Enrolled participants will be randomized in a balanced manner to CogState brief battery in both the Main Study and the SubStudy. CogState consists of four tasks that respectively measure the functions of attention, processing speed, visual learning, and working memory. The CogState Brief Battery is an approximately 15 minute computerized battery with demonstrated reliability, validity, and short term stability, that was developed expressly for maximal sensitivity to detect change. CogState can be administered via the internet or on a stand-alone computer and is available in over 50 languages.

Enrolled participants will be randomized in a balanced manner to CDR-AS in both the Main Study and the SubStudy. CDR-AS is fully automated system that targets the core aspects of cognitive function crucial for everyday behavior which are vulnerable to numerous insults including aging, fatigue, disease, pathology, trauma, diet, and pharmaceuticals. CDR-AS is an approximately 20-minute computerized battery designed to reliably measure changes in cognitive function in clinical trial situations.

Enrolled participants will be randomized in a balanced manner to DKEFS in the Main Study and at one site of the SubStudy. The DKEFS is a paper and pencil measure of verbal and nonverbal executive functions that has been normed and validated for children and adults from 8-89 years of age. The measure consists of nine subtests. For the purposes of this study, the Trail Making Test (TMT) and Verbal Fluency subtests will be used.

Enrolled participants will be randomized in a balanced manner to COGNITO at the other site of the SubStudy. COGNITO is an approximately 45 to 60 minute computerized neuropsychometric examination based on well-known cognitive tests designed for both cognition research and clinical assessment. COGNITO assesses reaction time, primary and working memory, visuospatial and verbal secondary memory, implicit learning, language skills, functional and semantic categorization of visual data, focused and divided attention, and crystallized intelligence. Responses are made via a tactile screen which permits the recording of response latency (deducting reaction time provides an estimation of information processing time).

Cognition will be evaluated at baseline and longitudinally with the Mini-Mental State Examination (MMSE), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Neuropsychological Assessment Battery (NAB)-Executive Function module, NAB-Memory module, CogState Brief Battery (CBB), Cognitive Drug Research Assessment System (CDR-AS), and Delis Kaplan Executive Function System (DKEFS), as well as the Clinical Dementia Rating Scale.

The PACC is a retrospectively validated measure that is weighted towards episodic memory, and also includes a timed executive function test and a global cognitive screening test. The PACC includes: 1. Total Recall score from the Free and Cued Selective Reminding Test - Immediate Recall [FCSRT-IR] (0-48 words); 2. Delayed Paragraph Recall total score on single administration of the Logical Memory story from the Wechsler Memory Scale [WMS]-Revised (0-25 story units); 3. Digit Symbol Substitution Test score from the Wechsler Adult Intelligence Scale [WAIS]-Revised (0-135 symbols), and 4. MMSE score (0-30 points). The component scores are transformed using an established normalization method into z-scores. Each of the 4 component change scores is divided by the baseline sample standard deviation of that component. Z-score implies how many standard deviations higher or lower the score is compared with the baseline score.

This brief test is for cognitive assessment, detection, and characterization of dementia in the elderly as well as neuropsychological screening for younger patients. The RBANS Index scores include Immediate Memory Index, Visuospatial/Construction Index, Language Index, Attention Index and the Delayed Memory Index. The sum of these 5 Index scores is converted to a Total Scale value via a mapping table. The Total Scale is a norm-based t score based on a distribution with a mean of 100 and standard deviation of 15.

RBANS is a battery developed for cognitive assessment, detection, and characterization of dementia in the elderly as well as neuropsychological screening for younger patients. The RBANS includes 12 subtests that measure 5 indices: the Attention Index is composed of Digit Span and Coding, the Language Index consists of Picture Naming and Semantic Fluency subtests, the Visuospatial/Construction Index is made up of Figure Copy and Line Orientation subtests, the Immediate Memory Index is composed of List Learning and Story Memory subtests, and the Delayed Memory Index consists of List Recall, List Recognition, Story Recall, and Figure Recall subtests. The sum of these 5 Index scores is converted to a Total Scale value via a mapping table. The Total Scale is a norm-based t score based on a distribution with a mean of 100 and standard deviation of 15.