Association of β-Amyloid Level, Clinical Progression, and Longitudinal Cognitive Change in Normal Older Individuals

Objective To determine the effect of beta-amyloid (A beta) 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 A beta PET and >= 3 years follow-up were included (n = 534; age 72 +/- 6 years; 27% A beta positive; follow-up 5.3 +/- 1.7 years). A beta 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 A beta 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 A beta, the hazard ratio for progression for moderate A beta 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 A beta 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.

Automated summary

The study found that in cognitively normal older individuals, the level of beta-amyloid is related to the risk of progression to mild cognitive impairment or dementia. Higher levels of beta-amyloid were associated with increased risk of developing cognitive decline, indicating a potential biomarker for dementia risk assessment and preclinical AD trial design.