Clinical trial NCT04289402: Individualized Brain Stimulation to Improve Mobility in Alzheimer's Disease
Official title: Modulating Brain Activity to Improve Cognitive-motor Function in Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Alzheimer Dementia
Presenile Alzheimer Dementia
Aging
Keywords: Aging
Lead sponsor: Hebrew SeniorLife
Sponsor class: OTHER
First posted: 2020-02-28
Enrollment: 24
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The investigators will conduct a single site, sham-controlled, double-blinded, randomized trial of tDCS. Participants will complete baseline cognitive and physical functioning assessments, as well as a structural MRI of the brain. They will then be assigned to a two-week, 10-session intervention of either personalized tDCS sham (i.e., control) stimulation, via permuted block randomization stratified by sex to ensure that equal number of men and women are randomized to each intervention arm.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Recruitment efficiency
timeFrame: 1 year
measure: Retention
timeFrame: 1 year
measure: Blinding
timeFrame: Immediately after intervention
measure: Montreal Cognitive Assessment (MoCA) total score
timeFrame: Change from baseline to two-week follow-up
measure: Dual task gait speed
timeFrame: Change from baseline to two-week follow-up
measure: Dual task standing postural sway area
timeFrame: Change from baseline to two-week follow-up
Secondary outcomes:
measure: Trail making test A-B
timeFrame: Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
measure: Digit Span
timeFrame: Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
measure: Digit Symbol Substitution Test
timeFrame: Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
measure: Category and Phonemic Fluency Test
timeFrame: Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
measure: Hopkins Verbal Learning Test
timeFrame: Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
measure: Dual task stride time variability
timeFrame: Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
measure: Dual task standing postural sway speed
timeFrame: Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
measure: Timed Up-and-Go
timeFrame: Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
measure: Five-day accelerometry-based physical activity
timeFrame: Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
measure: Centers for Epidemiologic Studies Depression Scale
timeFrame: Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
Other outcomes:
Locations:
city: Roslindale
country: United States
facility: Hebrew Rehabilitation Center
state: Massachusetts
Study officials:
affiliation: Hebrew SeniorLife
name: Brad Manor, PhD
role: PRINCIPAL_INVESTIGATOR
References: