Document Type

Journal Article




School of Medical and Health Sciences / Centre of Excellence for Alzheimer’s Disease Research and Care




Commonwealth Scientific Industrial and Research Or-ganization [CSIRO]

Edith Cowan University [ECU]

Mental Health Research Institute [MHRI]

National AgeingResearch Institute [NARI],

Austin Health, CogState Ltd

National Healthand Medical Research Council (NHMRC)

DementiaCollaborative Research Centres program (DCRC2)

Science and Industry EndowmentFund (SIEF)

Cooperative Research Centre forMental Health (CRCMH)

Alzheimer’s Australia Dementia Research Fellowship

Yulgilbar Foundation


Lim, Y. Y., Snyder, P. J., Pietrzak, R. H., Ukiqi, A., Villemagne, V. L., Ames, D., ... Maruff, P. (2016). 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. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 2(1), 19-26.



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.


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.


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.


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.



Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.