Longitudinal Trajectories of the Cognitive Function Index in the A4 Study - 21/11/24
, J.D. Grill 2, D.M. Rentz 1, G.A. Marshall 1, M.C. Donohue 3, A. Liu 3, P.S. Aisen 3, R.A. Sperling 1A4 Study team
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Abstract |
Background |
The Anti-Amyloid in Asymptomatic Alzheimer’s Disease (A4) Study failed to show a treatment benefit with solanezumab, but the longitudinal consequences of elevated amyloid were observed in study participants with objective decline on the Preclinical Alzheimer Cognitive Composite (PACC) and subjective decline on the combined Cognitive Function Index (participant + study partner CFI), during the trial period.
Objectives |
We sought to expand on previous findings by comparing longitudinal patterns of participant and study partner CFI separately and their associations with the PACC stratified by baseline amyloid tertile over the course of the A4 Study.
Design |
Cognitively unimpaired older adult participants and their study partners were independently administered the CFI at screen prior to amyloid PET disclosure and then at 3 subsequent visits (week 48, week 168, week 240) of the study. PACC collected at visits concurrent with CFI administration were also examined longitudinally.
Setting |
The A4 Study was conducted at 67 sites in Australia, Canada, Japan, and the United States.
Participants |
1,147 participants with elevated amyloid based on florbetapir PET were enrolled in the A4 Study and included in these analyses. 583 were on placebo and 564 were treated with solanezumab.
Measurements |
The PACC was used to assess objective cognitive performance and the CFI was used to assess change in everyday cognitive functioning by the participant and their study partner independently. Amyloid level was characterized by Centiloid tertiles (<46.1 CL, 46.1 to 77.2 CL, >77.2 CL). Participants were aware of their elevated amyloid status, but not their CL tertile, or specific level of amyloid. Longitudinal correlations between participant and study partner CFI and PACC were examined at all visits where assessments were available. The impact of baseline amyloid tertile on CFI and PACC associations was also examined.
Results |
Both participant and study partner CFI increased over the duration of the study indicating worsening cognitive functioning. Results did not differ by treatment group. The association between higher CFI and worse PACC for both for participant and study partner became progressively stronger over the course of the study. PACC had a significantly higher correlation with study partner CFI than with participant CFI by week 168. The stronger correlations between study partner CFI and PACC were driven by those in the highest amyloid tertile.
Conclusion |
Both participant and study partner report captured subtle changes in everyday cognitive functioning for participants with biomarker confirmed and disclosed preclinical AD. Moreover, study partner report was most highly aligned with cognitive decline, particularly among those with the highest amyloid load.
Il testo completo di questo articolo è disponibile in PDF.Key words : Amyloid, positron emission tomography, preclinical Alzheimer’s disease, subjective cognitive decline
Mappa
| Research in context 1. Systematic Review: The Cognitive Function Index is an instrument developed to assess change in cognitive functioning that can be completed by participants and study partners. We searched the literature for the development and use of the CFI as an outcome measure in observational studies and clinical trials. We sought to determine the differential patterns of participant and study partner report among those who participated in the Anti-Amyloid in Asymptomatic Alzheimer’s Disease (A4) secondary prevention study. 2. Interpretation: Both participant and study partner CFI increased over the duration of the study indicating worsening cognitive functioning. The association between higher CFI and worse PACC for participant and study partner became progressively stronger over the course of the study. The stronger correlations between study partner CFI and PACC were driven by those in the highest amyloid tertile. Collecting both participant and study partner report in prevention trials is important, even at the preclinical stage. 3. Future Directions: Future work that further explores the differential patterns of participant and study partner report at an individual item level (i.e., specific memory concerns) will have applications for future clinical trials and eventually clinical care. |
Vol 11 - N° 4
P. 838-845 - Agosto 2024 Ritorno al numero
Articolo precedente
- Relationship between Plasma P-Tau217 and Amyloid PET in Racial and Ethnic Underrepresented Groups (RE-URG) Compared with Non RE-URG in LEARN and A4
- Doris Molina-Henry, O. Langford, M.C. Donohue, R. Raman, P. Aisen, K.A. Johnson, R.A. Rissman, R. Sperling, A4 & LEARN Study Teams
- Change in Digital Cognitive Test Performance between Solanezumab and Placebo Groups in Preclinical Alzheimer’s Disease: Secondary Analyses from the A4 Study
- Kathryn V. Papp, P. Maruff, D.M. Rentz, M.C. Donohue, A. Liu, P.S. Aisen, R.A. Sperling, A4 Study Team
Benvenuto su EM|consulte, il riferimento dei professionisti della salute.