Background and purpose: The aim of this prospective study is to evaluate post -whole brain radiotherapy (WBRT) changes in hippocampal concentration of N-acetylaspartate (h-tNAA) as a marker of neuronal loss and to correlate those changes to neurocognitive function. Material and methods: Thirty-five patients with brain metastases underwent baseline single slice multivoxel MR spectroscopy (MRS) examination for measurement of hippocampal h-tNAA together with baseline battery of neurocognitive tests focused on memory (Auditory Verbal Learning Test and Brief Visuospatial Memory Test - Revised) as well as quality of life questionnaires (EORTC QLQ-C30 a EORTC QLQ-BN20). Eighteen patients completed follow-up evaluation four months after standard WBRT (2 laterolateral fields, 10 x 3.0 Gy, 6 MV photons) and were included in this analysis. MRS and cognitive examinations were repeated and compared to baseline measurements. Results: Statistically significant decreases in h-tNAA were observed in the right (8.52-7.42 mM; -12.9%, 95%Cl: -7.6 to -16.4%) as well as in the left hippocampus (8.64-7.60 mM; -12%, 95%Cl: -7.9 to -16.2%). Statistically significant decline was observed in all AVLT and BVMT-R subtests with exception of AVLT_Recognition. Quality of life declined after WBRT (mean Delta-14.1 +/- 20.3 points in transformed 0100 point scale; p = 0.018) with no correlation to changes in hippocampal metabolite concentrations. Moderate positive correlation was observed between left h-tNAA concentration decrease and AVLT_TR decline (r = +0.32; p = 0.24) as well as with AVLT_DR (r = +0.33; p = 0.22) decline. Changes in right htNAA/Cr negatively correlated with AVLT_DR (r = -0.48; p = 0.061). No correlation between right hippocampus h-tNAA and memory decline (AVLT) was observed. Conclusions: Our results suggest hippocampal NAA concentrations decline after WBRT and MRS may be a useful biomarker for monitoring neuronal loss after radiotherapy. 2016 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 122 (2017) 373-379