Background: The relationship between Alzheimer's disease (AD)-related pathology and cognition was not exactly consistent.
Objective: To explore whether the association between AD pathology and cognition can be moderated by frailty.
Methods: We included 1711 participants from the Alzheimer's Disease Neuroimaging Initiative database. Levels of cerebrospinal fluid amyloid-β, p-tau, and t-tau were identified for AD-related pathology based on the amyloid-β/tau/neurodegeneration (AT[N]) framework. Frailty was measured using a modified Frailty Index-11 (mFI-11). Regression and interaction models were utilized to assess the relationship among frailty, AT(N) profiles, and cognition. Moderation models analyzed the correlation between AT(N) profiles and cognition across three frailty levels. All analyses were corrected for age, sex, education, and APOEɛ4 status.
Results: In this study, frailty (odds ratio [OR] = 1.71, p < 0.001) and AT(N) profiles (OR = 2.00, p < 0.001) were independently associated with cognitive status. The model fit was improved when frailty was added to the model examining the relationship between AT(N) profiles and cognition (p < 0.001). There was a significant interaction between frailty and AT(N) profiles in relation to cognitive status (OR = 1.12, pinteraction = 0.028). Comparable results were obtained when Mini-Mental State Examination scores were utilized as the measure of cognitive performance. The association between AT(N) profiles and cognition was stronger with the levels of frailty.
Conclusions: Frailty may diminish patients' resilience to AD pathology and accelerate cognitive decline resulting from abnormal AD-related pathology. In summary, frailty contributes to elucidating the relationship between AD-related pathology and cognitive impairment.
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http://dx.doi.org/10.3233/JAD-231489 | DOI Listing |
Alzheimers Res Ther
December 2024
University of Pompeu Fabra (UPF), Barcelona, Spain.
Background: Cerebrospinal fluid (CSF) biomarkers of synaptic dysfunction, neuroinflammation, and glial response, complementing Alzheimer's disease (AD) core biomarkers, have improved the pathophysiological characterization of the disease. Here, we tested the hypothesis that the co-expression of multiple CSF biomarkers will help the identification of AD-like phenotypes when biomarker positivity thresholds are not met yet.
Methods: Two hundred and seventy cognitively unimpaired adults with family history (FH) of sporadic AD (mean age = 60.
J Gerontol A Biol Sci Med Sci
November 2024
Nutrition and Metabolic Health Research Group, Department of Biochemistry and Biotechnology, Rovira i Virgili University (URV), 43201 Reus, Spain.
Front Dement
October 2024
Department of Psychiatry and Psychotherapy, Medical Faculty University Hospital Magdeburg, Otto von Guericke University, Magdeburg, Germany.
Introduction: Prior research identified four neurochemical cerebrospinal fluid (CSF) biomarkers, Aβ1-42, Aβ1-40, tTau, and pTau(181), as core diagnostic markers for Alzheimer's disease (AD). Determination of AD biomarkers using immunoassays can support differential diagnosis of AD vs. several neuropsychiatric disorders, which is important because the respective treatment regimens differ.
View Article and Find Full Text PDFMol Neurodegener
October 2024
Université Paris Cité, EA 4468, APHP, Hospital Broca, Memory Resource and Research Centre of de Paris-Broca-Ile de France, Paris, F-75013, France.
Background: Current AT(N) stratification for Alzheimer's disease (AD) accounts for complex combinations of amyloid (A), tau proteinopathy (T) and neurodegeneration (N) signatures. Understanding the transition between these different stages is a major challenge, especially in view of the recent development of disease modifying therapy.
Methods: This is an observational study, CSF levels of Tau, pTau181, pTau217, Aβ38/40/42, sAPPα/β, BACE1 and neurogranin were measured in the BALTAZAR cohort of cognitively impaired patients and in the Alzheimer's Disease Neuroimaging Initiative (ADNI).
J Alzheimers Dis
August 2024
Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
Background: The relationship between Alzheimer's disease (AD)-related pathology and cognition was not exactly consistent.
Objective: To explore whether the association between AD pathology and cognition can be moderated by frailty.
Methods: We included 1711 participants from the Alzheimer's Disease Neuroimaging Initiative database.
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