Effects of Atomoxetine in Mild Cognitive Impairment

Inclusion * Subjects must have a subjective memory concern as reported by subject, study partner or clinician. * Meets Alzheimer's Disease Neuroimaging Initiative (ADNI) criteria for diagnosis of MCI. Subjects with amnestic (single or multi-domain) will be eligible, as both subtypes of MCI are at high risk for progression to AD. * Abnormal memory function documented by assessment using the Logical Memory subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale-Revised (the maximum score is 25): * \<11 for 16 or more years of education * \<9 for 8-15 years of education * \<6 for \<7 years of education * Mini-Mental State Exam score between 24 and 30 (inclusive). Exceptions may be made for subjects with less than 8 years of education at the discretion of the PI. * Clinical Dementia Rating = 0.5. Memory Box score must be at least 0.5. * General cognition and functional performance sufficiently preserved such that a diagnosis of AD cannot be made by the physician at the time of the screening visit. * Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to screen. * Stability of Permitted Medications for 4 weeks. In particular, subjects may washout from excluded medication for at least 4 weeks prior to screening. * Geriatric Depression Scale (GDS) ≤ than 6. * Male or female outpatients aged 50-90 (inclusive). * Study partner has regular contact with the subject adequate to provide a reliable assessment of the subject's level of function, and can be available for all clinic visits, either in person or by telephone, for the duration of the study. * Visual and auditory acuity adequate for neuropsychological testing. * Good general health with no diseases expected to interfere with the study. * For women of child-bearing potential (i.e., one who is biologically capable of becoming pregnant), must be willing to use a medically acceptable form or birth control or practice abstinence for the duration of her participation in the trial. Acceptable methods of birth control include: oral or patch contraception, or medroxyprogesterone (Depo-Provera®) or other intramuscular contraceptive injection, or implantation of levonorgestrel (Norplant®) system, an Intrauterine Device (IUD), a reliably-employed barrier method (e.g. diaphragm, cervical cap or condom), or a male partner who is surgically sterilized. * Modified Rosen Hachinski ≤ 4. * Completed six grades of education or has a good work history (sufficient to exclude mental retardation). * Able to communicate in English with study personnel. * Able to understand the nature of the study and must provide written informed consent prior to conduct of any study procedures. * Willing to undergo repeated MRIs (3Tesla) and at least three Positron-Emission Tomography (PET) scans. No medical contraindications to MRI. * Agrees to blood collection for Apolipoprotein (APOE) epsilon, CYP2D6 and biomarker testing. * Agrees to lumbar puncture over the course of the study for the collection of CSF. CSF levels of Ab42, total Tau, and Tau phosphorylated at threonine 181 consistent with underlying AD pathology according to established threshold values at Emory and the ADNI Biomarker Core Exclusion * Any significant neurologic disease other than MCI and suspected incipient AD, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, poorly controlled seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities. * Screening/baseline MRI scan with evidence of infection, large vessel infarction or other focal structural lesions that could account for the memory deficits. Subjects with multiple lacunes or lacunes in a critical memory structure are excluded. * Contraindication to MRI due to presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body, or excessive weight. * Presence of clinically significant suicide risk, based on the Investigator's judgment informed by a structured clinician interview. Any suicide attempt within the past 1 year of the screening visit is exclusionary. * Major depression, bipolar disorder as described in DSM-IV within the past 1 year, or history of schizophrenia (DSM-IV). Psychotic features, agitation or behavioral problems within the last 3 months which could lead to difficulty complying with the protocol. * History of alcohol or substance abuse or dependence within the past 2 years (DSM-IV criteria). * Allergic to any component of atomoxetine (Strattera). * Any uncontrolled medical condition that is expected to preclude completion of the study, or any medical condition which would represent a contraindication to atomoxetine pharmacotherapy (e.g. hepatic insufficiency, untreated hypertension, untreated cardiovascular or cerebrovascular disease). * Known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems. * History of narrow angle glaucoma. * History of pheochromocytoma. * Clinically significant abnormal findings on screening laboratory tests or physical exam. Abnormalities in Vitamin B12 level, Thyroid Function Tests (TFTs) or Liver Function Tests (LFTs) that might interfere with the study. A low Vitamin B12 level is exclusionary, unless follow-up labs (homocysteine and methylmalonic acid indicate that it is not physiologically significant. * Slow metabolizer of atomoxetine (i.e., CYP2D6 polymorphism). * Women who are pregnant or lactating, or who plan to become pregnant during the study. * Current use of warfarin (exclusionary for lumbar puncture). * Inability to obtain initial CSF sample. * Use within 60 days of a monoamine oxidase inhibitor or a potent CYP2D6 inhibitor. * Current use of anti-psychotic medication. * Current use of the following anti-depressant medications that act on NET: duloxetine, venlafaxine, desvenlafaxine, imipramine, or amitryptiline. * Current participation in another clinical trial. Participation in clinical studies involving neuropsychological measures being collected more than one time per year. * CSF profile is not consistent with underlying Alzheimer's Disease pathology. * Reasonable likelihood for non-compliance with the protocol or any other reason, in the opinion of the investigator, prohibits enrollment of subject into the study. * Exceptions to these guidelines may be considered on a case-by-case basis at the discretion of the protocol director.