Development of Novel Measures for Alzheimer's Disease Prevention Trials

Study Overview
=================
Brief Summary
-----------------
This protocol focuses on novel measures of cognition and everyday function that have robust psychometrics and reduced practiced effects. They will be deployed in a parallel group study in which participants are randomized to assessment type (novel vs established) and receive serial assessments over a one year period in order to highlight contrasts between novel and established measures.

Detailed Description
-----------------
This protocol has the goal of validating novel cognitive and everyday functional measures that have sharply attenuated practice effects and are not prone to ceiling effects for use in preclinical Alzheimer's disease (AD) trials in which participants are cognitively within normal limits. To implement this, we will conduct an innovative parallel group study in which 400 healthy, non-cognitively impaired older subjects are randomized to one of two groups based on assessment type (novel instruments vs. established) and receive three serial assessments over a one year period. Novel cognitive measures include tests of executive function, episodic memory, and processing speed combined into a single composite. Novel functional measures involve computerized performance based, ecologically relevant instrumental activities. We will compare our novel No Practice Effects (NPE) cognitive battery and Miami Computerized Functional Assessment Scale (CFAS) against established measures that include the ADAS-COG in order to determine which battery (novel or established) has better psychometric properties and is less sensitive to practice effects in this clinical trials structure.

Official Title
-----------------
Development of Novel Measures of Cognition and Function for Alzheimer's Disease Prevention Trials

Conditions
-----------------
Healthy Participants

Intervention / Treatment
-----------------
* Other: No Practice Effects (NPE) cognitive battery, and Miami Computerized Functional Assessment Scale (CFAS)
* Other: Preclinical Alzheimer's Cognitive Composite (PACC), Alzheimer's Disease Assessment Scale-Cognitive Scale (ADAS-Cog), and Functional Assessment Questionnaire (FAQ)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: English speaking participants, ages 60-85 years MMSE score of 24 or greater Logical Memory II score of 9 or greater for subjects with 16 or more years of education, 5 or more for subjects with 8-15 years of education, and 3 or greater for subjects with 0-7 years of education Presence of subjective memory complaints not exclusionary A family member or other individual who is in contact with the subject and consents to serve as informant during the study. Exclusion Criteria: Diagnosis of stroke or excessive risk of CVD Neurologic disease including movement disorders, MS, epilepsy, and TBI (with greater than 15 min loss of consciousness) Untreated diabetes Current DSM-5 Axis I psychiatric diagnosis of schizophrenia schizoaffective disorder or bipolar disorder; current major depression as determined by a Geriatric Depression Scale score of greater than 5. Current alcohol or substance use disorder Active treatment of cancer MMSE score below 24 and Logical Memory below 9 for subjects with 16 or more years of education, 5 for subjects with 8-15 years of education, and 3 for subjects with 0-7 years of education Females who are pre-menopausal and are pregnant. Use of antidepressants with large anticholinergic properties will be excluded. These include: amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, isocarboxazide, lithium, maprotiline, mirtazapine, nortriptyline, tranylcypromine trimipramine, and phenelzine.

Ages Eligible for Study
-----------------
Minimum Age: 60 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Novel measures of cognition and everyday function<br>No Practice Effects (NPE) cognitive battery Miami Computerized Functional Assessment Scale (CFAS) Participants will receive three serial assessments of the NPE and CFAS over a one year period. Assessments will take place at baseline, week 12, and week 52. | Other: No Practice Effects (NPE) cognitive battery, and Miami Computerized Functional Assessment Scale (CFAS)<br>* Novel measures of Cognitive and Everyday function<br>|
| Active Comparator: Established measures of cognition and everyday function<br>Preclinical Alzheimer's Cognitive Composite (PACC) Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) Functional Assessment Questionnaire (FAQ). Participants will receive three serial assessments of the PACC, ADAS-Cog and FAQ over a one year period. Assessments will take place at baseline, week 12, and week 52. | Other: Preclinical Alzheimer's Cognitive Composite (PACC), Alzheimer's Disease Assessment Scale-Cognitive Scale (ADAS-Cog), and Functional Assessment Questionnaire (FAQ)<br>* Established measures of Cognitive and Everyday Function<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Computerized Functional Assessment Scale (CFAS). | Novel computerized measure of everyday function. Testing format is a set of simulations (ATM use, Kiosk ticket purchase , Prescription refill , and Doctor's visit ). We will construct a z score based on the rate measure which accounts for both speed and accuracy. Higher scores suggest greater cognitive function while lower scores indicate greater cognitive impairment. | Baseline to Week 52; change in score will be assessed | 
| No Practice Effect (NPE) Cognitive Battery. | Novel measure of cognitive function. Scores can be age-adjusted by decade. The majority of the subtests ( including tests of Cognitive Control/Executive Processes, Working Memory,Speed of Processing,Verbal Fluency and Episodic Memory)are computerized or partially computerized. All tests have three equivalent alternate forms. We will construct a z-score averaged composite based on scores of the subtests at baseline. Higher scores suggest greater cognitive function while lower scores indicate greater cognitive impairment. | Baseline to Week 52; change in score will be assessed | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Alzheimer's disease, Neuropsychological Testing, Healthy Older Individuals, Psychometrics, Prevention, Clinical Trial