Premium
Incidence of subjective cognitive decline is associated with amyloid‐β pathology, whereas stability relates to neurodegeneration
Author(s) -
SánchezBenavides Gonzalo,
GrauRivera Oriol,
SuárezCalvet Marc,
MilàAlomà Marta,
NiñerolaBaizán Aida,
Perissinotti Andrés,
Salvadó Gemma,
ArenazaUrquijo Eider M.,
Gispert Juan Domingo,
VilorTejedor Natalia,
SalaVila Aleix,
CrousBou Marta,
GonzálezdeEchávarri José Maria,
Minguillón Carolina,
Fauria Karine,
Cacciaglia Raffaele,
Operto Greg,
Falcon Carles,
Kollmorgen Gwendlyn,
Zetterberg Henrik,
Blennow Kaj,
Molinuevo Jose Luis
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.045293
Subject(s) - medicine , cognitive decline , neurodegeneration , incidence (geometry) , logistic regression , disease , amyloid (mycology) , neuroimaging , oncology , neurogranin , biomarker , pathology , dementia , psychiatry , biology , physics , optics , biochemistry , protein kinase c , enzyme
Background Subjective Cognitive Decline (SCD) is a risk factor for cognitive decline and increases the likelihood of abnormal Alzheimer’s disease (AD) biomarkers. A set of SCD features (SCD plus ) has been proposed to be more strongly related with AD pathology, like onset within 5 years. Limited evidence suggest that there is an association between recent SCD onset and amyloid‐β (Aβ) levels but longitudinal studies exploring this association are lacking. Our objective was to explore the association between incidence and stability of SCD and biomarkers of AD pathology, synaptic dysfunction and neurodegeneration. Method We analyzed clinical, neuroimaging and cerebrospinal fluid (CSF)‐biomarkers data from 261 cognitively unimpaired individuals from the ALFA+ study [mean age 57(5) at baseline]. SCD status was recorded at baseline and follow‐up [mean interval 48.5(8.6) months, 80% before 60 months] using the SCD‐Q question: Do you perceive memory or cognitive difficulties? Individuals were classified as Stable‐SCD [SCD at both visits (n=28)], Incident‐SCD [SCD only at follow‐up (n=44)], Unstable‐SCD [SCD only at baseline (n=21)], and non‐SCD [no SCD at any visit (n=168)]. All remained cognitively unimpaired at follow‐up. We defined amyloid status by visual reads (Aβ+/Aβ‐) from [ 18 F]flutemetamol PET scans. Aβ40, Aβ42, p‐tau, t‐tau, neurogranin and Neurofilament Light (NfL) were measured with Roche NeuroToolKit and Elecsys® immunoassays (Roche Diagnostics). Logistic regression models were used to predict Aβ status and ANCOVA models to explore differences in biomarkers, adjusting for age, sex and interval between visits. Result The proportion of Aβ+ individuals was higher in Incident‐SCD as compared to non‐SCD (OR=2.5, p=0.04, Table 1). Further, Incident‐SCD group displayed lower Aβ42/Aβ40 than non‐SCD (p=0.02, partial Eta 2 =0.02). While Stable‐SCD did not show differences in amyloid measures as compared to controls, NfL was significantly increased (p<0.0001, p‐Eta 2 =0.08) and t‐tau approached significance (p=0.08). Conclusion Recent SCD onset was associated with amyloid‐β pathology, while stable SCD, even without clinical progression, was associated to biomarkers of neurodegeneration but not to amyloid pathology. These results support the usefulness of the onset in the last 5 years as SCD plus feature to detect amyloid pathology, while also highlights the role of neurodegeneration in SCD maintenance.