Clinical Impact and Prognostic Value of Alzheimer Disease Biomarkers in the Very Old
Ceriello, Chiara (Universitat Autònoma de Barcelona. Departament de Medicina)
Torres Bonafonte, Olga H. (Institut de Recerca Sant Pau)
Rubio Guerra, Sara (Institut de Recerca Sant Pau)
Garcia Castro, Jesús (Institut de Recerca Sant Pau)
Selma Gonzalez, Judit (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Sala Matavera, Isabel (Universitat Autònoma de Barcelona. Departament de Psicologia Clínica i de la Salut)
Sánchez-Saudinós, María Belén (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Videla Toro, Laura (Institut de Recerca Sant Pau)
Vera-Campuzano, Elena (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Arranz Martínez, Javier (Institut de Recerca Sant Pau)
Rodríguez-Baz, Íñigo (Institut de Recerca Sant Pau)
Maure Blesa, Lucia (Institut de Recerca Sant Pau)
Dols Icardo, Oriol (Institut de Recerca Sant Pau)
Valldeneu, Silvia (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Barroeta, Isabel (Institut de Recerca Sant Pau)
Santos Santos, Miguel Ángel (Institut de Recerca Sant Pau)
Carmona Iragui, Maria (Institut de Recerca Sant Pau)
Vaqué-Alcázar, Lídia (Institut de Recerca Sant Pau)
Álvarez-Sánchez, Esther (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Lorente, Oriol (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Carreras, Mireia (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Bejanin, Alexandre (Institut de Recerca Sant Pau)
Belbin, Olivia (Institut de Recerca Sant Pau)
Lleó, Alberto (Universitat Autònoma de Barcelona. Departament de Medicina)
Fortea, Juan (Universitat Autònoma de Barcelona. Departament de Medicina)
Alcolea, Daniel (Institut de Recerca Sant Pau)
Illán-Gala, Ignacio (Institut de Recerca Sant Pau)

Data:	2026
Resum:	Background and Objectives: Alzheimer disease (AD) is increasingly viewed as a clinical-biological continuum, but the utility of biomarkers in individuals aged ≥80 years, the so-called “very old,” remains uncertain, because of concerns about its clinical usefulness. This study aimed to determine the clinical impact and prognostic value of AD biomarkers in very old individuals. Methods: We performed a retrospective longitudinal cohort study within the Sant Pau Initiative on Neurodegeneration (SPIN, Barcelona, Spain), a memory clinic–based research cohort. Patients were referred from primary care physicians or community neurologists for evaluation within a public universal health care catchment area. We included SPIN participants evaluated between October 2013 and May 2024 who were aged ≥80 years and had mild cognitive impairment (MCI) at the baseline visit. Participants underwent standardized clinical and neuropsychological assessments and had CSF and plasma biomarker measurements available. AD biology was defined by the CSF phosphorylated tau at threonine 181/amyloid-β 42 ratio. Plasma phosphorylated tau at threonine 217 (p-Tau217) was evaluated for (1) diagnostic accuracy for AD biology and (2) prognostic associations with longitudinal cognitive change (Mini-Mental State Examination [MMSE]) and progression to dementia. Analyses used linear mixed-effects models for MMSE trajectories and Cox regression for dementia conversion. Results: A total of 167 participants were included (mean age 82. 3 years, 59% women) with a mean follow-up of 35. 8 months; the ones with AD biology (n = 116, 69%) had worse baseline cognitive performance, particularly in memory, compared with those without (Cohen d = 0. 34, p = 0. 03). Plasma p-Tau217 showed excellent diagnostic accuracy for detecting AD biology (0. 93, 95% CI 0. 88–0. 98; cutoff 0. 19 pg/mL; sensitivity 94. 5%; specificity 84%). Over time, participants with AD biology declined faster on the MMSE than those without (−0. 47 vs −0. 18 points per year; p < 0. 01). Cox models showed an increased risk of progression to a dementia stage among individuals with higher plasma p-Tau217 concentrations (hazard ratio 1. 49, 95% CI 1. 05–2. 13, p = 0. 026). Discussion: In very old individuals with MCI, AD biology (CSF) and plasma p-Tau217 identify individuals at higher risk of faster cognitive decline and progression to dementia. Limitations of this study include the single-center design and the modest sample size.
Ajuts:	Generalitat de Catalunya 2021/SGR-00979 Ministerio de Economía y Competitividad PI14/01126 Instituto de Salud Carlos III PI17/01019 Instituto de Salud Carlos III PI18/00335 Instituto de Salud Carlos III PI19/00882 Instituto de Salud Carlos III PI18/00435 Instituto de Salud Carlos III PI22/00611 Instituto de Salud Carlos III PI17/01896 Instituto de Salud Carlos III PI22/00307 Instituto de Salud Carlos III AC19/00103 Instituto de Salud Carlos III ICI23/00032 Instituto de Salud Carlos III PI20/01473 Instituto de Salud Carlos III PI24/01087 Instituto de Salud Carlos III PI23/01786 Instituto de Salud Carlos III PI21/00791 Instituto de Salud Carlos III PI2400598 Generalitat de Catalunya 2017/SGR-00547 Fundació la Marató de TV3 20141210 Fundació la Marató de TV3 044412 Fundació la Marató de TV3 20142610
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Neurology, Vol. 107, Num. 1 (June 2026) , ISSN 1526-632X

DOI: 10.1212/WNL.0000000000218180

12 p, 822.7 KB

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