Trial-Ready Cohort-Down Syndrome (TRC-DS)

The primary aim of the TRC-DS is enrollment of 120 participants into the trial ready cohort, with up to 550 participants in total including co-enrollment with the Alzheimer Biomarkers Consortium - Down Syndrome (ABC-DS) study, to support future referral and enrollment into primary Alzheimer's disease (AD) prevention trials for adults with DS.

The Cued Recall Test is modified from a version developed for adults from the typical population. Twelve items are presented for learning, 4 at a time, with each item accompanied by a unique category cue. The testing phase consists of 3 trials. Each trial begins with free recall of the test items; following free recall, a category cue is provided for those items not spontaneously recalled. Two scores are generated from the test, a Free Recall Score and a Total Score (Free Recall plus items recalled when the category cue is provided). A cut-off of < 23 on the Total Score resulted in a sensitivity of 91% and a specificity of 84% when individuals with DS and a diagnosis of dementia were compared to their healthy peers without dementia.

The Neuropsychiatric Inventory (NPI) is a well-validated, reliable, multi-item instrument to assess psychopathology in AD based on an interview with a caregiver or qualified study partner. It evaluates both the frequency and severity of 12 neuropsychiatric features including delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, aberrant motor behavior, sleep, and appetite and eating disorders. A higher NPI score means that the participant is displaying more behavioral symptoms. The minimum score is 0 and the maximum is 144. A score of 0-20 is mild, 20-50 moderate and greater than 50 means significant behavioral symptoms.

The DSMSE is an omnibus measure of neuropsychological function that assesses a broad range of skills and is easy to administer. It is divided into items that test recall for personal information, orientation to season and day of week, memory, language, visuospatial function, and praxis. Recall for personal information is tested with questions about the subject's name, age and birth date. Orientation items ask the day of the week and season of the year. Memory in the DSMSE is assessed with items that require immediate and delayed recall of three objects and for the location of three hidden objects. Language items include confrontation naming, sentence repetition, and comprehension of one, two, and three step commands. Visuospatial items are three-dimensional block constructions. Praxis items include transitive and intransitive limb movements and a sequential task.

The Vineland Adaptive Behavior Scale 3 (VABS-II) I is a normed assessment tool that assesses adaptive behavior across the areas of communication, activities of daily living, and socialization. The tool is self-administered via interview toby a study partner using a tablet (e.g. iPad), takes approximately 45 minutes to complete and may be done remotely.

The VABS-III scores range from 20-140. Higher scores indicate higher functioning. Specifically, these include 'very high' (domain and Adaptive Behavior Scale (ABC) Standard Scores of 130-140), "moderately high" (domain and ABC Standard Scores of 115-129), "adequate" (domain and ABC Standard Scores of 86-114), "moderately low" (domain and ABC Standard Scores of 71-85), and "low" (domain and ABC Standard Scores of 20-70).

The National Task Group Early Detection Screen for Dementia (NTG-EDSD) is a screening tool which measures changes typically observed in dementia. It is composed of four primary sections about relative demographics, ratings of health, mental health, and life stressors, a review of multiple domains associated with adult functioning, and a review of chronic medical conditions. The NTG-EDSD is completed by a staff member who interviews the caregiver. It contains 40 questions/question groups and takes 15 mins to administer.

In the Stroop Dog and Cat Task, a linear sequence of 16 pictures (8 cats, 8 dogs) are presented in a pre-determined random order. In the control condition the subject says the name of each picture and is urged to do so rapidly. In the experimental (inhibition) condition the participant is required to say 'cat' for the picture of each dog and 'dog' for the cat. For each condition the participant is given a brief practice period. Performance on the Stroop Dog and Cat was significantly related to informant-reported memory changes in 103 adults with DS with mild-moderate intellectual disability in the age range of 36 - 72 years.

CGIC-DS is a semi-structured interview with the study partner of participants with DS lasting ~20 min. 3 areas are assessed - cognition, daily living function, mood/behavior. Items to probe in these areas were developed empirically by clinicians familiar with AD in persons with DS. 11 items are probed for cognition, 8 for daily living function, 6 for behavior/mood. For each domain, a general item is included to cover areas of importance for the participant which are not part of the regular probes. At baseline, the study partner is interviewed about performance in these areas. For visits at which change from baseline is scored, the study partner is interviewed and asked about changes in each item. For each of the 3 domains, a change score is assigned on a 7-pt scale: 1 = marked improvement, 2 = moderately improvement, 3 = minimal improvement, 4 = no change, 5 = minimal worsening, 6 = moderate worsening, 7 = marked worsening. An overall score is assigned using the same 7-pt scheme.