Universität zu Köln

Martino-Adami, Pamela V. ORCID: 0000-0002-1067-1495, Chatterjee, Madhurima ORCID: 0000-0003-1647-3307, Kleineidam, Luca, Weyerer, Siegfried, Bickel, Horst, Wiese, Birgitt, Riedel-Heller, Steffi G., Scherer, Martin, Blennow, Kaj, Zetterberg, Henrik, Wagner, Michael ORCID: 0000-0003-2589-6440, Schneider, Anja and Ramirez, Alfredo ORCID: 0000-0003-4991-763X (2024). Prognostic value of Alzheimer's disease plasma biomarkers in the oldest-old: a prospective primary care-based study. The Lancet Regional Health - Europe, 45. pp. 1-13. Elsevier. ISSN 2666-7762

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Abstract

[Artikel-Nr.: 101030] Background: Blood-based biomarkers offer a promising, less invasive, and more cost-effective alternative for Alzheimer's disease screening compared to cerebrospinal fluid or imaging biomarkers. However, they have been extensively studied only in memory clinic-based cohorts. We aimed to validate them in a more heterogeneous, older patient population from primary care. Methods: We measured plasma Aβ42/Aβ40, P-tau181, NfL, and GFAP in 1007 individuals without dementia, aged 79–94 years, from the longitudinal, primary care-based German AgeCoDe study. We assessed the association with cognitive decline, disease progression, and the capacity to predict future dementia of the Alzheimer's type (DAT). We also evaluated biomarker dynamics in 305 individuals with a follow-up sample (∼8 years later). Findings: Higher levels of P-tau181 (HR = 1.32 [95% CI: 1.17–1.51]), NfL (HR = 1.19 [95% CI: 1.03–1.36]), and GFAP (HR = 1.36 [95% CI: 1.22–1.52]), and a lower Aβ42/Aβ40 ratio (HR = 0.80 [95% CI: 0.68–0.95]) were associated with an increased risk of progressing to clinically-diagnosed DAT. Additionally, higher levels of P-tau181 (β = −0.49 [95% CI: −0.71 to 0.26]), NfL (β = −0.29 [95% CI: −0.52 to 0.06]), and GFAP (β = −0.60 [95% CI: −0.83 to 0.38]) were linked to faster cognitive decline. A two-step DAT prediction strategy combining initial MMSE with biomarkers improved the identification of individuals in the prodromal stage for potential treatment eligibility. Biomarker levels changed over time, with increases in P-tau181 (β = 0.19 [95% CI: 0.14–0.25]), NfL (β = 2.88 [95% CI: 2.18–3.59]), and GFAP (β = 8.23 [95% CI: 6.71–9.75]). NfL (β = 2.47 [95% CI: 1.04–3.89]) and GFAP (β = 4.45 [95% CI: 1.38–7.51]) exhibited a faster increase in individuals progressing to DAT. Interpretation: Evaluating plasma biomarkers, alongside brief cognitive assessments, might enhance the precision of risk assessment for DAT progression in primary care.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Martino-Adami, Pamela V. UNSPECIFIED https://orcid.org/0000-0002-1067-1495 UNSPECIFIED Chatterjee, Madhurima UNSPECIFIED https://orcid.org/0000-0003-1647-3307 UNSPECIFIED Kleineidam, Luca UNSPECIFIED UNSPECIFIED UNSPECIFIED Weyerer, Siegfried UNSPECIFIED UNSPECIFIED UNSPECIFIED Bickel, Horst UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiese, Birgitt UNSPECIFIED UNSPECIFIED UNSPECIFIED Riedel-Heller, Steffi G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Scherer, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Blennow, Kaj UNSPECIFIED UNSPECIFIED UNSPECIFIED Zetterberg, Henrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagner, Michael UNSPECIFIED https://orcid.org/0000-0003-2589-6440 UNSPECIFIED Schneider, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Ramirez, Alfredo UNSPECIFIED https://orcid.org/0000-0003-4991-763X UNSPECIFIED
URN:	urn:nbn:de:hbz:38-814366
Identification Number:	10.1016/j.lanepe.2024.101030
Journal or Publication Title:	The Lancet Regional Health - Europe
Volume:	45
Page Range:	pp. 1-13
Number of Pages:	13
Date:	October 2024
Publisher:	Elsevier
ISSN:	2666-7762
Language:	English
Faculty:	Faculty of Medicine
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases Faculty of Medicine > Psychiatrie und Psychotherapie > Klinik und Poliklinik für Psychiatrie und Psychotherapie
Subjects:	Psychology Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language Alzheimer’s disease ; Plasma biomarkers ; Oldest-old population ; Primary care ; Cognitive impairment ; Disease prognosis English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81436