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

OBJECTIVE: To determine the effect of ß-amyloid (Aß) 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 Aß PET and ≥3 years follow-up were included (n = 534; age 72 ± 6 years; 27% Aß positive; follow-up 5.3 ± 1.7 years). Aß 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: Aß 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 Aß, the hazard ratio for progression for moderate Aß 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 Aß 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.

Added value of amyloid PET in individualized risk predictions for MCI patients.

INTRODUCTION: To construct a prognostic model based on amyloid positron emission tomography (PET) to predict clinical progression in individual patients with mild cognitive impairment (MCI). METHODS: We included 411 MCI patients from the Alzheimer's Disease Neuroimaging Initiative. Prognostic models were constructed with Cox regression with demographics, magnetic resonance imaging, and/or amyloid PET to predict progression to Alzheimer's disease dementia. The models were validated in the Amsterdam Dementia Cohort. RESULTS: The combined model (Harrell's C = 0.82 [0.78-0.86]) was significantly superior to demographics (ß = 0.100, P < .001), magnetic resonance imaging (ß = 0.037, P = .011), and PET only models (ß = 0.053, P = .003).The models can be used to calculate individualized risk, for example, a female MCI patient (age = 60, APOE ε4 positive, Mini-Mental State Examination = 25, hippocampal volume = 5.8 cm3, amyloid PET positive) has 35% (19-57) risk in one year and 85% (64-97) risk in three years. Model performances in the Amsterdam Dementia Cohort were reasonable. DISCUSSION: The present study facilitates the interpretation of an amyloid PET result in the context of a patient's own characteristics and clinical assessment.