Memory Improvement Through Nicotine Dosing (MIND)

• Subjective memory concern reported by participant, study partner, or doctor
• Abnormal memory function
• Mini-Mental State Examination score of 24-30
• Clinical Dementia Rating of 0.5 (very mild dementia)
• General cognition and functional performance such that a diagnosis of Alzheimer's cannot be made
• Medications stable for at least 4 weeks; memantine (Namenda) is allowed if stable for at least 12 weeks
• Geriatric Depression Scale score of 9 or less
• Study partner who has contact on average 10 or more hours per week and can attend most visits
• Adequate visual and auditory ability to allow neuropsychological testing
• Good general health with no diseases, disorders, or significant abnormalities that could interfere with the study
• If female, must be 2 years postmenopausal or surgically sterile
• Completed six grades of education or has a good work history
• Fluent in English

• Regular use of tobacco products within the past year, including cigarettes, pipes, cigars, chewing tobacco, e-cigarettes, nicotine patches, gum, and sprays
• Any significant neurologic disease, such as Alzheimer's, Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis
• History of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities
• Major depression; bipolar disorder within the past year; or psychotic features, agitation, or behavioral problems within past 3 months
• History of schizophrenia
• History of alcohol or substance abuse or dependence within the past 2 years
• Significant or unstable medical condition, including uncontrolled hypertension or diabetes, or significant heart, lung, kidney, liver, endocrine, or other systemic disease
• 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
• Significant abnormalities in B12 or thyroid function tests that might interfere with the study
• Significant abnormalities in screening laboratories or electrocardiogram
• Residence in skilled nursing facility
• Use of centrally acting anti-cholinergic drugs, such as donepezil (Aricept) and rivastigmine (Exelon), or other excluded medications
• Use of any investigational drugs within 30 days or 5 half-lives, whichever is longer

Participants will be randomized to wear either a nicotine skin patch or a placebo for 2 years during waking hours. The nicotine dosage will start at 3.5 mg and increase over 6 weeks to 21 mg for the majority of the trial, tapering down in the final month. Researchers will measure changes in attention, cognitive impairment, memory, mood, and functional performance. Researchers will also look at changes in biomarkers in cerebrospinal fluid and on brain imaging of some participants.

University of Southern California

• National Institute on Aging (NIA)
• Vanderbilt University
• Alzheimer's Therapeutic Research Institute