Individualized Brain Stimulation to Improve Mobility in Alzheimer's Disease

Not Applicable

Recruiting

• Conditions: Presenile Alzheimer Dementia; Alzheimer Dementia; Aging
• Interventions: Other: Personalized tDCS; Other: Active-Sham

• Registration Number: NCT04289402
• Lead Sponsor: Hebrew SeniorLife

Brief Summary

The objective of this study is to conduct a pilot, randomized sham-controlled trials to determine the feasibility and effects of a 10-session personalized tDCS intervention targeting the left dorsolateral prefrontal cortex on cognitive function, dual task standing and walking, and other metrics of mobility in 24 older adults with mild AD living in supportive housing.

Detailed Description

Beyond the profound impact on memory, Alzheimer's disease (AD) neuropathology, even in its early stages, affects the prefrontal lobes leading to executive dysfunction and mobility disturbances. Prefrontal cortex functions, including executive control, attention, and working memory, are known to decline with the progression of AD. In older adults, better performance on executive cognitive tasks is associated with greater activation of the left dorsolateral prefrontal cortex (dlPFC). Reduced activation within the dlPFC is believed to play a role in both the executive and physical functioning declines seen in AD, significantly contributing to loss of functional independence. In mild AD, an individual's state of executive functioning is a sensitive predictor of the ability to stand and walk safely, especially when performing additional cognitive tasks (i.e., dual tasking). Therefore, the investigators contend that by facilitating the excitability of the left dlPFC, some of the early cognitive and mobility impairments of AD may be reduced, ultimately leading to more functional independence, increased physical activity, and improved quality of life.

tDCS provides a noninvasive means of facilitating the excitability of the prefrontal cortex and its connected neural networks, and thus holds promise as a therapy to improve the executive control of cognition and mobility in older adults with mild AD. tDCS modulates cortical excitability by passing low-level currents through electrodes placed upon the scalp over the dlPFC. These currents induce electrical fields within the brain that in turn polarize neuronal populations and alter their likelihood of firing. The research team demonstrated in older adults aged 65 years and older with executive dysfunction and slow gait that 10 sessions of 20-minutes of tDCS targeting the left dlPFC improved cognitive and physical functioning for at least two weeks following the intervention. Considerable evidence, including our preliminary studies, now suggest that multi-session tDCS interventions targeting the dlPFC may induce measurable and meaningful improvements in cognitive and/or mobility outcomes in relatively healthy adults and in those with mild-to-moderate executive dysfunction. Still, the size and duration of tDCS-induced benefits in older adults with executive dysfunction have not been established. Moreover, to date, tDCS delivery has not attempted to account for interpersonal differences in older adults, particularly the high inter-individual variance in skin, skull, brain, and cerebrospinal fluid and how each of these characteristics impacts the current flow. Such personalization is now possible with the current flow modeling the investigators propose.

The overall aim of the study is to conduct a pilot, randomized sham-controlled trial to determine the feasibility and effects of a 10-session personalized tDCS intervention targeting the left dlPFC on cognitive function, dual task standing and walking, and other metrics of mobility in 24 older adults with mild AD living in supportive housing. The investigators will include personalized current flow modeling approach using baseline structural MRIs to determine the tDCS electrode placement and stimulation parameters to optimize current flow to each participant's brain. The investigators do not expect tDCS to revere the structural brain changes that result from AD, but instead maximize the function of remaining, intact brain neurons and frontal networks, and thereby improve functional outcomes in people suffering from the neurodegenerative process.

The investigators hypothesize that, in older adults 65 years and older with mild AD, a personalized tDCS intervention targeting the left dlPFC, as compared to sham, will mitigate dual task costs to the control of gait and standing posture and enhance executive functioning.

Study Timeline

• Study Start: 2020-01-31
• Study First Submitted: 2020-02-13
• Study First Submitted QC: 2020-02-26
• Study First Posted: 2020-02-28
• Status Verified: 2024-07
• Last Update Submitted: 2024-11-03
• Last Update Posted: 2024-11-05
• Primary Completion: 2025-01-31
• Study Completion: 2025-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• Men and women aged 65 and older living within supportive housing facilities
• Mild Alzheimer's disease (AD) defined by the combination of 1) at least mild cognitive impairment defined as a modified TICS score of ≤ 34, 2) informant-report of Instrumental Activities of Daily Living impairment as defined as a score of ≥ 6 on the NACC Functional Activities Questionnaire, and 3) a Clinical Dementia Rating score of 1.

Exclusion Criteria

• Inability to secure informant participation
• Unwillingness to cooperate or participate in the study protocol
• An inability to ambulate without the assistance of another person (canes or walkers allowed)
• A clinical history of stroke, Parkinson's disease or parkinsonian symptoms, multiple sclerosis, normal pressure hydrocephalus, or other neurological conditions outside of mild AD.
• Any report of severe lower-extremity arthritis or physician-diagnosis of peripheral neuropathy
• Use of antipsychotics, anti-seizure, benzodiazepines, or other neuroactive medications
• Severe depression defined by a Center for Epidemiologic Studies Depression scale score greater than 16
• Any report of physician-diagnosis of schizophrenia, bipolar disorder, or other psychiatric illness
• Contraindications to MRI or tDCS, including reported seizure within the past two years, use of neuropsychological-active drugs, the risk of metal objects anywhere in the body, self-reported presence of specific implanted medical devices (e.g., deep brain stimulator, medication infusion pump, cochlear implant, pacemakers, etc.), or the presence of any active dermatological condition, such as eczema, on the scalp

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Personalized tDCS	Personalized tDCS	Baseline MRIs will enable personalization of tDCS via current flow modeling for optimization to each participant with the goal of generating an average electric field of 0.25 V/m within their identified left dlPFC. The direct current delivered by any one electrode will not exceed 2.0 mA and the total amount of current from all electrodes will not exceed 4 mA. Each 20-minutes session will begin and end with a 60-second ramp up/down of current amplitude to maximize comfort.
Active-Sham	Active-Sham	The investigators will use an active sham in which very low-level currents (0.5 mA total) will be transferred between electrodes in close proximity on the scalp throughout the entire 20-minute session. This intervention will be optimized to each participant to deliver currents designed to not significantly influence their cortical tissue, but still mimic the cutaneous sensations induced by tDCS.

Primary Outcome Measures

Name	Time	Method
Montreal Cognitive Assessment (MoCA) total score	Change from baseline to two-week follow-up	This common test assesses global cognitive function. Maximum score on the MoCA is 30 points (minimum = 0), with higher scores associated with better outcomes.
Dual task standing postural sway area	Change from baseline to two-week follow-up	This metric assesses the ability to control standing posture while performing a secondary cognitive task.
Recruitment efficiency	1 year	The number of residents that need to be screened in order to enroll one participant into the trial.
Retention	1 year	The percentage of enrolled participants who complete the trial.
Blinding	Immediately after intervention	A blinding efficacy questionnaire will be used to record participant guesses of their assigned intervention (real or placebo), as well as the confidence of these guesses on a scale from 1=Not confident to 10=Extremely confident.
Dual task gait speed	Change from baseline to two-week follow-up	This metric assesses the ability to control gait while performing a secondary cognitive task.

Secondary Outcome Measures

Name	Time	Method
Timed Up-and-Go	Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention	This metric assesses mobility.
Centers for Epidemiologic Studies Depression Scale	Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention	This metric assesses mood.
Digit Span	Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention	This common test assesses working memory.
Digit Symbol Substitution Test	Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention	This common test assesses sustained attention and motor speed.
Dual task standing postural sway speed	Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention	This metric assesses the ability to control standing posture while performing a secondary cognitive task.
Trail making test A-B	Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention	This metric assesses cognitive executive function.
Category and Phonemic Fluency Test	Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention	This common test assesses word retrieval.
Hopkins Verbal Learning Test	Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention	This common test assesses memory.
Dual task stride time variability	Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention	This metric assesses the ability to control gait while performing a secondary cognitive task.
Five-day accelerometry-based physical activity	Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention	This metric assesses the quantity and quality of habitual physical activity.

Trial Locations

Locations (1)

Hebrew Rehabilitation Center; 🇺🇸 Roslindale, Massachusetts, United States