Sensitivity of composite scores to amyloid burden in preclinical Alzheimer's disease: introducing the Z-scores of attention, verbal fluency, 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 β-amyloid (Aβ)-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 Aβ (Aβ+) and very high Aβ (Aβ++) in cognitively normal (CN) older adults on three multidomain cognitive composite scores and one single-domain (EM) composite score. Methods: CN older adults (n = 423) underwent Aβ 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 Aβ+ CN older adults, Aβ++ CN older adults showed faster rates of decline across all cognitive composites, with the largest decline observed for ZAVEN composite (d = 1.07). Similarly, compared with Aβ- CN older adults, Aβ+ CN older adults also showed faster rates of cognitive decline, but only for the ADCS-PACC no MMSE (d = 0.43), EM (d = 0.53), and ZAVEN (d = 0.50) composites. Discussion: Aβ-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 function (verbal fluency; i.e., the ZAVEN) rendered this composite more sensitive even in detecting Aβ-related cognitive decline between Aβ+ and Aβ++ CN older adults.