Rasagiline Rescue in Alzheimer's Disease Clinical Trial

The primary outcome measure is the change from baseline to week 24 in FDG-PET as measured by Standard Uptake Units Regional (SUVR) in several pre-specified brain regions including the medial temporal, lateral temporal, posterior cingulate - precuneus, inferior parietal, middle frontal, anterior cingulate, and striatum. The SUVR change was calculated by subtracting the value at 24 weeks from baseline values. Negative values indicate increased hypometabolism (i.e. worsening of cell function).

The ADAS-Cog 11 (Alzheimer's Disease Assessment Scale - Cognitive 11) is a psychometric instrument that evaluates memory, attention, reasoning, language, orientation, and praxis. A higher score indicates more impairment. Scores from the original portion of the test range from 0 (best) to 70 (worse). We used total ADAS-Cog 11 scores, which is a sum of individual subscales. We calculated the change by subtracting the ADAS Cog score at week 24 from baseline score. A positive change indicates cognitive worsening.

Measure Description: The MMSE (Mini Mental Status Examination) is a brief, frequently used screening instrument for AD drug studies. The MMSE evaluates orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two overlapping pentagons. A lower score indicates more cognitive impairment. The highest score is 30, range is between 0 (severe impairment) and 30 (cognitively normal). We calculated the change in scores by subtracting week 24 score from baseline. A negative score indicates clinical worsening.

Measure Description: The ADCS-ADL (Alzheimer's Disease Cooperative Study-Activities of Daily Living) is an activities-of-daily-living inventory developed by the ADCS to assess functional performance in participants with AD. Using a structured interview format, study partners are queried as to whether participants attempted each item in the inventory during the past 4 weeks and their level of performance. The ADCS-ADL provides a total score from 0-78, with a lower score indicating greater severity. We calculated change by subtracting scores on week 24 test from the baseline score. A negative score indicates worsening ability to complete ADLs.

Measure Description: The behavioral outcome measure for this trial is the NPI (Neuropsychiatric Inventory). The NPI evaluates both the frequency and severity of 10 neuropsychiatric disturbances. Frequency assessments range from 1 (occasionally, less than once per week) to 4 (very frequently, once or more per day or continuously) as well as severity (1=mild, 2=moderate, 3=severe). The overall score is calculated by summing the severity and frequency of the subscale measures. The range of scores is 0-40. A score of 0 indicates no behavioral impairment and a score of 40 indicates severe behavioral impairment. We calculated change by subtracting Week 24 scores from baseline scores. A positive change indicates behavioral worsening.

Measure Description: The Digit Span consists of repetition of increasing long strings of digits presented at 1 per second as read by the examiner and repeated by the subject.The score is the maximum number of digits the patient can repeat until they fail twice in a row. The reverse digit span is identical to the forward digit span except that the patient repeats the presented digits in reverse order. The score is the maximum number of digits the patient can repeat in reverse order until they fail twice in a row. Each correct response is worth one point with a maximum total score of 28. A higher score is better. We calculated change by subtracting week 24 score from baseline score. A negative score indicates worse performance over the course of study.

Measure Description: Study participants are instructed, "I want to see how many words you can say beginning with a certain letter in one minute." The study participant's responses are recorded on the worksheet. Study participants are then given an additional one minute for each of two different letters using similar instructions. The score is the total number of acceptable words for the three trials combined. A higher score represents better performance.

Responses are then judged for their acceptability (example for the use of proper nouns, numbers, repetitions and stem word with a different ending). The score is the total number of acceptable words for the three trials combined. A higher score represents better performance. We calculated change by subtracting week 24 scores from baseline scores. A negative score indicates worse performance.

Measure Description: The QoL-AD (Quality of Life - Alzheimer's Disease) is a commonly used 13 item QoL scale that assesses items specific to QoL in patients with cognitive impairment. It is administered to the research partner with answers for the patient. Points are assigned to each item as follows: poor = 1, fair = 2, good = 3, excellent = 4.The total score is the sum of all 13 items. The range of score is from 0-52. We calculated the change by subtracting the scores on week 24 score from baseline. A negative value indicates worsening quality of life.