Reversing Maladaptive Reorganization in Frail Brains

Study Overview
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Brief Summary
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Neuroscientific models of maladaptive aging emphasize the loss of sensorimotor stimulation and reduced modulatory capacities as core processes in the development of maladaptive plastic changes of the brain and subsequent cognitive and bodily decline as determinants of frailty and multimorbidity in old age. The investigators plan to analyze anatomical, neurophysiological, and neuropsychological correlates of maladaptive plasticity in frail persons and plan to test how innovative interventions that target maladaptive plasticity alter brain function and neurocognitive skills. There are novel interventions that have been shown to target the neurocognitive deficits and enhance plasticity in brain areas that are affected first in the progress of aging. Specifically, sensory training has been employed to enhance relevant input to the brain and to improve neuromodulatory function and has yielded high effect sizes. The investigators will perform proof of concept studies to examine the utility of sensorimotor training and examine the role of brain-derived neurotrophic growth factor to enhance brain plasticity and memory functions, as well as their transfer to other cognitive domains. The investigators will implement motivational enhancement strategies using virtual reality in these treatments that can further boost training effects and plasticity, but have not been employed in these treatments so far. Biomarkers for the remediation of maladaptive changes will involve neuropsychological assessments, brain imaging, brain-derived neurotrophic factor (BDNF) levels, and BDNF genotype. Thus, the investigators will be able to comprehensively characterize dysfunctional plasticity and the specific mechanisms of the interventions that are employed and investigate innovative clinical trials.

Official Title
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Reversing Maladaptive Reorganization in Frail Brains: Sensorimotor Training, Brain Plasticity and the Role of Brain-derived Neurotrophic Factor

Conditions
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Neuroplasticity, Sensorimotor

Intervention / Treatment
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* Behavioral: Trainings app


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Frail individuals (Fried criteria) Exclusion Criteria: Alzheimer or strong cognitive/dementia impairments, strong neurological impairments, age below 65

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sensorimotor training<br>The participants will receive a tablet-based app for at home training that contains sensorimotor components. | Behavioral: Trainings app<br>* Sensorimotor trainings app for at home Training (tablet-based)<br>|
| Active Comparator: Control training<br>The participants will receive a tablet-based app for at home training that contains relaxing components. | Behavioral: Trainings app<br>* Sensorimotor trainings app for at home Training (tablet-based)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuroplasticity measures of brain Imaging I: brain responses at rest and task-based (sensorimotor) | Blood oxygenation level dependent (BOLD) signal changes | 2 months | 
| Body parameter: weight and height | Information on weight and height will be combined to report BMI in kg/m^2 | 2 months | 
| Body parameter: muscles | Muscle strength in electromyogram amplitudes | 2 months | 
| Neuroplasticity measures of brain Imaging: brain size | Volume of different brain regions | 2 months | 
| Neuroplasticity measures of brain Imaging: brain diffusion | Brain diffusion in fractional anisotropy values | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Well-being | Questionnaire data on mood and mental health will be standardized and integrated into one mean score of well-being (computation of a mean values across the questionnaire scores) | 2-3 months | 
| Cognitive health | Behavioral performance data during cognitive testing will be standardized integrated into one mean score of cognitive functioning (computation of a mean value across response times in the cogniitve tests) | 2-3 months |