Olfactory Function and Delayed Neurocognitive Recovery

NCT ID: NCT03441074

Last Updated: 2025-07-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 131 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-01
• Study Completion Date: 2022-12-31

Brief Summary

To explore whether odor enrichment can reduce the risk of delayed neurocognitive recovery as an intervention strategy.

Detailed Description

Postoperative neurocognitive disorder, one of the most common postoperative complications in older adults, includes acute postoperative delirium, delayed neurocognitive recovery (within the 30 days recovery period, dNCR), and postoperative neurocognitive dysfunction (from expected recovery 30 days to 12 months). Previous studies showed that the incidence of dNCR ranged from 18% to 40% and is mainly characterized by cognitive impairment, which can develop into long-term cognitive impairment, even elevating the risk of Alzheimer's Disease (AD) related dementia and premature mortality. These symptoms can have significant adverse effects on quality of life and may increase the risk of other physical and psychological disorders, potentially impacting social stability. These statistics underscore the importance of early detection and timely intervention in mitigating the long-term effects of dNCR. Despite the significance of dNCR, effective treatment options remain elusive.

Based on these insights, previous studies have explored the impact of olfactory enrichment in animal models. Zhang et al. demonstrated that surgery and anesthesia could cause olfactory impairment, which might contribute to dNCR, while suggesting that odor enrichment, a non-pharmacological intervention, could reduce postoperative cognitive impairment in animal models. Olfactory enrichment, also known as olfactory training, is a safe and affordable treatment and may have preventative or supportive effects on olfactory function or cognitive function. Evidence supports its effectiveness in treating olfactory function from various causes and in reducing cognitive impairment.

Despite these findings, there is limited research on whether odor enrichment can serve as a mitigating strategy for dNCR among human populations. To address this gap, we conducted a clinical study to investigate whether odor enrichment could mitigate dNCR in geriatric patients and to explore the relationship between olfactory function and dNCR.

Conditions

Delayed Neurocognitive Recovery

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Intervention Group

Patients randomly assigned to intervention group will get odor enrichment during the perioperative period

Group Type: EXPERIMENTAL

Odor Enrichment

Intervention Type: BEHAVIORAL

Patients in intervention group will get odor enrichment during perioperative period (3 days before the surgery and 7 days after the surgery). Odor-enriched participants were exposed daily for 24 hours to different aromatic fragrances (phenyl ethyl alcohol - rose; eucalyptol - eucalyptus; citronellal - lemon; eugenol - cloves) referred to previous studies. Odors were changed for each subject after 24 hours. According to previous studies, 10 drops of the 100% essential oil (0.5 ml) were dropped on a fabric which was placed in tea bags hanging at the hospital bedside.

Non-intervention Group

Patients randomly assigned to non-intervention group will not get any odor enrichment during the perioperative period

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Odor Enrichment

Patients in intervention group will get odor enrichment during perioperative period (3 days before the surgery and 7 days after the surgery). Odor-enriched participants were exposed daily for 24 hours to different aromatic fragrances (phenyl ethyl alcohol - rose; eucalyptol - eucalyptus; citronellal - lemon; eugenol - cloves) referred to previous studies. Odors were changed for each subject after 24 hours. According to previous studies, 10 drops of the 100% essential oil (0.5 ml) were dropped on a fabric which was placed in tea bags hanging at the hospital bedside.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

1. were aged at least 65 years old;

2. were expected a postoperative hospital stay of at least 7 days;

3. had American Society of Anesthesiologist (ASA) class I to II;

4. were native Mandarin speakers;

5. had been referred for a total knee or hip replacement under general anesthesia.

Exclusion Criteria

1. were prior diagnosed of neurologic diseases by the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10);

2. had a history of mental disorders diagnosed using the Diagnostic and Statistical Manual of Mental Disorders (DSM-5);

3. had a history of illness or surgery with nasal or sinus;

4. caught cold within one week;

5. impaired vision or auditory function which may affect the assessments;

6. were unwilling to comply with the protocol or procedures;

7. did not pass the Mini-mental State Examination (illiterates get less than 18 points, primary school graduates get less than 20 points, secondary school graduates or higher get less than 24 points) .

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Shanghai 10th People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yuan Shen, MD, PhD

Chief of Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yuan Shen

Role: PRINCIPAL_INVESTIGATOR

Shanghai 10th People's Hospital

Locations

Shanghai Tenth People's Hospital

Shanghai, Shanghai Municipality, China

Countries

China

References

Kim MS, Yoon JH, Kim HJ, Yong SW, Hong JM. Olfactory dysfunction is related to postoperative delirium in Parkinson's disease. J Neural Transm (Vienna). 2016 Jun;123(6):589-94. doi: 10.1007/s00702-016-1555-0. Epub 2016 Apr 20.

Reference Type: BACKGROUND

PMID: 27098668 (View on PubMed)

Brown CH 4th, Morrissey C, Ono M, Yenokyan G, Selnes OA, Walston J, Max L, LaFlam A, Neufeld K, Gottesman RF, Hogue CW. Impaired olfaction and risk of delirium or cognitive decline after cardiac surgery. J Am Geriatr Soc. 2015 Jan;63(1):16-23. doi: 10.1111/jgs.13198.

Reference Type: BACKGROUND

PMID: 25597555 (View on PubMed)

Zhang C, Han Y, Liu X, Tan H, Dong Y, Zhang Y, Liang F, Zheng H, Crosby G, Culley DJ, Marcantonio ER, Shen Y, Cao JL, Xie Z. Odor Enrichment Attenuates the Anesthesia/Surgery-induced Cognitive Impairment. Ann Surg. 2023 Jun 1;277(6):e1387-e1396. doi: 10.1097/SLA.0000000000005599. Epub 2022 Jul 18.

Reference Type: BACKGROUND

PMID: 35848747 (View on PubMed)

Pieniak M, Oleszkiewicz A, Avaro V, Calegari F, Hummel T. Olfactory training - Thirteen years of research reviewed. Neurosci Biobehav Rev. 2022 Oct;141:104853. doi: 10.1016/j.neubiorev.2022.104853. Epub 2022 Sep 5.

Reference Type: BACKGROUND

PMID: 36064146 (View on PubMed)

Other Identifiers

dsyy003

Identifier Type: -

Identifier Source: org_study_id