A Solution for Improving Recruitment into Prodromal Alzheimer’s Disease Trials: CANTAB Recruit


12 December 2016

A Solution for Improving Recruitment into Prodromal Alzheimer’s Disease Trials: CANTAB Recruit

Screening patients into prodromal Alzheimer’s trials can be costly and time-consuming Kenton Zavitz, PhD, Director of Clinical Affairs & Rosemary Abbott, PhD, Principal Statistical Analyst look at a solution for improving recruitment into trials. 

By Kenton Zavitz, PhD, Director of Clinical Affairs & Rosemary Abbott, PhD, Principal Statistical Analyst



Key points

  • Screening patients into prodromal Alzheimer’s trials can be costly and time-consuming
  • CANTAB Paired Associates Learning task is associated with hippocampal and temporal-frontal network function and is a sensitive and specific indicator of Mild Cognitive Impairment (MCI)
  • CANTAB Recruit offers a solution with a highly sensitive cognitive assessment prescreening tool that can be administered on a home computer to reduce the rate of costly in-clinic screen failures

Last week, we looked at the challenge of detecting prodromal Alzheimer’s disease, this week, we offer a solution. As we know the cost of screening a single patient prior to determining suitability for trial enrollment may be many of thousands of dollars and the screen fail rate can easily exceed 70% of subjects screened, further increasing costs and timelines.  Failure to recruit the planned number of participants in a timely manner can put a clinical development program at risk for clinical and commercial failure (Hughes 2012, Grill 2014). Therefore, finding the right people at the right time is key; Cambridge Cognition have now developed a tool to help fill the gap in finding cognitively impaired subjects for further screening.  

CANTAB Recruit

CANTAB Recruit is a computerized and automatically administered cognitive assessment tool for pre-screening participants for clinical trials. The platform is web-based, which allows for potential participants to register and complete the assessment remotely without the need to attend a clinic. Results from the cognitive assessment, and participant demographic information are recorded, and used to determine a participant’s suitability for further in-clinic screening procedures. 

CANTAB Recruit employs the Paired Associates Learning (PAL) task which is a sensitive measure of visual episodic memory and learning and is associated with hippocampal and temporal-frontal network function (de Rover 2011, Nathan 2015, Figure 1 below).  The PAL task has been selected for its reliability, validity and sensitivity to subtle episodic memory impairment that is correlated with brain amyloid burden, CSF tau levels and hippocampal volume (Barnett 2011, Nathan 2015, Scheltens 2014).     

Figure 1 shows the association between PAL task and Hippocampal Volume. Lower hippocampal volume is associated with poorer episodic memory (higher PAL errors), Nathan (2015).

Figure 1

The CANTAB PAL task is a sensitive and specific indicator of amnestic Mild Cognitive Impairment (MCI). Subjects with MCI who perform poorly on this test at baseline are a stable group with a clinically-relevant impairment that worsens over time (Cormack 2015).

Together these observations have implications for identifying patients at risk of developing AD and enriching a more homogenous population for clinical trials with fronto-striatal and hippocampal dependent attention and memory deficits, neurodegeneration and CSF biomarker abnormalities consistent with prodromal AD populations (Nathan 2015, Nathan 2016).

According to a recent meta-analysis in persons without dementia (Jansen 2015), the prevalence of cerebral amyloid pathology in the general population over 50 years is 29%. The proportion is higher amongst people with MCI (51%) than in those with normal cognition and increases with age (Jansen, 2015).  Administration of the PAL task using CANTAB Recruit can help identify individuals who are likely to be amyloid positive thereby reducing the number of subjects required for in-clinic screening to reach the target enrollment number.

Figure 2, based on subjects aged 50+ from the EDAR study¹  shows that sample ‘enrichment’ is based on our knowledge of the sensitivity and specificity of the PAL task together with the pre-test probability of amyloid positivity in the general population (i.e. 29%). As the level of impairment on the PAL tasks increases, the number of subjects that require CSF sampling (or amyloid PET imaging) to identify cerebral amyloid positivity is reduced. The percentage reduction is a trade-off between sensitivity and specificity (maximizing true positives and minimizing false negatives) with the maximum enrichment in the example below, falling at PAL error cut point E. CANTAB Recruit can be tailored to the sponsor’s specific trial requirements, such as for more impaired (MCI) versus less impaired (‘asymptomatic at risk for AD’) populations.

Figure 2

¹ Based on data from subjects aged 50 plus from the European EDAR study (Early Diagnosis of AD and as Marker for Treatment Response). 

Key Features of CANTAB Recruit


Online cognitive screening task pre-qualifies subjects in their home to assess their suitability for study enrollment.


CANTAB® cognitive tasks provide sponsors with a sensitive, proven and reliable measure of cognition.


Customizable HIPAA/GDPR compliant data capture allows sponsor to gather patient identifiable information, demographic data and answers to study specific questionnaires .


Online platform integrates into digital outreach and patient engagement strategies used by clinical trial sponsors, CROs and clinical sites.


Compatible with commonly used browsers on Windows and Mac with in-built technical validation checks to ensure maximum user accessibility and consistent data quality.

The user-focused interface, on-screen instructions, voiceover guidance and accessibility all help to give users of any age a simple and easy to follow experience.


Expert neuroanalytics enable datasets to be analyzed and reported to study sites and sponsors in accordance with inclusion/exclusion criteria.

Find out more about our tools to help recruitment rates for your study or speak to one of our scientists about using data to enrich study populations.


Hughes L, Kalali A, Vanbelle C, Cascade E. Innovative Digital Patient Recruitment Strategies in Prodromal AD trials. Poster at CTAD Annual Meeting, October 29-31, 2012.

Grill JD, Galvin JE. Facilitating Alzheimer disease research recruitment. Alzheimer Dis Assoc Disord. 2014 Jan-Mar;28(1):1-8.

de Rover, M., Pironti, V. a, McCabe, J. a, Acosta-Cabronero, J., Arana, F. S., Morein-Zamir, S., … Sahakian, B. J. (2011). Hippocampal dysfunction in patients with mild cognitive impairment: a functional neuroimaging study of a visuospatial paired associates learning task. Neuropsychologia, 49(7), 2060–70.

Barnett JH, Blackwell AD, Damian M. Cognitive & CSF Biomarkers in Older Adults, MCI, and Dementia. ICAD 2011 presentation.

Nathan PJ, Abbott R, Galluzzi S et al. Characterization of cognitive function with the CANTAB in individuals with amnestic MCI in relation to hippocampal volume, amyloid and tau status: Preliminary baseline results from the PharmaCog/European-ADNI Study. AAIC 2015 presentation. 

Scheltens P et al.  Baseline patient characteristics from the Phase 3 SCarlet RoAD trial, a study of gantenerumab in patients with prodromal AD. Presented at CTAD 2014, JPAD 2014; 1:231-2

Cormack F, Barnett JH, Nathan PJ et al. Stability of amnestic MCI: Cantab paired associate learning as a predictor of a consistent diagnosis. AAIC 2015 presentation.

Nathan PJ, Abbott R, Lim YY, et al. CSF b-Amyloid and APOE ɛ4 Related Decline in Episodic Memory over 12 months measured using the CANTAB in individuals with amnestic Mild Cognitive Impairment (MCI): Results from the European-ADNI/Pharmacog study. AAIC 2016 presentation.

Jansen WJ, Ossenkoppele R, Knol DL et al.  Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA. 2015 May 19;313(19):1924-38. 

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