Olfactory Training in Mild Cognitive Impairment (OTMCI)

September 2, 2026 updated by: Jeffrey Motter
Sense of smell tends to decline in individuals with early Alzheimer's disease, typically earlier than when other senses and thinking abilities begin to decline. Memory for new odors is particularly diminished in these individuals. Existing treatments for AD do not improve these symptoms. A targeted treatment for improving sense of smell, called 'Olfactory Training', has been used to improve sense of smell in people with various forms of smell loss, though it is not known whether it can improve smell abilities and thinking abilities in patients who are at high risk of developing Alzheimer's disease. The investigators will conduct a randomized clinical trial with patients who have mild cognitive impairment (MCI). This is an early phase of memory loss that is worse than normal aging and may precede Alzheimer's disease. Patients will be randomized to either olfactory memory training or visual memory training for 3 months, with a final follow-up visit at 6 months. This study will attempt to determine if olfactory training is a useful for improving smell abilities, thinking abilities, and everyday functioning by examining change in these outcomes over time.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

There is an urgent and unmet need to develop interventions capable of improving cognition and everyday functioning in individuals at risk for cognitive decline. Olfactory training consists of systematic exposures to odors, with multiple reviews and meta-analyses concluding it has beneficial effects on cognition and olfaction. The application of olfactory training for preventing cognitive decline in MCI has received limited attention. The overarching goal of the research to be carried out in this application is to determine the feasibility and efficacy of Olfactory Memory Training (OMT) for patients with mild cognitive impairment (MCI). 30 patients with MCI will be recruited from the Memory Disorders Center at the New York State Psychiatric Institute and randomized to 3 months of OMT or active control training. OMT will involve an odor memory task, during which patients sample containers consisting of pairs of commercially available odors (flavored tea leaves). During each training session, non-descript containers are placed on a grid. On each trial, patients sample two containers, and attempt to find a match. The active control involves Visual Memory Training (VMT) with matching of abstract symbols rather than odors. Patients will complete 48 training sessions at home lasting approximately 10 minutes each. At baseline, 3 months, and 6 months follow-up, patients will complete a battery of cognitive, olfactory, and functional measures. In Aim 1, the investigators will compare change in cognitive (Preclinical Alzheimer Composite-5 [PACC5]) and olfactory functioning (Sniffin' Sticks Threshold, Discrimination, and Identification [TDI]) over 6 months in OMT versus VMT. In Aim 2, the investigators will compare change in everyday functioning (Alzheimer's Disease Cooperative Study-Activities of Daily Living scale - Prevention Instrument [ADCS-ADL-PI]) over 6 months in OMT versus VMT. If successful, this study has potential to develop a low-cost and scalable intervention. This study will inform the design of subsequent larger trials of OMT.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age 55-89 at the time of informed consent.
  2. Montreal Cognitive Assessment score >=17.
  3. Subjective cognitive complaints, i.e., memory or other cognitive complaints, e.g., naming/language.
  4. Meets criteria for cognitive impairment (CI), including either early mild cognitive impairment (eMCI) or late mild cognitive impairment (lMCI), defined as memory function documented by scoring below the education adjusted cutoff on the Logical Memory II subscale (Story A, Delayed Paragraph Recall) from the Wechsler Memory Scale (WMS) - III (the maximum score is 25). The criteria for MCI (includes eMCI and lMCI) are as follows: eMCI is defined by a WMS-III Logical memory delayed recall score of 3-6 with 0-7 years of education, score of 5-9 with 8-15 years of education, and score of 9-11 with 16 or more years of education. lMCI is defined by a WMS-III Logical Memory delayed recall score ≤ 2 with 0-7 years of education, score ≤ 4 with 8-15 years of education, and score ≤ 8 with ≥ 16 years of education.
  5. An informant (relative, friend, other caregiver) who contacts the participant at least weekly is required to provide information about the participant's functioning. If the informant drops out, an alternate informant can be designated by the participant.

Exclusion Criteria:

  1. Diagnosis of dementia of any type.
  2. Neurological disorders including Parkinson's disease, Huntington's disease, multiple sclerosis, stroke, epilepsy, traumatic brain injury (moderate to severe, with greater than 30 min loss of consciousness), and other neurologic disorders with focal signs (e.g., amyotrophic lateral sclerosis).
  3. Current clinical diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, alcohol use disorder, or substance use disorder (Diagnostic and Statistical Manual of Mental Disorders (DSM)-5-Text Revision criteria).
  4. Current unstable or untreated major depression, Geriatric Depression Scale (Short Form) score >= 6, or active suicidality based on a suicide scale (Columbia-Suicide Severity Rating Scale Screen version: positive answer to question 1 or 2 followed by item 6 positive answer leads to exclusion. Negative answer to questions 1 and 2: interview ends and the participant is not excluded for active suicidality).
  5. Acute, severe unstable medical illness in the judgment of the clinician. For cancer, acutely ill participants (including those with metastases) are excluded, but history of successfully treated cancer does not result in exclusion.
  6. Participation concurrently in another therapeutic clinical trial of a cognitive enhancing drug or device or procedure.
  7. Current upper respiratory infection (participant rescheduled as soon as this improves), current smoker >1 pack daily (past smoking has been shown not to affect odor identification scores), self-reported congenital anosmia.
  8. Severe vision, hearing, or tactile impairment that would prevent the participant from performing the cognitive tests accurately. This will be a clinical determination.
  9. History of severe or recent asthma (defined as use of an inhaler for asthma, use of other asthma medication, or occurrence of an asthma attack within the last ten years), known special sensitivities to volatile chemicals, anyone who believes she is pregnant or is nursing a baby, and anyone who is on nasally administered medications other than people on nasal steroids to control rhinitis, allergic and otherwise.
  10. Sino-nasal Outcome Test-22 nasal domain score >21, or individual score = 5, representing severe nasal symptoms that interfere with olfaction.
  11. Allergies to any odors used in the olfactory testing or olfactory memory training.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Olfactory Memory Training
Behavioral: Olfactory Memory Training
Participants will complete 48 OMT sessions at home lasting approximately 10 minutes each over 3 months.
Active Comparator: Visual Memory Training
Behavioral: Visual Memory Training
Participants will complete 48 VMT sessions at home lasting approximately 10 minutes each over 3 months.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Sniffin' Sticks TDI (Threshold, Discrimination, and Identification composite)
Time Frame: Baseline, 3 Months, 6 Months
The Sniffin' Sticks TDI test consists of a threshold test, a discrimination test, and an identification test. The results of the three subtests makes a total TDI score, where the minimum score is 1 and the maximum score is 48. A score >30 indicates normal olfactory function, a score between 15-30 indicates hyposmia and a score <15 indicates anosmia in the form of severely impaired or complete loss of olfaction.
Baseline, 3 Months, 6 Months
Change in Preclinical Alzheimer's Cognitive Composite 5 (PACC5)
Time Frame: Baseline, 3 Months, 6 Months
The PACC5 provides a comprehensive assessment of Alzheimer's disease-relevant cognitive impairment and to serve as a tool with validated sensitivity to detect cognitive decline over time. It is comprised of five tests: Mini-Mental State Examination (total score range 0-30), Wechsler Memory Scale-Revised Logical Memory Delayed Recall (total score range 0-25), Digit-Symbol Coding Test (total score range 0-93), Free and Cued Selective Reminding Test Free + Total Recall (total score range 0-96), and Category Fluency Test (graded by number of correct words belonging in the categories of animals, fruits, and vegetables; not graded on a scale). The PACC5 is computed as an averaged z-score of all five tests.
Baseline, 3 Months, 6 Months
Change in Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL-PI)
Time Frame: Baseline, 3 Months, 6 Months
The range of scores of the 15 items ADL question is 0-45 with higher scores indicating better daily functioning. This is the ADCS-ADL-PI outcome measure. In addition, there is a range of scores for the 5 items of physical function questions, which is 0-5 with higher scores indicating intact physical functioning.
Baseline, 3 Months, 6 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Jeffrey Motter

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Alzheimer's Association

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jeffrey N Motter, PhD, Research Foundation for Mental Hygiene, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 7, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 31, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 31, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 9, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 9, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 13, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 4, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 2, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Pro00082984
  • AARG-24-1301387 (Other Grant/Funding Number: Alzheimer's Association)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The investigators will make de-identified data available to qualified users through a data repository.

IPD Sharing Time Frame

The research community will have access to data starting 6 months after the publication of the results that address the Aims of the study.

IPD Sharing Supporting Information Type

  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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