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Structural neuroimaging in preclinical dementia: From microstructural deficits and grey matter atrophy to macroscale connectomic changes.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Gabel, Silvy 
Mirette, Habib 
Su, Li 
Williams, Guy B 

Abstract

The last decade has witnessed a proliferation of neuroimaging studies characterising brain changes associated with Alzheimer's disease (AD), where both widespread atrophy and 'signature' brain regions have been implicated. In parallel, a prolonged latency period has been established in AD, with abnormal cerebral changes beginning many years before symptom onset. This raises the possibility of early therapeutic intervention, even before symptoms, when treatments could have the greatest effect on disease-course modification. Two important prerequisites of this endeavour are (1) accurate characterisation or risk stratification and (2) monitoring of progression using neuroimaging outcomes as a surrogate biomarker in those without symptoms but who will develop AD, here referred to as preclinical AD. Structural neuroimaging modalities have been used to identify brain changes related to risk factors for AD, such as familial genetic mutations, risk genes (for example apolipoprotein epsilon-4 allele), and/or family history. In this review, we summarise structural imaging findings in preclinical AD. Overall, the literature suggests early vulnerability in characteristic regions, such as the medial temporal lobe structures and the precuneus, as well as white matter tracts in the fornix, cingulum and corpus callosum. We conclude that while structural markers are promising, more research and validation studies are needed before future secondary prevention trials can adopt structural imaging biomarkers as either stratification or surrogate biomarkers.

Description

Keywords

Alzheimer’s disease, Cognitive impairment, Diffusion weighted imaging, Magnetic resonance imaging, Neurodegeneration, Neuroimaging, Preclinical dementia, Alzheimer Disease, Asymptomatic Diseases, Atrophy, Biomarkers, Connectome, Dementia, Disease Progression, Gray Matter, Humans, Neuroimaging

Journal Title

Ageing Res Rev

Conference Name

Journal ISSN

1568-1637
1872-9649

Volume Title

35

Publisher

Elsevier BV
Sponsorship
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
This study was supported by the National Institute for Health Research (NIHR, RG64473), Cambridge Biomedical Research Centre and Biomedical Research Unit in Dementia, and the Alzheimer's Society. Elijah Mak was in the receipt of the Gates Cambridge studentship.