eprintid: 10073276 rev_number: 16 eprint_status: archive userid: 608 dir: disk0/10/07/32/76 datestamp: 2019-05-10 14:30:58 lastmod: 2021-11-23 23:29:51 status_changed: 2019-05-10 14:30:58 type: article metadata_visibility: show creators_name: Wolz, R creators_name: Schwarz, AJ creators_name: Gray, KR creators_name: Yu, P creators_name: Hill, DLG creators_name: Alzheimer's Disease Neuroimaging Initiative, title: Enrichment of clinical trials in MCI due to AD using markers of amyloid and neurodegeneration ispublished: pub divisions: UCL divisions: B04 divisions: C05 divisions: F42 keywords: Aged, Alzheimer Disease, Amyloid beta-Peptides, Biomarkers, Brain, Clinical Trials as Topic, Cognitive Dysfunction, Cohort Studies, Female, Humans, Male, Mental Status Schedule, Nerve Degeneration, Positron-Emission Tomography note: This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions. abstract: OBJECTIVE: To investigate the effect of enriching mild cognitive impairment (MCI) clinical trials using combined markers of amyloid pathology and neurodegeneration. METHODS: We evaluate an implementation of the recent National Institute for Aging-Alzheimer's Association (NIA-AA) diagnostic criteria for MCI due to Alzheimer disease (AD) as inclusion criteria in clinical trials and assess the effect of enrichment with amyloid (A+), neurodegeneration (N+), and their combination (A+N+) on the rate of clinical progression, required sample sizes, and estimates of trial time and cost. RESULTS: Enrichment based on an individual marker (A+ or N+) substantially improves all assessed trial characteristics. Combined enrichment (A+N+) further improves these results with a reduction in required sample sizes by 45% to 60%, depending on the endpoint. CONCLUSIONS: Operationalizing the NIA-AA diagnostic criteria for clinical trial screening has the potential to substantially improve the statistical power of trials in MCI due to AD by identifying a more rapidly progressing patient population. date: 2016-09-20 date_type: published official_url: https://doi.org/10.1212/WNL.0000000000003126 full_text_type: pub pmcid: PMC5035986 language: eng article_type_text: Journal Article verified: verified_manual elements_id: 1614043 doi: 10.1212/WNL.0000000000003126 pii: WNL.0000000000003126 lyricists_name: Hill, Derek lyricists_id: DHILL80 actors_name: Hill, Derek actors_id: DHILL80 actors_role: owner full_text_status: restricted publication: Neurology volume: 87 number: 12 pagerange: 1235-1241 event_location: United States issn: 1526-632X citation: Wolz, R; Schwarz, AJ; Gray, KR; Yu, P; Hill, DLG; Alzheimer's Disease Neuroimaging Initiative; (2016) Enrichment of clinical trials in MCI due to AD using markers of amyloid and neurodegeneration. Neurology , 87 (12) pp. 1235-1241. 10.1212/WNL.0000000000003126 <https://doi.org/10.1212/WNL.0000000000003126>. document_url: https://discovery.ucl.ac.uk/id/eprint/10073276/1/1235.full.pdf