rTMS in Older Adults With MCI and AUD

Targeting the Shared Substrates of Alcohol Misuse and Cognitive Impairment: Accelerated rTMS for Older Adults With Alcohol Use Disorder

Alcohol misuse is a risk factor for early onset cognitive impairment, contributing to 10% of early onset dementia, with risk corresponding to consumption. Additionally, continued drinking risks worsening cognitive decline and dementia progression, while worsening cognitive impairment contributes to drinking escalation. Repetitive transcranial magnetic stimulation (rTMS) has been shown to improve cognition in Alzheimer's Disease and Related Dimentias (ADRD) and separately reduce heavy drinking in alcohol use disorder. Our objective is to optimize rTMS for simultaneous mitigation of both drinking and cognitive dysfunction in older adults.

Alcohol misuse is a risk factor for early onset cognitive impairment, contributing to 10% of early onset dementia, with risk corresponding to consumption. Additionally, continued drinking risks worsening cognitive decline and dementia progression, while worsening cognitive impairment contributes to drinking escalation. Notably, there exists no intervention targeting the intersection of alcohol misuse and cognitive dysfunction in older adults. It is unclear whether alcohol contributes to a specific form of Alzheimer's Disease and Related Dementias (ADRD) and furthermore whether the impairments and structural brain changes represent classical ADRD neurodegenerative patterns. Despite the unclear etiopathogenesis, there is emerging evidence that repetitive transcranial magnetic stimulation (rTMS) to upregulate executive/cognitive control circuitry can improve cognition in ADRD, and separately reduce heavy drinking in AUD. Our long-term objective is to optimize rTMS for simultaneous mitigation of both drinking and cognitive dysfunction in older adults towards breaking this cycle and thwarting progression to dementia.

Inclusion Criteria:

• Age 60-85.
• English as a first/primary language.
• Current alcohol use disorder
• Alcohol consumption of at least 4 heavy drinking days (defined as ≥ 4 drinks for women and ≥ 5 for men) per week during the 30-days prior to enrolling;
• Meets actuarial neuropsychological criteria for MCI: ≥2 impaired scores within one cognitive domain, or ≥1 impaired scores in ≥3 domains, where an impaired score is defined as ≤16th percentile using demographically-corrected norms.
• Not pregnant (will administer pregnancy test to confirm)
• Functional visual and auditory acuity to complete all assessments.

Exclusion Criteria:

• Prior diagnosis of Dementia or Major Neurocognitive Disorder per NIA-AA or DSM-5 criteria, and TICS ≤ 22 suggestive of dementia.
• Current substance use disorder other than AUD or nicotine use disorder, bipolar disorder, or schizophrenia spectrum or other psychotic disorder.
• Daily/weekly anticholinergic or sedative use. Stimulants may be allowed pending investigator review. Cholinesterase inhibitors, NMDA receptor antagonists, and antidepressants are allowed if on a stable regimen of 4 weeks prior to enrollment.
• History of significant or unstable condition/s that may impact cognition such as significant cardiac, cerebrovascular, or metabolic disease, developmental disorder, or other neurologic disease (e.g. movement disorder, moderate to severe brain injury, seizures).
• MRI and TMS contraindications (e.g. implants, claustrophobia, conditions/treatments that lower seizure threshold, taking medications that have short half-lives, no identifiable motor threshold).
• Enrolled in a clinical trial or has received an investigational medication or device in the last 30 days.
• Pregnant (will administer pregnancy test to confirm)