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ESCITALOPRAM DECREASES LONGITUDINAL CSF ABETA CONCENTRATION IN COGNITIVELY NORMAL SUBJECTS AGE 60-85

      Background

      In this study we examined the hypothesis that, as in previous transgenic mouse, retrospective human studies (Cirrito et al., 2011) and acute CSF studies in humans (Sheline et al., 2014), chronic dosing of escitalopram would lower CSF levels of amyloid beta (Aβ) levels in humans. Participants in secondary prevention trials for Alzheimer’s disease (AD) will be exposed to a compound for multiple years; thus, particularly in a clinically asymptomatic population, the compound would need to have a proven safety record, as is true for SSRIs.

      Methods

      A randomized double-blind placebo controlled study was performed to determine the effect of 20 mg/day of the SSRI antidepressant, escitalopram, on CSF Aβ42 protein levels. Following a baseline lumbar puncture (LP), healthy cognitively normal 60-85 year old male and female volunteers received either placebo or 20 mg/day of escitalopram for 2 weeks. A validated candidate reference mrm mass spectrometry method (Korecka, et al, 2014) was used to measure CSF levels of Aβ42.

      Results

      Placebo (n = 20) and escitalopram (n = 18) treated subjects did not differ on any demographic variables. Escitalopram-treated subjects had significantly greater lowering of mean total Aβ concentrations (1143.38 +/- 601.52 pg/mL baseline to 1004.17 +/- 514.27)), a 10.9% decrease post-escitalopram, compared with placebo-treated (1327.69 +/- 547.62 pg/mL baseline to 1334.98 +/- 493.2 post-placebo), a 2.58% increase (p = 0.011).

      Conclusions

      We corroborate our prior findings in a prospective human study now showing that chronic escitalopram lowers CSF Aβ42 concentrations compared with placebo. Ongoing studies will determine effects following a longer (8 weeks) duration of exposure. The ability to safely decrease Aβ42 concentrations is potentially important as a preventive strategy for AD.