The proposed study is to evaluate initial efficacy and safety of the BBB disruption with transcranial MRI-guided focused ultrasound (ExAblate 4000 type 2.0) in patients with Alzheimer's disease.

This study iw designed as a prospective, single-site, single-aarm, nonrandomized study. Assessments will be made before and three months after 2 sessions of BBB disruption with radiologic, nuclear medicine imaging and neurophysiological examinations. Relative safety will be evaluated using a common description of Significant Clinical Complications for patients treated in this study.

Inclusion Criteria:

• Age between 50 and 85 years, inclusive.
• Total score of 23 or less on the Korean version of Mini Mental state Exam (K-MMSE)
• FBB (18F-Florbetaben)-PET test result positive
• FDB (18F-Fluorodeoxyglucose)-PET test results suspected of Alzheimer disease-induced neurodegeneration
• Mild cognitive impairment or dementia caused by Alzheimer's disease
• A participant who has been given a drug at a stable dose for at least three months to improve symptoms of Alzheimer's disease
• Able to communicate during the ExAblate BBB disruption procedure
• Able and willing to give informed consent
• Able to attend all study visits

Exclusion Criteria:

• CGA-NPI (Caregiver-Administrated Neuropsychiatry Inventory) severity score of more than 2 points for any of "Delusion", "Hallucination" or "Agitation/Aggression"

• Known sensitivity/allergy or contraindications to MRI contrast agent(Gadovist®) or the ultrasound contrast agent (Definity®)

• Contraindications to MRI such as non-MRI compatible implanted devices.

• Any of the following items in MRI

  1. severe ischemic changes
  2. active or chronic infection/inflammation
  3. acute or chronic hemorrhage
  4. tumor/space occupying lesion
  5. meningeal enhancement
  6. intracranial hypotension

• More than 30% of the skull area traversed by the sonication pathway is covered by scars, scalp disorders (e.g., eczema), or atrophy of the scalp

• Active seizure disorder or epilepsy (seizures despite medical treatment)

• History of a bleeding disorder, coagulopathy

• Cardiac disease or unstable hemodynamics

• Severely impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2

• Severe brain atrophy

• HIV (Human immunodeficiency virus) positive, who have a high probability of developing HIV encephalitis due to the influx of HIV in to the brain parenchyma

• Subjects with evidence of cranial or systemic infection

• A homozygosity of Apolipoprotein E allele (ApoE4) known to have a thin blood-brain barrier

• Positive pregnancy test (women of childbearing potential)

• A participant in other clinical trials or have experience in other clinical trials within 90 days from the screening date