Behavioural Brain Research 149 (2004) 123–133 Research report Modeling a task that is sensitive to dementia of the Alzheimer’s type: individual differences in acquisition of a visuo-spatial paired-associate learning task in rhesus monkeys Michael A. Taffe ∗ , Michael R. Weed 1 , Tannia Gutierrez 2 , Sophia A. Davis, Lisa H. Gold 3 Department of Neuropharmacology, CVN-7, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA Received 5 May 2003; received in revised form 5 June 2003; accepted 14 June 2003 Abstract Early detection of progressive diseases such as Alzheimer’s Disease (AD) is crucial for both the treatment and study of the disease. Performance on a visuo-spatial paired-associates learning (vsPAL) task was recently shown to reliably predict a diagnosis of AD in aged populations. The present study reports the development of this vsPAL task for use in nonhuman primates. Translation of vsPAL to a nonhuman model may provide improved preclinical tools for study of the etiology and treatment of dementia. Twelve young adult male rhesus monkeys were trained to perform the vsPAL task concurrently with tests comprising a nonhuman primate neuropsychological test battery. Monkeys successfully learned to perform vsPAL and did so in a task-difficulty ranked fashion. Despite significant individual differences in capability in the acquisition of the recognition memory aspects of the task, all monkeys evidenced the ability to learn within-trial, i.e. to improve with repeated stimulus-location pairings. These results support the use of vsPAL performance under various challenge conditions to investigate the possible substrates of early cognitive decline in AD. Comparison of performance on vsPAL with performance on other memory tasks in the battery will be of more general use in differentiating mechanisms involved in various aspects of mnemonic function. © 2003 Elsevier B.V. All rights reserved. Keywords: Learning; Memory; CANTAB; Alzheimer’s; Cognition 1. Introduction Although conclusive diagnosis of Alzheimer’s Disease (AD) currently requires postmortem examination of brain tissue, the most commonly used diagnostic tool for identi- fying affected individuals prior to death is a battery of neu- ropsychological tests. A diagnosis of “probable Alzheimer’s Disease” may then be inferred from patterns of specific performance deficits [17,39]. Neuropsychological testing is likely to remain the standard given the relative inexpense of such tests compared with alternative diagnostics such as imaging [15,18] and given the absence of a reliable ante- ∗ Corresponding author. Tel.: +1-858-784-7228; fax: +1-858-784-7405. E-mail address: mtaffe@scripps.edu (M.A. Taffe). 1 Present address: Behavioral Biology Research Center, Johns Hopkins Medical School, 5510 Nathan Shock Drive, Suite 3000, Baltimore, MD 21224-6823, USA. 2 Present address: Department of Psychology, The University of Georgia, Athens, GA 30602-3013, USA. 3 Present address: Pharmacia Corporation, Mail Code 7251-209-431.2, 301 Henrietta Street, Kalamazoo, MI 49007, USA. mortem biomarker. Consequently, refinement of the sensitiv- ity and the specificity of the cognitive/behavioral tests used to evaluate cognitive function remains a continuing goal. Improving the specificity of such tests is particularly crucial to differentiate AD individuals from other popula- tions who may perform poorly on neuropsychological tests when proposing to use any risky or invasive treatment. For example, elderly subjects with major depression perform poorly on tests of memory that AD subjects also perform poorly (see [13,40] for review). Refinement of the sen- sitivity of neuropsychological tests would allow possible disease-modifying treatments (e.g. [2,12]) to be employed at the earliest stages of neuronal loss, thereby minimizing damage and maximizing quality of life. Finally, on a more practical level any reduction in the number of test-battery items required to detect AD would lead to a reduced cost of clinical evaluation and decreased burden on the evaluated patients. These reasons and others have motivated a num- ber of attempts to determine which behavioral tests may be most specific for, and sensitive to, cognitive impairments early in AD (e.g. [4,5,16,21]). 0166-4328/$ – see front matter © 2003 Elsevier B.V. All rights reserved. doi:10.1016/S0166-4328(03)00214-6