There is interest in using cerebrospinal fluid (CSF) biomarkers to enrich mild cognitive impairment (MCI) clinical trials; however, there are conflicting views on their utility. We identified MCI subjects with CSF from the Alzheimer's Disease Neuroimaging Initiative. We measured brain and hippocampal atrophy rates, ventricular expansion rates, and decline in ADAS-Cog 13 and MMSE over one year. We examined proportionate and absolute reductions in mean outcome measures. Using a CSF Aβ1-42 cut-off (192 pg/ml), we estimated sample size ratios for clinical trials based on these outcomes for targeted (i.e., low-Aβ-MCI subjects only) compared with unrestricted recruitment. We further examined sample size ratios assuming only low-Aβ-MCIs would benefit from treatment. We found that for proportionate reductions in mean outcomes targeted recruitment led to significantly smaller sample sizes for all outcomes apart from ADAS-Cog. No sample size reduction was demonstrated for outcomes based on absolute reductions. Excluding subjects who would not benefit from treatment always reduces sample sizes. Using CSF biomarkers as inclusion criteria for AD trials increases the number of subjects needing to be screened but may reduce required sample sizes and reduce the risk of exposing patients without amyloid pathology to treatment side-effects. Whether targeted recruitment reduces required sample sizes depends critically on assumptions regarding treatment effects.