Individualized Brain Stimulation to Improve Mobility in Alzheimer's Disease

Aging Clinical Trial

— ISTIM-AD  

Official title:

Modulating Brain Activity to Improve Cognitive-motor Function in Alzheimer's Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04289402
• Other study ID #: 3P30AG031679-09S1
• Status: Recruiting
• Phase: N/A
• Start date: January 31, 2020
• Est. completion date: December 30, 2024

Study information

• Verified date: January 2024
• Source: Hebrew SeniorLife
• Contact: Peggy Gagnon
• Phone: 617-971-5303
• Email: gagnon[@]hsl.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: December 30, 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aging
• Alzheimer Dementia
• Alzheimer Disease
• Dementia
• Presenile Alzheimer Dementia

Intervention

Other:
• Personalized tDCS
The participant will receive 10, 20-minutes sessions of personalized tDCS Monday-Friday, at approximately the same time of day, over two consecutive weeks.
• Active-Sham
The participant will receive 20, 20-minute sessions of active-sham stimulation Monday-Friday, at approximately the same time of day, over two consecutive weeks.

Locations

Country	Name	City	State
United States	Hebrew Rehabilitation Center	Roslindale	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Hebrew SeniorLife

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recruitment efficiency	The number of residents that need to be screened in order to enroll one participant into the trial.	1 year
Primary	Retention	The percentage of enrolled participants who complete the trial.	1 year
Primary	Blinding	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.	Immediately after intervention
Primary	Montreal Cognitive Assessment (MoCA) total score	This common test assesses global cognitive function. Maximum score on the MoCA is 30 points (minimum = 0), with higher scores associated with better outcomes.	Change from baseline to two-week follow-up
Primary	Dual task gait speed	This metric assesses the ability to control gait while performing a secondary cognitive task.	Change from baseline to two-week follow-up
Primary	Dual task standing postural sway area	This metric assesses the ability to control standing posture while performing a secondary cognitive task.	Change from baseline to two-week follow-up
Secondary	Trail making test A-B	This metric assesses cognitive executive function.	Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
Secondary	Digit Span	This common test assesses working memory.	Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
Secondary	Digit Symbol Substitution Test	This common test assesses sustained attention and motor speed.	Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
Secondary	Category and Phonemic Fluency Test	This common test assesses word retrieval.	Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
Secondary	Hopkins Verbal Learning Test	This common test assesses memory.	Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
Secondary	Dual task stride time variability	This metric assesses the ability to control gait while performing a secondary cognitive task.	Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
Secondary	Dual task standing postural sway speed	This metric assesses the ability to control standing posture while performing a secondary cognitive task.	Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
Secondary	Timed Up-and-Go	This metric assesses mobility.	Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
Secondary	Five-day accelerometry-based physical activity	This metric assesses the quantity and quality of habitual physical activity.	Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
Secondary	Centers for Epidemiologic Studies Depression Scale	This metric assesses mood.	Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention