Depression Treatment and Aβ Dynamics: A Study of Alzheimer's Disease Risk (ABD Study)
This study will examine the biological factors that may modulate the relationship between depression and the development of Alzheimer's disease (AD). Since the direction of causation between depression and the biological factors associated with AD is unknown, the only way to understand cause and associated risk is to treat the depressive symptoms and examine the effects on AD biomarkers. The study involves an FDA-approved treatment for major depressive disorder. It will compare the SSRI antidepressant escitalopram with placebo. The hypothesis is that a reduction in depressive symptoms will be associated with a normalization of CSF AD biomarkers as well as peripheral inflammatory markers. This research would contribute to fundamental knowledge about potentially modifiable risks of Alzheimer's disease (AD).
• 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.
⁃ 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 or non-clinically significant abnormalities on routine laboratory tests, will be included.
‣ If study partner is not available, the CDR will be skipped.