Early and late change on the preclinical Alzheimer's cognitive composite in clinically normal older individuals with elevated amyloid β

Abstract

Introduction Sensitive detection of cognitive decline over the course of preclinical Alzheimer’s disease is critical as the field moves toward secondary prevention trials. Methods We examined Aβ-related change in several variations of the preclinical Alzheimer cognitive composite (PACC) and each individual PACC component in clinically normal (CN) older participants in the Harvard Aging Brain Study. We then examined the PACC variations in the Alzheimer’s Disease Cooperative Study Prevention Instrument Study as a replication cohort. Results Aβ+ CN individuals demonstrated longitudinal decline on all individual PACC components and all PACC variations. Aβ group differences emerged earlier when Free and Cued Selective Reminding Test Free Recall was included in the PACC. PACC decline was associated with Clinical Dementia Rating progression. Discussion This independent data set and a replication cohort confirm the ability of the PACC to capture both early and late cognitive decline during the preclinical stages of Alzheimer’s disease, which may prove advantageous in the prevention trial design.

Morphometric Definition of Alzheimer's Disease Stages by Means of The Tomography Dementia Rating Scale (TDR)

“…The presented data are confirmed by studies of other authors who showed the presence of atrophic changes in temporal lobes in patients suffering from AD [3,12,16,19] and the absence of similar atrophic changes in patients suffering from neurodegenerative lesions of another etiology such as dementia with Lewi bodies and vascular cognitive lesions [6].…”

Clinical and cognitive characteristics of preclinical Alzheimer's disease in the Japanese Alzheimer's Disease Neuroimaging Initiative cohort

“…The PACC is composed of the MMSE, two memory tests: the logical memory and the free and cued selective reminding test, and the digit symbol substitution test [7]. Individuals with preclinical AD exhibited longitudinal decline on every component of the PACC [13]. Furthermore, Papp et al.…”

“…The PACC is composed of the MMSE, two memory tests: the logical memory and the free and cued selective reminding test, and the digit symbol substitution test [7]. Individuals with preclinical AD exhibited longitudinal decline on every component of the PACC [13]. Furthermore, Papp et al developed the PACC5, which added category fluency tests to the PACC as a cognitive composite more sensitive to amyloid-related cognitive decline in preclinical AD than the PACC [14].…”

Measuring longitudinal cognition: Individual tests versus composites

“…Three domain-specific theoretical composites, previously used in WRAP, represent immediate learning (THEO-IMM-LRN), delayed recall (THEO-DEL-REC), and executive function (THEO-EXEC-FN) [24] ( Table 2, columns 6-8). We also considered five global composites ( Table 2, columns 9-13), including the global preclinical Alzheimer's composite (PACC4-MMSE) [8]; a three-test PACC version omitting MMSE, due to its limited sensitivity in middle-aged healthy samples (PACC3) [30]; and a PACC version replacing MMSE with the CFL (PACC4-CFL) [31]. Furthermore, because one PACC test, DIGSYM, is not available in the National Alzheimer's Coordinating Center Uniform Data Set, Third Edition [6], we included two experimental versions of the PACC4 substituting TMT-B for DIGSYM, both with (PACC4-TMTB) and without (PACC3-TMTB) MMSE.…”