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NCT Number: NCT07036328

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

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.

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Key information

Conditions

Alzheimer Disease Alzheimer Disease, Early Onset Brain Diseases Central Nervous System Diseases Dementia Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Tauopathies

Age range

50 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

repetitive transcranial magnetic stimulation

Device

20 Hz repetitive transcranial magnetic stimulation targeted at the precuneus

Sham repetitive transcranial magnetic stimulation

Device

20 Hz sham repetitive transcranial magnetic stimulation targeted at the precuneus

Primary outcomes

  1. CDR - Sum of Boxes

    Time frame: from enrollment to 3 month follow-up

    Clinical dementia rating - sum of boxes

Secondary outcomes

  1. Magnetoencephalography (MEG): Spectral analysis

    Time frame: from baseline to week 24 (post-treatment)

    Power spectral density (µV²/Hz) computed for different frequency bands .

  2. Cerebrospinal fluid (CSF) biomarkers

    Time frame: from baseline to week 24 (post-treatment)

    Cerebrospinal fluid (CSF) biomarkers are typically reported in picograms per milliliter (pg/mL). This applies to:

    Amyloid-beta (Aβ₁-₄₂): pg/mL Total tau (t-tau): pg/mL Phosphorylated tau (p-tau, e.g., p-tau181): pg/mL

  3. Neuropsychological evaluation: Trail Making Test

    Time frame: from baseline to week 24 (post-treatment)

    Assesses visual attention, processing speed, and task switching. Unit: Seconds (completion time)

  4. Amsterdam instrumental activities of daily living questionnaire (AmsterdamiADL);

    Time frame: baseline to 3 month follow-up

    The Amsterdam Instrumental Activities of Daily Living (A-IADL) Questionnaire is a validated tool that assesses cognitive functioning through everyday tasks, with scores ranging from approximately 20 (severe impairment) to 70 (no impairment).

  5. Mini mental state examination (MMSE)

    Time frame: baseline to 3-month follow up.

    The mini-mental state examination (MMSE) test is a 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. Higher is better.

  6. Neuropsychiatric Inventory Questionnaire (NPI-Q)

    Time frame: baseline to 3 month follow up

    The Neuropsychiatric Inventory Questionnaire (NPI-Q) is a brief, informant-based tool that assesses 12 neuropsychiatric symptoms in dementia, with total severity scores ranging from 0 to 36 and distress scores from 0 to 60.

  7. Quick Inventory of Depressive Symptomatology (QIDS)

    Time frame: baseline to 3-month follow up

    The Quick Inventory of Depressive Symptomatology (QIDS) is a clinician-rated tool that measures the severity of depressive symptoms, with total scores ranging from 0 (no depression) to 27 (severe depression).

  8. Magnetoencephalography (MEG): Corrected Amplitude Envelope Correlation (AEC-c)

    Time frame: From baseline to week 24 (post-treatment)

    Correlation of the amplitude envelopes of band-pass filtered signals, corrected for signal leakage.

  9. Magnetoencephalography (MEG): Phase Lag Index (PLI)

    Time frame: baseline to week 24 (post-treatment)

    A measure of phase synchronization that is robust to volume conduction.

  10. Magnetoencephalography (MEG): Joint Permutation Entropy (JPE)

    Time frame: baseline to week 24 (post-treatment)

    A nonlinear measure of signal complexity and diversity in joint time series.

  11. Neuropsychological evaluation: Verbal Fluency Test

    Time frame: baseline to week 24 (post-treatment)

    Measures verbal production and executive functioning.

    Phonemic fluency (letters D, A, T) Unit: Number of words per 1 minute

    Semantic fluency (animals) Unit: Number of words per 1 minute

  12. Neuropsychological evaluation: Visual Association Test (VAT)

    Time frame: baseline to week 24 (post-treatment)

    Detects signs of anterograde amnesia through object-pair associations. Unit: Number of correct associations (maximum score: 12)

  13. Neuropsychological evaluation: Stroop Color and Word Test

    Time frame: baseline to week 24 (post-treament)

    Evaluates cognitive flexibility, inhibition, and processing speed. Unit: Seconds (per condition), Errors (count)

  14. Neuropsychological evaluation: WAIS-III Digit Span (Forward and Backward)

    Time frame: baseline to week 24 (post-treatment)

    Assesses attention and verbal working memory. Unit: Span length (maximum correctly repeated digit sequences)

  15. Neuropsychological evaluation: Rey Auditory Verbal Learning Test (RAVLT)

    Time frame: baseling to week 24 (post-treatment)

    Evaluates verbal learning and declarative memory.

    Immediate recall (Trials I-V) Unit: Total number of words recalled

    Delayed recall Unit: Number of words recalled

    Recognition Unit: Number of correct recognitions

Study contacts

Contact information is provided by the study sponsor or research team.

Willem De Haan, PhD

CONTACT

[email protected]

020-444 8548

Sponsors and collaborators

Lead sponsor

Willem de Haan

Other

Registry information

Official study title

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

Acronym: TMSLA

Important dates

Study start
2025
Primary completion
2028
Study completion
2028
First posted
Jun 25, 2025
Registry last updated
May 12, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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