34 Chapter 2 At long-term follow-up (9-15 months) performance on most cognitive constructs either returned to baseline values or remained stable compared to mid-term follow-up. Mehta et al. found slight improvements or stable functioning (N = 9) regarding verbal fluency, information processing speed and fine motor coordination compared to baseline.18 In the Zhu et al. cohort (N = 22) 48% of the patients had deteriorated on L&M performance, which is comparable to the 50% at mid-term follow-up, suggesting most patients had stable cognitive performance from mid- to long-term follow-up.40 Similarly, for the 9 patients in the Onodera et al. study performance on tests for verbal fluency and information processing speed remained stable over the entire study L&M performance (delayed recognition) significantly declined compared to both baseline and mid-term follow-up and a similar trend was seen for EF.25 Forest plots of the incidence of patients with cognitive decline for each construct at each time point are presented in the Supplementary Materials. The analyses indicated significant heterogeneity between studies for L&M at midterm follow-up. The meta-analysis suggests an increase in the number of patients with cognitive decline over time until mid-term follow-up, with a (relatively) stable or even lower incidence was found at long-term (Figure 2a). In accordance with the results described above, Gondi et al. reported a trend towards deteriorated performance on L&M tasks 1 month after WBRT, which stabilized and reverted back to baseline values after that time point.26 In the Mehta et al. cohort time to neurocognitive deterioration was on average shortest for fine motor coordination, L&M and EF.18 Additionally, they found that time to neurocognitive deterioration significantly differed between patients showing a volume reduction below or above 45% after 2 months, with patients with more volume reduction (classified as good responders) having a longer time to deterioration on fine motor coordination. At short-term follow-up (1-4 months) after SRS the majority of studies reported a decline in cognitive performance when compared to baseline. Overall, declined performance was most common regarding L&M (23-54%) and fine motor coordination (35-46%).29,31,32 Similarly, between 13-19% of the patients in the Minniti et al. cohort (N = 32) showed a mean decline of 10-14% from baseline.44For the other assessed cognitive constructs (verbal fluency, attention, information processing speed and EF) the amount of patients in the Chang et al. study that had deteriorated were balanced out by the patients that had improved.29 Contrarily, 18% showed a decline in EF in the other study by Chang et al. (N= 20) and 17% on information processing speed in the study by Brown et al. (N = 60).31,32 Both studies found least deterioration on tasks for attention (6%) and verbal fluency (2%). The two other
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