SEATTLE INSTITUTE FOR BIOMEDICAL AND CLINICAL RESEARCH

Project objective: This project will perform annual cognitive evaluations on subjects previously enrolled in the Alzheimer's Disease Anti-Inflammatory Protection Trial (ADAPT). The purpose of these evaluations is to extend observations on the ADAPT outcomes of incident AD dementia and age-related cognitive decline in relation to treatment assignment in ADAPT (randomized to naproxen, celecoxib, or placebo). We seek in particular to discover whether naproxen can cause a long-term reduction in the incidence of AD dementia. We also seek to characterize a bi-directional or bi-phasic response of elderly people to naproxen (or, if any, to celecoxib) with a brief interval of increased incidence followed by a more substantial epoch of diminished risk. A secondary aim is to determine whether the limited exposures in ADAPT to either of the two NSAID treatments produced long-term change in age-related cognitive decline as a possible early manifestation of AD pathology. Research Plan: This is a follow-up study, utilizing a defined cohort. Subjects will undergo annual neuropsychological testing via telephone for 2 years. Methodology: All subjects previously enrolled in the Alzheimer's Disease Anti-Inflammatory Protection Trial (ADAPT) not known to be deceased will be mailed a study introduction letter. Field site personnel will then telephone these potential subjects to gauge their interest in the study. During this initial call, if the subject consents, a cognitive assessment will take place. This Comprehensive Telephone Assessment will include the following neuropsychological tests: Telephone Interview for Cognitive Status (TICS), Narrative Passages from the Rivermead Behavioral Memory Test (RBMT), Generative Verbal Fluency, delayed recall of TICS word list and the RBMT Narrative Passage. If applicable, a collateral respondent may be interviewed to complete the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Subjects will be given the results of their cognitive testing during a follow-up telephone call. Subjects with scores within the cognitively normally range will be administered a brief medical history questionnaire during this follow-up call. Subjects scoring below a certain threshold on the telephone assessment will be seen in-person for further cognitive testing, medical history review, and a physical exam. Results from the in-person visits will be used at diagnostic consensus conferences. The primary study analyses will compare the incidence of all-cause dementia and AD dementia in each ADAPT treatment group against placebo (not against each other). All subjects will be placed into two categories, cognitive normal or abnormal. The latter group will be identified as having Cognitive Impairment, No Dementia or DSM-IV or NINCDS dementia.

Clarification of Codes