Structural neuroimaging in preclinical dementia: From microstructural deficits and grey matter atrophy to macroscale connectomic changes
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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.
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Structural and functional brain alterations have been detected in vivo during the asymptomatic stage of AD.
“structural and functional brain alterations have been detected in vivo during the asymptomatic stage of AD [8, 9].”
From Neuroimaging advances regarding subjective cognitive decline in preclinical Alzheimer's disease (2020) · cites this paper as [9]
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APOE ɛ4 exacerbates age-dependent deficits in cortical microstructure
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Self-citation
- Authors
- Mak, E., Gabel, S., Mirette, H., Su, L., Williams, G. B., Waldman, A., Wells, K., Ritchie, K., Ritchie, C., & O’Brien, J.
- Affiliations
- University of Cambridge (GB)
- University of Edinburgh (GB)
- Imperial College London (GB)
- Inserm (FR)
- Venue
- Ageing Research Reviews
- Publisher
- Elsevier BV
- Published
- 2017-05
- Volume
- 35
- Pages
- 250-264
- ISSN
- 1568-1637 (ISSN-L)
- OpenAlex
- W2537534180
- Cited by
- 71
- References
- 169
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 11 · 2023: 8 · 2022: 11 · 2021: 6 · 2020: 6 · 2019: 6 · 2018: 7 · 2017: 4 · 2016: 1
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Ageing Research Reviews (publishedVersion)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Cambridge University Hospitals
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- preclinical Alzheimer's disease, structural neuroimaging, gray matter atrophy, white matter microstructure, connectomics, medial temporal lobe, precuneus, fornix, cingulum, corpus callosum, risk stratification, surrogate markers, disease progression monitoring, secondary prevention
- MeSH terms
- Alzheimer Disease, Atrophy, Dementia, Humans, Biomarkers, Disease Progression, Asymptomatic Diseases, Neuroimaging, Connectome, Gray Matter
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