Olfactory Training in Mild Cognitive Impairment

NCT06825403 | Recruiting

• 2 other identifiers: Pro00082984AARG-24-1301387
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mild Cognitive Impairment

Keywords

Olfactory Training; Olfactory Memory Training; Visual Training; Visual Memory Training; Olfaction; Memory Disorders; Cognitive Disorders; Cognitive Impairment; Mild Cognitive Impairment; Cognitive Training

Outcome Measures

Primary Outcomes (3)

• Change in Preclinical Alzheimer's Cognitive Composite 5 (PACC5)

  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 Sniffin' Sticks TDI (Threshold, Discrimination, and Identification composite)

  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 Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL-PI)

  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

Study Arms (2)

Olfactory Memory Training

ACTIVE COMPARATOR

Behavioral: Olfactory Memory Training

Visual Memory Training

ACTIVE COMPARATOR

Behavioral: Visual Memory Training

Interventions

Visual Memory Training BEHAVIORAL

Participants will complete 48 VMT sessions at home lasting approximately 10 minutes each over 3 months.

Visual Memory Training

Olfactory Memory Training BEHAVIORAL

Participants will complete 48 OMT sessions at home lasting approximately 10 minutes each over 3 months.

Olfactory Memory Training

Eligibility Criteria

• Age: 55 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 55-89 at the time of informed consent.
• Montreal Cognitive Assessment score \>=17.
• Subjective cognitive complaints, i.e., memory or other cognitive complaints, e.g., naming/language.
• 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.
• 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.

You may not qualify if:

• Diagnosis of dementia of any type.
• 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).
• 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).
• Participation concurrently in another therapeutic clinical trial of a cognitive enhancing drug or device or procedure.
• 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.
• Severe vision, hearing, or tactile impairment that would prevent the participant from performing the cognitive tests accurately. This will be a clinical determination.
• 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.
• Sino-nasal Outcome Test-22 nasal domain score \>21, or individual score = 5, representing severe nasal symptoms that interfere with olfaction.
• Allergies to any odors used in the olfactory testing or olfactory memory training.

Sponsors & Collaborators

• Jeffrey Motter: lead
• Alzheimer's Association: collaborator

Study Sites (1)

New York State Psychiatric Institute

New York, New York, 10032, United States

RECRUITING

MeSH Terms

Conditions

Cognitive Dysfunction; Anosmia; Memory Disorders

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Olfaction Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurobehavioral Manifestations

Study Officials

• Jeffrey N Motter, PhD

  Research Foundation for Mental Hygiene, Inc.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jeffrey N Motter, PhD

CONTACT

6467748654; jeffrey.motter@nyspi.columbia.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Due to the pilot nature of the study and fundamental differences between OMT and VMT, neither the participants nor research personnel will be blinded to treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Research Scientist

Model Details: Participants will be randomized 1:1 to either Olfactory Memory Training (OMT) or Visual Memory Training (VMT) by random number generators.

Study Record Dates

• First Submitted: February 9, 2025
• First Posted: February 13, 2025
• Study Start: August 7, 2025
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2028
• Last Updated: March 19, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ICF
• 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.

Locations

US (1)