Escitalopram Effects on CSF Amyloid Beta

Alzheimers disease (AD) is a devastating illness, estimated to affect 5 million patients in the United States alone and projected to increase dramatically over the next decades as the population ages unless preventive measures can be developed. The investigators have preliminary evidence that selective serotonin reuptake inhibitor (SSRI) antidepressants lower the amount of amyloid plaques in the human brain. The interventions now propose to study the effects of an SSRI (escitalopram) on levels of amyloid beta peptide (the major constituent of the plaques) in the cerebrospinal fluid (CSF) of cognitively normal older adults.

The investigators will measure CSF Amyloid Beta levels before and after two weeks or eight weeks of treatment with escitalopram using a double blind placebo-controlled study design with approximately 30 cognitively normal participants, age 60-85, with a MOCA of 23 or higher. They will be recruited from the community. Participants will be randomized (approximately 30 per group).

Participants in the 2 week arm will have 3 study visits:

1. Screening Visit: Consent and screening procedures will be complete. Participants will be randomized 1:1 to receive escitalopram or placebo.
2. Study Visit 1: This visit will take approximately 45 minutes - 1 hour; participants will have a lumbar puncture (LP) in order to obtain cerebrospinal fluid (CSF), a blood draw, and will receive study medication.
3. Study Visit 2: This visit will take approximately 45 minutes - 1 hour; participants will have a lumbar puncture (LP) in order to obtain cerebrospinal fluid (CSF), a blood draw, will receive taper-down study medication, and will complete an end-of-study questionnaire.

Participants in the 8-week arm(s) will have 4 study visits:

1. Screening Visit: Consent and screening procedures will be complete. Participants will be randomized 1:1 to receive escitalopram or placebo.
2. Study Visit 1: This visit will take approximately 45 minutes - 1 hour; participants will have a lumbar puncture (LP) in order to obtain cerebrospinal fluid (CSF), a blood draw, and will receive 4 weeks of study medication.
3. Study Visit 2: Researchers will check in with participants and participants will receive another 4 weeks of study medication.
4. Study Visit 3:This visit will take approximately 45 minutes - 1 hour; participants will have a lumbar puncture (LP) in order to obtain cerebrospinal fluid (CSF), a blood draw, will receive taper-down study medication, and will complete an end-of-study questionnaire.

The current proposal will test whether clinically relevant doses of an SSRI reduce CSF levels of Amyloid Beta in healthy older human participants. The investigators hypothesize that compared to placebo, participants receiving escitalopram will show significantly lower Amyloid Beta levels in the second CSF sample.

Eligibility Criteria:
Inclusion Criteria:

* 1) Age 60-85 (inclusive), male and female, any race.
* 2) Capacity to give informed consent and follow study procedures.
* 3) English speaking.
* 4) MOCA = 23 or greater

Exclusion Criteria:

* 1) Known history of relevant severe drug allergy or hypersensitivity (e.g. to Citalopram or Escitalopram)
* 2) Does not speak English
* 3) Cannot give informed consent
* 4) Diagnosis of Major Depression
* 5) Previous history of neurological disorders, such as Parkinson's disease, Alzheimer's disease or traumatic brain injury, cognitive impairment or dementia.
* 6) Diagnosis of a chronic psychiatric illness
* 7) Significant hearing or visual impairment
* 8) Bleeding diathesis
* 9) Clinically significant hepatic, renal, pulmonary, metabolic or endocrine disturbances as indicated by history, which in the opinion of the investigator might pose a potential safety risk to the subject.
* 10) Current clinically significant cardiovascular disease. Clinically significant cardiovascular disease usually includes one or more of the following: cardiac surgery or myocardial infarction within the last 4 weeks; unstable angina; acute decompensated congestive heart failure or class IV heart failure; current significant cardiac arrhythmia or conduction disturbance, particularly those resulting in ventricular fibrillation, or causing syncope or near syncope; uncontrolled high blood pressure; QTc greater than 450msec (by history for subjects with cardiac disease); documented prior stroke.
* 11) Clinically significant abnormalities on EKG. Primary AV block or Right bundle branch block are not necessarily exclusionary.
* 12) History of drug or alcohol abuse within the last year or prior prolonged history of abuse
* 13) Use of an Investigational medicine within the past 30 days 14) Use of Coumadin, Warfarin or other blood thinners within the past 6 months
* 15) Use of antipsychotic medication or antidepressant medication (e.g. MAOIs, SSRIs, SNRIs).
* 16) Use of the following drug/drug classes: Pimozide, Triptans, Tricyclics, Lithium, Tramadol
* 17) Use of over-the-counter supplements such as tryptophan or St. Johns Wort 18) Any other factor that in the investigator's judgment may affect patient safety or compliance (e.g. distance greater than 100 miles from the research institution)