tFUS for Memory in mNCD and Healthy Adults

Dementia is an ongoing and growing public health crisis in the US and worldwide. Currently, there are an estimated 6.2 million Americans living with Alzheimer's Disease (AD) the most common form of dementia accounting for roughly 75% of cases. With a growing aging population, this number is estimated to be 13.8 million in the US and 152.8 million people worldwide by 2050 with a 14% lifetime prevalence. It is difficult to treat AD, making it critical to intervene as early as possible. Mild neurocognitive disorder (mNCD) is an early stage of memory and cognitive ability loss that is more severe than normal cognitive decline due to aging. Each year, approximately 15% of people with mNCD develop dementia, making it a critical juncture where intervention could be particularly impactful. Previous research has utilized a novel technique, called transcranial focused ultrasound (tFUS), to change brain function and has measured changes to brain activity through electroencephalography (EEG) using scalp electrodes. This study will apply tFUS to the hippocampus to examine the effects on memory in healthy adults in mNCD.

Inclusion criteria

for Healthy Older Adults

• Age 50-85
• English as a first/primary language
• Capacity to consent
• No Diagnosis of mNCD or dementia

Exclusion criteria

for Healthy Older Adults

• Current substance use disorder, bipolar disorder, or schizophrenia spectrum or other psychotic diagnosis
• Daily/weekly anticholinergic or sedative use. Stimulants may be used pending investigator review. Cholinesterase inhibitors, NMDA receptor antagonists, and antidepressants are allowed if on a stable regimen for 4 weeks prior to enrollment
• History of significant or unstable conditions that may impact cognition, such as significant cardiac, cerebrovascular, or metabolic disease, developmental disorder, or other neurologic disease (e.g., moderate to severe TBI, seizures)
• MRI or tFUS contraindications (e.g., metal implants, claustrophobia, conditions or treatments that lower seizure threshold, taking medications that have short half-lives)
• Enrolled in a clinical trial or has received an investigational medication or device in the last 30 days

Inclusion criteria

for mNCD

• Age 50-85
• English as a first/primary language
• Diagnosed with mNCD by a healthcare provider within the past 2 years per NIA-AA or DSM-5 criteria
• Has ≥ 2 impaired scores within one cognitive domain OR ≥ 1 impaired score in ≥ 3 domains, where impaired score is defined as ≤ 16th percentile using demographically-corrected norms
• Must have a co-participant (e.g., spouse, adult child, relative, sibling, cohabitor, friend, or caregiver) with at least weekly in-person contact with the participant

Exclusion criteria

for mNCD

• Prior diagnosis of dementia or major neurocognitive disorder per NIA-AA or DSM-5 criteria, and telephone interview for cognitive status (TICS) score ≤ 22
• Current substance use disorder, bipolar disorder, or schizophrenia spectrum or other psychotic diagnosis
• Daily/weekly anticholinergic or sedative use. Stimulants may be used pending investigator review. Cholinesterase inhibitors, NMDA receptor antagonists, and antidepressants are allowed if on a stable regimen for 4 weeks prior to enrollment
• History of significant or unstable conditions that may impact cognition, such as significant cardiac, cerebrovascular, or metabolic disease, developmental disorder, or other neurologic disease (e.g., moderate to severe TBI, seizures)
• MRI or tFUS contraindications (e.g., metal implants, claustrophobia, conditions or treatments than lower seizure threshold, taking medications that have short half-lives)
• Enrolled in a clinical trial or has received an investigational medication or device in the last 30 days