Aftobetin-HCl and Fluorescence Detection Measured by Sapphire II to Determine the Number and Timing of Administrations

This is an interventional diagnostic trial for Mild Cognitive Impairment Read More

For MCI and mild AD subjects:

1. Aged 55-90 years old inclusive;
2. Able to provide informed consent;
3. Subject must have a reported memory concern verified by study partner (a study partner is someone willing to participate as a source of information and has at least weekly contact with the subject);
4. Capable of cooperating for the duration of the study with procedures and assessments;

5. Magnetic Resonance Imaging (MRI) Scan within 9 months with:

   1. Modified Hachinski Score <4
   2. No evidence of infection, infarction (ischemic or hemorrhagic), or other focal lesions (tumors, subdural hematomas, malformations, etc.)
6. Geriatric Depression Scale (GDS) score of <6;
7. Neuropsychiatric Inventory (NPI) total score <10 and <4 in any NPI domain;

8. Sufficient vision in at least one eye and hearing to participate in cognitive testing

   For MCI subjects:

9. Meets National Institute on Aging-Alzheimer's Association (NIA-AA) core clinical criteria for Mild Cognitive Impairment due to AD1;
10. Clinical dementia Rating Scale Score (CDR) of 0.5 (memory box score must = 0.5);
11. Mini-Mental State Exam (MMSE) score of >24;
12. Abnormal memory function on education adjusted Wechsler Memory Scale Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) - Revised (16 years: <11; 8-15 years: <9; 0-7 years: <6);

13. Absence of dementia: no significant impairment in cognitive functioning or Activities of Daily Living (AODLs) - Functional Assessment Questionaire (FAQ) score of <6. The FAQ is answered by the study partner;

    For Mild AD subjects:

14. Meets National Institute on Aging-Alzheimer's Association (NIA-AA) core clinical criteria for probable AD dementia2;
15. CDR between 0.5 or 1;
16. MMSE score between 20 to 26 (inclusive);
17. Abnormal memory function on education adjusted Wechsler Memory Scale Logical Memory II subscale -(Delayed Paragraph Recall, Paragraph A only) -Revised (16 years: <8; 8-15 years: <4; 0-7 years: <2);

18. Functional Assessment Questionaire (FAQ) score of >6. The FAQ is answered by the study partner;

    For CN subjects:

19. Subject must be free of memory complaints;
20. Cognitively normal, based on an absence of significant impairment in cognitive functions or activities of daily living;
21. Normal memory function documented by scoring above education adjusted cut-offs on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale - Revised (≥11 for 16 or more years of education; ≥9 for 8-15 years of education;
22. MMSE score of 29-30;
23. CDR Scale Score of 0;
24. Aged 25-40 years old inclusive; and
25. Negative family history for onset of memory dysfunction in first or second degree relatives before age 65.

Exclusion Criteria:

1. Serious underlying medical disease which in the opinion of the investigator may interfere with the participant's ability to participate in the study such as unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, active malignancy or infectious disease;
2. Non-AD causes of dementia that could cause impaired memory ruled out by standardized work up for dementia;
3. Significant neurologic disease (e.g., Parkinson's Disease, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis);
4. Clinically relevant, abnormal serum chemistry, B12, TSH, and CBC <6 months of study entry;
5. History of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities, learning disability or mental retardation;
6. Significant psychiatric illness in last year such as major depression, bipolar, obsessive compulsive or psychotic disorder;
7. History of alcohol or substance abuse in last year;
8. Pain or sleep disorder that could interfere with cognitive testing;
9. Known hypersensitivity to Amyvid (Florbetapir-F 18) or any components of injection formulation or contraindication to PET scan (e.g., pregnant, lactating, or of childbearing potential) in subjects requiring a PET scan.
10. Receiving any investigational medications or participated in a trial with investigational medications within 30 days prior study entry;
11. History of bilateral cataract surgery;
12. Active ocular inflammation or infection;
13. History of physical injury or other serious eye disease;
14. Corneal disease that prevents visualization of the lens, e.g, Fuch's dystrophy or keratokonus;
15. Inability to tolerate the PET environment, e.g., due to physical size and/or claustrophobia in subjects requiring a PET scan.
16. Serious suicidal ideation in the opinion of the investigator or answers 'yes' to Item 4 or 5 on the Columbia Suicide Severity Rating Scale (CSSRS) at screening;
17. Inability to undergo MRI procedure (e.g., metal implant, metallic devices, e.g., non-MRI-safe cardiac pacemaker or neuro-stimulator, some artificial joints, metal pins, surgical clips, other implanted metal, or claustrophobia or discomfort in confined spaces)

18. May not be taking any of the following psychoactive medications:

    • Regular use narcotic analgesics (>2 doses/ week)
    • Clonidine, neuroleptics, antidepressants with central anticholinergic activity
    • Other agents with central anticholinergic activity such as diphenhydramine, hydroxyzine, benztropine
    • Diazepam, clonazepam, temazepam, chlordiazepoxide, or triazolam

Note: it is permitted to remain on the following psychoactive medications provided the subject has been receiving them for greater than or equal to 4 weeks:

• Antidepressants lacking significant anticholinergic side effects
• Estrogen replacement therapy
• Gingko biloba
• Sedative hypnotics: lorazepam, buspirone, oxazepam, zolpidem, zaleplon, alprazolam, chloral hydrate

Note: it is permitted to remain on the following psychoactive medications provided the subject has been receiving them for greater than or equal to 12 weeks:

• Cholinesterase inhibitors
• Memantine Note: the washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics) must be at least 4 weeks prior to screening.