2.6. Specific methodology for cognition/behavior assessment

The ADAS-Cog ^[33] is an instrument specifically designed to evaluate the severity of the fundamental alterations in cognitive and behavioral function that are characteristic of patients with AD.

Functional ability is assessed by means of the ADCS-ADL test ^[34], which offers detailed descriptions of each activity and requests the informer to describe the actions or behaviors observed.

Mini-Mental State Examination ^[32] is widely used to assess cognitive alterations and is the most commonly used brief screening test.

The specific NPS battery consists of processing speed tests such as the Symbol Digit Modalities Test ^[38], developed principally for examining visual attention and tracking, concentration, and psychomotor speed; language/attention tests such as the Semantic Verbal Fluency ^[35] allowing voluntary access to a certain vocabulary assessing reduction in verbal spontaneity and fluency difficulties; the Neuropsychological Assessment Battery Naming Test ^[36], designed to highlight deficits in visual confrontation naming skills and to identify aphasia; and the Rey Auditory Verbal Learning Test ^[37] consisting of words presented in the same order that the subject listens to and must remember and repeat.

Neuropsychiatric disorders assessment includes NPI, to evaluate the most frequent neuropsychiatric manifestations of dementia and also to determine their frequency and intensity; CSDD to evaluate the signs and symptoms of major depression in patients with dementia; CDR-Sb, a clinical test validated in patients with AD that assesses six domains: memory, orientation, judgment and problem solving, social and occupational activities, domestic activities and hobbies, and personal care; and ADCS-CGIC, an instrument for the reliable assessment of global change from the baseline in a clinical trial.

Other tests include the Columbia-Suicide Severity Rating Scale to quantify the severity of suicidal ideation and behavior to estimate the rate of suicidality; the QoL-AD designed specifically to obtain a rating of the quality of life from both the patient and the caregiver; and the RUD-Lite to assess the amount of health-related resource use among patients.

Importantly, the evaluators/raters of the tests in the trial have no access to any information allowing them to identify patient assignment to treatment. Blinding of the evaluators to patient treatment is confirmed when evaluators sign a document to that effect.

The established order of tests at each visit is as follows: with the patient, the first evaluator rates MMSE (when stated by the protocol), ADAS-Cog, NPS battery, QoL-AD, and Columbia-Suicide Severity Rating Scale. Next, the global impairment and clinical impression scales (CDR-Sb and ADCS-CGIC) are administered by the second evaluator. With the caregiver, the second evaluator (while the first evaluator is administering the aforementioned battery with the patient) administers the global impairment and clinical impression scale (CDR-Sb, ADCS-CGIC). The first evaluator, once he/she has finished the NPS battery with the patient, interviews the caregiver to evaluate the patient functionality and behavior: NPI, ADCS-ADL, CSDD, QoL-AD, and RUD-Lite.