Yvette I Sheline1, B Joy Snider2, Joanne C Beer2, Darsol Seok2, Anne M Fagan2, Raymond F Suckow2, Jin-Moo Lee2, Teresa Waligorska2, Magdalena Korecka2, Irem Aselcioglu2, John C Morris2, Leslie M Shaw2, John R Cirrito2. 1. From the Center for Neuromodulation in Depression and Stress, Department of Psychiatry (Y.I.S., D.S., I.A.), and Departments of Radiology (Y.I.S.), Neurology (Y.I.S.), Biostatistics, Epidemiology and Bioinformatics (J.C.B.), and Pathology (T.W., M.K., L.M.S.), University of Pennsylvania, Philadelphia; Department of Neurology, The Knight Alzheimer Disease Research Center, Hope Center for Neurological Disorders (B.J.S., A.M.F., J.-M.L., J.C.M., J.R.C.), Washington University School of Medicine, St Louis MO; and New York State Psychiatric Institute and Department of Psychiatry (R.F.S.), Columbia University, New York. sheline@pennmedicine.upenn.edu. 2. From the Center for Neuromodulation in Depression and Stress, Department of Psychiatry (Y.I.S., D.S., I.A.), and Departments of Radiology (Y.I.S.), Neurology (Y.I.S.), Biostatistics, Epidemiology and Bioinformatics (J.C.B.), and Pathology (T.W., M.K., L.M.S.), University of Pennsylvania, Philadelphia; Department of Neurology, The Knight Alzheimer Disease Research Center, Hope Center for Neurological Disorders (B.J.S., A.M.F., J.-M.L., J.C.M., J.R.C.), Washington University School of Medicine, St Louis MO; and New York State Psychiatric Institute and Department of Psychiatry (R.F.S.), Columbia University, New York.
Abstract
OBJECTIVE: To determine whether treatment with escitalopram compared with placebo would lower CSF β-amyloid 42 (Aβ42) levels. RATIONALE: Serotonin signaling suppresses Aβ42 in animal models of Alzheimer disease (AD) and young healthy humans. In a prospective study in older adults, we examined dose and treatment duration effects of escitalopram. METHODS: Using lumbar punctures to sample CSF levels before and after a course of escitalopram treatment, cognitively normal older adults (n = 114) were assigned to placebo, 20 mg escitalopram × 2 weeks, 20 mg escitalopram × 8 weeks, or 30 mg escitalopram × 8 weeks; CSF sampled pretreatment and posttreatment and within-subject percent change in Aβ42 was used as the primary outcome in subsequent analyses. RESULTS: An overall 9.4% greater reduction in CSF Aβ42 was found in escitalopram-treated compared with placebo-treated groups (p < 0.001, 95% confidence interval [CI] 4.9%-14.2%, d = 0.81). Positive baseline Aβ status (CSF Aβ42 levels <250 pg/mL) was associated with smaller Aβ42 reduction (p = 0.006, 95% CI -16.7% to 0.5%, d = -0.52) compared with negative baseline amyloid status (CSF Aβ42 levels >250 pg/mL). CONCLUSIONS: Short-term longitudinal doses of escitalopram decreased CSF Aβ42 in cognitively normal older adults, the target group for AD prevention. CLINICALTRIALSGOV IDENTIFIER: NCT02161458. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for cognitively normal older adults, escitalopram decreases CSF Aβ42.
OBJECTIVE: To determine whether treatment with escitalopram compared with placebo would lower CSF β-amyloid 42 (Aβ42) levels. RATIONALE: Serotonin signaling suppresses Aβ42 in animal models of Alzheimer disease (AD) and young healthy humans. In a prospective study in older adults, we examined dose and treatment duration effects of escitalopram. METHODS: Using lumbar punctures to sample CSF levels before and after a course of escitalopram treatment, cognitively normal older adults (n = 114) were assigned to placebo, 20 mg escitalopram × 2 weeks, 20 mg escitalopram × 8 weeks, or 30 mg escitalopram × 8 weeks; CSF sampled pretreatment and posttreatment and within-subject percent change in Aβ42 was used as the primary outcome in subsequent analyses. RESULTS: An overall 9.4% greater reduction in CSF Aβ42 was found in escitalopram-treated compared with placebo-treated groups (p < 0.001, 95% confidence interval [CI] 4.9%-14.2%, d = 0.81). Positive baseline Aβ status (CSF Aβ42 levels <250 pg/mL) was associated with smaller Aβ42 reduction (p = 0.006, 95% CI -16.7% to 0.5%, d = -0.52) compared with negative baseline amyloid status (CSF Aβ42 levels >250 pg/mL). CONCLUSIONS: Short-term longitudinal doses of escitalopram decreased CSF Aβ42 in cognitively normal older adults, the target group for AD prevention. CLINICALTRIALSGOV IDENTIFIER: NCT02161458. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for cognitively normal older adults, escitalopram decreases CSF Aβ42.
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