Diabetes Mellitus
Conditions
Keywords
Diabetes Mellitus, Cognition
Brief summary
An urgent need exists to identify effective interventions to arrest or reverse dementia and cognitive loss at its earliest stages. The proposed pilot randomized clinical trial will investigate the short and long-term effects of hyperbaric oxygen therapy on cognitive functioning, cerebral blood flow, and glucose uptake in diabetic elderly with mild cognitive impairment. and provide the basis for a large-scale multi-center study of hyperbaric oxygen therapy effects on cognition in diabetes. The potential to preserve, or even enhance, cognition in elderly at high risk of cognitive decline and dementia has major implications for the affected individuals and their support systems that bear the social and financial burdens of long-term caregiving.
Detailed description
This resubmission responds to PAR-16-365-Pilot Clinical Trials for the Spectrum of Alzheimer's Disease and Age-related Cognitive Decline (R01). It will examine the efficacy of hyperbaric oxygen therapy (HBOT) in improving cognitive functioning in cognitively impaired elderly with diabetes (T2D), who have high risk for dementia. It is a collaboration of the Icahn School of Medicine at Mount Sinai, NY, the University of Wisconsin, the Sagol Center for Hyperbaric Medicine and Research at Asaf Harofeh Medical Center, Israel-one of the world's largest and busiest hyperbaric units-and the Sheba Medical Center, Israel. HBOT is a treatment in which oxygen-enriched air (up to 100%) is administered to patients at a pressure above the ambient atmosphere. The combined action of hyperoxia and hyperbaric pressure leads to significant improvements in tissue oxygenation, resulting in cerebrovascular benefits with improved ischemic damage and cerebral blood flow. Recently, the researchers of this group published compelling evidence from clinical trials indicating HBOT neurotherapeutic effects in stroke, with better cognitive function and elevated brain activity in SPECT. New preliminary data suggests potential neurotherapeutic effects of HBOT on T2D elderly with mild cognitive impairment (MCI), showing better cognitive performance and brain activity. The researchers propose a randomized controlled clinical trial examining the short (12 weeks) and long-term (12 months) efficacy of HBOT. The researchers will test hypotheses that HBOT compared to a sham condition improves cognitive function and increases cerebral blood flow and glucose utilization in MCI patients with T2D. Such patients are at high dementia risk and enriched in cerebrovascular disease, and thus have high potential for benefitting from HBOT. Aim 1 examines the potential beneficial effects of HBOT on cognition (with a primary composite measure of executive functions and episodic memory, both affected by T2D). Aim 2 examines effects of HBOT on ischemic injury which will be measured by CBF at the level of capillaries in gray matter (by MRI arterial spin labeling), and in macrovessels (by a novel 4D Flow MRI technology developed by the researchers of this group). Aim 3 focuses on effects of HBOT on cerebral glucose utilization using \[F18\]FDG-PET. Finally, Aim 4 investigates mediation by the biomarkers, i.e. whether their inclusion in a mediation model will attenuate the effect of HBOT on cognition, suggesting them as underlying mechanisms. This study will be performed in Israel, where there is optimal infrastructure and expertise for all the study components at significantly lower costs. HBOT can be widely deployed in the US so if successful, this pilot study will provide the basis for a multi-center large-scale clinical trial for definitive evidence of its benefits to cognition in T2D patients at high dementia risk. Despite advances in the understanding of risk factors and the pathologic basis for dementia, treatments are of very limited effects. As the proportion of elderly increases, the accelerating prevalence of T2D and dementia amplifies this application's public health impact.
Interventions
DEVICEHBOT intervention
HBOT is a treatment in which oxygen-enriched air (up to 100%) is administered to patients at a pressure. HBOT intervention arm - 3 months of HBOT treatment, 9 months observation all participants receive HBOT treatment for 3 months at year 2
DEVICESham intervention
Sham was selected as the control condition rather than usual care to equate intervention groups with respect to other variables that could influence cognition and functional status, such as a new challenge (completing an activity program), peer socialization, and attention from staff.
Sponsors
Sheba Medical Center
Assaf-Harofeh Medical Center
University of Wisconsin, Madison
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of T2D * Diagnosis of MCI * \> the age of 65 * Hebrew fluency * An informant
Exclusion criteria
* Brain disease that affects cognition (e.g. Parkinson's disease, schizophrenia). * Stroke * Epilepsy * Chest pathology incompatible with HBOT * Inner ear disease * Claustrophobia * Cholinesterase inhibitors * Subjects with an indication for HBOT * Counter-indication for MRI or PET * Individuals with severe cataracts must have cataract operations before enrolling in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Global Cognition Score | baseline, 12, weeks, 6 months and 12 months | This analysis involves 11 cognitive performance variables, each measuring a specific aspect of cognition. In general, higher scores indicate better performance (Digit Symbol measures processing speed, Semantic Fluency measures verbal fluency, Word Recall Task measures immediate verbal memory, Delayed Word Recall Test measures delayed verbal memory, and Recall Unit measures immediate and delayed story recall), except for two variables (Trail Making Test Part A measures processing speed, Trail Making Test Part B measures cognitive flexibility) that measure time (where higher values indicate worse performance). These variables are standardized using Z-scores, which allow for combining and comparing values across different scales. The standardized values (Z-scores) of all 11 measures are averaged to create the composite score. Full range of composite score is -1 to 1. Higher composite Z-score reflects better cognitive performance and more favorable outcomes. |
| Cerebral Blood Flow | baseline, 3 months, and 12 months | Cerebral blood flow (CBF) via arterial spin labeling magnetic resonance imaging (ASL-MRI). CBF is defined as the blood volume that flows per unit mass per unit time in brain tissue. |
| Whole Brain SUVr (FDG-PET) | Baseline, 12 weeks, 12 months | Measures how actively the brain uses glucose, highlighting areas with abnormal activity that may signal diseases like Alzheimer's. Dimmer areas suggest reduced activity seen in disorders like dementia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Alzheimer's Disease Cooperative Study-Activities of Daily Living - Prevention Questionnaire (ADL-PI) | baseline, 12 weeks, 6 months, and 12 months | ADL questionnaire Participant The ADL-PI was developed, comprising 15 ADL (e.g. managing medications, managing finances) and 5 physical function (e.g. shopping and meal preparation) questions. All responses relate to the 3 months prior to the time of rating. Total range 0-30, higher scores indicate greater impairment. |
| NIH Computerized Cognitive Test | Baseline, 12 weeks, 6 months, 12 months | The sum z-scores for 3 computer-based tests (not language dependent), developed through NIH; EXAMINER assessing executive abilities: http://examiner.ucsf.edu). Early in the study, it became clear that participants-older adults with significant frailty, multiple chronic conditions (average \>4 per participant), and high medication burden (mean \>5 medications)-were finding the assessment protocol burdensome. The protocol already required repeated cognitive testing, MRI, FDG-PET imaging, and other assessments, leading many participants to report fatigue and difficulty concentrating. To prioritize participant well-being, decision made not to add the NIH computerized cognitive tests. The existing paper-and-pencil battery was well-established, sensitive to cognitive changes, and adequately covered executive function and episodic memory. The NIH computerized cognitive test was never administered, and no data was collected at any time. |
| Total Mini-Mental State Examination (MMSE) | Baseline, 12 weeks, 6 months, and 12 months | Total range 0-30, higher scores indicate better cognitive function. |
| Alzheimer's Disease Cooperative Study-Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL MCI) | Baseline, 12 weeks, 6 months, and 12 months | ADL Informant This tool is based on caregiver's report to assess participants' abilities to perform basic and instrumental activities of daily living (ADLs) like bathing, walking and self-grooming. All responses should relate to the 4 weeks prior to the time of rating. Full Scale range from 0-53, higher score indicates more impairment for the participant. |
| Clinical Dementia Rating-Sum of Boxes (CDR-SB) | baseline, 12, weeks, 6 months and 12 months | Clinical Dementia Rating-Sum of Boxes (CDR-SB), which summarizes impairment in 6 domains (memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care) based on subject and informant interviews. Scores in each of these are combined to obtain a composite score ranging from 0 (no symptoms of dementia) through 3 (severe symptoms of dementia). Total scale from 0-18. Higher scores indicating worse cognitive status. |
| Beck Depression Inventory (BDI) | baseline, 12 weeks, 6 months and 12 months | This is a 21-item, self-report questionnaire that measures attitudes and symptoms of depression during the last week (i.e. mood, feelings of hopelessness, failure, guilt, self-esteem, etc.). Each question has a set of at least four possible responses, ranging in intensity. Total scale 0-63. Higher scores indicate more severe symptoms of depression. |
Countries
Israel, United States
Participant flow
Recruitment details
155 participants were enrolled from August 10, 2017, to April 17, 2023. The Covid-19 pandemic caused a 14-month pause, affecting follow-up numbers, but the trial was concluded successfully.
Participants by arm
| Arm | Count |
|---|---|
| HBOT Intervention The multiplace HBOT unit at Asaf Harofeh. The inside looks like an airplane, with comfortable chairs for 11 subjects and the nurse who stays throughout the session. The HBOT protocol is 90 minutes, 5 times/week, 60 sessions, 100% oxygen at 2 ATA with 5 minute air breaks every 20 minutes. | 77 |
| Sham Intervention The sham condition replicates all experiential aspects of the HBOT therapy except for the degree of pressure and oxygen levels. The sham condition exposes subjects to 1.1 ATA, which provides a pressure sensation in addition to the noise of air circulation. Pressure then decreases very slowly during the next half hour; in the last 5 minutes of the session, air is circulated again with its related noise. | 78 |
| Total | 155 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 4 |
| Overall Study | Death | 3 | 1 |
| Overall Study | Lack of Efficacy | 5 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 5 |
Baseline characteristics
| Characteristic | HBOT Intervention | Sham Intervention | Total |
|---|---|---|---|
| Age, Continuous | 71.7 years STANDARD_DEVIATION 4.182 | 70.2 years STANDARD_DEVIATION 3.56 | 70.94 years STANDARD_DEVIATION 3.938 |
| Clinical Dementia Rating - Sum of Boxes (CDR-SB) | 1.6 units on a scale STANDARD_DEVIATION 1.16 | 1.51 units on a scale STANDARD_DEVIATION 0.8 | 1.56 units on a scale STANDARD_DEVIATION 0.99 |
| Race/Ethnicity, Customized Ashkenazi | 41 Participants | 32 Participants | 73 Participants |
| Race/Ethnicity, Customized MENA: Middle Eastern North African | 33 Participants | 44 Participants | 77 Participants |
| Race/Ethnicity, Customized Unknown | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Female | 27 Participants | 21 Participants | 48 Participants |
| Sex: Female, Male Male | 50 Participants | 57 Participants | 107 Participants |
| Total Beck Depression Inventory | 5.52 units on a scale STANDARD_DEVIATION 3.89 | 5.34 units on a scale STANDARD_DEVIATION 4.02 | 5.43 units on a scale STANDARD_DEVIATION 3.95 |
| Total Mini-Mental State Examination | 28.55 units on a scale STANDARD_DEVIATION 1.28 | 28.49 units on a scale STANDARD_DEVIATION 1.36 | 28.52 units on a scale STANDARD_DEVIATION 1.32 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 77 | 1 / 78 |
| other Total, other adverse events | 55 / 77 | 51 / 78 |
| serious Total, serious adverse events | 18 / 77 | 6 / 78 |
Outcome results
Primary
Cerebral Blood Flow
Cerebral blood flow (CBF) via arterial spin labeling magnetic resonance imaging (ASL-MRI). CBF is defined as the blood volume that flows per unit mass per unit time in brain tissue.
Time frame: baseline, 3 months, and 12 months
Population: The Covid-19 pandemic caused a 14-month pause, affecting follow-up numbers
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HBOT Intervention | Cerebral Blood Flow | Baseline | 219.39 ml blood∕100 g tissue min | Standard Deviation 60.92 |
| HBOT Intervention | Cerebral Blood Flow | 3 months | 227.68 ml blood∕100 g tissue min | Standard Deviation 68.67 |
| HBOT Intervention | Cerebral Blood Flow | 12 months | 216.91 ml blood∕100 g tissue min | Standard Deviation 50.54 |
| Sham Intervention | Cerebral Blood Flow | Baseline | 207.86 ml blood∕100 g tissue min | Standard Deviation 83.5 |
| Sham Intervention | Cerebral Blood Flow | 3 months | 227.64 ml blood∕100 g tissue min | Standard Deviation 49.02 |
| Sham Intervention | Cerebral Blood Flow | 12 months | 216.91 ml blood∕100 g tissue min | Standard Deviation 50.54 |
Primary
Change in Global Cognition Score
This analysis involves 11 cognitive performance variables, each measuring a specific aspect of cognition. In general, higher scores indicate better performance (Digit Symbol measures processing speed, Semantic Fluency measures verbal fluency, Word Recall Task measures immediate verbal memory, Delayed Word Recall Test measures delayed verbal memory, and Recall Unit measures immediate and delayed story recall), except for two variables (Trail Making Test Part A measures processing speed, Trail Making Test Part B measures cognitive flexibility) that measure time (where higher values indicate worse performance). These variables are standardized using Z-scores, which allow for combining and comparing values across different scales. The standardized values (Z-scores) of all 11 measures are averaged to create the composite score. Full range of composite score is -1 to 1. Higher composite Z-score reflects better cognitive performance and more favorable outcomes.
Time frame: baseline, 12, weeks, 6 months and 12 months
Population: The Covid-19 pandemic caused a 14-month pause, affecting follow-up numbers.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HBOT Intervention | Change in Global Cognition Score | Visit 3 - 6 months | 0.38 Composite z-score | Standard Deviation 0.68 |
| HBOT Intervention | Change in Global Cognition Score | Visit 2 - 12 weeks | 0.18 Composite z-score | Standard Deviation 0.67 |
| HBOT Intervention | Change in Global Cognition Score | Visit 4- 12 months | 0.34 Composite z-score | Standard Deviation 0.65 |
| HBOT Intervention | Change in Global Cognition Score | Visit 1 - Baseline | -0.012 Composite z-score | Standard Deviation 0.65 |
| Sham Intervention | Change in Global Cognition Score | Visit 4- 12 months | 0.37 Composite z-score | Standard Deviation 0.77 |
| Sham Intervention | Change in Global Cognition Score | Visit 2 - 12 weeks | 0.32 Composite z-score | Standard Deviation 0.73 |
| Sham Intervention | Change in Global Cognition Score | Visit 3 - 6 months | 0.48 Composite z-score | Standard Deviation 0.64 |
| Sham Intervention | Change in Global Cognition Score | Visit 1 - Baseline | 0.021 Composite z-score | Standard Deviation 0.61 |
Primary
Whole Brain SUVr (FDG-PET)
Measures how actively the brain uses glucose, highlighting areas with abnormal activity that may signal diseases like Alzheimer's. Dimmer areas suggest reduced activity seen in disorders like dementia.
Time frame: Baseline, 12 weeks, 12 months
Population: The Covid-19 pandemic caused a 14-month pause, affecting follow-up numbers
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HBOT Intervention | Whole Brain SUVr (FDG-PET) | Visit 1 - Baseline | 0.009 Standardized Uptake Value (SUV) | Standard Deviation 0.907 |
| HBOT Intervention | Whole Brain SUVr (FDG-PET) | Visit 2 - 12 weeks | -0.128 Standardized Uptake Value (SUV) | Standard Deviation 1.265 |
| HBOT Intervention | Whole Brain SUVr (FDG-PET) | Visit 4 - 12 months | -0.266 Standardized Uptake Value (SUV) | Standard Deviation 0.934 |
| Sham Intervention | Whole Brain SUVr (FDG-PET) | Visit 4 - 12 months | -0.0004 Standardized Uptake Value (SUV) | Standard Deviation 0.828 |
| Sham Intervention | Whole Brain SUVr (FDG-PET) | Visit 1 - Baseline | -0.022 Standardized Uptake Value (SUV) | Standard Deviation 1.117 |
| Sham Intervention | Whole Brain SUVr (FDG-PET) | Visit 2 - 12 weeks | 0.379 Standardized Uptake Value (SUV) | Standard Deviation 0.973 |
Secondary
Alzheimer's Disease Cooperative Study-Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL MCI)
ADL Informant This tool is based on caregiver's report to assess participants' abilities to perform basic and instrumental activities of daily living (ADLs) like bathing, walking and self-grooming. All responses should relate to the 4 weeks prior to the time of rating. Full Scale range from 0-53, higher score indicates more impairment for the participant.
Time frame: Baseline, 12 weeks, 6 months, and 12 months
Population: The Covid-19 pandemic caused a 14-month pause, affecting follow-up numbers
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HBOT Intervention | Alzheimer's Disease Cooperative Study-Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL MCI) | Baseline | 45.24 score on a scale | Standard Deviation 6.12 |
| HBOT Intervention | Alzheimer's Disease Cooperative Study-Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL MCI) | 12 weeks | 47.5 score on a scale | Standard Deviation 5.67 |
| HBOT Intervention | Alzheimer's Disease Cooperative Study-Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL MCI) | 6 months | 47.69 score on a scale | Standard Deviation 5.66 |
| HBOT Intervention | Alzheimer's Disease Cooperative Study-Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL MCI) | 12 months | 48.98 score on a scale | Standard Deviation 3.67 |
| Sham Intervention | Alzheimer's Disease Cooperative Study-Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL MCI) | 12 months | 48.32 score on a scale | Standard Deviation 6.07 |
| Sham Intervention | Alzheimer's Disease Cooperative Study-Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL MCI) | Baseline | 44.71 score on a scale | Standard Deviation 5.9 |
| Sham Intervention | Alzheimer's Disease Cooperative Study-Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL MCI) | 6 months | 47.29 score on a scale | Standard Deviation 5.33 |
| Sham Intervention | Alzheimer's Disease Cooperative Study-Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL MCI) | 12 weeks | 48.41 score on a scale | Standard Deviation 4.49 |
Secondary
Alzheimer's Disease Cooperative Study-Activities of Daily Living - Prevention Questionnaire (ADL-PI)
ADL questionnaire Participant The ADL-PI was developed, comprising 15 ADL (e.g. managing medications, managing finances) and 5 physical function (e.g. shopping and meal preparation) questions. All responses relate to the 3 months prior to the time of rating. Total range 0-30, higher scores indicate greater impairment.
Time frame: baseline, 12 weeks, 6 months, and 12 months
Population: The Covid-19 pandemic caused a 14-month pause, affecting follow-up numbers
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HBOT Intervention | Alzheimer's Disease Cooperative Study-Activities of Daily Living - Prevention Questionnaire (ADL-PI) | Baseline | 24.34 score on a scale | Standard Deviation 4.041 |
| HBOT Intervention | Alzheimer's Disease Cooperative Study-Activities of Daily Living - Prevention Questionnaire (ADL-PI) | 12 weeks | 25.43 score on a scale | Standard Deviation 4.53 |
| HBOT Intervention | Alzheimer's Disease Cooperative Study-Activities of Daily Living - Prevention Questionnaire (ADL-PI) | 6 months | 25.71 score on a scale | Standard Deviation 3.76 |
| HBOT Intervention | Alzheimer's Disease Cooperative Study-Activities of Daily Living - Prevention Questionnaire (ADL-PI) | 12 months | 26.29 score on a scale | Standard Deviation 3.2 |
| Sham Intervention | Alzheimer's Disease Cooperative Study-Activities of Daily Living - Prevention Questionnaire (ADL-PI) | 12 months | 25.47 score on a scale | Standard Deviation 4.02 |
| Sham Intervention | Alzheimer's Disease Cooperative Study-Activities of Daily Living - Prevention Questionnaire (ADL-PI) | Baseline | 24.60 score on a scale | Standard Deviation 3.81 |
| Sham Intervention | Alzheimer's Disease Cooperative Study-Activities of Daily Living - Prevention Questionnaire (ADL-PI) | 6 months | 25.84 score on a scale | Standard Deviation 4 |
| Sham Intervention | Alzheimer's Disease Cooperative Study-Activities of Daily Living - Prevention Questionnaire (ADL-PI) | 12 weeks | 25.58 score on a scale | Standard Deviation 3.99 |
Secondary
Beck Depression Inventory (BDI)
This is a 21-item, self-report questionnaire that measures attitudes and symptoms of depression during the last week (i.e. mood, feelings of hopelessness, failure, guilt, self-esteem, etc.). Each question has a set of at least four possible responses, ranging in intensity. Total scale 0-63. Higher scores indicate more severe symptoms of depression.
Time frame: baseline, 12 weeks, 6 months and 12 months
Population: The Covid-19 pandemic caused a 14-month pause, affecting follow-up numbers
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HBOT Intervention | Beck Depression Inventory (BDI) | Baseline | 5.43 score on a scale | Standard Deviation 3.8 |
| HBOT Intervention | Beck Depression Inventory (BDI) | 12 weeks | 5.57 score on a scale | Standard Deviation 4.8 |
| HBOT Intervention | Beck Depression Inventory (BDI) | 6 months | 6.62 score on a scale | Standard Deviation 6.51 |
| HBOT Intervention | Beck Depression Inventory (BDI) | 12 months | 6.14 score on a scale | Standard Deviation 5.8 |
| Sham Intervention | Beck Depression Inventory (BDI) | 12 months | 5.64 score on a scale | Standard Deviation 5.3 |
| Sham Intervention | Beck Depression Inventory (BDI) | Baseline | 5.31 score on a scale | Standard Deviation 4 |
| Sham Intervention | Beck Depression Inventory (BDI) | 6 months | 4.88 score on a scale | Standard Deviation 3.61 |
| Sham Intervention | Beck Depression Inventory (BDI) | 12 weeks | 4.74 score on a scale | Standard Deviation 4.32 |
Secondary
Clinical Dementia Rating-Sum of Boxes (CDR-SB)
Clinical Dementia Rating-Sum of Boxes (CDR-SB), which summarizes impairment in 6 domains (memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care) based on subject and informant interviews. Scores in each of these are combined to obtain a composite score ranging from 0 (no symptoms of dementia) through 3 (severe symptoms of dementia). Total scale from 0-18. Higher scores indicating worse cognitive status.
Time frame: baseline, 12, weeks, 6 months and 12 months
Population: The Covid-19 pandemic caused a 14-month pause, affecting follow-up numbers
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HBOT Intervention | Clinical Dementia Rating-Sum of Boxes (CDR-SB) | Baseline | 1.60 score on a scale | Standard Deviation 1.16 |
| HBOT Intervention | Clinical Dementia Rating-Sum of Boxes (CDR-SB) | 12 weeks | 0.75 score on a scale | Standard Deviation 0.86 |
| HBOT Intervention | Clinical Dementia Rating-Sum of Boxes (CDR-SB) | 6 months | 0.61 score on a scale | Standard Deviation 0.62 |
| HBOT Intervention | Clinical Dementia Rating-Sum of Boxes (CDR-SB) | 12 months | 0.71 score on a scale | Standard Deviation 0.75 |
| Sham Intervention | Clinical Dementia Rating-Sum of Boxes (CDR-SB) | 12 months | 0.87 score on a scale | Standard Deviation 1.39 |
| Sham Intervention | Clinical Dementia Rating-Sum of Boxes (CDR-SB) | Baseline | 1.51 score on a scale | Standard Deviation 0.8 |
| Sham Intervention | Clinical Dementia Rating-Sum of Boxes (CDR-SB) | 6 months | 0.76 score on a scale | Standard Deviation 0.79 |
| Sham Intervention | Clinical Dementia Rating-Sum of Boxes (CDR-SB) | 12 weeks | 0.67 score on a scale | Standard Deviation 0.81 |
Secondary
NIH Computerized Cognitive Test
The sum z-scores for 3 computer-based tests (not language dependent), developed through NIH; EXAMINER assessing executive abilities: http://examiner.ucsf.edu). Early in the study, it became clear that participants-older adults with significant frailty, multiple chronic conditions (average \>4 per participant), and high medication burden (mean \>5 medications)-were finding the assessment protocol burdensome. The protocol already required repeated cognitive testing, MRI, FDG-PET imaging, and other assessments, leading many participants to report fatigue and difficulty concentrating. To prioritize participant well-being, decision made not to add the NIH computerized cognitive tests. The existing paper-and-pencil battery was well-established, sensitive to cognitive changes, and adequately covered executive function and episodic memory. The NIH computerized cognitive test was never administered, and no data was collected at any time.
Time frame: Baseline, 12 weeks, 6 months, 12 months
Population: Data not collected due to decision not to administered instruments. This decision was based on participant frailty and protocol intensity-not technical issues or non-compliance-and was made to ensure feasibility and ethical conduct of the study.~The NIH computerized cognitive test was never administered, and no data was collected at any time.
Secondary
Total Mini-Mental State Examination (MMSE)
Total range 0-30, higher scores indicate better cognitive function.
Time frame: Baseline, 12 weeks, 6 months, and 12 months
Population: The Covid-19 pandemic caused a 14-month pause, affecting follow-up numbers
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HBOT Intervention | Total Mini-Mental State Examination (MMSE) | Baseline | 28.56 score on a scale | Standard Deviation 1.3 |
| HBOT Intervention | Total Mini-Mental State Examination (MMSE) | 12 weeks | 28.26 score on a scale | Standard Deviation 1.63 |
| HBOT Intervention | Total Mini-Mental State Examination (MMSE) | 6 months | 28.04 score on a scale | Standard Deviation 1.89 |
| HBOT Intervention | Total Mini-Mental State Examination (MMSE) | 12 months | 28.32 score on a scale | Standard Deviation 1.68 |
| Sham Intervention | Total Mini-Mental State Examination (MMSE) | 12 months | 28.18 score on a scale | Standard Deviation 2.21 |
| Sham Intervention | Total Mini-Mental State Examination (MMSE) | Baseline | 28.49 score on a scale | Standard Deviation 1.37 |
| Sham Intervention | Total Mini-Mental State Examination (MMSE) | 6 months | 28.53 score on a scale | Standard Deviation 1.53 |
| Sham Intervention | Total Mini-Mental State Examination (MMSE) | 12 weeks | 28.38 score on a scale | Standard Deviation 1.77 |