The Efficacy of Modified Olfactory Training for MCI High-Risk Individuals

Assessing Modified Olfactory Training to Prevent Cognitive Decline in MCI High-Risk Individuals: A Randomized Controlled Trial Protocol

The goal of this clinical trial is to validate the effectiveness of the modified olfactory training device, the main questions it aims to answer are: Is it possible that the device can delay the progression of MCI in older adults? Compared to the conventional device, how efficient is the modified olfactory training device for improving cognitive function?

Study Overview

• Status: Not yet recruiting
• Conditions: Mild Cognitive Impairment (MCI); ELDERLY PEOPLE; Subjective Cognitive Decline (SCD); Olfactory Dysfunction
• Intervention / Treatment: Combination product: Modified olfactory training device; Combination product: Conventional olfactory training device

Detailed Description

Mild Cognitive Impairment (MCI) represents an intermediary stage between normal aging and dementia, with a significant proportion of cases progressing to dementia. No simple and effective therapeutic strategies are available to halt or reverse this progression. Olfactory dysfunction, a common early clinical manifestation of neurodegenerative diseases such as Alzheimer's Disease (AD), often precedes cognitive decline. Subjective Cognitive Decline (SCD) is increasingly recognized as a prodromal stage of MCI and dementia, which, together with olfactory dysfunction, provides a critical window for early intervention.

Conventional olfactory training (COT) has been shown to improve olfactory function, cognitive abilities, and brain connectivity in healthy elderly individuals, suggesting its potential to enhance neuroplasticity. Preliminary studies indicate that modified olfactory training (MOT) may yield superior outcomes compared to COT, with higher rates of olfactory recovery and improved deposition in the olfactory fissure. However, the efficacy of MOT in delaying or preventing the progression of olfactory dysfunction to MCI remains unclear.

In this study, the investigators planned to recruit 114 patients and divided them into three groups for control group and olfactory training with conventional and modified devices, and validate the effectiveness of the modified device based on changes in cognitive function and the comparison of the outcomes of the three groups.

• Study Type: Interventional
• Enrollment (Estimated): 114
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dawei Wu; Phone Number: 13522503401; Email: davidwuorl@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100191
      • Dawei Wu
      • Principal Investigator: Dawei Wu, MD, PhD
      • Contact: Dawei Wu, MD, PhD; Phone Number: +86 13522503401; Email: davidwuorl@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age and Gender: Individuals aged 60-80 years, regardless of gender.
2. Diagnosis of Idiopathic Olfactory Dysfunction: overall TDI score below 30.75 points using the Sniffin' Sticks test. Without olfactory impairment due to traumatic, sinusitis-related, congenital, toxic/drug-induced causes, post-operative conditions, tumors, or post-upper respiratory infections.
3. Diagnosis of Subjective Cognitive Decline: Montreal Cognitive Assessment (MoCA) score >24 for middle school level and above, >19 for elementary school level, and >13 for illiterate individuals. Amyloid β (Aβ) deposition in the brain (defined as Aβ42 < 550 ∼ 813 pg/ml)， the higher Formula of Hulstaert (defined as [(Aβ42/(240 + 1.18 × tau) ≤1]）, and hippocampus atrophy.
4. Consent: Willingness to sign an informed consent form.

Exclusion Criteria:

1. Comorbid Chronic Diseases or Severe Concurrent Illnesses: Individuals with conditions such as hypertension, diabetes, bronchopneumonia, malignant tumors， or chronic obstructive pulmonary disease.

4. Recent Medication Use: Exclusion of participants who have taken corticosteroids, antimicrobials, leukotriene antagonists, or antihistamines within the last four weeks.

5. Inability to Comply with Study Requirements: Based on the researcher's judgment, individuals who are unable to tolerate olfactory function tests and treatment， complete the study or comply with its requirements due to memory or behavioral abnormalities, depression, severe alcohol consumption, or previous non-compliance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: the Modified Olfactory Training Group; Participants will use a modified olfactory training device based on expiratory pressure. Four odors will be used: rose, mint, lemon, and clove. Each odorant is sniffed for 10 seconds per session, with a 10-second interval between odors. Each training session lasts 5 minutes and is conducted twice daily, before breakfast and at bedtime, for a duration of two years.	Combination product: Modified olfactory training device; Participants will use a modified olfactory training device based on expiratory pressure. The advantages of the improved device are as follows: bi-directional airflow, positive pressure and the function of voice prompts and automatic counting.
Active Comparator: the Conventional Training Group; Patients will receive the conventional olfactory training device. Patients had to sniff one odor for approximately 10 seconds and turn to another after a rest of 10 seconds. Each training session lasts 5 minutes and is conducted twice daily, before breakfast and at bedtime, for a duration of two years.	Combination product: Conventional olfactory training device; This device involves four brown glass jars (total volume 5 mL) with one of the four odors in each (1mL each, soaked in cotton pads to prevent spilling). The following odors were used: phenyl ethyl alcohol (PEA): rose, menthol: mint, citronellal: lemon, and eugenol: cloves. All jars were labeled with the odor name.
No Intervention: the Control Group; Participants will not receive any olfactory training and will be advised to observe and wait for spontaneous recovery of olfactory function.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montreal Cognitive Assessment (MoCA) score	The MoCA score will be used to evaluate cognitive function across several domains including memory, attention, language, and orientation.	Baseline,Month 3,Month 6,Month 12,Month 24
Biomarkers of cognition (Blood/CSF)	This measure includes plasma and CSF levels of UGOT p-tau217, CSF Aβ42, p-tau181, total tau, and amyloid β 42 to total tau ratios. These biomarkers will help in assessing the biochemical progression of cognitive impairment.	Baseline,Month 3,Month 6,Month 12,Month 24
Neuroimaging assessments	This includes MRI scans focusing on temporal lobes and other brain regions, and amyloid PET scans to detect amyloid plaques. These imaging techniques will provide insights into structural and functional changes in the brain associated with cognitive decline.	Baseline,Month 3,Month 6,Month 12,Month 24
The Sniffin' Sticks test	a clinically significant olfactory improvement as measured by Sniffin' Sticks threshold, discrimination, and identification（TDI)( more than 6 scores)	Baseline,Month 3,Month 6,Month 12,Month 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Auditory Verbal Learning Test (AVLT)	Evaluates immediate memory recall, learning rate, and delayed recall, providing insights into verbal learning and memory.	Baseline,Month 3,Month 6,Month 12,Month 24
Digit Span Test (DST)	Assesses attention and working memory through forward and backward number recall tasks.	Baseline,Month 3,Month 6,Month 12,Month 24
Trail Making Test (TMT)	Measures visual attention and task switching by requiring participants to connect a sequence of numbers and letters as quickly as possible.	Baseline,Month 3,Month 6,Month 12,Month 24
Clock Drawing Test (CDT)	Used to assess visual-spatial abilities and executive function by having participants draw a clock showing a specific time.	Baseline,Month 3,Month 6,Month 12,Month 24
Boston Naming Test (BNT)	Measures language function, specifically object naming ability, which is crucial for everyday communication.	Baseline,Month 3,Month 6,Month 12,Month 24
Verbal Fluency Test (VFT)	Assesses cognitive flexibility and semantic memory by requiring participants to generate as many words as possible from a category in a limited time.	Baseline,Month 3,Month 6,Month 12,Month 24
Activities of Daily Living Scale (ADL)	Evaluates the participant's ability to perform everyday tasks independently, reflecting functional status.	Baseline,Month 3,Month 6,Month 12,Month 24
Instrumental Activities of Daily Living (IADL)	Assesses more complex daily living skills critical for independent living, such as managing finances and medication.	Baseline,Month 3,Month 6,Month 12,Month 24
Neuropsychiatric Inventory (NPI)	Measures behavioral changes including depression, anxiety, aggression, and apathy among others, providing a comprehensive overview of psychological status.	Baseline,Month 3,Month 6,Month 12,Month 24
Hamilton Anxiety Scale (HAMA)	Assesses the severity of anxiety symptoms, which can impact cognitive and daily functioning.	Baseline,Month 3,Month 6,Month 12,Month 24
Hamilton Depression Scale (HAMD)	Used to quantify the level of depressive symptoms, aiding in the assessment of mood disorders which can co-occur with cognitive decline.	Baseline,Month 3,Month 6,Month 12,Month 24
Olfactory bulb volume	Measurement of the olfactory bulb volume using MRI to assess changes or improvements in olfactory structures which might correlate with training efficacy.	Baseline,Month 3,Month 6,Month 12,Month 24

Collaborators and Investigators

• Sponsor: Peking University Third Hospital
• Collaborators: Peking University Sixth Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 22, 2025
• Primary Completion (Estimated): March 22, 2027
• Study Completion (Estimated): May 22, 2027

Study Registration Dates

• First Submitted: February 6, 2025
• First Submitted That Met QC Criteria: February 6, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 6, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Mild Cognitive Impairment (MCI); elderly population; Olfactory Dysfunction; Subjective Cognitive Decline (SCD); olfactory training
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: 9059101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We will decide whether to share the individual participant data after the study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No