Cognitive & Behavioral Assessment Sensitivity of composite scores to amyloid burden in preclinical Alzheimer'sdisease:IntroducingtheZ-scoresofAttention,Verbalfluency, and Episodic memory for Nondemented older adults composite score

Introduction: Cognitive composite scores developed for preclinical Alzheimer’s disease (AD) often consist of multiple cognitive domains as they may provide greater sensitivity to detect b-amyloid (Ab)–related cognitive decline than episodic memory (EM) composite scores alone. However, this has never been empirically tested. We compared the rate of cognitive decline associated with high Ab (Ab1) and very high Ab (Ab11) in cognitively normal (CN) older adults on three multidomain cognitive composite scores and one single-domain (EM) composite score. Methods: CN older adults (n 5 423) underwent Ab neuroimaging and completed neuropsychological assessments at baseline, and at 18-, 36-, 54-, and 72-month follow-ups. Four cognitive composite scores were computed: the ADCS-PACC (ADCS-Preclinical Alzheimer Cognitive Composite), ADCS-PACC without the inclusion of the mini-mental state examination (MMSE), an EM composite, and the Z-scores of Attention, Verbal fluency, and Episodic memory for Nondemented older adults (ZAVEN) composite. Results: Compared with Ab1 CN older adults, Ab11 CN older adults showed faster rates of decline across all cognitive composites, with the largest decline observed for ZAVEN composite (d 5 1.07). Similarly, compared with Ab2 CN older adults, Ab1 CN older adults also showed faster rates of cognitive decline, but only for the ADCS-PACC no MMSE (d 5 0.43), EM (d 5 0.53), and ZAVEN (d 5 0.50) composites. Discussion: Ab-related cognitive decline is best detected using validated neuropsychological instruments. Removal of the MMSE from the ADCS-PACC and replacing it with a test of executive