Transcranial Magnetic Stimulation to Slow Down Cognitive Decline in Alzheimer's Disease

Transcranial Magnetic Stimulation (TMS) to Slow Down Cognitive Decline in Alzheimer's Disease (AD): TMSLA - a Monocentric Randomized Controlled Trial.

New amyloid-targeting drugs for Alzheimer's disease (AD) offer minimal or unclear efficacy and often cause adverse events, highlighting the need for new therapies. In recent years, repetitive transcranial magnetic stimulation (rTMS) has shown increasing success. A recent randomized, double-blind, sham-controlled, phase 2 demonstrated promising results from a 24-week rTMS treatment protocol targeting the precuneus. This brain region is considered a main hub of the human brain connectome and a prominent area of AD pathology. The results showed stable cognitive performance and increased brain activity in the treatment group, whereas the sham group worsened. A replication study is planned to further investigate the working mechanism of precuneus-rTMS in AD and to improve understanding of its therapeutic potential.

Inclusion Criteria:

• Biomarker-supported Alzheimer's disease (abnormal CSF p-tau/Aβ42 ratio of > 0.023 or amyloid PET positive).
• Between 50 and 85 years old.
• Clinical Dementia Rating (CDR) score of 0.5 or 1.
• Mini-Mental State Examination (MMSE) score between 18 and 27.
• Presence of a caregiver.

Exclusion Criteria:

• Medical history of neurodegenerative diseases other than AD, stroke, or epilepsy.
• Severe psychiatric dysregulation, hampering successful study participation and leading to possible cognitive impairment. Eligibility for participation will be based on clinical evaluation by an expert neurologist and/or psychiatrist.
• Extensive cerebrovascular damage on MRI classified as Fazekas level 2 or 3. Patients with abnormalities classified as Fazekas level 3 are excluded. For Fazekas level 2, patient's eligibility for participation will be evaluated by an expert neurologist.
• Presence of metal in the head or cranial/thoracic implants, including cochlear implants.
• Cholinesterase inhibitors with unstable dosage in the last 2 months.
• Extreme claustrophobia or metallic objects in or on the body, preventing MRI and MEG examination.
• Previous rTMS treatment (for blinding reasons).