Amyloid PET in Sporadic Early- Versus Late-Onset Alzheimer's Disease: Comparison of the LEADS and ADNI Cohorts.

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY Annals of Neurology Pub Date : 2025-03-17 DOI:10.1002/ana.27233

Julien Lagarde, Piyush Maiti, Daniel R Schonhaut, Ganna Blazhenets, Jiaxiuxiu Zhang, Ani Eloyan, Maryanne Thangarajah, Alexander Taurone, Isabel Elaine Allen, David N Soleimani-Meigooni, Ehud Zeltzer, Charles Windon, Maison Abu Raya, Agathe Vrillon, Karen Smith, Ranjani Shankar, Alinda Amuiri, Salma Rocha, Dustin B Hammers, Jeffrey L Dage, Kelly N Nudelman, Kala Kirby, Paul Aisen, Robert Koeppe, Susan M Landau, Maria C Carrillo, Alexandra Touroutoglou, Michael Brickhouse, Prashanthi Vemuri, Laurel Beckett, Rema Raman, Alireza Atri, Gregory S Day, Ranjan Duara, Neill R Graff-Radford, Lawrence S Honig, David T Jones, Joseph C Masdeu, Mario F Mendez, Kyle Womack, Erik Musiek, Chiadi U Onyike, Meghan Riddle, Ian M Grant, Emily Rogalski, Erik C B Johnson, Stephen Salloway, Sharon Sha, R Scott Turner, Thomas S Wingo, David A Wolk, Bradford C Dickerson, Liana G Apostolova, Renaud La Joie, Gil D Rabinovici

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引用次数: 0

Abstract

Objective: Early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) differ in many respects. Here, we address the issue of possible differences in fibrillar amyloid pathology as measured by positron emission tomography (PET), which remains unresolved due to the lack of large-scale comparative studies.

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.

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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.