Document Type
Journal Article
Publication Title
Neurology
Publisher
Wolters Kluwer
School
School of Medical and Health Sciences
RAS ID
32580
Funders
Core funding for the study was provided by the CSIRO Flagship Collaboration Fund and the Science and Industry Endowment Fund in partnership with Austin Health, University of Melbourne, Edith Cowan University, Florey Institute of Neuroscience and Mental Health, Alzheimer's Australia, and the National Ageing Research Institute. The study also received funding from the National Health and Medical Research Council, the Dementia Collaborative Research Centres program, the McCusker Alzheimer's Research Foundation, and Operational Infrastructure Support from the Government of Victoria.
Abstract
Objective To determine the effect of β-amyloid (Aβ) level on progression risk to mild cognitive impairment (MCI) or dementia and longitudinal cognitive change in cognitively normal (CN) older individuals. Methods All CN from the Australian Imaging Biomarkers and Lifestyle study with Aβ PET and ≥ 3 years follow-up were included (n = 534; age 72 ± 6 years; 27% Aβ positive; follow-up 5.3 ± 1.7 years). Aβ level was divided using the standardized 0–100 Centiloid scale: < 15 CL negative, 15–25 CL uncertain, 26–50 CL moderate, 51–100 CL high, > 100 CL very high, noting > 25 CL approximates a positive scan. Cox proportional hazards analysis and linear mixed effect models were used to assess risk of progression and cognitive decline. Results Aβ levels in 63% were negative, 10% uncertain, 10% moderate, 14% high, and 3% very high. Fifty-seven (11%) progressed to MCI or dementia. Compared to negative Aβ, the hazard ratio for progression for moderate Aβ was 3.2 (95% confidence interval [CI] 1.3–7.6; p < 0.05), for high was 7.0 (95% CI 3.7–13.3; p < 0.001), and for very high was 11.4 (95% CI 5.1–25.8; p < 0.001). Decline in cognitive composite score was minimal in the moderate group (−0.02 SD/year, p = 0.05), while the high and very high declined substantially (high −0.08 SD/year, p < 0.001; very high −0.35 SD/year, p < 0.001). Conclusion The risk of MCI or dementia over 5 years in older CN is related to Aβ level on PET, 5% if negative vs 25% if positive but ranging from 12% if 26–50 CL to 28% if 51–100 CL and 50% if > 100 CL. This information may be useful for dementia risk counseling and aid design of preclinical AD trials.
DOI
10.1212/WNL.0000000000011222
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Comments
van der Kall, L. M., Truong, T., Burnham, S. C., Doré, V., Mulligan, R. S., Bozinovski, S., ... Rowe, C. C. (2021). Association of β-amyloid level, clinical progression, and longitudinal cognitive change in normal older individuals. Neurology, 96(5), e662-e670. https://doi.org/10.1212/WNL.0000000000011222