title: Structural neuroimaging in preclinical dementia: From microstructural deficits and grey matter atrophy to macroscale connectomic changes.
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.
authors: Department of Psychiatry, School of Clinical Medicine, Addenbrooke's Hospital, University of Cambridge, United Kingdom.
authors: Elijah
authors: E
authors: Mak
authors: Department of Psychiatry, School of Clinical Medicine, Addenbrooke's Hospital, University of Cambridge, United Kingdom.
authors: Silvy
authors: S
authors: Gabel
authors: Imperial College London, United Kingdom.
authors: Habib
authors: H
authors: Mirette
authors: Department of Psychiatry, School of Clinical Medicine, Addenbrooke's Hospital, University of Cambridge, United Kingdom.
authors: Li
authors: L
authors: Su
authors: Wolfson Brain Imaging Centre, University of Cambridge, United Kingdom.
authors: Guy B
authors: GB
authors: Williams
authors: Centre for Dementia Prevention, University of Edinburgh,United Kingdom.
authors: Adam
authors: A
authors: Waldman
authors: Imperial College London, United Kingdom.
authors: Katie
authors: K
authors: Wells
authors: INSERM U1061 Neuropsychiatry, France; Faculty of Medicine, University of Montpellier, France.
authors: Karen
authors: K
authors: Ritchie
authors: Centre for Dementia Prevention, University of Edinburgh,United Kingdom.
authors: Craig
authors: C
authors: Ritchie
authors: Department of Psychiatry, School of Clinical Medicine, Addenbrooke's Hospital, University of Cambridge, United Kingdom. Electronic address: john.obrien@medschl.cam.ac.uk.
authors: John
authors: J
authors: O'Brien
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis*; D058070:Asymptomatic Diseases; D001284:Atrophy / Q000000981:diagnostic imaging / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D063132:Connectome / Q000379:methods; D003704:Dementia / Q000175:diagnosis*; D018450:Disease Progression; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D059906:Neuroimaging / Q000379:methods*
chemical_list: D015415:Biomarkers
keywords: Alzheimer’s disease; Cognitive impairment; Diffusion weighted imaging; Magnetic resonance imaging; Neurodegeneration; Neuroimaging; Preclinical dementia