Inclusion Criteria:  Male and female subjects, age 60+ years inclusive, at the time of signing the informed consent. Meeting Structured Clinical Interview (SCID-5-RV) for DSM-5 criteria for Major depressive disorder. Montgomery-Åsberg Depression Rating Scale (MADRS) ≥18. Have results of a physical examination, neurological examination, vitals, and EKG within normal limits at screening. Cognitively unimpaired at screening visit as defined by Mini-Mental State Examination (MMSE) >27. Clinical Dementia Rating Scale (CDR) Global of 0. A score of 85 or greater on the RBANS delayed memory index score. 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. Medically stable with no significant cerebrovascular, neurological, or systemic disease expected to interfere with the study. Adequate auditory acuity and normal-to-corrected vision. Have a reliable and competent study partner who can accompany the subject to the Screening Visit to verify absence of impairment in cognitive functions or activities of daily living. Willing to undergo brain MRI, urine drug screen and blood sampling for routine laboratory testing, lumbar puncture, APOE genotyping and plasma drug levels. Only individuals with normal hepatic and renal function including normal creatinine clearance will be included.  Exclusion Criteria:  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. Mental retardation, or other serious neurological disorder (e.g. Parkinson's disease or other movement disorders). Subjects with a Fazekas scale >2. 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 other than recurrent MDD including schizophrenia, bipolar disorder, dysthymic disorder, panic disorder, agoraphobia, specific phobia, social phobia, obsessive compulsive disorder, post-traumatic disorder, or any psychotic disorder. A current significant risk for suicidality based on the Columbia-Suicide-Severity Rating Scale (C-SSRS). Insulin dependent diabetes. Evidence of clinically relevant or unstable cardiac, pulmonary, endocrine or hematological conditions. Any prosthetic devices (e.g., pacemaker or surgical clips) that constitutes a hazard for MRI imaging. Positive urine drug screen for illicit drugs. History of poor tolerance to, poor response to, or ongoing treatment with escitalopram. If taking antidepressants, currently taking fluoxetine, due to the length of time required to washout.  Currently taking medications potentially affecting cognition other than SSRIs; narcotic analgesics,chronic use of medications with anticholinergic activity, Anti-Parkinsonian medications (carbidopa/levodopa, amantadine, bromocriptine, pergolide, selegiline).  Others medications that are exclusionary include: amphetamines, amphetamine-like compounds, appetite suppressants, phenothiazines, reserpine, buspirone, clonidine, disulfiram, guanethidine, theophylline, melatonin, salicylates, cholinesterase inhibitors and memantine. Continuous aspirin (any dosage) use and St. John's Wort are excluded. For subjects taking antidepressants at screening, no dosage changes for ≥3 months.