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Observational Study
. 2025 Aug;14(4):100064.
doi: 10.1016/j.tjfa.2025.100064. Epub 2025 Jul 1.

Associations between intrinsic capacity, plasma p-tau181 and cognitive function over a 5-year follow-up among community-dwelling older adults: a secondary analysis of the MAPT Study

Kelly Virecoulon Giudici  1 , Philipe de Souto Barreto  2 , Christelle Cantet  2 , Henrik Zetterberg  3 , Kaj Blennow  4 , Bruno Vellas  2 ; MAPT/DSA group
Affiliations
Observational Study

Associations between intrinsic capacity, plasma p-tau181 and cognitive function over a 5-year follow-up among community-dwelling older adults: a secondary analysis of the MAPT Study

Kelly Virecoulon Giudici et al. J Frailty Aging. 2025 Aug.

Abstract

Background: Intrinsic capacity (IC) is a recent key concept proposed by the World Health Organization (WHO) based on aspects of functional ability (both physical and mental) rather than the presence or absence of diseases, with a potential to predict several health outcomes.

Objective: To explore associations between IC and cognitive function (prospectively), and between IC and plasma p-tau181 (cross-sectionally and prospectively) among community-dwelling older adults.

Methods: Observational study with 491 subjects ≥70 years (67.4 % female, mean 75.3 years, SD=4.4), participants from the Multidomain Alzheimer Preventive Trial (MAPT). IC domains (locomotion, cognition, psychological, vitality) were combined into a 0-100 score. Alternative classification was based on the number of domains' abnormalities. Plasma p-tau181 was measured at baseline and 36 months of follow-up. A composite cognitive score (CCS) based on four tests was determined at baseline, 6, 12, 24, 36, 48 and 60 months.

Results: Inverse cross-sectional associations were observed between baseline IC score and p-tau181 (unadjusted model: β=-0.08, 95 %CI -0.13 to -0.03; p = 0.0025). A significant mean difference in p-tau181 3-year changes was observed between participants with low and normal IC (based on IC score) (adjusted model: 1.71, 95 %CI 0.01 to 3.40; p = 0.0483). Prospective 5-year associations between IC and CCS were only observed in unadjusted analysis according to the alternative IC classification (-0.21, 95 %CI -0.38 to -0.04; p = 0.0156).

Conclusion: IC was associated with plasma p-tau181 and cognitive function, but findings varied according to the method of IC classification. Further research may help settle the role of IC as a predictor of neurodegenerative diseases such as AD. In this regard, multidomain interventions have potential to protect IC over the aging process and prevent cognitive impairment, and should also be encouraged.

Keywords: Aging; Cognitive function; Intrinsic capacity; Older adults; P-tau181.

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Conflict of interest statement

Declaration of competing interest HZ has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZpath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Enigma, LabCorp, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Quanterix, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures sponsored by Alzecure, BioArctic, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, Roche, and WebMD, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). KB has served as a consultant and at advisory boards for Abbvie, AC Immune, ALZPath, AriBio, Beckman-Coulter, BioArctic, Biogen, Eisai, Lilly, Moleac Pte. Ltd, Neurimmune, Novartis, Ono Pharma, Prothena, Quanterix, Roche Diagnostics, Sanofi and Siemens Healthineers; has served at data monitoring committees for Julius Clinical and Novartis; has given lectures, produced educational materials and participated in educational programs for AC Immune, Biogen, Celdara Medical, Eisai and Roche Diagnostics; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. The other authors declare no conflicts.

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