P3‐031: CLINICAL MEANINGFULNESS OF SHORT‐TERM COGNITIVE DECLINE ON THE PRECLINICAL ALZHEIMER'S COGNITIVE COMPOSITE‐5 (PACC‐5) IN NORMAL OLDER ADULTS WITH ELEVATED β‐AMYLOID
Year: 2019
Type: article
Abstract: The need to demonstrate "clinical meaningfulness" of slowing cognitive decline is imperative for secondary prevention treatment approval in Alzheimer's disease (AD). This poses a significant challenge as individuals in preclinical disease stages may not manifest functional progression within the short time-course of a clinical trial making it difficult to assess treatment effects. Our objective was to determine whether 3-year cognitive trajectories among clinically normal older adults with elevated β-amyloid (Aβ+) predict subsequent diagnosis of Mild Cognitive Impairment (MCI) at years 3, 4, 5 and 6 of the study. Cox regression analyses were used to determine whether 3-year cognitive slopes on the Preclinical Alzheimer Cognitive Composite (PACC5) predicted MCI diagnosis controlling for age, sex, education, and baseline cognition. Clinically normal (CN) older adults (n=267) with abnormal AD biomarkers (elevated β-amyloid on molecular neuroimaging) were selected from the Harvard Aging Brain Study (HABS), the Australian Imaging, Biomarker and Lifestyle Study (AIBL), and the AD Neuroimaging Initiative (ADNI). Aβ+ participants declined annually on PACC5 an average of −0.12 standard deviations in HABS, −0.10 in AIBL, and −0.15 standard deviations in ADNI. Rates of MCI progression at or after 3 years were 20% (HABS), 26% (AIBL), and 32% (ADNI). Steeper PACC5 decline was associated with increased risk for MCI diagnosis across all cohorts (HABS, p=0.033; AIBL, p=0.000; and ADNI, p=0.019). For example, in a "decliner" group defined as slope< median, hazard for MCI diagnosis increased by a factor of 4.92 in HABS, 4.21 in AIBL, and 2.73 in ADNI. Additionally, steeper PACC5 decline was associated with increased risk for subtler functional impairment, i.e., progression to a Global Clinical Dementia Rating score of 0.5 (without diagnosis of MCI) at any follow-up.
Source: Alzheimer s & Dementia
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2981166949