Memantine for Prevention of Cognitive Decline in Patients With Breast Cancer

The Hopkins Verbal Learning Test-Revised (HVLT-R) is an objective measure of verbal learning and memory. The examiner reads a list of 12 nouns to the participant, who repeats as many words as remembered. Approximately 20-25 minutes later, participants are asked to recall as many words as possible. Then, the examiner reads a list of 24 words, including the 12 words from the original list, and the participant is asked to determine which words were and were not on the original list. These tasks result in three subscales: total recall (range: 0-36; higher is better), delayed recall (range: 0-12; higher is better), and the Recognition Discrimination Index (range: 0-12; higher is better).

The Trail Making Test (TMT) is an objective measure of processing speed (part A) and executive function (part B). In part A, the participant is given a diagram of 25 circles, labeled 1 - 25, and asked to connect the circles in ascending order. In part B, the diagram of 25 circles includes some with numbers (1-13) and some with letters (A-L), and the participant is asked to connect the circles alternating between numbers and letters. Performance is measured in the number of seconds required to complete each task (lower is better).

The Rapid Visual Processing test (RVP) is a computerized cognitive assessment of processing speed and sustained attention. The RVP will be administered using Cambridge Neuropsychological Test Automated Battery (CANTAB) eclipse software (Cambridge Cognition, Cambridge, UK). The participant is shown a series of pseudo-random digits from 2 to 9 and asked to recognize target digit sequences by pressing a button on the screen as quickly as possible. The investigators will measure total correct responses (higher is better).

This test was added at the start of the COVID-19 pandemic as a substitute for the Trail Making Test.

The One Touch Stockings (OTS) of Cambridge is a computerized cognitive assessment of executive function. The OTS will be administered using Cambridge Neuropsychological Test Automated Battery (CANTAB) eclipse software (Cambridge Cognition, Cambridge, UK). The participant is shown two displays with three colored balls presented as stacks suspended from a beam and a row of numbered boxes along the bottom of the screen. The participant is asked to work out in their head how many moves are required to match the two displays. The investigators will measure mean number of choices to the correct response (lower is better).

The Digit Span is an objective measure of attention and working memory. The participant is asked to recite sequences of numbers in forward, backwards, and sequential order. The score for each sequence type is the number of correct responses (higher is better).

The Controlled Oral Word Association Test (COWA) is an objective measure of verbal fluency. The participant is asked to name as many words as possible, excluding proper nouns, in one minute. This is repeated for a total for three different letters. The score is the total number of different words produced between all three letters (higher is better).

The Animal Naming Test (ANT) is an objective measure of semantic fluency. The participant is asked to name as many animals as possible in one minute. The score is the number of unique animals stated (higher is better).

The National Institute of Health's Patient-Reported Outcomes Measurement Information System (PROMIS) contains a cognitive function bank. The PROMIS Cognitive Function 8a short form will be used. Scores for all PROMIS measures are reported on the T-score metric in which the mean=50 and standard deviation (SD) = 10 are centered on the general population means. Higher scores represent greater degrees of cognitive complaints.

The National Institute of Health's Patient-Reported Outcomes Measurement Information System (PROMIS) contains a depression bank. The PROMIS Depression 8a short form will be used. Scores for all PROMIS measures are reported on the T-score metric in which the mean=50 and standard deviation (SD) = 10 are centered on the general population means. Higher scores represent greater degrees of depression. We evaluated the proportion of patients with at least moderately severe symptoms (T-score ≥ 65) at baseline and follow-up.

The National Institute of Health's Patient-Reported Outcomes Measurement Information System (PROMIS) contains an anxiety bank. The PROMIS Emotional Distress-Anxiety - Short Form 6a will be used. Scores for all PROMIS measures are reported on the T-score metric in which the mean=50 and standard deviation (SD) = 10 are centered on the general population means. Higher scores represent greater degrees of anxiety. We evaluated the proportion of patients with at least moderately severe symptoms (T-score ≥ 65) at baseline and follow-up.

The number of subjects with Karnofsky Performance Status equal to or more than 80, at baseline and 4 weeks after chemotherapy were compared.

The Patient-reported Karnofsky Performance Status (KPS) provides a self-characterization of functional status, ranging from severe/requiring continuous nursing care to normal/no complaints/no symptoms of the disease. Scores range from 30 to 100. Higher scores indicate better function.

The Functional Assessment of Cancer Therapy-General (FACT-G) is a 27-item patient-administered assessment of general quality-of-life measures in cancer patients. It has been validated in the literature and permits the measurement of a number of symptoms including nausea, pain, and insomnia. Responses to each item are on a 5-point Likert scale. The FACT-G total score (range: 0-108; higher is better) will be assessed.

Feasibility will be based on recruitment success as measured by the proportion of invited participants who enroll.

Feasibility will be based on retention success as measured by the proportion of enrolled participants who are not eligible for analysis of the primary outcome.

Feasibility will be based on adherence success as measured by the proportion of self-reported doses of memantine taken.

Safety is based on the number of all adverse events (AE) associated with memantine. The following most common side effects of memantine were explicitly solicited: headache, dizziness, confusion, constipation, diarrhea, and fatigue.

AE was assessed and graded according to the NCI Common Terminology Criteria. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.