Imperial College London
Alternate

Professor Sir Roy Anderson FRS, FMedSci

Faculty of Medicine, School of Public Health

Professor in Infectious Disease Epidemiology
 
 
 
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Contact

 

roy.anderson Website

 
 
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Assistant

 

Mrs Clare Mylchreest +44 (0)7766 331 301

 
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Location

 

LG35Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Hadjichrysanthou:2020:10.1186/s13195-020-00636-z,
author = {Hadjichrysanthou, C and Evans, S and Bajaj, S and Siakallis, LC and McRae-McKee, K and de, Wolf F and Anderson, RM},
doi = {10.1186/s13195-020-00636-z},
journal = {Alzheimers Research & Therapy},
pages = {1--16},
title = {The dynamics of biomarkers across the clinical spectrum of Alzheimer's disease},
url = {http://dx.doi.org/10.1186/s13195-020-00636-z},
volume = {12},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundQuantifying changes in the levels of biological and cognitive markers prior to the clinical presentation of Alzheimer’s disease (AD) will provide a template for understanding the underlying aetiology of the clinical syndrome and, concomitantly, for improving early diagnosis, clinical trial recruitment and treatment assessment. This study aims to characterise continuous changes of such markers and determine their rate of change and temporal order throughout the AD continuum.MethodsThe methodology is founded on the development of stochastic models to estimate the expected time to reach different clinical disease states, for different risk groups, and synchronise short-term individual biomarker data onto a disease progression timeline. Twenty-seven markers are considered, including a range of cognitive scores, cerebrospinal (CSF) and plasma fluid proteins, and brain structural and molecular imaging measures. Data from 2014 participants in the Alzheimer’s Disease Neuroimaging Initiative database is utilised.ResultsThe model suggests that detectable memory dysfunction could occur up to three decades prior to the onset of dementia due to AD (ADem). This is closely followed by changes in amyloid-β CSF levels and the first cognitive decline, as assessed by sensitive measures. Hippocampal atrophy could be observed as early as the initial amyloid-β accumulation. Brain hypometabolism starts later, about 14 years before onset, along with changes in the levels of total and phosphorylated tau proteins. Loss of functional abilities occurs rapidly around ADem onset. Neurofilament light is the only protein with notable early changes in plasma levels. The rate of change varies, with CSF, memory, amyloid PET and brain structural measures exhibiting the highest rate before the onset of ADem, followed by a decline. The probability of progressing to a more severe clinical state increases almost exponentially with age. In accordance with previous stu
AU  - Hadjichrysanthou,C
AU  - Evans,S
AU  - Bajaj,S
AU  - Siakallis,LC
AU  - McRae-McKee,K
AU  - de,Wolf F
AU  - Anderson,RM
DO  - 10.1186/s13195-020-00636-z
EP  - 16
PY  - 2020///
SN  - 1758-9193
SP  - 1
TI  - The dynamics of biomarkers across the clinical spectrum of Alzheimer's disease
T2  - Alzheimers Research & Therapy
UR  - http://dx.doi.org/10.1186/s13195-020-00636-z
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000542186200001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://alzres.biomedcentral.com/articles/10.1186/s13195-020-00636-z
UR  - http://hdl.handle.net/10044/1/80649
VL  - 12
ER  -
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