. The currently available methods for diagnosis and for the evaluation of treatment in this vulnerable cohort are limited. The aims of the ComOn (COgnitive and Motor interactions in the Older populatioN) study are (i) to define quantitative markers with clinical relevance for motor and cognitive deficits, (ii) to investigate the interaction between both motor and cognitive deficits and (iii) to assess health status as well as treatment outcome of 1000 geriatric inpatients in hospitals of Kiel (Germany), Brescia (Italy), Porto (Portugal), Curitiba (Brazil) and Bochum (Germany). METHODS: This is a prospective, explorative observational multi-center study. In addition to the comprehensive geriatric assessment, quantitative measures of reduced mobility and motor and cognitive deficits are performed before and after a two week's inpatient stay. Components of the assessment are mobile technology-based assessments of gait, balance and transfer performance, neuropsychological tests, frailty, sarcopenia, autonomic dysfunction and sensation, and questionnaires to assess behavioral deficits, activities of daily living, quality of life, fear of falling and dysphagia. Structural MRI and an unsupervised 24/7 home assessment of mobility are performed in a subgroup of participants. The study will also investigate the minimal clinically relevant change of the investigated parameters. DISCUSSION: This study will help form a better understanding of symptoms and their complex interactions and treatment effects in a large geriatric cohort.

Validation of a Lower Back "Wearable"-Based Sit-to-Stand and Stand-to-Sit Algorithm for Patients With Parkinson's Disease and Older Adults in a Home-Like Environment.

Introduction: Impaired sit-to-stand and stand-to-sit movements (postural transitions, PTs) in patients with Parkinson's disease (PD) and older adults (OA) are associated with risk of falling and reduced quality of life. Inertial measurement units (IMUs, also called "wearables") are powerful tools to monitor PT kinematics. The purpose of this study was to develop and validate an algorithm, based on a single IMU positioned at the lower back, for PT detection and description in the above-mentioned groups in a home-like environment. Methods: Four PD patients (two with dyskinesia) and one OA served as algorithm training group, and 21 PD patients (16 without and 5 with dyskinesia) and 11 OA served as test group. All wore an IMU on the lower back and were videotaped while performing everyday activities for 90-180 min in a non-standardized home-like environment. Accelerometer and gyroscope signals were analyzed using discrete wavelet transformation (DWT), a six degrees-of-freedom (DOF) fusion algorithm and vertical displacement estimation. Results: From the test group, 1,001 PTs, defined by video reference, were analyzed. The accuracy of the algorithm for the detection of PTs against video observation was 82% for PD patients without dyskinesia, 47% for PD patients with dyskinesia and 85% for OA. The overall accuracy of the PT direction detection was comparable across groups and yielded 98%. Mean PT duration values were 1.96 s for PD patients and 1.74 s for OA based on the algorithm (p < 0.001) and 1.77 s for PD patients and 1.51 s for OA based on clinical observation (p < 0.001). Conclusion: Validation of the PT detection algorithm in a home-like environment shows acceptable accuracy against the video reference in PD patients without dyskinesia and controls. Current limitations are the PT detection in PD patients with dyskinesia and the use of video observation as the video reference. Potential reasons are discussed.

Do Children and Adolescents Have Different Types of Trauma Narratives and Does It Matter? Reliability and Face Validation for a Narrative Taxonomy.

The construction of trauma narratives is a major component of several psychotherapy approaches for trauma-related problems, but questions remain as to whether fully expressive narratives are necessary and whether it is detrimental to ask avoidant youths to tell their narratives repeatedly. Characteristics of trauma narratives during psychotherapy have not been examined in youths and this represents a salient gap in knowledge. This study aimed to begin filling this gap by identifying categories of trauma narratives and empirically validating them. Youths (N = 47) aged 7 to 18 years, who were involved in a randomized controlled trial, received cognitive behavioral therapy. Transcripts of all narrative exposure therapy sessions for each youth were rated. Four categories were identified and were named expressive, avoidant, fabricated, and undemonstrative. Interrater reliability for identifying these categories was good, and face validation of the categories was supported by statistically significant differences between categories on the number of data elements of the trauma events, negative emotion words, and positive emotion words. These promising findings indicate that different types of narrative styles can be reliably identified. There was strong evidence for reduction of posttraumatic stress symptoms in each of the categories (Cohen's d = 0.9 to 2.5). Favorable treatment outcomes for all categories suggest that more remembering is not always better and clients appeared to effectively deal with memories in different ways.