slow enrollment

The goal of this clinical trial is to learn whether a new smell test works as well as the standard clinical smell test, if there is a link between sense of smell and variations in the retina, and if these results could be used as a way to identify early stages of Alzheimer's disease. The main questions it aims to answer are:

• Whether the test is as effective and reliable as the standard test
• Whether there is a link between the results of the smell test and the structure of the back of the eye

Participants will:

• complete a short questionnaire
• have pictures of the inside of their eyes taken
• perform two smell tests

Inclusion Criteria:

• Adults who are ≥ 50 and ≤ 80 years of age

• Fluent in English

• Able to provide written consent

• Able to complete a 2.5-3-hour clinical visit, including sitting for spectral domain optical coherence tomography (SD-OCT) imaging for 30 minutes and taking cognitive and olfactory tests for 90-120 minutes

• Cognitive Ability and Family History of Alzheimer's Disease/Mild Cognitive Impairment (AD/MCI):

  • Cohort 1: Cognitively unimpaired, no family history of MCI or AD, and MMSE ≥ 26

  • Cohort 2: Cognitively unimpaired, a positive family history of MCI or AD, and MMSE ≥ 26

  • Cohort 3: An MMSE score > 22 and ≤ 25 and either

    • Clinically diagnosed MCI due to AD
    • A participant in a Wisconsin ADRC research registry with either clinically diagnosed MCI or self-reported MCI

• Cohorts 1 and 2: proficient in independent use of mobile smart devices

Exclusion Criteria:

• A history of significant ocular or nasal trauma that required medical/surgical intervention
• A history of intraocular surgery except cataract extraction
• A cataract extraction within 3 months prior to enrollment
• Diagnosis of visually significant intraocular disease (such as late-stage age-related macular degeneration, glaucoma, or other optic nerve conditions related to brain tumor or multiple sclerosis), drug related vision loss or retinal damage
• Optic neuritis on both eyes
• Current use of medications that may interfere with olfactory functions
• Current use of hydroxychloroquine and tamoxifen, which are known to cause retinal toxicity that may confound OCT interpretation
• A history of recurrent or chronic oto-pharyngeal-laryngeal (ORL) disease (such as chronic rhinitis, nasal polyposis, or sinus disease), head trauma, toxic exposures, upper respiratory infections at time of assessment
• A family history or diagnosis of other neurodegenerative diseases (e.g., multiple sclerosis, Parkinson's disease, Huntington's disease) or conditions that, in the opinion of the Investigators, may affect cognitive or olfactory functions
• Olfactory loss due to COVID (current olfactory loss and/or temporary loss that has been regained)

Adults (50-80 years of age) in three cohorts:

Cohort 1: 10 participants cognitively unimpaired with no family history of AD Cohort 2: 10 participants cognitively unimpaired with a family history of AD Cohort 3: 10 participants with clinically diagnosed MCI or from the Wisconsin ADRC registry and clinically diagnosed or self-reported MCI