Smell memory training for people with mild cognitive impairment

Olfactory Training in Mild Cognitive Impairment

This trial will test whether a home-based smell memory training program helps people aged 55–89 with mild cognitive impairment improve their sense of smell and thinking skills.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 55 Years to 89 Years
• Sex: All
• Sponsor: New York State Psychiatric Institute (Academic / other)
• Locations: 1 site (New York, New York)
• Trial ID: NCT06825403 on ClinicalTrials.gov

What this trial studies

Researchers will recruit 30 patients with mild cognitive impairment and randomize them to three months of olfactory memory training or an active visual memory training control. Participants will complete 48 home sessions of about 10 minutes each, and undergo cognitive, olfactory, and daily function testing at baseline, 3 months, and 6 months. The olfactory training uses paired odor-matching tasks with commercially available scented materials, while the control uses matching of abstract visual symbols. The study is single-site at the New York State Psychiatric Institute and focuses on feasibility and preliminary efficacy.

Who should consider this trial

Good fit: Ideal candidates are adults 55–89 with subjective cognitive complaints, a MoCA score of at least 17, and objective mild cognitive impairment defined by education-adjusted delayed paragraph recall cutoffs on the WMS-III Logical Memory test.

Not a fit: People with more advanced dementia, severe non-neurodegenerative smell loss (e.g., recent nasal injury), those outside the age or cognitive criteria, or unable to complete home sessions or clinic visits are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this low-cost, at-home training could improve smell ability and potentially support memory or everyday cognitive function in people with MCI.

How similar studies have performed: Previous olfactory training studies have improved smell ability in other forms of smell loss and some meta-analyses suggest cognitive benefits, but application specifically to MCI has been limited and is not yet established.

Eligibility criteria

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.

Where this trial is running

New York, New York

• New York State Psychiatric Institute — New York, New York, United States (Recruiting)

Study contacts

• Principal investigator: Jeffrey N Motter, PhD — Research Foundation for Mental Hygiene, Inc.
• Study coordinator: Jeffrey N Motter, PhD

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