Exploring the Association Between Visual Field Testing and CERAD Neuropsychological Battery in Idiopathic Normal Pressure Hydrocephalus Patients.

Background: Association between visual field test indices and The Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery (CERAD-NB) is unknown. Idiopathic normal pressure hydrocephalus (iNPH) patients provide a unique set of patient data for analysis. Objective: To assess the reliability of visual field testing using the CERAD-NB in patients with iNPH and to investigate the association between visual field test results and cognitive function. Methods: 62 probable iNPH patients were subjected to comprehensive ophthalmological examination, ophthalmological optical coherence tomography imaging studies, visual field testing, and CERAD-NB. Based on visual field indices, the patients were divided into two groups: unreliable (n = 19) and reliable (n = 43). Independent T-test analysis was performed to examine the relationship between visual field test results and cognitive function. Pearson Chi-square test was used for non-continuous variables. Results: The unreliable group performed worse in CERAD-NB subtests compared to the reliable group. Statistically significant differences were observed in nine out of ten subtests, with only Clock Drawing showing no statistical significance. Pairwise comparison of the groups showed no statistical significance between amyloid-ß (Aß) biopsy, hyperphosphorylated tau biopsy, apolipoprotein E allele or the ophthalmological status of the patient. But there was a statistically significant difference in cerebrospinal fluid Aß42 and age between the groups. Conclusions: Patients with unreliable visual field tests performed worse on CERAD-NB subtests. CERAD-NB subtests do not provide a specific cut-off value to refrain patients from visual field testing. Should patients with unreliable visual field tests be screened for cognitive impairment?

Description of the Method for Evaluating Digital Endpoints in Alzheimer Disease Study: Protocol for an Exploratory, Cross-sectional Study.

BACKGROUND: More sensitive and less burdensome efficacy end points are urgently needed to improve the effectiveness of clinical drug development for Alzheimer disease (AD). Although conventional end points lack sensitivity, digital technologies hold promise for amplifying the detection of treatment signals and capturing cognitive anomalies at earlier disease stages. Using digital technologies and combining several test modalities allow for the collection of richer information about cognitive and functional status, which is not ascertainable via conventional paper-and-pencil tests. OBJECTIVE: This study aimed to assess the psychometric properties, operational feasibility, and patient acceptance of 10 promising technologies that are to be used as efficacy end points to measure cognition in future clinical drug trials. METHODS: The Method for Evaluating Digital Endpoints in Alzheimer Disease study is an exploratory, cross-sectional, noninterventional study that will evaluate 10 digital technologies' ability to accurately classify participants into 4 cohorts according to the severity of cognitive impairment and dementia. Moreover, this study will assess the psychometric properties of each of the tested digital technologies, including the acceptable range to assess ceiling and floor effects, concurrent validity to correlate digital outcome measures to traditional paper-and-pencil tests in AD, reliability to compare test and retest, and responsiveness to evaluate the sensitivity to change in a mild cognitive challenge model. This study included 50 eligible male and female participants (aged between 60 and 80 years), of whom 13 (26%) were amyloid-negative, cognitively healthy participants (controls); 12 (24%) were amyloid-positive, cognitively healthy participants (presymptomatic); 13 (26%) had mild cognitive impairment (predementia); and 12 (24%) had mild AD (mild dementia). This study involved 4 in-clinic visits. During the initial visit, all participants completed all conventional paper-and-pencil assessments. During the following 3 visits, the participants underwent a series of novel digital assessments. RESULTS: Participant recruitment and data collection began in June 2020 and continued until June 2021. Hence, the data collection occurred during the COVID-19 pandemic (SARS-CoV-2 virus pandemic). Data were successfully collected from all digital technologies to evaluate statistical and operational performance and patient acceptance. This paper reports the baseline demographics and characteristics of the population studied as well as the study's progress during the pandemic. CONCLUSIONS: This study was designed to generate feasibility insights and validation data to help advance novel digital technologies in clinical drug development. The learnings from this study will help guide future methods for assessing novel digital technologies and inform clinical drug trials in early AD, aiming to enhance clinical end point strategies with digital technologies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35442.