Reversing Maladaptive Reorganization in Frail Brains (FRAILBRAIN)

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

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.

Study Overview

• Status: Completed
• Conditions: Neuroplasticity; Sensorimotor
• Intervention / Treatment: Behavioral: Trainings app

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Mannheim, Germany, 68159
    • CIMH - Department of Cognitive and Clinical Neuroscience

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Frail individuals (Fried criteria)

Exclusion Criteria:

• Alzheimer or strong cognitive/dementia impairments, strong neurological impairments, age below 65

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Central Institute of Mental Health, Mannheim

Publications and helpful links

General Publications

• Beier F, Loffler M, Nees F, Hausner L, Frolich L, Flor H. Sensory and motor correlates of frailty: dissociation between frailty phenotype and frailty index. BMC Geriatr. 2022 Sep 15;22(1):755. doi: 10.1186/s12877-022-03416-6.
• Beier F, Löffler M, Nees F, Hausner L, Frölich L, Flor H. Promoting neuroplasticity and neuropsychological functioning in frailty through an app-based sensorimotor training: study protocol for a randomized trial. BMC Geriatr. 2021 Jun 3;21(1):343. doi: 10.1186/s12877-021-02293-9.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2017
• Primary Completion (Actual): September 1, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: September 4, 2018
• First Submitted That Met QC Criteria: September 8, 2018
• First Posted (Actual): September 11, 2018

Study Record Updates

• Last Update Posted (Actual): July 19, 2022
• Last Update Submitted That Met QC Criteria: July 18, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: FRAILBRAIN

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No