Personalized Intermittent Theta Burst Stimulation for Cognitive Impairment Related to Cerebral Small Vessel Disease

This study will evaluate whether personalized intermittent theta burst stimulation (iTBS), a form of noninvasive transcranial magnetic stimulation, can safely improve cognitive function in people with cognitive impairment related to cerebral small vessel disease. The study will enroll 160 adults aged 45-85 years with mild cognitive impairment or mild vascular dementia related to cerebral small vessel disease. Participants will be randomly assigned in equal numbers to receive active iTBS or sham stimulation. Brain magnetic resonance imaging (MRI) will be used to identify an individualized stimulation target in the left prefrontal cortex. Sham stimulation will mimic the treatment experience without delivering effective magnetic stimulation. Participants and outcome assessors will not know which treatment participants receive. Treatment will last 24 weeks. Participants will receive four stimulation sessions per day for five consecutive days during the first week, followed by four sessions on one day each week during weeks 2-24. Cognitive assessments will be performed before treatment, during treatment, at the end of treatment, and three months after treatment ends. The main outcome is the change in Montreal Cognitive Assessment (MoCA) score from baseline to week 24. Brain MRI, electroencephalography (EEG), and adverse event monitoring will be used to examine changes in brain function and treatment safety.

Inclusion Criteria: 1. Aged 45-85 years, of either sex. 2. Cognitive decline in memory or another cognitive domain, reported by the participant or an informant, lasting at least three months; brain MRI evidence of cerebral small vessel disease (CSVD); and a diagnosis of CSVD-related vascular cognitive impairment. 3. Vascular mild cognitive impairment or mild vascular dementia. Vascular mild cognitive impairment is defined as impairment in one or more cognitive domains with largely preserved independence in daily activities. Mild vascular dementia is defined as cognitive impairment that mildly affects instrumental activities of daily living or activities of daily living, while the participant remains able to complete study assessments and treatment. 4. Neuropsychological evidence of cognitive impairment: Mini-Mental State Examination (MMSE) score ≥18 and \