Amyloid PET in Sporadic Early- Versus Late-Onset Alzheimer's Disease: Comparison of the LEADS and ADNI Cohorts.
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Lagarde Julien, Maiti Piyush, Schonhaut Daniel R, Blazhenets Ganna, Zhang Jiaxiuxiu, Eloyan Ani, Thangarajah Maryanne, Taurone Alexander, Allen Isabel Elaine, Soleimani-Meigooni David N, Zeltzer Ehud, Windon Charles, Abu Raya Maison, Vrillon Agathe, Smith Karen, Shankar Ranjani, Amuiri Alinda, Rocha Salma, Hammers Dustin B, Dage Jeffrey L, Nudelman Kelly N, Kirby Kala, Aisen Paul, Koeppe Robert, Landau Susan M, Carrillo Maria C, Touroutoglou Alexandra, Brickhouse Michael, Vemuri Prashanthi, Beckett Laurel, Raman Rema, Atri Alireza, Day Gregory S, Duara Ranjan, Graff-Radford Neill R, Honig Lawrence S, Jones David T, Masdeu Joseph C, Mendez Mario F, Womack Kyle, Musiek Erik, Onyike Chiadi U, Riddle Meghan, Grant Ian M, Rogalski Emily, Johnson Erik C B, Salloway Stephen, Sha Sharon, Turner R Scott, Wingo Thomas S, Wolk David A, Dickerson Bradford C, Apostolova Liana G, La Joie Renaud, Rabinovici Gil D, LEADS Consortium for the Alzheimer's Disease Neuroimaging Initiative
Аннотация
METHODS: Three hundred ninety-nine cognitively impaired participants younger than 65 years of age from the multicenter Longitudinal Early-onset Alzheimer's Disease Study (LEADS) and 450 cognitively impaired participants older than 65 years from the Alzheimer's Disease Neuroimaging Initiative (ADNI) underwent clinical assessment, brain magnetic resonance imaging (MRI), and amyloid PET and were included in this study. We compared amyloid PET outcomes (positivity rate based on visual read and quantified tracer uptake expressed as Centiloids [CLs]) between the 2 cohorts and studied their association with age, sex, APOE genotype, and cognition.
RESULTS: The amyloid positivity rate was higher in LEADS (78%, 95% confidence interval [CI] = 74-82) than in ADNI (71%, 95% CI = 67-75, p = 0.02). Lower Mini-Mental State Examination (MMSE) and APOE4 genotype increased the odds of amyloid positivity in both cohorts. Visually positive scans had higher CLs in LEADS (EOAD, mean = 95.3 ± 26.1) than in ADNI (LOAD, mean = 80.9 ± 36.8, p < 0.0001), predominantly in parietal cortex/precuneus, superior temporal, and frontal cortices. In amyloid-positive patients, (1) CLs were higher in female patients in both cohorts; (2) APOE4 carriership was associated with lower CLs in EOAD, which was not observed in LOAD; and (3) correlations between CLs and MMSE scores were significantly stronger in EOAD than in LOAD.
INTERPRETATION: Differences in the burden of amyloid pathology may contribute to differences in clinical and anatomic patterns in sporadic EOAD and LOAD, and have implications for optimizing therapeutic strategies in each group. ANN NEUROL 2025;98:236-248.