Partnered Rhythmic Rehabilitation for Enhanced Motor-Cognition in Prodromal Alzheimer's Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 76
- 试验地点
- 1
- 主要终点
- Number of Injurious Falls
研究概览
简要总结
Interventions that affect many different aspects of human ability rather than just one aspect of human health are more likely to be successful in preventing and treating Alzheimer's disease (AD). Functional decline in AD is severely impacted by impaired ability to do physical actions while having to make decisions and concentrating, something scientists call motor-cognitive integration. Combined motor and cognitive training has been recommended for people with early AD, thus this study will use partnered, rhythmic rehabilitation (PRR), as an intervention to simultaneously target cardiovascular, social and motor-cognitive domains important to AD. PRR is moderate intensity, cognitively-engaging social dance that targets postural control systems, involves learning multiple, varied stepping and rhythmic patterns, and fosters tactile communication of motor goals between partners, enhancing social interaction's effect on cognition. Previous research demonstrates that PRR classes are safe and result in no injurious falls.
This study is a 12-month long Phase II single- blind randomized clinical trial using PRR in 66 patients with early AD. Participants with early AD will be randomly assigned to participate in PRR or a walking program for three months of biweekly sessions, followed by nine months of weekly sessions of PRR or walking. The overarching hypothesis is that PRR is safe, tolerable and associated with improved motor-cognitive function, and brain (neuronal), vascular (blood vessels) and inflammatory biomarkers that might affect function.
详细描述
For people with early Alzheimer's disease (AD), treatment options to prevent declined function are extremely limited, because AD affects many areas of function. In early AD, people may have trouble physically doing things while also thinking, which is necessary for many activities in daily life. This problem might be helped by doing activities that challenge the mind and the body at the same time. Partnered rhythmic rehabilitation (PRR), which targets fitness, cognition, mobility and social engagement and may prevent future functional problems in AD.
This is a phase II single-blind randomized clinical trial to assess the safety, tolerability, and efficacy of PRR in individuals in the early stages of AD, also called prodromal AD (pAD) . Participants will be randomly assigned to 90-minute PRR or WALK classes. Both interventions will receive equal contact and monitoring from study staff. Participants will have two phases of intervention. In the three-month Training phase, participants will be assigned to 20, biweekly (90-minute) lessons over 12 weeks. In the nine-month Maintenance phase, participants will attend weekly lessons at least 3 times per month. Participants will undergo either PRR or Walking Exercise (WALK) interventions for one year, which will use de-escalating doses: two times per week for three months (Training) and weekly for nine months (Maintenance).
The first study aim is to determine acceptability, safety, tolerability and satisfaction with PRR in pAD. The second aim is to determine a) efficacy of PRR vs. WALK for improving motor-cognitive integration in pAD; b) to identify sensitive endpoints to power a future phase III trial. The researchers will also explore potential mechanisms by which PRR affects pAD. These mechanisms include functional brain measures, vascular, and inflammation measures (arterial stiffness; cerebral perfusion, task functional magnetic resonance imaging [fMRI]; inflammatory markers: cytokines and chemokines, endothelial adhesion markers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Investigator)
入排标准
- 年龄范围
- 50 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Amnestic mild cognitive impairment (MCI) will be defined using the AD Neuroimaging Initiative (ADNI) criteria (http://www.adni-info.org/Scientists/ADNIStudyProcedures.aspx). All MCI participants in ADNI are required to have an amnestic subtype defined as:
- •Subjective memory concern or a memory problem noted by their partner
- •Abnormal memory function documented by a specified education adjusted cutoff score on the delayed paragraph recall of the Anna Thompson story of the Logical Memory subtest from the Wechsler Memory Scale-Revised
- •Mini-Mental State Exam (MMSE) score between 24 and 30 (inclusive). Exceptions may be made for subjects with less than 8 years of education at the discretion of the PI
- •Single or multi-domain amnestic MCI (both subtypes are at high risk for progression to AD)
- •Clinical Dementia Rating (CDR) = 0.5 (Memory Box score must be at least 0.5)
- •General functional performance sufficiently preserved
- •Ability to walk 10 or more feet without an assistive device
- •Completed six grades of education or has a good work history (sufficient to exclude intellectual disabilities)
- •Achieves less than 150 minutes of moderate intensity or 75 minutes of vigorous intensity aerobic activity per week, which is the recommended amount of weekly exercise as per the US Department of Health and Human Services. Not involved in any structured exercise program within the past 3 months (brisk walks are considered formal exercise but leisurely walks are not)
- •Not hospitalized within the last 60 days
- •Willing to commit to a one year research program
排除标准
- •Acute medical illness requiring hospitalization
- •Uncontrolled congestive heart failure
- •History of stroke in the past three years
- •Inability to perform study procedures
- •Inability to perform MRI (e.g. metal implants or cardiac pacemaker, claustrophobia)
- •Medical or physical conditions that would preclude participation (e.g., severe arthritis or mobility problems, uncontrolled hypertension or diabetes, renal failure, history of angina with activity)
- •On medications that could adversely affect cognition, eg: antipsychotics, opioids, stimulants, chemotherapy, anti-parkinsonian drugs (eg Levodopa), neurologic prescriptions to treat Multiple sclerosis and/or Parkinson's. Patients will also be excluded if they are not on stable doses of Aricept, or anticholinesterase inhibitors, eg Namenda, for at least 3 months
- •Psychotic disorders
- •Confounding neurologic conditions (e.g., active central nervous system (CNS) opportunistic infections, seizure disorders, head injury with loss of consciousness >30 minutes, intracranial neoplasms, stroke with neurological or neuropsychiatric sequelae)
- •Substance Use Disorder, Major Depressive and Generalized Anxiety Disorders within six months of evaluation
研究组 & 干预措施
Partnered Rhythmic Rehabilitation (PRR)
Participants in this study are will receive the PRR intervention. Participants will have two phases of intervention. In the three-month Training phase, participants will be assigned to 20, biweekly (90-minute) lessons over 12 weeks. In the nine-month Maintenance phase, participants will attend weekly lessons at least 3 times per month.
干预措施: Partnered Rhythmic Rehabilitation (PRR) (Other)
Group walking (WALK)
Participants in this study are will receive the WALK intervention. Participants will have two phases of intervention. In the three-month Training phase, participants will be assigned to 20, biweekly (90-minute) lessons over 12 weeks. In the nine-month Maintenance phase, participants will attend weekly lessons at least 3 times per month.
干预措施: Group walking (WALK) (Other)
结局指标
主要结局
Number of Injurious Falls
时间窗: Month 12
The primary safety outcome is the number of injurious falls as a result of participation in PRR. PRR will be considered safe if no injurious falls are observed during PRR instruction.
Change in Acceptability
时间窗: Baseline, Month 12
Acceptability of the intervention will be assessed by conducting two pre-session focus groups with 8-10 pAD participants. Focus groups will assess barriers and facilitators of PRR as therapy for motor-cognitive performance of functional activity issues. Post training, the researchers will conduct two focus groups with 8 participants each to assess satisfaction with PRR, perceived effect of PRR on participation in life's activities, impact of touch on therapy, overall perceived impact of cognitive impairment on benefits/results from PRR, and solicit recommendations for improvement. Responses will be open ended rather than on a pre-determined scale.
Change in Four Square Step Test (FSST) Time
时间窗: Baseline, 3 months, 12 months
The Four Square Step Test (FSST) assesses mechanisms underlying motor-cognitive integration. FSST requires participants to step clockwise then counterclockwise into four squares created by rods arranged on the ground in a cross. Participants are instructed to perform FSST "as quickly and as safely as you can," to not touch the rods and make both feet contact the floor in each square. Timing begins when the participant initiates movement and stops when both feet are back in the starting square after completing the sequence. Trials will be repeated if the participant does not understand the instructions, fails to complete the sequence accurately, loses balance, or touches a rod. Three successful trials will be recorded and fastest time selected for analyses.
Attrition
时间窗: Month 12
Tolerability will be assessed by the number of participants completing the study. PRR will be considered tolerable if attrition is less than or equal to 15 percent.
次要结局
- Change in Backward Gait Speed(Baseline, 3 months, 12 months)
- Change in Body Position Spatial Task (BPST)(Baseline, 3 months, 12 months)
- Change in Mini-Balance Evaluation Systems Test (Mini-BESTest) Score(Baseline, 3 months, 12 months)
- Change in Fast Gait Speed(Baseline, 3 months, 12 months)
- Change in Timed Up and Go (TUG) Test - Cognitive Time(Baseline, 3 months, 12 months)
- Change in Composite Physical Function (CPF) Scale Score(Baseline, 3 months, 12 months)
- Change in 6 Minute Walk Test (6MWT) Distance(Baseline, 3 months, 12 months)
- Change in Flanker Task Score(Baseline, 3 months, 12 months)
- Change in Reverse Corsi Blocks Levels Completed(Baseline, 3 months, 12 months)
- Change in Lawton Instrumental Activities of Daily Living (IADL) Score(Baseline, 3 months, 12 months)
- Change in Short Physical Performance Battery (SPPB) Score(Baseline, 3 months, 12 months)
- Change in Preferred Gait Speed(Baseline, 3 months, 12 months)
- Change in Montreal Cognitive Assessment (MoCA) Score(Baseline, 3 months, 12 months)
- Change in Clinical Dementia Rating (CDR) Questionnaire Score(Baseline, 3 months, 12 months)
- Change in Spatial 1-Back Test Score(Baseline, 3 months, 12 months)
- Change in Dot Counting Test Score(Baseline, 3 months, 12 months)
- Change in Verbal Fluency Test Score(Baseline, 3 months, 12 months)
- Change in Multidimensional Scale of Perceived Social Support (MSPSS) Score(Baseline, 3 months, 12 months)
- Change in Set Shifting Score(Baseline, 3 months, 12 months)
- Change in Patient Health Questionnaire (PHQ-9) Score(Baseline, 3 months, 12 months)
研究者
Madeleine Eve Hackney
Associate Professor
Emory University