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Refers to Enrico Premi, Marcello Giunta, Armin Iraji, Srinivas Rachakonda, Vince D. Calhoun, Stefano Gazzina, Alberto Benussi, Roberto Gasparotti, Silvana Archetti, Martina Bocchetta, Dave Cash, Emily Todd, Georgia Peakman, Rhian Convery, John C. van Swieten, Lize Jiskoot, Raquel Sanchez-Valle, Fermin Moreno, Robert Laforce, Caroline Graff, Matthis Synofzik, Daniela Galimberti, James B. Rowe, Mario Masellis, Carmela Tartaglia, Elizabeth Finger, Rik Vandenberghe, Alexandre de Mendonça, Fabrizio Tagliavini, Chris R. Butler, Isabel Santana, Alexander Gerhard, Isabelle Le Ber, Florence Pasquier, Simon Ducharme, Johannes Levin, Adrian Danek, Sandro Sorbi, Markus Otto, Jonathan D. Rohrer, Barbara Borroni Dissemination in time and space in presymptomatic granulin mutation carriers: a GENFI spatial chronnectome study. Neurobiology of Aging, Volume 108, December 2021, Pages 155-167 DOI of original article: 10.1016/j.neurobiolaging.2021.09.001. © 2022 Elsevier Inc. The authors regret that the GENFI authors were listed at the end of the article in the Appendix. The GENFI authors are also part of co-authors. The updated author list is below. The authors would like to apologise for any inconvenience caused.

Copyright © Author(s) (or their employer(s)) 2022. Introduction: We have previously reported the initial clinical and imaging findings of a woman with a novel MAPT Q351R mutation.1 2 We continued to assess her following these case reports until she died and have now analysed her brain at postmortem. Her case was of unique interest due to the novelty of the mutation and its clinical features1 as well as the strong binding seen on flortaucipir positron emission tomography (PET) imaging,2 which was suggestive of a very specific pathological finding, that of a mixed 3R/4R tauopathy, similar to that seen in other MAPT mutations (V337M and R406W),3 4 and consistent with the same type of paired helical filament tau pathology seen in Alzheimer’s disease (AD). She is the first patient with this mutation to come to autopsy and we report the findings in this study. Methods: A patient with a Q351R mutation was seen over a 20-year period, during which time she was assessed clinically, and with repeated MR brain imaging (11 scans in total) as well as flortaucipir PET imaging. In this report, her MR imaging is compared against a cohort of 43 healthy individuals (all women; mean age 61.5 years old, range 49.7–68.5 years old). All participants gave their consent to take part. At the time of death, her brain was donated to the Queen Square Brain Bank for Neurological Disorders and underwent postmortem analysis. Results: Clinical history She presented to a specialist cognitive neurology clinic in her late 40s with a 4-year history of amnestic symptoms and mild behavioural change, mainly in the form of apathy. Neurological examination was normal, but her initial neuropsychological assessment showed the presence of episodic and semantic memory impairment with other cognitive domains intact.1 Following this, there was a slow progression of cognitive and behavioural symptoms over the next 20 years, with increasing forgetfulness and apathy, as well as prominent disinhibition, change in appetite and musicophilia. In addition, 13 years into her illness, she developed parkinsonism with bradykinesia, rigidity and both resting and postural tremor. She was still living at home and was able to attend research appointments until her mid 60s. She died in her late 60s, 24 years into her illness. Brain imaging: MR imaging throughout the course of her illness showed slowly progressive atrophy with a whole brain atrophy rate over the whole course of the illness of 0.7% per year (figure 1A). The pattern of involvement was initially dominated by focal medial temporal atrophy affecting the amygdala and anterior more than posterior hippocampus. Over time, there was progressive cortical involvement also, affecting the temporal and insular cortices and later the frontal and anterior cingulate cortices. Striatal atrophy, particularly ventrally, was seen later in the condition as well (figure 1B,C). In contrast, posterior cortical regions were relatively spared. Flortaucipir PET imaging showed strong binding of the tracer2 similar to that seen in both AD and a small subgroup of MAPT mutations (R406W and V337M) (figure 1D). Alzheimer's Research UK; Alzheimer's Society; Brain Research UK; The Wolfson Foundation; UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK; Miriam Marks Brain Research UK Senior Fellowship; MRC Clinician Scientist Fellowship (MR/M008525/1); NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH); Alzheimer’s Society and by the NIHR UCLH Biomedical Research Centre; NIHR UCL/H Biomedical Research Centre; UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK.

Data Availability Statement: Anonymised data are available on request to the corresponding author. Supporting Information: APPENDIX S1 available at: https://movementdisorders.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Fmds.29123&file=mds29123-sup-0001-supinfo.pdf (PDF document, 3 MB). Copyright © 2022 The Authors. Background: Cognitive impairment is common in neurological presentations of Wilson's disease (WD). Various domains can be affected, and subclinical deficits have been reported in patients with hepatic presentations. Associations with imaging abnormalities have not been systematically tested. Objective: The aim was to determine the neuroanatomical basis for cognitive deficits in WD. Methods: We performed a 16-item neuropsychological test battery and magnetic resonance brain imaging in 40 patients with WD. The scores for each test were compared between patients with neurological and hepatic presentations and with normative data. Associations with Unified Wilson's Disease Rating Scale neurological examination subscores were examined. Quantitative, whole-brain, multimodal imaging analyses were used to identify associations with neuroimaging abnormalities in chronically treated stable patients. Results: Abstract reasoning, executive function, processing speed, calculation, and visuospatial function scores were lower in patients with neurological presentations than in those with hepatic presentations and correlated with neurological examination subscores. Deficits in abstract reasoning and phonemic fluency were associated with lower putamen volumes even after controlling for neurological severity. About half of patients with hepatic presentations had poor performance in memory for faces, cognitive flexibility, or associative learning relative to normative data. These deficits were associated with widespread cortical atrophy and/or white matter diffusion abnormalities. Conclusions: Subtle cognitive deficits in patients with seemingly hepatic presentations represent a distinct neurological phenotype associated with diffuse cortical and white matter pathology. This may precede the classical neurological phenotype characterized by movement disorders and executive dysfunction and be associated with basal ganglia damage. A binary phenotypic classification for WD may no longer be appropriate. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. Association of British Neurologists. Grant Number: N/A; Guarantors of Brain; Wilson's Disease Support Group UK; University College London Hospitals Biomedical Research Centre; Health Research; Open access funding enabled and organized by Projekt DEAL.