High Frequency Stimulation to Improve Cognition, Mobility, and Affect in Individuals With and Without Subjective Cognitive Decline

The goal is to determine whether three months of at least three times / week of sensory flicker stimulation improves cognition, mobility, and affect in healthy older adults and older adults with and without Subjective Cognitive Decline (SCD). 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).

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Subjects; Subjective Cognitive Decline (SCD)
• Intervention / Treatment: Behavioral: Flicker Stimulation; Behavioral: Control Stimulation; Behavioral: 40 Hz Visual Occlusion; Behavioral: Control - Visual Occlusion

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rachael Seidler; Phone Number: 7348340385; Email: rachaelseidler@ufl.edu

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32611
      • University of Florida
      • Contact: Rachael Seidler; Phone Number: 734-834-0385; Email: rachaelseidler@ufl.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Community dwelling men and women 65-89 years old
• Ability to walk unassisted for 10 min
• English speaking

Additional Inclusion Criteria for SCD:

• 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).

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Control; Participants in this group will receive control stimulation rather than a constant flicker frequency.	Behavioral: Control Stimulation; The control group will receive a control stimulation rather than a constant flicker frequency.
Experimental: 40 Hz Visual Occlusion; Participants will wear visual occlusion glasses with visible flickering.	Behavioral: 40 Hz Visual Occlusion; Participant will wear visual occlusion glasses with visible stimulation flickering at 40 Hz
Sham Comparator: Control - Visual Occlusion; Participants will receive visual stimulation at a control frequency that is not 40 Hz	Behavioral: Control - Visual Occlusion; Participants will receive visible stimulation at a frequency that is not 40 Hz.
Experimental: Flicker Stimulation - Infrared; Participants in this group will receive infrared sensory visual flicker stimulation.	Behavioral: Flicker Stimulation; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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; - A little; - Moderately; - Quite a Lot; - 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)
Cognition	Investigators will comprehensively assess behavior at three times (baseline, half-way through (1.5 months), and after the intervention (3months)) using the TabCAT. Composite Scores will serve as primary metrics for cognition.	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, halfway through (1.5 months), 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, halfway through (1.5 months), 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, halfway through (1.5 months), and post-intervention (3 months)

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Rachael Seidler, University of Florida

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): October 31, 2028

Study Registration Dates

• First Submitted: September 10, 2025
• First Submitted That Met QC Criteria: February 5, 2026
• First Posted (Actual): February 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: IRB202500587

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