Trial Outcomes & Findings for Improving the Recovery and Outcome Every Day After the ICU (NCT NCT03095417)

NCT ID: NCT03095417

Last Updated: 2024-03-27

Results Overview

The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) will measure cognitive status. The z-scores for the subscales have a mean of 0 and standard deviation of 1. The overall z-score is the mean of the 7-item z-scores. Z-scores above the standard deviation represent better cognitive outcomes.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 249 participants
• Primary outcome timeframe: 6 months post study randomization
• Results posted on: 2024-03-27

Participant Flow

Per protocol subjects were considered to be enrolled in the study at the time of completion of the informed consent process. 249 subjects were enrolled. 153 subjects were randomized to one of the four study groups.

Participant milestones

Measure	Physical Exercise and Cognitive Training Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. Physical Exercise Intervention: In home exercise intervention. Cognitive Training Intervention: Online cognitive training modules.	Physical Exercise and Cognitive Control Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Physical Exercise Intervention: In home exercise intervention. Cognitive Control: Online control puzzles and games.	Cognitive Training and Stretching Control Stretching Control: This consists of up to 10 minutes of gentle stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. ly directing one session per week and available as needed for rest of the sessions. Cognitive Training Intervention: Online cognitive training modules. Stretching Control: In home stretching.	Cognitive Control and Stretching Control Stretching Control: This consists of up to 10 minutes of stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Stretching Control: In home stretching. Cognitive Control: Online control puzzles and games.
Overall Study STARTED	41	41	36	35
Overall Study COMPLETED	28	30	27	24
Overall Study NOT COMPLETED	13	11	9	11

Reasons for withdrawal

Measure	Physical Exercise and Cognitive Training Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. Physical Exercise Intervention: In home exercise intervention. Cognitive Training Intervention: Online cognitive training modules.	Physical Exercise and Cognitive Control Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Physical Exercise Intervention: In home exercise intervention. Cognitive Control: Online control puzzles and games.	Cognitive Training and Stretching Control Stretching Control: This consists of up to 10 minutes of gentle stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. ly directing one session per week and available as needed for rest of the sessions. Cognitive Training Intervention: Online cognitive training modules. Stretching Control: In home stretching.	Cognitive Control and Stretching Control Stretching Control: This consists of up to 10 minutes of stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Stretching Control: In home stretching. Cognitive Control: Online control puzzles and games.
Overall Study missed	1	2	0	1
Overall Study Lost to Follow-up	2	2	1	0
Overall Study refusal	0	1	0	1
Overall Study Withdrawal by Subject	8	2	5	4
Overall Study Physician Decision	1	2	2	2
Overall Study Death	1	2	1	3

Baseline Characteristics

Improving the Recovery and Outcome Every Day After the ICU

Baseline characteristics by cohort

Measure	Physical Exercise and Cognitive Training n=41 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. Physical Exercise Intervention: In home exercise intervention. Cognitive Training Intervention: Online cognitive training modules.	Physical Exercise and Cognitive Control n=41 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Physical Exercise Intervention: In home exercise intervention. Cognitive Control: Online control puzzles and games.	Cognitive Training and Stretching Control n=36 Participants Stretching Control: This consists of up to 10 minutes of gentle stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. ly directing one session per week and available as needed for rest of the sessions. Cognitive Training Intervention: Online cognitive training modules. Stretching Control: In home stretching.	Cognitive Control and Stretching Control n=35 Participants Stretching Control: This consists of up to 10 minutes of stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Stretching Control: In home stretching. Cognitive Control: Online control puzzles and games.	Total n=153 Participants Total of all reporting groups
Age, Continuous	64.3 years n=5 Participants	64.4 years n=7 Participants	64.6 years n=5 Participants	65.4 years n=4 Participants	64.7 years n=21 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	29 Participants n=7 Participants	22 Participants n=5 Participants	18 Participants n=4 Participants	100 Participants n=21 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	12 Participants n=7 Participants	14 Participants n=5 Participants	17 Participants n=4 Participants	53 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	41 Participants n=5 Participants	41 Participants n=7 Participants	36 Participants n=5 Participants	35 Participants n=4 Participants	153 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants	14 Participants n=7 Participants	13 Participants n=5 Participants	17 Participants n=4 Participants	54 Participants n=21 Participants
Race (NIH/OMB) White	30 Participants n=5 Participants	27 Participants n=7 Participants	21 Participants n=5 Participants	17 Participants n=4 Participants	95 Participants n=21 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment United States	41 participants n=5 Participants	41 participants n=7 Participants	36 participants n=5 Participants	35 participants n=4 Participants	153 participants n=21 Participants

PRIMARY outcome

Timeframe: 6 months post study randomization

Population: Only participants who were able to complete the scale are included in the analysis.

The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) will measure cognitive status.

The z-scores for the subscales have a mean of 0 and standard deviation of 1. The overall z-score is the mean of the 7-item z-scores. Z-scores above the standard deviation represent better cognitive outcomes.

Outcome measures

Measure	Physical Exercise and Cognitive Training n=27 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. Physical Exercise Intervention: In home exercise intervention. Cognitive Training Intervention: Online cognitive training modules.	Physical Exercise and Cognitive Control n=30 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Physical Exercise Intervention: In home exercise intervention. Cognitive Control: Online control puzzles and games.	Cognitive Training and Stretching Control n=27 Participants Stretching Control: This consists of up to 10 minutes of gentle stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. ly directing one session per week and available as needed for rest of the sessions. Cognitive Training Intervention: Online cognitive training modules. Stretching Control: In home stretching.	Cognitive Control and Stretching Control n=24 Participants Stretching Control: This consists of up to 10 minutes of stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Stretching Control: In home stretching. Cognitive Control: Online control puzzles and games.
Cognitive Status Outcome at 6 Months	0.24 Z-score Standard Deviation 0.64	0.36 Z-score Standard Deviation 0.59	0.21 Z-score Standard Deviation 0.58	0.35 Z-score Standard Deviation 0.64

PRIMARY outcome

Timeframe: 3 months post study randomization

Population: Only participants who were able to complete the scale are included in the analysis.

The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) will measure cognitive status.

The z-scores for the subscales have a mean of 0 and standard deviation of 1. The overall z-score is the mean of the 7-item z-scores. Z-scores above the standard deviation represent better cognitive outcomes.

Outcome measures

Measure	Physical Exercise and Cognitive Training n=27 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. Physical Exercise Intervention: In home exercise intervention. Cognitive Training Intervention: Online cognitive training modules.	Physical Exercise and Cognitive Control n=28 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Physical Exercise Intervention: In home exercise intervention. Cognitive Control: Online control puzzles and games.	Cognitive Training and Stretching Control n=27 Participants Stretching Control: This consists of up to 10 minutes of gentle stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. ly directing one session per week and available as needed for rest of the sessions. Cognitive Training Intervention: Online cognitive training modules. Stretching Control: In home stretching.	Cognitive Control and Stretching Control n=25 Participants Stretching Control: This consists of up to 10 minutes of stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Stretching Control: In home stretching. Cognitive Control: Online control puzzles and games.
Cognitive Status Outcome at 3 Months	-0.21 Z-score Standard Deviation 0.69	0.28 Z-score Standard Deviation 0.58	-0.13 Z-score Standard Deviation 0.65	-0.07 Z-score Standard Deviation 0.59

SECONDARY outcome

Timeframe: 3 month post study randomization

Population: Only participants who were able to complete the scale are included in the analysis. Post COVID-19 no SPPB or 2 Minute Step Tests were performed.

The Short Physical Performance Battery (SPPB) will measure physical training effects on balance and strength.

Ranges from 0-12: higher score is better outcome

Outcome measures

Measure	Physical Exercise and Cognitive Training n=10 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. Physical Exercise Intervention: In home exercise intervention. Cognitive Training Intervention: Online cognitive training modules.	Physical Exercise and Cognitive Control n=15 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Physical Exercise Intervention: In home exercise intervention. Cognitive Control: Online control puzzles and games.	Cognitive Training and Stretching Control n=12 Participants Stretching Control: This consists of up to 10 minutes of gentle stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. ly directing one session per week and available as needed for rest of the sessions. Cognitive Training Intervention: Online cognitive training modules. Stretching Control: In home stretching.	Cognitive Control and Stretching Control n=11 Participants Stretching Control: This consists of up to 10 minutes of stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Stretching Control: In home stretching. Cognitive Control: Online control puzzles and games.
Physical Performance Scores at 3 Months	6.60 score on a scale Standard Deviation 4.86	7.80 score on a scale Standard Deviation 4.18	4.92 score on a scale Standard Deviation 4.46	8.18 score on a scale Standard Deviation 3.37

SECONDARY outcome

Timeframe: 6 month post study randomization

Population: Only participants who were able to complete the scale are included in the analysis. Post COVID-19 no SPPB or 2 Minute Step Tests were performed.

The Short Physical Performance Battery (SPPB) will measure physical training effects on balance and strength.

Ranges from 0-12: higher score is better outcome

Outcome measures

Measure	Physical Exercise and Cognitive Training n=12 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. Physical Exercise Intervention: In home exercise intervention. Cognitive Training Intervention: Online cognitive training modules.	Physical Exercise and Cognitive Control n=14 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Physical Exercise Intervention: In home exercise intervention. Cognitive Control: Online control puzzles and games.	Cognitive Training and Stretching Control n=7 Participants Stretching Control: This consists of up to 10 minutes of gentle stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. ly directing one session per week and available as needed for rest of the sessions. Cognitive Training Intervention: Online cognitive training modules. Stretching Control: In home stretching.	Cognitive Control and Stretching Control n=12 Participants Stretching Control: This consists of up to 10 minutes of stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Stretching Control: In home stretching. Cognitive Control: Online control puzzles and games.
Physical Performance Scores at 6 Months	5.00 score on a scale Standard Deviation 4.99	7.07 score on a scale Standard Deviation 4.53	6.57 score on a scale Standard Deviation 3.31	7.00 score on a scale Standard Deviation 4.31

SECONDARY outcome

Timeframe: 3 month post study randomization

Population: Only participants who were able to complete the scale are included in the analysis. Post COVID-19 no SPPB or 2 Minute Step Tests were performed.

The 2-Minute Step Test will measure physical training effects on cardiovascular fitness.

Number of steps, higher = better outcome

Outcome measures

Measure	Physical Exercise and Cognitive Training n=10 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. Physical Exercise Intervention: In home exercise intervention. Cognitive Training Intervention: Online cognitive training modules.	Physical Exercise and Cognitive Control n=12 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Physical Exercise Intervention: In home exercise intervention. Cognitive Control: Online control puzzles and games.	Cognitive Training and Stretching Control n=12 Participants Stretching Control: This consists of up to 10 minutes of gentle stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. ly directing one session per week and available as needed for rest of the sessions. Cognitive Training Intervention: Online cognitive training modules. Stretching Control: In home stretching.	Cognitive Control and Stretching Control n=9 Participants Stretching Control: This consists of up to 10 minutes of stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Stretching Control: In home stretching. Cognitive Control: Online control puzzles and games.
Cardiovascular Fitness Scores at 3 Months	47.30 number of steps in place in 2 minutes Standard Deviation 38.27	45.67 number of steps in place in 2 minutes Standard Deviation 43.08	27.67 number of steps in place in 2 minutes Standard Deviation 38.00	41.44 number of steps in place in 2 minutes Standard Deviation 27.75

SECONDARY outcome

Timeframe: 6 month post study randomization

Population: Only participants who were able to complete the scale are included in the analysis. Post COVID-19 no SPPB or 2 Minute Step Tests were performed.

The 2-Minute Step Test will measure physical training effects on cardiovascular fitness.

Number of steps, higher = better outcome

Outcome measures

Measure	Physical Exercise and Cognitive Training n=12 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. Physical Exercise Intervention: In home exercise intervention. Cognitive Training Intervention: Online cognitive training modules.	Physical Exercise and Cognitive Control n=13 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Physical Exercise Intervention: In home exercise intervention. Cognitive Control: Online control puzzles and games.	Cognitive Training and Stretching Control n=7 Participants Stretching Control: This consists of up to 10 minutes of gentle stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. ly directing one session per week and available as needed for rest of the sessions. Cognitive Training Intervention: Online cognitive training modules. Stretching Control: In home stretching.	Cognitive Control and Stretching Control n=11 Participants Stretching Control: This consists of up to 10 minutes of stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Stretching Control: In home stretching. Cognitive Control: Online control puzzles and games.
Cardiovascular Fitness Scores at 6 Months	35.25 number of steps in place in 2 minutes Standard Deviation 36.86	40.00 number of steps in place in 2 minutes Standard Deviation 37.21	36.29 number of steps in place in 2 minutes Standard Deviation 31.28	32.36 number of steps in place in 2 minutes Standard Deviation 39.16

SECONDARY outcome

Timeframe: 3 month post study randomization

The Patient Health Questionnaire-9 (PHQ-9) will measure intervention effects on depression levels.

Ranges from 0-27, higher score is worse outcome

Outcome measures

Measure	Physical Exercise and Cognitive Training n=27 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. Physical Exercise Intervention: In home exercise intervention. Cognitive Training Intervention: Online cognitive training modules.	Physical Exercise and Cognitive Control n=29 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Physical Exercise Intervention: In home exercise intervention. Cognitive Control: Online control puzzles and games.	Cognitive Training and Stretching Control n=28 Participants Stretching Control: This consists of up to 10 minutes of gentle stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. ly directing one session per week and available as needed for rest of the sessions. Cognitive Training Intervention: Online cognitive training modules. Stretching Control: In home stretching.	Cognitive Control and Stretching Control n=25 Participants Stretching Control: This consists of up to 10 minutes of stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Stretching Control: In home stretching. Cognitive Control: Online control puzzles and games.
Depression Scores at 3 Months	7.19 score on a scale Standard Deviation 6.73	6.03 score on a scale Standard Deviation 4.91	5.36 score on a scale Standard Deviation 4.98	5.84 score on a scale Standard Deviation 5.01

SECONDARY outcome

Timeframe: 6 month post study randomization

The Patient Health Questionnaire-9 (PHQ-9) will measure intervention effects on depression levels.

Ranges from 0-27, higher score is worse outcome

Outcome measures

Measure	Physical Exercise and Cognitive Training n=28 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. Physical Exercise Intervention: In home exercise intervention. Cognitive Training Intervention: Online cognitive training modules.	Physical Exercise and Cognitive Control n=30 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Physical Exercise Intervention: In home exercise intervention. Cognitive Control: Online control puzzles and games.	Cognitive Training and Stretching Control n=27 Participants Stretching Control: This consists of up to 10 minutes of gentle stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. ly directing one session per week and available as needed for rest of the sessions. Cognitive Training Intervention: Online cognitive training modules. Stretching Control: In home stretching.	Cognitive Control and Stretching Control n=24 Participants Stretching Control: This consists of up to 10 minutes of stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Stretching Control: In home stretching. Cognitive Control: Online control puzzles and games.
Depression Scores at 6 Months	7.79 score on a scale Standard Deviation 6.06	5.90 score on a scale Standard Deviation 4.93	5.04 score on a scale Standard Deviation 6.45	5.67 score on a scale Standard Deviation 5.58

SECONDARY outcome

Timeframe: 3 month post study randomization

The Generalized Anxiety Disorder Scale (GAD-7) will measure intervention effects on anxiety levels.

Ranges from 0-21, higher score is worse outcome

Outcome measures

Measure	Physical Exercise and Cognitive Training n=27 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. Physical Exercise Intervention: In home exercise intervention. Cognitive Training Intervention: Online cognitive training modules.	Physical Exercise and Cognitive Control n=29 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Physical Exercise Intervention: In home exercise intervention. Cognitive Control: Online control puzzles and games.	Cognitive Training and Stretching Control n=28 Participants Stretching Control: This consists of up to 10 minutes of gentle stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. ly directing one session per week and available as needed for rest of the sessions. Cognitive Training Intervention: Online cognitive training modules. Stretching Control: In home stretching.	Cognitive Control and Stretching Control n=25 Participants Stretching Control: This consists of up to 10 minutes of stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Stretching Control: In home stretching. Cognitive Control: Online control puzzles and games.
Anxiety Scores at 3 Months	4.27 score on a scale Standard Deviation 5.39	4.48 score on a scale Standard Deviation 5.91	3.32 score on a scale Standard Deviation 4.37	4.24 score on a scale Standard Deviation 4.82

SECONDARY outcome

Timeframe: 6 month post study randomization

The Generalized Anxiety Disorder Scale (GAD-7) will measure intervention effects on anxiety levels.

Ranges from 0-21, higher score is worse outcome

Outcome measures

Measure	Physical Exercise and Cognitive Training n=28 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. Physical Exercise Intervention: In home exercise intervention. Cognitive Training Intervention: Online cognitive training modules.	Physical Exercise and Cognitive Control n=30 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Physical Exercise Intervention: In home exercise intervention. Cognitive Control: Online control puzzles and games.	Cognitive Training and Stretching Control n=27 Participants Stretching Control: This consists of up to 10 minutes of gentle stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. ly directing one session per week and available as needed for rest of the sessions. Cognitive Training Intervention: Online cognitive training modules. Stretching Control: In home stretching.	Cognitive Control and Stretching Control n=24 Participants Stretching Control: This consists of up to 10 minutes of stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Stretching Control: In home stretching. Cognitive Control: Online control puzzles and games.
Anxiety Scores at 6 Months	4.25 score on a scale Standard Deviation 5.64	4.33 score on a scale Standard Deviation 5.41	3.48 score on a scale Standard Deviation 5.91	3.13 score on a scale Standard Deviation 4.20

SECONDARY outcome

Timeframe: 3 month post study randomization

The Medical Outcomes Study 36 item short form (SF-36) will measure participant quality of life scores.

range of 0 - 100 (higher = better outcome)

Outcome measures

Measure	Physical Exercise and Cognitive Training n=27 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. Physical Exercise Intervention: In home exercise intervention. Cognitive Training Intervention: Online cognitive training modules.	Physical Exercise and Cognitive Control n=29 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Physical Exercise Intervention: In home exercise intervention. Cognitive Control: Online control puzzles and games.	Cognitive Training and Stretching Control n=28 Participants Stretching Control: This consists of up to 10 minutes of gentle stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. ly directing one session per week and available as needed for rest of the sessions. Cognitive Training Intervention: Online cognitive training modules. Stretching Control: In home stretching.	Cognitive Control and Stretching Control n=25 Participants Stretching Control: This consists of up to 10 minutes of stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Stretching Control: In home stretching. Cognitive Control: Online control puzzles and games.
Quality of Life Scores at 3 Months	34.49 score on a scale Standard Deviation 12.51	34.25 score on a scale Standard Deviation 12.37	31.74 score on a scale Standard Deviation 11.42	33.57 score on a scale Standard Deviation 11.49

SECONDARY outcome

Timeframe: 6 month post study randomization

The Medical Outcomes Study 36 item short form (SF-36) will measure participant quality of life scores.

range of 0 - 100 (higher = better outcome)

Outcome measures

Measure	Physical Exercise and Cognitive Training n=28 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. Physical Exercise Intervention: In home exercise intervention. Cognitive Training Intervention: Online cognitive training modules.	Physical Exercise and Cognitive Control n=30 Participants Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Physical Exercise Intervention: In home exercise intervention. Cognitive Control: Online control puzzles and games.	Cognitive Training and Stretching Control n=27 Participants Stretching Control: This consists of up to 10 minutes of gentle stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. ly directing one session per week and available as needed for rest of the sessions. Cognitive Training Intervention: Online cognitive training modules. Stretching Control: In home stretching.	Cognitive Control and Stretching Control n=23 Participants Stretching Control: This consists of up to 10 minutes of stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Stretching Control: In home stretching. Cognitive Control: Online control puzzles and games.
Quality of Life Scores at 6 Months	34.72 score on a scale Standard Deviation 13.14	34.08 score on a scale Standard Deviation 11.64	33.36 score on a scale Standard Deviation 10.77	34.40 score on a scale Standard Deviation 9.97

Adverse Events

Physical Exercise and Cognitive Training

Serious events: 0 serious events

Other events: 2 other events

Deaths: 1 deaths

Physical Exercise and Cognitive Control

Serious events: 1 serious events

Other events: 3 other events

Deaths: 2 deaths

Cognitive Training and Stretching Control

Serious events: 0 serious events

Other events: 1 other events

Deaths: 1 deaths

Cognitive Control and Stretching Control

Serious events: 0 serious events

Other events: 0 other events

Deaths: 3 deaths

Serious adverse events

Measure	Physical Exercise and Cognitive Training n=41 participants at risk Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. Physical Exercise Intervention: In home exercise intervention. Cognitive Training Intervention: Online cognitive training modules.	Physical Exercise and Cognitive Control n=41 participants at risk Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Physical Exercise Intervention: In home exercise intervention. Cognitive Control: Online control puzzles and games.	Cognitive Training and Stretching Control n=36 participants at risk Stretching Control: This consists of up to 10 minutes of gentle stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. ly directing one session per week and available as needed for rest of the sessions. Cognitive Training Intervention: Online cognitive training modules. Stretching Control: In home stretching.	Cognitive Control and Stretching Control n=35 participants at risk Stretching Control: This consists of up to 10 minutes of stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Stretching Control: In home stretching. Cognitive Control: Online control puzzles and games.
Cardiac disorders elevated heart rate	0.00% 0/41 • Participants were assessed for adverse events from the time of informed consent process completion until the end of study participation. This was approximately 6 months if the study was completed.	2.4% 1/41 • Participants were assessed for adverse events from the time of informed consent process completion until the end of study participation. This was approximately 6 months if the study was completed.	0.00% 0/36 • Participants were assessed for adverse events from the time of informed consent process completion until the end of study participation. This was approximately 6 months if the study was completed.	0.00% 0/35 • Participants were assessed for adverse events from the time of informed consent process completion until the end of study participation. This was approximately 6 months if the study was completed.

Other adverse events

Measure	Physical Exercise and Cognitive Training n=41 participants at risk Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. Physical Exercise Intervention: In home exercise intervention. Cognitive Training Intervention: Online cognitive training modules.	Physical Exercise and Cognitive Control n=41 participants at risk Physical Exercise Intervention: The physical exercise portion of the combined intervention consists of 45 minutes of multi-modal physical exercise focused on seated aerobic and progressive resistance training designed to improve aerobic capacity, muscular strength and endurance consistent with current exercise recommendations. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Physical Exercise Intervention: In home exercise intervention. Cognitive Control: Online control puzzles and games.	Cognitive Training and Stretching Control n=36 participants at risk Stretching Control: This consists of up to 10 minutes of gentle stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Intervention: The cognitive portion of the combined intervention consists of a suite of 24 programs called Brain HQ developed by Posit Science Inc., organized into six categories: attention, speed, memory, people skills, intelligence, and navigation. The DDD-ECT trial will use 45-minute sessions of Brain HQ exercises. The modules are designed to improve time-order judgment, visual discrimination, spatial-match, forward-span, instruction-following, and memory. ly directing one session per week and available as needed for rest of the sessions. Cognitive Training Intervention: Online cognitive training modules. Stretching Control: In home stretching.	Cognitive Control and Stretching Control n=35 participants at risk Stretching Control: This consists of up to 10 minutes of stretching. The study team will deliver 3 sessions per week for 3 months. Cognitive Control: This consists of up to 20 minutes of puzzles and games, 2 days per week for 3 months. The participants will use on-line Brain HQ Control Games hosted by Posit Science, Inc. as an attention control. Stretching Control: In home stretching. Cognitive Control: Online control puzzles and games.
Cardiac disorders elevated heart rate	2.4% 1/41 • Number of events 1 • Participants were assessed for adverse events from the time of informed consent process completion until the end of study participation. This was approximately 6 months if the study was completed.	2.4% 1/41 • Number of events 1 • Participants were assessed for adverse events from the time of informed consent process completion until the end of study participation. This was approximately 6 months if the study was completed.	2.8% 1/36 • Number of events 1 • Participants were assessed for adverse events from the time of informed consent process completion until the end of study participation. This was approximately 6 months if the study was completed.	0.00% 0/35 • Participants were assessed for adverse events from the time of informed consent process completion until the end of study participation. This was approximately 6 months if the study was completed.
Respiratory, thoracic and mediastinal disorders O2 saturation lower than 88%	2.4% 1/41 • Number of events 1 • Participants were assessed for adverse events from the time of informed consent process completion until the end of study participation. This was approximately 6 months if the study was completed.	4.9% 2/41 • Number of events 2 • Participants were assessed for adverse events from the time of informed consent process completion until the end of study participation. This was approximately 6 months if the study was completed.	0.00% 0/36 • Participants were assessed for adverse events from the time of informed consent process completion until the end of study participation. This was approximately 6 months if the study was completed.	0.00% 0/35 • Participants were assessed for adverse events from the time of informed consent process completion until the end of study participation. This was approximately 6 months if the study was completed.

Additional Information

Babar Khan, MD, MS

Indiana University

Phone: (317) 274-9132

Email: bakhan@iu.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place