Long-Term Nicotine Treatment of Mild Cognitive Impairment
significant cognitive, clinical and functional improvement in participants with MCI. Neuronal
nicotinic receptors have long been known to play a critical role in memory function in
preclinical studies, with nicotine improving attention, learning, and memory function.
The study will enroll 300 participants for a 2 year period. Participants will be randomized
(50:50) to either the transdermal nicotine, beginning at 7mg/day, and increasing to 21mg/day,
or placebo skin patch.
1. Participant must have a subjective memory concern as reported by participant, study
partner, or clinician
2. Abnormal memory function documented by scoring within the education adjusted ranges on
the Logical Memory II subscale (Delayed Paragraph Recall) from the Wechsler Memory
Scale – Revised:
– less than or equal to 11 for 16 or more years of education
– less than or equal to 9 for 8 – 15 years of education
– less than or equal to 6 for 0 – 7 years of education
3. Mini-Mental State Exam score between 24 and 30, inclusive
4. Clinical Dementia Rating (CDR) Global = 0.5. Memory Box score must be at least 0.5
5. General cognition and functional performance sufficiently preserved such that a
diagnosis of Alzheimer’s disease dementia cannot be made by the site physician at the
time of the screening visit
6. Age 55-90 (inclusive)
7. Stable permitted medications for 4 weeks or longer as specified in Section 6,
• Memantine and cholinesterase inhibitors are allowable if stable for 12 weeks prior
8. Geriatric Depression Scale score of less than or equal to 14
9. Study Partner is available who has frequent contact with the participant (e.g. an
average of 10 hours per week or more), and can accompany the participant to most
visits to answer questions about the participant
10. Adequate visual and auditory acuity to allow neuropsychological testing
11. Good general health with no additional diseases/disorders expected to interfere with
12. Participant is not pregnant, lactating, or of childbearing potential (i.e. women must
be two years post-menopausal or surgically sterile)
13. Completed six grades of education or has a good work history
14. Must speak English fluently
1. Regular use of tobacco products within the past year, such as smoking (cigarettes,
pipes, cigars, etc.) or use of other nicotine products (chewing tobacco, e-cigarettes,
nicotine patches, gum, sprays, etc.).
2. Any significant neurologic disease such as Alzheimer’s disease dementia, Parkinson’s
disease, multi-infarct dementia, Huntington’s disease, normal pressure hydrocephalus,
brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma,
multiple sclerosis, or history of significant head trauma followed by persistent
neurologic deficits or known structural brain abnormalities.
3. Major depression, bipolar disorder as described in DSM-V within the past 1 year or
psychotic features, agitation or behavioral problems within 3 months, which could lead
to difficulty complying with the protocol
4. History of schizophrenia (DSM V criteria)
5. History of alcohol or substance abuse or dependence within the past 2 years (DSM V
6. Clinically significant or unstable medical condition, including uncontrolled
hypertension, uncontrolled diabetes, or significant cardiac, pulmonary, renal,
hepatic, endocrine, or other systemic disease in the opinion of the Investigator, may
either put the participant at risk because of participation in the study, or influence
the results, or the participant’s ability to participate in the study.
7. Has had a history within the last 5 years of a primary or recurrent malignant disease
with the exception of non-melanoma skin cancers, resected cutaneous squamous cell
carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ
prostate cancer with normal prostate-specific antigen post-treatment
8. Clinically significant abnormalities in B12 or TFTs (Thyroid Function Tests) that
might interfere with the study. A low B12 is exclusionary, unless the required
follow-up labs (homocysteine (HC) and methylmalonic acid (MMA)) indicate that it is
not physiologically significant.
9. Clinically significant abnormalities in screening laboratories or ECG.
10. Residence in skilled nursing facility.
11. Use of any excluded medication as described in the protocol, including:
– Use of centrally acting anti-cholinergic drugs
– Use of any investigational drugs within 30 days or 5 half-lives, whichever is
longer, prior to screening.
12. For CSF sub-study participants, a current blood clotting or bleeding disorder, or
significantly abnormal PT or PTT (partial thromboplastin time) at screening
13. For MRI sub-study participants, contraindications for MRI studies, including
claustrophobia, the presence of metal (ferromagnetic) implants, or cardiac pacemaker.
14. Patients whom the Site PI deems to be otherwise ineligible.
- USC Rancho Los Amigos, Downey, California, United States, 90242
- Hoag Memorial Hospital Presbyterian, Newport Beach, California, United States, 92663
- Sharp Mesa Vista Hospital, San Diego, California, United States, 92123
- Syrentis Clinical Research, Santa Ana, California, United States, 92705