Escitalopram Effects on CSF Amyloid Beta

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.

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)