Feasibility and usability of remote monitoring in Alzheimer’s disease

Introduction: Remote monitoring technologies (RMTs) can measure cognitive and functional decline objectively at-home, and offer opportunities to measure passively and continuously, possibly improving sensitivity and reducing participant burden in clinical trials. However, there is skepticism that age and cognitive or functional impairment may render participants unable or unwilling to comply with complex RMT protocols. We therefore assessed the feasibility and usability of a complex RMT protocol in all syndromic stages of Alzheimer’s disease and in healthy control participants.Methods: For 8 weeks, participants (N=229) used two activity trackers, two interactive apps with either daily or weekly cognitive tasks, and optionally a wearable camera. A subset of participants participated in a 4-week sub-study (N=45) using fixed at-home sensors, a wearable EEG sleep headband and a driving performance device. Feasibility was assessed by evaluating compliance and drop-out rates. Usability was assessed by problem rates (e.g., understanding instructions, discomfort, forgetting to use the RMT or technical problems) as discussed during bi-weekly semi-structured interviews.Results: Most problems were found for the active apps and EEG sleep headband. Problem rates increased and compliance rates decreased with disease severity, but the study remained feasible.Conclusions: This study shows that a highly complex RMT protocol is feasible, even in a mild-to-moderate AD population, encouraging other researchers to use RMTs in their study designs. We recommend evaluating the design of individual devices carefully before finalizing study protocols, considering RMTs which allow for real-time compliance monitoring, and engaging the partners of study participants in the research.<br/

Singular nonlinear (n-1,1) conjugate boundary value problems

Solutions are obtained for the boundary value problem, y (n) + f(x,y) = 0, y (i)(0) = y(1) = 0, 0 i n – 2, where f(x,y) is singular at y = 0. An application is made of a fixed point theorem for operators that are decreasing with respect to a cone

Norms for Imaging Markers of Brain Reserve

Brain reserve allows some people to be more resilient to neurodegeneration processes and brain diseases. Structural markers of brain reserve are hippocampus, lateral ventricles, and white matter lesions volume (HV, LVV, WMLV). Subjects in the low end of the distribution of these markers are at higher risk to develop brain diseases such as Alzheimer's disease. We described the distribution of the above markers in a large group of cognitively-intact persons. A sample of 158 people aged between 40 to 90 years (mean ± SD: 60 ± 12 years, education 9 ± 4 years, MMSE score 28 ± 2) belonging to the Italian Brain Normative Archive was selected. HV, LVV, and WMLV were measured with validated procedures. The HV and LVV were measured by manual segmentation and the Freesurfer software, respectively, and normalized by head size; WMLV was measured with semi-automated thresholding. Test-retest reliability was >0.83 for all measures. No relationship was found between HV and age, whereas a significant relationship was found for LVV and WMLV (ventricle left: B 0.02, 95% CI 0.22 to 0.34; ventricle right: B 0.02 95% CI 0.23 to 0.34 p < 0.001; WML: B 0.04; 95% CI 0.03 to 0.06 p < 0.005). The 5th percentile threshold indicating lower brain reserve were: (i) HV below 2,260 mm(3) at 40 and 2,000 mm(3) at 90; (ii) LVV above 17,000 mm(3) at 40 and 60,000 mm(3) at 90; and (iii) WMLV above 1,200 mm(3) at 40 and 8,700 mm(3) at 90. Normative data of brain reserve markers can be used to estimate the brain resilience to neurodegeneration

White matter lesions in the elderly: effect on brain plasticity and reserve

The effect of white matter lesions (WMLs) on the brain of elderly individuals is unclear. Most debate has focused on the clinical effect of WMLs on cognitive impairment. Large cross-sectional and longitudinal clinic- and population-based studies suggest that the effect of WMLs on global cognitive performance is relatively small, only individuals with the most severe degrees of WMLs having clinically relevant effects. Here, we review recent data suggesting that WMLs might affect brain function through impairment of brain plasticity and reserve. The clinical effect consists in inability of the brain to respond to interventions such as psychotropic drug medications or rehabilitative interventions

APOE4 is associated with greater atrophy of the hippocampal formation in Alzheimer's disease

Prior studies reported that the hippocampal volume is smaller in Alzheimer's disease patients carrying the Apolipoprotein E ε4 allele (APOE4) versus patients who are non-carriers of this allele. This effect however has not been detected consistently, possibly because of the regionally-specific involvement of the hippocampal formation in Alzheimer's disease. The aim of this study was to analyze the local effect of APOE4 on hippocampal atrophy in Alzheimer's disease patients. Using high-resolution T1-weighted images we investigated 14 patients heterozygous for the ε4 allele (age 72 ± 8 SD years; MMSE 20 ± 4 SD) and 14 patients not carrying the ε4 allele (age 71 ± 10; MMSE 20 ± 5 SD), and 28 age-, sex-, and education-matched controls (age 71 ± 8; MMSE 29 ± 1 SD). The hippocampal formation was outlined with manual tracing and 3D parametric surface models were created for each subject. Radial atrophy was assessed on the whole hippocampal surface using the UCLA mapping technique. E4 carriers and non-carriers did not differ in their level of impairment in global cognition (p = 0.91, Mann–Whitney test) or memory (p > 0.29). Hippocampal surface analysis showed the typical pattern of CA1 and subicular tissue atrophy in both ε4-carriers and non-carriers compared with controls (e4 carriers: p < 0.0002; ε4 non-carriers: p < 0.01, permutation test). The left hippocampal volume was significantly smaller in ε4-carriers than non-carriers (p = 0.044, Mann–Whitney test), the effect of APOE4 mapping to the subicular/CA1 region (p = 0.041, permutation test). Differences were not statistically significant in the right hippocampus (p > 0.20, permutation test). These findings show that hippocampal atrophy is greater in APOE4 carriers in regions typically affected by pathology. APOE4 may affect the structural expression of Alzheimer's disease