Associations of Prediabetes, Diabetes and Glucose‐Related Markers With Cognition and Neuroimaging in a 2‐Year Multidomain Lifestyle Randomised Controlled Trial - UTU Research Portal

A1 Refereed original research article in a scientific journal

Associations of Prediabetes, Diabetes and Glucose‐Related Markers With Cognition and Neuroimaging in a 2‐Year Multidomain Lifestyle Randomised Controlled Trial

Authors: Lorenzo, Thais; Ngandu, Tiia; Lehtisalo, Jenni; Antikainen, Riitta; Gispert, Juan Domingo; Kemppainen, Nina; Laatikainen, Tiina; Lindström, Jaana; Rinne, Juha; Soininen, Hilkka; Strandberg, Timo; Torre, Rafael de la; Tuomilehto, Jaakko; Solomon, Alina; Kivipelto, Miia

Publisher: Wiley

Publication year: 2025

Journal: Diabetes/Metabolism Research and Reviews

Journal name in source: Diabetes/Metabolism Research and Reviews

Article number: e70053

Volume: 41

Issue: 5

ISSN: 1520-7552

eISSN: 1520-7560

DOI: https://doi.org/10.1002/dmrr.70053

Web address : https://doi.org/10.1002/dmrr.70053

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/499381780

Abstract

Aims

Few longitudinal studies have explored Oral Glucose Tolerance Test markers (OGTT) and both cognitive and brain changes. We investigated OGTT and other glycaemia and insulin resistance markers, and cognitive and neuroimaging changes in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER).

Materials and Methods

At-risk individuals aged 60–77 years without dementia (N = 1259) were randomly enrolled in a 2-year multidomain lifestyle intervention or regular health advice program. 1025 participants without previously diagnosed diabetes underwent OGTT. Brain MRI scans were available for 132 participants and amyloid (PiB)-PET and FDG-PET scans for 47. Cognition was assessed using the modified Neuropsychological Test Battery (mNTB).

Results

Higher baseline dysglycaemia measures, particularly those from the OGTT, were connected to less favourable changes in multiple cognitive measures and hippocampal volume. Higher baseline triglyceride-glucose (TyG) index was associated with higher amyloid accumulation and decline in brain glucose metabolism. Higher baseline glycated haemoglobin (HbA1c) was related to favourable changes in processing speed and cortical thickness. There were no significant intervention-control differences in the change in glycaemia markers. Baseline dysglycaemia and glycaemia-related markers did not modify the previously reported intervention benefits on cognition.

Conclusions

Higher baseline dysglycaemia measures are linked to more deleterious changes in cognition. Specifically, OGTT measures may be the most sensitive for detecting subtle glycaemic abnormalities associated with both unfavourable cognitive and neuroimaging changes. However, HbA1c shows mixed associations with cognition and neuroimaging in people at risk of dementia without previously diagnosed diabetes. This study emphasises the importance of more accurate glucose-related markers when investigating early stages of glucose metabolism abnormalities and their relationship to subtle cognitive impairment and its structural brain correlates.

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Diabetes Metabolism Res - 2025 - Lorenzo - Associations of Prediabetes Diabetes and Glucose‐Related Markers With Cognition.pdf

Funding information in the publication:
This research was supported by the Instituto de Salud Carlos III, Spain (Grants MV21/00015 and FI18/00041). European Research Council (Grant 804371); EU Joint Programme—Neurodegenerative Disease Research (JPND) Multi-MeMo grant (Research Council of Finland, grant 357810); ERA PerMed Pattern-Cog grant; Alzheimerfonden (Sweden); Region Stockholm (ALF, Sweden); Juho Vainio Foundation (Finland); Finnish Cultural Foundation (Finland); Yrjö Jahnsson Foundation (Finland); EU Innovative Health Initiative Joint Undertaking (IHI JU) AD-RIDDLE (Grant 101132933). EU the Joint Programme - Neurodegenerative Disease Research (JPND) EURO-FINGERS grant; NordForsk NJ-FINGERS grant; Alzheimer's Research and Prevention Foundation (United States); Swedish Research Council; Region Stockholm (ALF, Sweden); Centre for Innovative Medicine (CIMED) at Karolinska Institute (Sweden); Stiftelsen Stockholms sjukhem (Sweden); Knut and Alice Wallenberg Foundation (Sweden); and Swedish research council for health, working life and welfare (FORTE); Juho Vainio Foundation (Finland); Kela (Finland); Research Council of Finland; EU Innovative Health Initiative Joint Undertaking (IHI JU) AD-RIDDLE (Grant 101132933). EU Joint Programme - Neurodegenerative Disease Research (JPND) EURO-FINGERS grant; Sigrid Jusélius Foundation (Finland); Juho Vainio Foundation (Finland); NordForsk NJ-FINGERS grant; Alzheimer's Research and Prevention Foundation (United States); Päivikki and Sakari Sohlberg Foundation (Finland); and Finnish Cultural Foundation (Finland). European Comission Innovative Health Initiative (Grant 101112145), the BrightFocus Foundation (Grant A2022034S), and La Marató de TV3 (Project 202318 30-31-32). Instituto de Salud Carlos III, Spain (Grant PI17/00223), Alzheimer Association (Grant 18PTC-R-592192), EU Joint Programme—Neurodegenerative Disease Research (JPND) Multi-MeMo grant (Instituto de Salud Carlos III, Spain, Grant AC22/00004); Generalitat de Catalunya, Spain (Grant 2017 SGR 138).