Cognitive Impairment, Delayed Neurocognitive Recovery, Older Patients, Postoperative Neurocognitive Disorder, Repetitive Transcranial Magnetic Stimulation
Conditions
Keywords
Older patients, Cognitive impairment, Repetitive transcranial magnetic stimulation, Delayed neurocognitive recovery, Postoperative neurocognitive disorder
Brief summary
Patients with preoperative cognitive impairment are at increased risks of delayed neurocognitive recovery (DNR) and postoperative neurocognitive disorder (POCD). Repetitive transcranial magnetic stimulation (rTMS) has been used to improve cognitive function in patients with cognitive impairement. This trial is designed to compare the effects of rTMS versus sham intervention on postoperative neurocognitive function in patients with preoperative cognitive impairment.
Detailed description
Mild cognitive impairment (MCI) affects 10-15% of the population over 65 years old. In patients for elective non-cardiac and emergency surgeries, the pooled prevalences of unrecognized cognitive impairment were 37.0% and 50.0%, respectively. Patients with preoperative cognitive impairment are at increased risk of delayed neurocognitive recovery (DNR) and postoperative neurocognitive disorder (POCD). Therefore, perioperative neurocognitive protection is particularly important for patients with preoperative cognitive impairment. Repetitive transcranial magnetic stimulation (rTMS) is a neural modulation technique. By acting on the brain and altering the membrane potential of cortical neurons, the generated pulsed magnetic fields affect neural metabolism and electrical activity and trigger a series of physiological and biochemical reactions. It was found that high frequency (\>5 Hz) rTMS increases cortical excitability, whereas low frequency (\<1Hz) rTMS reduces corticol excitability. The mechanism by which rTMS regulates brain function is generally believed to be related to the long-term enhancement and long-term inhibition of synaptic transmission function. The left dorsolateral prefrontal cortex (DLPFC) is an important target of rTMS intervention for improving cognitive function. A meta-analysis showed that high-frequency rTMS on the DLPFC and low-frequency rTMS on the right medial prefrontal cortex improved memory function; high frequency rTMS on the right inferior frontal gyrus enhanced executive ability in non-surgical patients with mild cognitive impairment or Alzheimer's disease. Another meta-analysis showed that high-frequency rTMS on DLPFC is an effective therapeutic option for improving cognitive function in Alzheimer patients. This trial is designed to compare the effects of rTMS versus sham intervention on postoperative neurocognitive function in patients with preoperative cognitive impairment.
Interventions
DEVICERepetitive transcranial magnetic stimulation
Repeated transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex (DLPFC) for a 5-day period (1 day before surgery and 4 consecutive days after surgery, twice daily \[10-12 am and 6-8 pm\], no intervention on the day of the surgery). Parameters of rTMS: 8 shaped coil, 10 Hz, 80% resting motor threshold (RMT), 2000 pulses (5s × 40 trains, 25 s interval), 20 minutes.
DEVICESham stimulation
Sham repeated transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex (DLPFC) for a 5-day period (1 day before surgery and 4 consecutive days after surgery, twice daily \[10-12 am and 6-8 pm\], no intervention on the day of the surgery). Parameters of rTMS: 8 shaped sham coil, 10 Hz, 80% resting motor threshold (RMT), 2000 pulses (5s × 40 trains, 25 s interval), 20 minutes.
Sponsors
The First Affiliated Hospital of Air Force Medicial University
Peking University Shenzhen Hospital
Peking University First Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged ≥65 years; 2. Patients with preoperative mild to moderate cognitive impairment, defined as 9\<Montreal Cognitive Assessment (MoCA)\<26; 3. Scheduled for elective non-cardiac surgery under general anesthesia, with an expected surgical duration of \>2 hours; 4. Expected to stay in hospital for at least 5 days after surgery.
Exclusion criteria
1. Left-handed; 2. Primary school education level or below; 3. Comorbid diseases including mental illness, intellectual disability, auditory and visual dysfunction, language impairment, severe neurological disorders, or other diseases that impede the completion of evaluation; 4. Neurosurgery; 5. Presence of contraindications to rTMS treatment, including epilepsy, pregnant or lactating women, or with a metal or electric implanted device (e.g., deep brain stimulator, ventriculoperitoneal shunt, aneurysm clip, pacemaker, cochlear implant, or surgical staples on the scalp); 6. Other situations that are deemed unsuitable for inclusion in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of delayed neurocognitive recovery | On the 5th day after surgery | Cognitive function is assessed with the Montreal Cognitive Assessment (MoCA; scores range from 0 to 30, with higher score indicating better function) before surgery and at 5 days after surgery. A MoCA score reduction of 1 standard deviation (SD) or more from baseline is defined as occurrence of delayed neurocognitive recovery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of delirium | Within 5 days after surgery | Delirium is assessed with the 3D-Confusion Assessment Method (for non-intubated patients) or Confusion Assessment Method for the Intensive Care Unit (for intubated patients) twice daily (8-10 am and 4-6 pm). |
| Incidence of postoperative neurocognitive disorder at 30 days after surgery | On the 30(±3)th day after surgery | Cognitive function is assessed with the Telephone Montreal Cognitive Assessment (T-MoCA; scores range from 0 to 22, with higher score indicating better function) at 30±3 days after surgery. A T-MoCA score reduction of 1 standard deviation (SD) or more from baseline is defined as occurrence of postoperative neurocognitive disorder. |
| Incidence of postoperative neurocognitive disorder at 180 days after surgery | On the 180(±15)th day after surgery | Cognitive function is assessed with the Telephone Montreal Cognitive Assessment (T-MoCA; scores range from 0 to 22, with higher score indicating better function) at 180±15 days after surgery. A T-MoCA score reduction of 1 standard deviation (SD) or more from baseline is defined as occurrence of postoperative neurocognitive disorder. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Quality of life at 180 days after surgery | On the 180(±15)th day after surgery | Quality of life is assessed with the World Health Organization Quality of Life brief version (WHOQOL-BREF), a 24-item questionnaire that assesses the quality of life in physical, psychological, and social relationship, and environmental domains. The score ranges from 0 to 100 for each domain, with higher score indicating better function. |
| Pain intensity within 5 days after surgery | Up to 5 days after surgery | Pain intnsity is assessed with the Numerical Rating Scale (NRS, an 11-point scale where 0 = no pain and 10 = the worst pain) twice daily (8-10 am and 4-6 pm) during the first 5 days after surgery. |
| Event-free survival within 180 days after surgery | Up to 180 days after surgery | Time interval from index surgery to cancer recurrence/metastasis/progression, new-onset cancer, new-onset serious illness (requiring hospitalization), or all-cause death, whichever comes first. |
| Length hospital stay after surgery | Up to 30 days after surgery | Length hospital stay after surgery. |
| Incidences of complications within 30 days after surgery | Up 30 days after surgery | Postoperative complications are defined as new-onset medical events other than delirium that are deemed harmful and require therapeutic intervention, that is grade II or higher on the Clavien-Dindo classification. |
| Quality of life at 30 days after surgery | On the 30(±3)th day after surgery | Quality of life is assessed with the World Health Organization Quality of Life brief version (WHOQOL-BREF), a 24-item questionnaire that assesses the quality of life in physical, psychological, and social relationship, and environmental domains. The score ranges from 0 to 100 for each domain, with higher score indicating better function. |
Countries
China
Contacts
Primary ContactDong-Xin Wang, MD, PhD
Backup ContactHao Kong, MD
Outcome results
None listed