Aβ Dynamics in LLMD

Eligibility Criteria

• 1. Male and female subjects, age 60+ years inclusive, at the time of signing the informed consent.
• 2. Meeting Structured Clinical Interview (SCID-5-RV) for DSM-5 criteria for Major depressive disorder.
• 3. Montgomery-Åsberg Depression Rating Scale (MADRS) ≥18.
• 4. Have results of a physical examination, neurological examination, vitals, and EKG within normal limits at screening.
• 5. Cognitively unimpaired at screening visit as defined by Mini-Mental State Examination (MMSE) \>27.
• 6. Clinical Dementia Rating Scale (CDR) Global of 0\*.
• 7. A score of 85 or greater on the RBANS delayed memory index score.
• 8. Fluent in English, because some of the instruments used in this study have not been translated and validated in other languages, and are able to read at a 6th grade level or equivalent, as determined by the PI.
• 9. Medically stable with no significant cerebrovascular, neurological, or systemic disease expected to interfere with the study.
• 10. Adequate auditory acuity and normal-to-corrected vision.
• 11. Willing to undergo brain MRI, urine drug screen and blood sampling for routine laboratory testing, lumbar puncture, APOE genotyping and plasma drug levels.
• 12. Only individuals with normal or non-clinically significant abnormalities on routine laboratory tests, will be included.
• * If study partner is not available, the CDR will be skipped.
• 1. History of brain tumor, MRI evidence of brain damage or brain disease including significant trauma, hydrocephalus, seizures, or confluent (or more extensive) white matter hyperintensities.
• 2. Mental retardation, or other serious neurological disorder (e.g. Parkinson's disease or other movement disorders).
• 3. Subjects with a Fazekas scale \>2.
• 4. Significant history of alcoholism or drug abuse in the past 2 years. Fulfilling SCID-5-RV/DSM-5 criteria for current or past diagnosis of any psychiatric disorder (e.g., schizophrenia, bipolar disorder, or any psychotic disorder) other than recurrent MDD or anxiety disorders (e.g., panic disorder, agoraphobia, etc.).
• 5. A current significant risk for suicidality based on the Columbia-Suicide-Severity Rating Scale (C-SSRS).
• 6. Insulin dependent diabetes.
• 7. Evidence of clinically relevant or unstable cardiac, pulmonary, endocrine or hematological conditions.
• 8. Any prosthetic devices (e.g., pacemaker or surgical clips) that constitutes a hazard for MRI imaging.
• 9. Positive urine drug screen for illicit drugs.
• 10. History of poor tolerance to, poor response to, or ongoing treatment with escitalopram.
• 11. If taking antidepressants, currently taking fluoxetine, due to the length of time required to washout.
• 12. Treatment with following medications will not be permitted. In some cases, medications will be allowed if medically prescribed and dose regimen stable. Note: Some medications (e.g., amphetamines, opiates) may appear on the routine urine drug test in the screening period but can be allowed as per protocol.
• * For subjects taking prescribed psychoactive medications and supplements (i.e., opioids, amphetamines, amphetamine-like substances, and cannabinoids), must be on a stable dose for 1 month prior to randomization.
• * Anti-Parkinsonian medications (carbidopa/levodopa, amantadine, bromocriptine, pergolide, selegiline).
• * Cholinesterase inhibitors and memantine
• * Continuous aspirin (any dosage) use which can affect platelet function is prohibited. Exception: If participant is on low dose aspirin for prophylaxis and is willing to temporarily discontinue prior to research blood draw (i.e., 2 days before).
• * Continuous use of other medications which are also known to affect platelet function, including nonsteroidal anti-inflammatory drugs (NSAIDs), anti-histamines. Exception: If participant is taking medication continuously and is willing to temporarily discontinue prior to research blood draw (i.e., 2 days before)