High Frequency Stimulation to Improve Cognition, Mobility, and Affect in Individuals With Subjective Cognitive Decline

NCT07395609 | Not Yet Recruiting

• 1 other identifier: IRB202500587
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The goal is to determine whether three months of at least three times / week of sensory flicker stimulation improves cognition, mobility, and affect in older adults with Subjective Cognitive Decline (SCD), relative to an SCD control group receiving white noise sensory stimulation. Investigators will also determine whether the intervention slows cortical thinning and declines in brain functional network segregation and changes in blood biomarkers of Alzheimer's Disease (AD).

Conditions

Subjective Cognitive Decline (SCD); Healthy Subjects

Outcome Measures

Primary Outcomes (12)

• Cognition

  Investigators will comprehensively assess behavior at three times (baseline, half-way through (1.5 months), and after the intervention (3months)) using the NIH Toolbox. Composite Scores of Fluid Cognition from the Cognition Toolbox will serve as primary metrics for cognition.

  Baseline, halfway through (1.5 months), and post-intervention (3 months)

• Grip strength

  Participants will grip a machine which measures their grip strength in kg.

  Baseline, halfway through (1.5 months), and post-intervention (3 months)

• 10m Gait Speed

  Participants will walk unassisted for 10 meters. Their speed will be measured in seconds.

  Baseline, halfway through (1.5 months), and post-intervention (3 months)

• Clinical Test of Sensory Interaction on Balance (CTSIB)

  Participants will, with eyes open and closed, walk on rough and smooth terrain. Investigators will measure sway area (measured in m\^2/s\^4).

  Baseline, halfway through (1.5 months), and post-intervention (3 months)

• Affect - POMS-2

  This test is used to assess transient feelings and mood among individuals aged 13 years and above. Scoring: 0 - Not at all 1. \- A little 2. \- Moderately 3. \- Quite a Lot 4. \- Extremely Except "Relaxed" and "Efficient", and they score the reverse:

  Baseline, halfway through (1.5 months), and post-intervention (3 months)

• Affect - Ryff Scales of Psychological Wellbeing

  Respondents agree or disagree with 42 statements using a 6-point scale (1 = strongly agree; 6 = strongly disagree).

  Baseline, halfway through (1.5 months), and post-intervention (3 months)

• Affect - Satisfaction with Life Scale

  The possible range of scores is 5-35. Scores between 5-9 indicate the respondent is extremely dissatisfied with life, whereas scores between 31-35 indicate the respondent is extremely satisfied.

  Baseline, halfway through (1.5 months), and post-intervention (3 months)

• Affect - Perceived Stress Scale

  Score is obtained by reverse-scoring items 4, 5, 7, and 8 and then summing the scores.

  Baseline, halfway through (1.5 months), and post-intervention (3 months)

• Affect - Apathy Evaluation Scale

  After recoding all necessary items, sum up all scores.

  Baseline, halfway through (1.5 months), and post-intervention (3 months)

• Brain Structure and Network Function

  Investigators will assess brain structure via a T1 MRI to measure cortical thickness in dorsolateral prefrontal, sensorimotor, and insular cortices using the CAT computational anatomy toolbox; brain network function via resting-state fMRI to capture functional segregation of dorsolateral prefrontal, sensorimotor, and insular networks (subserving cognition, mobility, and affect respectively) using the CONN toolbox.

  Baseline, and post-intervention (3 months)

• Blood-based AD pathology (Aβ17)

  Investigators will assess levels of Aβ17 \[units\], which is sensitive to AD. Blood samples will be processed on campus by UF's Florida Alzheimer's Disease Research Center Biomarker Core. Blood will be centrifuged and placed into -80°C storage maintained by the PIs. Coded blood samples will be analyzed in the final year of this project. These biomarker levels will not be shared with participants, as this is not a diagnostic laboratory.

  Baseline, and post-intervention (3 months)

• Blood-based AD pathology [p-tau]

  Investigators will assess levels of p-tau \[units\], which is sensitive to AD. Blood samples will be processed on campus by UF's Florida Alzheimer's Disease Research Center Biomarker Core. Blood will be centrifuged and placed into -80°C storage maintained by the PIs. Coded blood samples will be analyzed in the final year of this project. These biomarker levels will not be shared with participants, as this is not a diagnostic laboratory.

  Baseline, and post-intervention (3 months)

Study Arms (2)

Control

SHAM COMPARATOR

Participants in this group will receive white noise sensory stimulation rather than a constant flicker frequency.

Behavioral: Sham White Noise Stimulation

Flicker Stimulation

EXPERIMENTAL

Participants in this group will receive sensory visual plus auditory flicker stimulation.

Behavioral: Flicker Stimulation

Interventions

Flicker Stimulation BEHAVIORAL

Investigators will combine ultrasound (≥22 kHz) and near-infrared two-photon stimulation (890-940 nm) to deliver rhythmic input in a subliminal, comfortable manner, without the side effects associated with visible flicker.

Flicker Stimulation

Sham White Noise Stimulation BEHAVIORAL

The control group will receive white noise sensory stimulation rather than a constant flicker frequency.

Control

Eligibility Criteria

• Age: 65 Years - 89 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Community dwelling men and women 65-89 years old
• Ability to walk unassisted for 10 min
• English speaking
• No evidence of dementia or MCI based on cognitive screening (i.e., Montreal Cognitive Assessment (MoCA) score within normal limits for age, education, and sex using the NACC Uniform Data Set (UDS) norms8
• Global Clinic Dementia Rating (CDR) score must be 0 or 0.531
• Subjective report of cognitive complaints with scores \>20 on the Cognitive Change Index (CCI-20), a validated scale of subjective cognitive decline6; this scale consists of 20 items that are rated on a 5-point Likert scale, where 1= "Normal: No change compared to 5 years ago", 3= "Mild Problem: Some change compared to 5 years ago) and 5="Severe Problem: Much worse compared to 5 years ago"
• Family history of dementia/probable AD in first degree relative (parents, children, siblings)
• Normal functional behavior in terms of daily activities, based on the Functional Activities Scale32
• In line with recommendations of the SCD task force33 an informant must be available for two reasons: a) to provide information about the participant's cognition using the informant version of the CDR and CCI-20, and b) to corroborate normal IADL's on the Functional Activity Questionnaire32 (informant data will be collected via a phone call and linked by code with the participant data).

You may not qualify if:

• If participants score less than 21 on the Telephone Interview for Cognitive Status (TICS)
• Significant medical event requiring hospitalization in the past 6 months that has the potential to contaminate data being collected (fracture, hospitalization etc.)
• Severe visual impairment or corrected visual acuity less than 20/40, which would preclude completion of assessments
• Inability to undergo MRI brain imaging due to claustrophobia or implants such as pacemakers, heart valves, brain aneurysm clips, orthodontics, certain non-removable body jewelry, or shrapnel containing ferromagnetic metal
• History of severe stroke
• Any major ADL disability (unable to feed, dress, bath, use the toilet, or transfer)
• Report of lower extremity pain due to osteoarthritis that significantly limits mobility
• Diagnosis or treatment for rheumatoid arthritis
• Known neuromuscular disorder or overt neurological disease (e.g. Multiple Sclerosis, Rhabdomyolysis, Myasthenia Gravis, Ataxia, Apraxia, post-polio syndrome, mitochondrial myopathy, Parkinson's Disease, ALS etc.)
• Unable to communicate because of severe hearing loss or speech disorder
• Planned surgical procedure or hospitalization in the next 4 months (joint replacement, coronary artery bypass graft, etc.)
• Severe pulmonary disease, requiring the use of supplemental oxygen
• Terminal illness, as determined by a physician
• Severe cardiac disease, including NYHA Class III or IV congestive heart failure, clinically significant aortic stenosis, recent history of cardiac arrest, use of a cardiac defibrillator, or uncontrolled angina
• Use of walker or wheelchair

Sponsors & Collaborators

• University of Florida: lead

Study Sites (1)

University of Florida

Gainesville, Florida, 32611, United States

Location

Study Officials

• Rachael Seidler

  University of Florida

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachael Seidler

CONTACT

7348340385; rachaelseidler@ufl.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2025
• First Posted: February 9, 2026
• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): October 31, 2028
• Last Updated: April 28, 2026

Record last verified: 2025-08

Locations

US (1)