Firth, Nicholas CPrimativo, SilviaMarinescu, Razvan-ValentinShakespeare, Timothy JSuarez-Gonzalez, AidaLehmann, ManjaCarton, AmeliaOcal, DilekPavisic, IvannaPaterson, Ross WSlattery, Catherine FFoulkes, Alexander J MRidha, Basil HGil-Néciga, EulogioOxtoby, Neil PYoung, Alexandra LModat, MarcCardoso, M JorgeOurselin, SebastienRyan, Natalie SMiller, Bruce LRabinovici, Gil DWarrington, Elizabeth KRossor, Martin NFox, Nick CWarren, Jason DAlexander, Daniel CSchott, Jonathan MYong, Keir X XCrutch, Sebastian J2023-01-252023-01-252019http://hdl.handle.net/10668/14149Posterior cortical atrophy is a clinico-radiological syndrome characterized by progressive decline in visual processing and atrophy of posterior brain regions. With the majority of cases attributable to Alzheimer's disease and recent evidence for genetic risk factors specifically related to posterior cortical atrophy, the syndrome can provide important insights into selective vulnerability and phenotypic diversity. The present study describes the first major longitudinal investigation of posterior cortical atrophy disease progression. Three hundred and sixty-one individuals (117 posterior cortical atrophy, 106 typical Alzheimer's disease, 138 controls) fulfilling consensus criteria for posterior cortical atrophy-pure and typical Alzheimer's disease were recruited from three centres in the UK, Spain and USA. Participants underwent up to six annual assessments involving MRI scans and neuropsychological testing. We constructed longitudinal trajectories of regional brain volumes within posterior cortical atrophy and typical Alzheimer's disease using differential equation models. We compared and contrasted the order in which regional brain volumes become abnormal within posterior cortical atrophy and typical Alzheimer's disease using event-based models. We also examined trajectories of cognitive decline and the order in which different cognitive tests show abnormality using the same models. Temporally aligned trajectories for eight regions of interest revealed distinct (PenAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Alzheimer’s diseasebrain atrophydementiamemorystructural MRIAlzheimer DiseaseCase-Control StudiesCerebral CortexCognitive DysfunctionDisease ProgressionFemaleHumansLongitudinal StudiesMagnetic Resonance ImagingMaleMiddle AgedModels, NeurologicalNeuropsychological Testsresearch article31219516open access10.1093/brain/awz1361460-2156PMC6598737https://academic.oup.com/brain/article-pdf/142/7/2082/28881235/awz136.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598737/pdf