Educational Programs Based on Healthy Habits to Improve Quality of Life and Psychosocial Profile in Women With Neurodegenerative Diseases: the ADVICE Protocol Study (Phase 2)

Physical Self-Perception

Physical self-perception will be evaluated using six subscales-sports competence, physical condition, body attractiveness, physical strength, general physical self-perception, and overall self-perception-on a 5-point Likert scale

Time frame: Baseline (pre-intervention).

Physical Self-Perception

Physical self-perception will be evaluated using six subscales-sports competence, physical condition, body attractiveness, physical strength, general physical self-perception, and overall self-perception-on a 5-point Likert scale

Time frame: 48 hours after the last exercise session (post-intervention assessment).

Walking Endurance

Participants will undergo the 2-minute walk test, during which they will walk at their preferred, self-selected speed to assess walking endurance. The test course will be rectangular, with corners marked by cones. Participants will be allowed to rest during the test, if necessary, but the clock will not stop during these rest periods. The total distance covered will be recorded

Time frame: Baseline (pre-intervention).

Walking Endurance

Participants will undergo the 2-minute walk test, during which they will walk at their preferred, self-selected speed to assess walking endurance. The test course will be rectangular, with corners marked by cones. Participants will be allowed to rest during the test, if necessary, but the clock will not stop during these rest periods. The total distance covered will be recorded

Time frame: 48 hours after the last exercise session (post-intervention assessment).

Pain Catastrophizing

The Pain Catastrophizing Scale will measure catastrophic thoughts related to pain, focusing on rumination and helplessness, with responses on a similar scale

Time frame: Baseline (pre-intervention).

Pain Catastrophizing

The Pain Catastrophizing Scale will measure catastrophic thoughts related to pain, focusing on rumination and helplessness, with responses on a similar scale

Time frame: 48 hours after the last exercise session (post-intervention assessment).

Quality of Life questionnaire

The Multiple Sclerosis Quality of Life-54 will gauge quality of life across 14 subscales, yielding physical and mental health composite scores

Time frame: Baseline (pre-intervention).

Quality of Life questionnaire

The Multiple Sclerosis Quality of Life-54 will gauge quality of life across 14 subscales, yielding physical and mental health composite scores

Time frame: 48 hours after the last exercise session (post-intervention assessment).

State-Trait Anxiety

Description: The State-Trait Anxiety Inventory will measure both situational and general anxiety on a 4-point scale

Time frame: Baseline (pre-intervention).

State-Trait Anxiety

The State-Trait Anxiety Inventory will measure both situational and general anxiety on a 4-point scaleTime Frame: Before the first training session

Time frame: 48 hours after the last exercise session (post-intervention assessment).

Rate of force development

Participants will sit in a chair with both legs flexed at a 90-degree angle, and the tested ankle securely attached to a customized device with a load cell (MuscleLab Force Sensor, Ergotest AS, Langesund, Norway). They will perform three maximum contractions, each lasting 2 seconds, with 3 minutes of rest in between. The RFD will be analyzed. Testing will begin with the right leg, and the repetition with the highest recorded value for each leg will be used in the analysis

Time frame: Baseline (pre-intervention).

Rate of force development

Participants will sit in a chair with both legs flexed at a 90-degree angle, and the tested ankle securely attached to a customized device with a load cell (MuscleLab Force Sensor, Ergotest AS, Langesund, Norway). They will perform three maximum contractions, each lasting 2 seconds, with 3 minutes of rest in between. The RFD will be analyzed. Testing will begin with the right leg, and the repetition with the highest recorded value for each leg will be used in the analysis

Time frame: 48 hours after the last exercise session (post-intervention assessment).

Maximum Voluntary Isometric Contraction

Participants will sit in a chair with both legs flexed at a 90-degree angle, and the tested ankle securely attached to a customized device with a load cell (MuscleLab Force Sensor, Ergotest AS, Langesund, Norway).Participants will perform three 5-second MVIC, with 3 minutes of rest in between. Testing will always begin with the right leg, and the contraction with the highest recorded MVIC value will be used in the analysis Time Frame: Before the first training session

Time frame: Baseline (pre-intervention).

Maximum Voluntary Isometric Contraction

Participants will sit in a chair with both legs flexed at a 90-degree angle, and the tested ankle securely attached to a customized device with a load cell (MuscleLab Force Sensor, Ergotest AS, Langesund, Norway).Participants will perform three 5-second MVIC, with 3 minutes of rest in between. Testing will always begin with the right leg, and the contraction with the highest recorded MVIC value will be used in the analysis Time Frame: Before the first training session

Time frame: 48 hours after the last exercise session (post-intervention assessment).

Maximal neural drive

To measure neural drive, the electromyographic activity (sEMG) of the right leg's vastus lateralis will be recorded during the MVIC (Delsys Trigno, Delsys Inc., Boston, MA) with skin prepared and electrode positioning following SENIAM guidelines. EMG peak will be analyzed. The EMG peak during MVIC will represent the maximum neural drive

Time frame: Baseline (pre-intervention).

Maximal neural drive

To measure neural drive, the electromyographic activity (sEMG) of the right leg's vastus lateralis will be recorded during the MVIC (Delsys Trigno, Delsys Inc., Boston, MA) with skin prepared and electrode positioning following SENIAM guidelines. EMG peak will be analyzed. The EMG peak during MVIC will represent the maximum neural drive

Time frame: 48 hours after the last exercise session (post-intervention assessment).

Central activation ratio

Two bipolar electrodes (10×15 cm) will be placed on the right quadriceps, with electrical stimulation controlled by Signal 6.0 software (CED, Cambridge, England) at 100 Hz frequency, 50 pulses, 0.009 s pulse duration, and 0.01 s interval, set to 40-50% of MVIC. Central activation ratio (CAR) will be assessed through a sequence of one supramaximal twitch, a 100 Hz tetanic train, an MVIC with superimposed tetanic train, followed by a potentiated tetanic train and a potentiated supramaximal twitch. This sequence will be repeated twice with 2-minute rests, and twitch-to-tetanus ratio, MVIC peak, and maximum force values will be calculated for CAR. The CAR will be calculated using the following formula: "CAR= " "Force during MVIC" /"Force during MVIC + supramaximal stimulation"

Time frame: Baseline (pre-intervention).

Central activation ratio

Two bipolar electrodes (10×15 cm) will be placed on the right quadriceps, with electrical stimulation controlled by Signal 6.0 software (CED, Cambridge, England) at 100 Hz frequency, 50 pulses, 0.009 s pulse duration, and 0.01 s interval, set to 40-50% of MVIC. Central activation ratio (CAR) will be assessed through a sequence of one supramaximal twitch, a 100 Hz tetanic train, an MVIC with superimposed tetanic train, followed by a potentiated tetanic train and a potentiated supramaximal twitch. This sequence will be repeated twice with 2-minute rests, and twitch-to-tetanus ratio, MVIC peak, and maximum force values will be calculated for CAR. The CAR will be calculated using the following formula: "CAR= " "Force during MVIC" /"Force during MVIC + supramaximal stimulation"

Time frame: 48 hours after the last exercise session (post-intervention assessment).

Upper Limb Maximum Strength

Isometric grip strength will be measured with an electronic dynamometer (K-Force Grip, Kinvent, Montpellier, France) as participants stand with elbows extended. Each hand will perform 3 trials, with 30 seconds rest between attempts

Time frame: Baseline (pre-intervention).

Upper Limb Maximum Strength

Isometric grip strength will be measured with an electronic dynamometer (K-Force Grip, Kinvent, Montpellier, France) as participants stand with elbows extended. Each hand will perform 3 trials, with 30 seconds rest between attempts

Time frame: 48 hours after the last exercise session (post-intervention assessment).

Spasticity

The Pendulum Test is used to assess the level of spasticity by evaluating the resistance to passive movement in the affected limb. The test involves moving the limb in a pendulum-like motion and observing the fluidity of the movement, with increased resistance indicating higher spasticity levels

Time frame: Before the first session of the intervention program

Spasticity

The Pendulum Test is used to assess the level of spasticity by evaluating the resistance to passive movement in the affected limb. The test involves moving the limb in a pendulum-like motion and observing the fluidity of the movement, with increased resistance indicating higher spasticity levels

Time frame: 48 hours after the last exercise session (post-intervention assessment).

Intrinsic muscle characteristics

Muscle characteristics (frequency, stiffness, degradation) assessed with MyotonPRO (MyotonPRO, Myoton AS, Estonia)

Time frame: Baseline (pre-intervention).

Intrinsic muscle characteristics

Muscle characteristics (frequency, stiffness, degradation) assessed with MyotonPRO (MyotonPRO, Myoton AS, Estonia)

Time frame: 48 hours after the last exercise session (post-intervention assessment).

Gait speed

Gait speed will be determined with the 10-meter walk test using two photocells (Ergotest Technology AS, Langesund, Norway) at 5 and 10 meters; participants will complete two maximum-speed trials, with the slower time recorded

Time frame: Baseline (pre-intervention).

Gait speed

Gait speed will be determined with the 10-meter walk test using two photocells (Ergotest Technology AS, Langesund, Norway) at 5 and 10 meters; participants will complete two maximum-speed trials, with the slower time recorded

Time frame: 48 hours after the last exercise session (post-intervention assessment).

Static balance with eyes open

Balance is measured with static trials on a force platform (Ergotest Technology AS, Langesund, Norway), where participants stand barefoot with arms at their sides for two 30-second trials each

Time frame: Baseline (pre-intervention).

Static balance with eyes open

Balance is measured with static trials on a force platform (Ergotest Technology AS, Langesund, Norway), where participants stand barefoot with arms at their sides for two 30-second trials each

Time frame: 48 hours after the last exercise session (post-intervention assessment).

Static balance with eyes closed

Balance is measured with static trials on a force platform (Ergotest Technology AS, Langesund, Norway), where participants stand barefoot with arms at their sides for two 30-second trials each

Time frame: Baseline (pre-intervention).

Static balance with eyes closed

Balance is measured with static trials on a force platform (Ergotest Technology AS, Langesund, Norway), where participants stand barefoot with arms at their sides for two 30-second trials each

Time frame: 48 hours after the last exercise session (post-intervention assessment).

Sit-to-stand

The sit-to-stand test requires participants to rise as quickly as possible from a seated position with 90º knee flexion and arms crossed

Time frame: Baseline (pre-intervention).

Sit-to-stand

The sit-to-stand test requires participants to rise as quickly as possible from a seated position with 90º knee flexion and arms crossed

Time frame: 48 hours after the last exercise session (post-intervention assessment).

Timed Up-and-Go test

In the Timed Up-and-Go test, participants move from sitting to standing, walk 3 meters, turn, return, and sit

Time frame: Baseline (pre-intervention).

Timed Up-and-Go test

In the Timed Up-and-Go test, participants move from sitting to standing, walk 3 meters, turn, return, and sit

Time frame: 48 hours after the last exercise session (post-intervention assessment).

Delayed onset muscle soreness

To measure delayed onset muscle soreness (DOMS), a 10-point visual analogue scale shall be used, where 1 = no pain and 10 = intolerable pain

Time frame: Baseline (pre-intervention).

Subjective Perception of Effort

Participants will be instructed and familiarized with the use of the RPE scale during the familiarization phase. RPE will be assessed before, during (after each exercise within the session), and after the training session using the Borg 6-20 RPE scale

Time frame: Baseline (pre-intervention).

Fatigue Visual Analog Scale (VAS-F)

The VAS-F will be used to measure fatigue. This scale, is subdivided into two subscales: fatigue and energy. The VAS-F features a 100 mm long horizontal line, with the term "none" at one end and "very severe" at the opposite end. Participants are required to mark the point on the line corresponding to their perception of the severity of fatigue between these two endpoints.

Time frame: Baseline (pre-intervention).

Anthropometric

Anthropometric measurements will be taken to assess body morphology, fat distribution, and potential alterations due to multiple sclerosis (MS), such as muscle atrophy or changes in body fat percentage. These measurements provide valuable information regarding comorbidities, including abdominal obesity and cardiovascular risk, which are particularly relevant in MS due to factors like reduced mobility or medication use

Time frame: Baseline (pre-intervention).

Anthropometric

Anthropometric measurements will be taken to assess body morphology, fat distribution, and potential alterations due to multiple sclerosis (MS), such as muscle atrophy or changes in body fat percentage. These measurements provide valuable information regarding comorbidities, including abdominal obesity and cardiovascular risk, which are particularly relevant in MS due to factors like reduced mobility or medication use

Time frame: 48 hours after the last exercise session (post-intervention assessment).

Bioimpedance

Bioimpedance will be used to assess body composition, including body fat percentage, lean mass, and total body water. These measurements are important for understanding changes in body composition due to multiple sclerosis (MS), as the disease can impact muscle mass, fluid balance, and fat distribution. Bioimpedance provides valuable insight into the health status and nutritional needs of individuals with MS

Time frame: Baseline (pre-intervention).

Bioimpedance

Bioimpedance will be used to assess body composition, including body fat percentage, lean mass, and total body water. These measurements are important for understanding changes in body composition due to multiple sclerosis (MS), as the disease can impact muscle mass, fluid balance, and fat distribution. Bioimpedance provides valuable insight into the health status and nutritional needs of individuals with MS

Time frame: 48 hours after the last exercise session (post-intervention assessment).

Physical Activity Levels

To assess physical activity in patients with multiple sclerosis (MS), both the International Physical Activity Questionnaire (IPAQ) and triaxial accelerometers can be adapted to account for the mobility limitations often experienced by these individuals. The IPAQ can be tailored by including questions that specifically address low-impact or moderate-intensity activities, considering factors such as fatigue and muscle weakness. Triaxial accelerometers, which measure movement in three planes (vertical, lateral, and anterior-posterior), provide a more detailed and precise measurement of physical activity, capturing even small movements or low-intensity activities such as walking short distances. Together, these tools allow for a comprehensive assessment of physical activity levels in MS patients, while considering their unique needs and capabilities. Additionally, the MET (Metabolic Equivalent of Task) methodology should be adjusted to reflect the lower intensity of activities commonly p

Time frame: Baseline (pre-intervention).

Physical Activity Levels

To assess physical activity in patients with multiple sclerosis (MS), both the International Physical Activity Questionnaire (IPAQ) and triaxial accelerometers can be adapted to account for the mobility limitations often experienced by these individuals. The IPAQ can be tailored by including questions that specifically address low-impact or moderate-intensity activities, considering factors such as fatigue and muscle weakness. Triaxial accelerometers, which measure movement in three planes (vertical, lateral, and anterior-posterior), provide a more detailed and precise measurement of physical activity, capturing even small movements or low-intensity activities such as walking short distances. Together, these tools allow for a comprehensive assessment of physical activity levels in MS patients, while considering their unique needs and capabilities. Additionally, the MET (Metabolic Equivalent of Task) methodology should be adjusted to reflect the lower intensity of activities commonly p

Time frame: 48 hours after the last exercise session (post-intervention assessment).

Dietary and Nutritional Follow-up

Mediterranean Diet adherence questionnaires and food diaries could be effective tools for evaluating nutrition, particularly if MS patients have poor consumption of essential nutrients for their overall health

Time frame: Baseline (pre-intervention).

Dietary and Nutritional Follow-up

Mediterranean Diet adherence questionnaires and food diaries could be effective tools for evaluating nutrition, particularly if MS patients have poor consumption of essential nutrients for their overall health

Time frame: 48 hours after the last exercise session (post-intervention assessment).

The Kurtzke Disability Scale

The Kurtzke Disability Scale (EDSS) is divided into 8 functional systems (FS); four primary: pyramidal function, cerebellar function, sensory function, and brainstem function; and four secondary: sphincters, vision, mental, and others. For each FS, a severity score is provided, ranging from 0 to 6 or 7. The overall score of the scale is measured on a 20-item scale (from 0 to 10 points, increasing in half-point increments). Up to 3.5, the score obtained in each FS and the number of affected FS automatically determine the EDSS score. From 4 to 7, the definition of each level is also given by the ability to walk (ability to walk without stopping, need for assistance)

Time frame: Baseline (pre-intervention).

The Kurtzke Disability Scale

The Kurtzke Disability Scale (EDSS) is divided into 8 functional systems (FS); four primary: pyramidal function, cerebellar function, sensory function, and brainstem function; and four secondary: sphincters, vision, mental, and others. For each FS, a severity score is provided, ranging from 0 to 6 or 7. The overall score of the scale is measured on a 20-item scale (from 0 to 10 points, increasing in half-point increments). Up to 3.5, the score obtained in each FS and the number of affected FS automatically determine the EDSS score. From 4 to 7, the definition of each level is also given by the ability to walk (ability to walk without stopping, need for assistance).

Time frame: 48 hours after the last exercise session (post-intervention assessment).

Subjective Sleep Quality Questionnaire

Subjective sleep quality will be measured using the Karolinska Sleep Diary questionnaire \[73\]. The questionnaire includes the following items: a) sleep quality (very poor \[1\] - very good \[5\]), b) sleep tranquility (very restless \[1\] - very calm \[5\]), c) ease of falling asleep (very difficult \[1\] - very easy \[5\]), d) awakenings (woke up too early \[1\] - did not wake up early \[3\]), e) ease of waking up (very difficult \[1\] - very easy \[5\]), f) feeling of rest (did not rest at all \[1\] - fully rested \[3\]), and g) sufficient sleep (no, definitely too little \[1\] - yes, definitely enough \[5\]).

Time frame: Baseline (pre-intervention).

Subjective Sleep Quality Questionnaire

Subjective sleep quality will be measured using the Karolinska Sleep Diary questionnaire \[73\]. The questionnaire includes the following items: a) sleep quality (very poor \[1\] - very good \[5\]), b) sleep tranquility (very restless \[1\] - very calm \[5\]), c) ease of falling asleep (very difficult \[1\] - very easy \[5\]), d) awakenings (woke up too early \[1\] - did not wake up early \[3\]), e) ease of waking up (very difficult \[1\] - very easy \[5\]), f) feeling of rest (did not rest at all \[1\] - fully rested \[3\]), and g) sufficient sleep (no, definitely too little \[1\] - yes, definitely enough \[5\]).

Time frame: 48 hours after the last exercise session (post-intervention assessment).

Sleep Quality Measured by Actigraph

Sleep quality based on actigraphy will be evaluated using the Actiwatch wGT3X-BT activity monitoring system (Cambridge Neurotechnology, Cambridge, UK) \[74\]. This device uses a piezoelectric accelerometer to measure activity. Participants will wear the Actiwatch on their non-dominant wrist. The lower sensitivity threshold for actigraphy will be set at 80 counts/epoch. Data analysis will begin at the start of the nighttime rest period (bedtime) and conclude at the start of daytime activity (wake-up time).

Time frame: The week prior to the start of the intervention. Baseline (pre-intervention).

Sleep Quality Measured by Actigraph

Sleep quality based on actigraphy will be evaluated using the Actiwatch wGT3X-BT activity monitoring system (Cambridge Neurotechnology, Cambridge, UK) \[74\]. This device uses a piezoelectric accelerometer to measure activity. Participants will wear the Actiwatch on their non-dominant wrist. The lower sensitivity threshold for actigraphy will be set at 80 counts/epoch. Data analysis will begin at the start of the nighttime rest period (bedtime) and conclude at the start of daytime activity (wake-up time)

Time frame: The week following the completion of the intervention (post-intervention assessment).

Delayed onset muscle soreness

To measure delayed onset muscle soreness (DOMS), a 10-point visual analogue scale shall be used, where 1 = no pain and 10 = intolerable pain

Time frame: Immediately after each physical exercise session (post-intervention assessment).

Subjective Perception of Effort

Participants will be instructed and familiarized with the use of the RPE scale during the familiarization phase. RPE will be assessed before, during (after each exercise within the session), and after the training session using the Borg 6-20 RPE scale

Time frame: Immediately after each physical exercise session (post-intervention assessment).

Fatigue Visual Analog Scale (VAS-F)

The VAS-F will be used to measure fatigue. This scale, is subdivided into two subscales: fatigue and energy. The VAS-F features a 100 mm long horizontal line, with the term "none" at one end and "very severe" at the opposite end. Participants are required to mark the point on the line corresponding to their perception of the severity of fatigue between these two endpoints.

Time frame: Immediately after each physical exercise session (post-intervention assessment).