This study is case-control, cross-sectional, descriptive, and non-experimental. The sampling technique was non-probabilistic. All the procedures were carried out remotely in tele-neuropsychology format 32 due to the health emergency caused by COVID-19 pandemic. The ethics committee of the Universidad Santo Tomás approved procedures, and all methods were carried out in accordance with the relevant guidelines and regulations.
Subjects
Data was collected from seventy right-handed and Chilean adult women. From the total sample, there was a group of fifty women diagnosed with FMS (mean age = 44.05, SD = 8.71) and nineteen healthy women as a paired-match (sex, age, nationality, demographic similarities) control group (mean age = 40.63, SD = 9.79). The sample size followed the gold standard reported in the meta-analysis by Bell et al. 19. Patients with FMS were diagnosed by a specialist following the 1990 American College of Rheumatology criteria for FMS 28 and were recruited from Fibromyalgia Associations located in distributed regions of Chile, while participants belonging to the control group were recruited based on demographic similarities with patients. Exclusion criteria for the control group were neurological or psychiatric disorders and medical background of severe somatic diseases. All participants signed an informed consent form before the beginning of the study.
Instruments
- Sociodemographic Questionnaire: We designed an open-ended and multiple options questionnaire instrument that measures general demographic characteristics (age, medications, illnesses, schooling, history of mental disorders, medical background, among other aspects). Additionally, in this questionnaire a likert scale was included to evaluate difficulties due to the pandemic (mood, physical pain, financial problems, family, health, fear of being infected, food, and fear of dying).
- Hospital Anxiety and Depression Scale (HAD) 33: The HAD is a self-assessment scale that detects states of depression and anxiety in patients with different chronic conditions, assessing the cognitive and behavioral symptoms of anxiety and depression. It is composed of two subscales (Depression and Anxiety), each of them has 7 items. Each score varies between 0 to 21. The response options range from: absence / minimum presence = 0 to maximum presence = 3. The higher the score obtained, the greater the intensity or severity of the symptoms. This scale has been validated in patients with FMS from a Spanish population and has good psychometric properties 33.
- Disexecutive Questionnaire (DEX-Sp) 34: The DEX-sp is a brief and easy to complete Likert-type self-report test with twenty items, and five response options between 'never' (0 points) and 'very often' (4 points) used to estimate executive dysfunction. This test assesses abstract thinking, planning, insight, temporal sequencing, impulse control, response inhibition, decision-making, as well as the presence of fables, impulsivity, euphoria, apathy, aggressiveness, restlessness motor, superficial affective responses, perseverance, distractibility, and disregard for social rules 35. This scale presents good psychometric properties and has been validated in the Spanish-speaking population 34.
Visual Analog Scale of Pain (VAS): The VAS is a subjective measure of acute and chronic pain intensity. Scores are recorded by making a handwritten mark on a 10-cm line representing a continuum between "no pain" and " the worst pain imaginable." The VAS is a reliable and valid scale for many patient populations 36. A value lower than 4 on the VAS means mild or mild-moderate pain, while a value between 4 and 6 implies moderate-severe pain. A value higher than 6 implies the presence of very intense pain.
Cognitive variables
- Hopkins Verbal Learning Test (HVLT) 37: The HVLT is a verbal memory test consisting of a 12-item word list composed of 3 semantic categories, which subjects should recall after the list has been read to them. This procedure is repeated three times. 25 minutes later, subjects are asked to recall the list of words again. Then, for a yes/no recognition, a list of 24 words is read, which consists of the 12 original/target words, 6 distractors from the same semantic categories and 6 unrelated distractors. This test provides scores for a learning curve, long-term memory, and recognition/discrimination. The HVLT is a valid instrument in the Latin American Spanish-speaking adult population with good psychometric properties 37.
- Symbol Digit Modalities Test (SDMT): The SDMT measures sustained attention and speed of information processing 38 consisting of nine digits paired with symbols underneath. Participants are asked to provide the corresponding number for each symbol for 90 s. The SDMT is a valid instrument in the Latin American Spanish-speaking adult population with good psychometric properties 39.
F-A-S Test: These tests evaluate executive functions since they demand participants to be flexible, organize information, provide effort, and control inhibition when it is needed 40. In order to evaluate these complex cognitive functions, we used the phonological and semantic fluency tasks, which both have been validated and normalized in the Latin American Spanish-speaking adult population with good psychometric properties 40.
- Phonological Verbal Fluency: This test aims to ask participants to create as many words as possible, beginning with a specific letter (F, A, S) for 60 seconds. If a participant does not respond within 10 seconds, the examiner gives prompts 40.
- Semantic Verbal Fluency: This test demands participants to produce items that belong to a given category (e.g., animals) within 60 seconds. The participants are also provided with prompts for this test when they do not respond within 10 seconds 40.
Digit Span tests: These are verbal tasks, with stimuli presented auditorily. These tests aim to assess attention (Digit Span Forward) and working memory capacity (Digit Span Reverse) 41.
- Digit Span Forward: In this test, the experimenter says a sequence of digits (one digit per second); at the end, the participant is asked to repeat the digits back to the experimenter in the same order that was given. The task begins with a few digit sequences, and then the number of digits increases 41.
- Digit Span Reverse: This version of the test has the same structure as the Digit Span Forward. The difference is that the participant is asked to repeat the digits in reverse order which requires manipulation of information, thus working memory function 41.
Procedure
After the ethics committee of the Universidad Santo Tomás approved the research project, this was formally presented at the Fibromyalgia Association of Chile. Women diagnosed with FMS members of the association along the country were voluntarily recruited. Afterward, patients were contacted to confirm computer/tablet or smartphone availability with an internet connection. Subsequently, they received an online form that included a brief description of the research, informed consent, sociodemographic questionnaire, medical history, and the instruments: difficulties due to the pandemic, the DEX-Sp, VAS, and HAD scales.
After the first data collection, the second part of the process was to conduct the online neurocognitive protocol consisting of the HVLT, SDMT, F-A-S, and Digit Span tests. The evaluation protocol lasted approximately 30 minutes and was applied through the Whereby platform from March to May 2021.
Later, the control group with similar characteristics as the FMS patient group was recruited. The control group was evaluated following the same procedure aforementioned. Finally, once all data were collected, statistical analyses were performed (Figure 2).
Data Analysis
The student's t-test was used to compare variables between groups. Additionally, Cohen's d test was performed to estimate the size effect. Moreover, we conducted the Chi square test and the Cramer's V test for nominal variables, respectively. To determine the association level between variables, we used the Pearson r correlation test. Furthermore, in order to determine the effect of pandemic difficulties, physical pain, and psychological distress on cognitive performance, a stepwise linear regression was used, including 5000 samples bootstrap. All statistical analyzes were performed using the SPSS 25 statistical software synchronized with JASP, considering a significance threshold of p <0.05.