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Longitudinal clinical, cognitive and biomarker profiles in dominantly inherited versus sporadic early-onset Alzheimer's disease

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dc.contributor.author Llibre Guerra, Jorge J.
dc.contributor.author Iaccarino, Leonardo
dc.contributor.author Coble, Dean
dc.contributor.author Edwards, Lauren
dc.contributor.author Li, Yan
dc.contributor.author McDade, Eric
dc.contributor.author Strom, Amelia
dc.contributor.author Gordon, Brian A.
dc.contributor.author Mundada, Nidhi
dc.contributor.author Schindler, Suzanne E.
dc.contributor.author Tsoy, Elena
dc.contributor.author Ma, Yinjiao
dc.contributor.author Lu, Ruijin
dc.contributor.author Fagan, Anne M.
dc.contributor.author Benzinger, Tammie L.S.
dc.contributor.author Soleimani Meigooni, David
dc.contributor.author Aschenbrenner, Andrew J.
dc.contributor.author Allegri, Ricardo Francisco
dc.contributor.author Patricio Alexis, Chrem Méndez
dc.contributor.author Surace, Ezequiel Ignacio
dc.date.accessioned 2024-03-15T14:57:02Z
dc.date.available 2024-03-15T14:57:02Z
dc.date.issued 2023-10-18
dc.identifier.citation Llibre-Guerra JJ, Iaccarino L, Coble D, Edwards L, Li Y, McDade E, et al. Longitudinal clinical, cognitive and biomarker profiles in dominantly inherited versus sporadic early-onset Alzheimer’s disease. Brain Commun. 2023;5(6):fcad280. es_ES
dc.identifier.uri https://doi.org/10.1093/braincomms/fcad280
dc.identifier.uri https://repositorio.fleni.org.ar/xmlui/handle/123456789/1042
dc.description.abstract Approximately 5% of Alzheimer's disease cases have an early age at onset (<65 years), with 5-10% of these cases attributed to dominantly inherited mutations and the remainder considered as sporadic. The extent to which dominantly inherited and sporadic early-onset Alzheimer's disease overlap is unknown. In this study, we explored the clinical, cognitive and biomarker profiles of early-onset Alzheimer's disease, focusing on commonalities and distinctions between dominantly inherited and sporadic cases. Our analysis included 117 participants with dominantly inherited Alzheimer's disease enrolled in the Dominantly Inherited Alzheimer Network and 118 individuals with sporadic early-onset Alzheimer's disease enrolled at the University of California San Francisco Alzheimer's Disease Research Center. Baseline differences in clinical and biomarker profiles between both groups were compared using t-tests. Differences in the rates of decline were compared using linear mixed-effects models. Individuals with dominantly inherited Alzheimer's disease exhibited an earlier age-at-symptom onset compared with the sporadic group [43.4 (SD ± 8.5) years versus 54.8 (SD ± 5.0) years, respectively, P < 0.001]. Sporadic cases showed a higher frequency of atypical clinical presentations relative to dominantly inherited (56.8% versus 8.5%, respectively) and a higher frequency of APOE-ε4 (50.0% versus 28.2%, P = 0.001). Compared with sporadic early onset, motor manifestations were higher in the dominantly inherited cohort [32.5% versus 16.9% at baseline (P = 0.006) and 46.1% versus 25.4% at last visit (P = 0.001)]. At baseline, the sporadic early-onset group performed worse on category fluency (P < 0.001), Trail Making Test Part B (P < 0.001) and digit span (P < 0.001). Longitudinally, both groups demonstrated similar rates of cognitive and functional decline in the early stages. After 10 years from symptom onset, dominantly inherited participants experienced a greater decline as measured by Clinical Dementia Rating Sum of Boxes [3.63 versus 1.82 points (P = 0.035)]. CSF amyloid beta-42 levels were comparable [244 (SD ± 39.3) pg/ml dominantly inherited versus 296 (SD ± 24.8) pg/ml sporadic early onset, P = 0.06]. CSF phosphorylated tau at threonine 181 levels were higher in the dominantly inherited Alzheimer's disease cohort (87.3 versus 59.7 pg/ml, P = 0.005), but no significant differences were found for t-tau levels (P = 0.35). In summary, sporadic and inherited Alzheimer's disease differed in baseline profiles; sporadic early onset is best distinguished from dominantly inherited by later age at onset, high frequency of atypical clinical presentations and worse executive performance at baseline. Despite these differences, shared pathways in longitudinal clinical decline and CSF biomarkers suggest potential common therapeutic targets for both populations, offering valuable insights for future research and clinical trial design. es_ES
dc.language.iso eng es_ES
dc.publisher Oxford University Press es_ES
dc.rights info:eu-repo/semantics/openAccess
dc.subject Alzheimer Disease es_ES
dc.subject Enfermedad de Alzheimer es_ES
dc.subject Biomarkers es_ES
dc.subject Biomarcadores es_ES
dc.title Longitudinal clinical, cognitive and biomarker profiles in dominantly inherited versus sporadic early-onset Alzheimer's disease es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.type info:eu-repo/semantics/publishedVersion
dc.description.fil Fil: Allegri, Ricardo Francisco. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría. Centro de Memoria y Envejecimiento; Argentina.
dc.description.fil Fil: Surace, Ezequiel Ignacio. Fleni. Departamento de Neuropatología y Biología Molecular. Laboratorio de Enfermedades Neurodegenerativas; Argentina. Fleni. Instituto de Neurociencias FLENI-CONICET. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.
dc.description.fil Fil: Chrem Méndez, Patricio Alexis. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría. Centro de Memoria y Envejecimiento; Argentina.
dc.relation.ispartofVOLUME 5
dc.relation.ispartofNUMBER 6
dc.relation.ispartofCOUNTRY Reino Unido
dc.relation.ispartofCITY Oxford
dc.relation.ispartofTITLE Brain communications
dc.relation.ispartofISSN 2632-1297
dc.type.snrd info:ar-repo/semantics/artículo es_ES


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