word count: 216 Manuscript word count: 7504 Highlights  We reviewed the literature of structural imaging changes in preclinical dementia.  There was a high overlap of brain regions implicated in both preclinical and sporadic AD.  The imaging literature in relation to AD risk factors was highly discrepant.  More research and validation studies of structural imaging techniques are needed. ABSTRACT The last decade has witnessed a proliferation of neuroimaging studies characterising brain

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... s 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.