Relationship of plasma biomarkers to digital cognitive tests in Alzheimer's disease

Author:

Toniolo Sofia12ORCID,Zhao Sijia3,Scholcz Anna3,Amein Benazir1,Ganse‐Dumrath Akke1,Heslegrave Amanda J.45,Thompson Sian2,Manohar Sanjay123,Zetterberg Henrik45678,Husain Masud123

Affiliation:

1. Nuffield Department of Clinical Neurosciences University of Oxford Oxford UK

2. Cognitive Disorders Clinic JR Hospital Oxford UK

3. Department of Experimental Psychology University of Oxford Oxford UK

4. UK Dementia Research Institute UCL London UK

5. Department of Neurodegenerative Disease UCL Institute of Neurology London UK

6. Institute of Neuroscience and Physiology University of Gothenburg Gothenburg Sweden

7. Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Mölndal Sweden

8. Hong Kong Center for Neurodegenerative Diseases Hong Kong China

Abstract

AbstractINTRODUCTIONA major limitation in Alzheimer's disease (AD) research is the lack of the ability to measure cognitive performance at scale—robustly, remotely, and frequently. Currently, there are no established online digital platforms validated against plasma biomarkers of AD.METHODSWe used a novel web‐based platform that assessed different cognitive functions in AD patients (N = 46) and elderly controls (N = 53) who were also evaluated for plasma biomarkers (amyloid beta 42/40 ratio, phosphorylated tau ([p‐tau]181, glial fibrillary acidic protein, neurofilament light chain). Their cognitive performance was compared to a second, larger group of elderly controls (N = 352).RESULTSPatients with AD were significantly impaired across all digital cognitive tests, with performance correlating with plasma biomarker levels, particularly p‐tau181. The combination of p‐tau181 and the single best‐performing digital test achieved high accuracy in group classification.DISCUSSIONThese findings show how online testing can now be deployed in patients with AD to measure cognitive function effectively and related to blood biomarkers of the disease.Highlights This is the first study comparing online digital testing to plasma biomarkers. Alzheimer's disease patients and two independent cohorts of elderly controls were assessed. Cognitive performance correlated with plasma biomarkers, particularly phosphorylated tau (p‐tau)181. Glial fibrillary acidic protein and neurofilament light chain, and less so the amyloid beta 42/40 ratio, were also associated with performance. The best cognitive metric performed at par to p‐tau181 in group classification.

Funder

Wellcome Trust

Vetenskapsrådet

Alzheimer's Association

Familjen Erling-Perssons Stiftelse

Stiftelsen för Gamla Tjänarinnor

Hjärnfonden

UK Dementia Research Institute

Publisher

Wiley

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