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New insights into atypical Alzheimer's disease in the era of biomarkers.

Jonathan Graff-Radford, Keir X X Yong, Liana G Apostolova, Femke H Bouwman, Maria Carrillo, Bradford C Dickerson, Gil D Rabinovici, Jonathan M Schott, David T Jones, Melissa E Murray,

Most patients with Alzheimer's disease present with amnestic problems; however, a substantial proportion, over-represented in young-onset cases, have atypical phenotypes including predominant visual, language, executive, behavioural, or motor dysfunction. In the past, these individuals often received a late diagnosis; however, availability of CSF and PET biomarkers of Alzheimer's disease pathologies ... Read more >>

Lancet Neurol (The Lancet. Neurology)
[2021, 20(3):222-234]

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Concordance of CSF measures of Alzheimer's pathology with amyloid PET status in a preclinical cohort: A comparison of Lumipulse and established immunoassays.

Ashvini Keshavan, Henrietta Wellington, Zhongbo Chen, Ayesha Khatun, Miles Chapman, Melanie Hart, David M Cash, William Coath, Thomas D Parker, Sarah M Buchanan, Sarah E Keuss, Matthew J Harris, Heidi Murray-Smith, Amanda Heslegrave, Nick C Fox, Henrik Zetterberg, Jonathan M Schott,

<h4>Introduction</h4>We assessed the concordance of cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau measured on the fully automated Lumipulse platform with pre-symptomatic Alzheimer's disease (AD) pathology on amyloid positron emission tomography (PET).<h4>Methods</h4>In 72 individuals from the Insight 46 study, CSF Aβ40, Aβ42, total tau (t-tau), and phosphorylated tau at site ... Read more >>

Alzheimers Dement (Amst) (Alzheimer's & dementia (Amsterdam, Netherlands))
[2021, 13(1):e12131]

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Population-based blood screening for preclinical Alzheimer's disease in a British birth cohort at age 70.

Ashvini Keshavan, Josef Pannee, Thomas K Karikari, Juan Lantero Rodriguez, Nicholas J Ashton, Jennifer M Nicholas, David M Cash, William Coath, Christopher A Lane, Thomas D Parker, Kirsty Lu, Sarah M Buchanan, Sarah E Keuss, Sarah-Naomi James, Heidi Murray-Smith, Andrew Wong, Anna Barnes, John C Dickson, Amanda Heslegrave, Erik Portelius, Marcus Richards, Nick C Fox, Henrik Zetterberg, Kaj Blennow, Jonathan M Schott,

Alzheimer's disease has a preclinical stage when cerebral amyloid-β deposition occurs before symptoms emerge, and when amyloid-β-targeted therapies may have maximum benefits. Existing amyloid-β status measurement techniques, including amyloid PET and CSF testing, are difficult to deploy at scale, so blood biomarkers are increasingly considered for screening. We compared three ... Read more >>

Brain (Brain : a journal of neurology)
[2021, :]

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Visuomotor integration deficits are common to familial and sporadic preclinical Alzheimer's disease.

Kirsty Lu, Jennifer M Nicholas, Philip S J Weston, Julie C Stout, Alison M O'Regan, Sarah-Naomi James, Sarah M Buchanan, Christopher A Lane, Thomas D Parker, Sarah E Keuss, Ashvini Keshavan, Heidi Murray-Smith, David M Cash, Carole H Sudre, Ian B Malone, William Coath, Andrew Wong, Marcus Richards, Susie M D Henley, Nick C Fox, Jonathan M Schott, Sebastian J Crutch,

We investigated whether subtle visuomotor deficits were detectable in familial and sporadic preclinical Alzheimer's disease. A circle-tracing task-with direct and indirect visual feedback, and dual-task subtraction-was completed by 31 individuals at 50% risk of familial Alzheimer's disease (19 presymptomatic mutation carriers; 12 non-carriers) and 390 cognitively normal older adults (members ... Read more >>

Brain Commun (Brain communications)
[2021, 3(1):fcab003]

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KL∗VS heterozygosity reduces brain amyloid in asymptomatic at-risk APOE∗4 carriers.

Michael E Belloy, Sarah J Eger, Yann Le Guen, Valerio Napolioni, Kacie D Deters, Hyun-Sik Yang, Marzia A Scelsi, Tenielle Porter, Sarah-Naomi James, Andrew Wong, Jonathan M Schott, Reisa A Sperling, Simon M Laws, Elisabeth C Mormino, Zihuai He, Summer S Han, Andre Altmann, Michael D Greicius, , , , ,

KLOTHO∗VS heterozygosity (KL∗VS<sup>HET+</sup>) was recently shown to be associated with reduced risk of Alzheimer's disease (AD) in APOE∗4 carriers. Additional studies suggest that KL∗VS<sup>HET+</sup> protects against amyloid burden in cognitively normal older subjects, but sample sizes were too small to draw definitive conclusions. We performed a well-powered meta-analysis across 5 ... Read more >>

Neurobiol Aging (Neurobiology of aging)
[2021, 101:123-129]

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Automated quantitative MRI volumetry reports support diagnostic interpretation in dementia: a multi-rater, clinical accuracy study.

Hugh G Pemberton, Olivia Goodkin, Ferran Prados, Ravi K Das, Sjoerd B Vos, James Moggridge, William Coath, Elizabeth Gordon, Ryan Barrett, Anne Schmitt, Hefina Whiteley-Jones, Christian Burd, Mike P Wattjes, Sven Haller, Meike W Vernooij, Lorna Harper, Nick C Fox, Ross W Paterson, Jonathan M Schott, Sotirios Bisdas, Mark White, Sebastien Ourselin, John S Thornton, Tarek A Yousry, M Jorge Cardoso, Frederik Barkhof, ,

<h4>Objectives</h4>We examined whether providing a quantitative report (QReport) of regional brain volumes improves radiologists' accuracy and confidence in detecting volume loss, and in differentiating Alzheimer's disease (AD) and frontotemporal dementia (FTD), compared with visual assessment alone.<h4>Methods</h4>Our forced-choice multi-rater clinical accuracy study used MRI from 16 AD patients, 14 FTD patients, ... Read more >>

Eur Radiol (European radiology)
[2021, :]

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Mild cognitive impairment: the Manchester consensus.

Ross A Dunne, Dag Aarsland, John T O'Brien, Clive Ballard, Sube Banerjee, Nick C Fox, Jeremy D Isaacs, Benjamin R Underwood, Richard J Perry, Dennis Chan, Tom Dening, Alan J Thomas, Jeffrey Schryer, Anne-Marie Jones, Alison R Evans, Charles Alessi, Elizabeth J Coulthard, James Pickett, Peter Elton, Roy W Jones, Susan Mitchell, Nigel Hooper, Chris Kalafatis, Jill G C Rasmussen, Helen Martin, Jonathan M Schott, Alistair Burns,

Given considerable variation in diagnostic and therapeutic practice, there is a need for national guidance on the use of neuroimaging, fluid biomarkers, cognitive testing, follow-up and diagnostic terminology in mild cognitive impairment (MCI). MCI is a heterogenous clinical syndrome reflecting a change in cognitive function and deficits on neuropsychological testing ... Read more >>

Age Ageing (Age and ageing)
[2021, 50(1):72-80]

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Diffuse axonal injury predicts neurodegeneration after moderate-severe traumatic brain injury.

Neil S N Graham, Amy Jolly, Karl Zimmerman, Niall J Bourke, Gregory Scott, James H Cole, Jonathan M Schott, David J Sharp,

Traumatic brain injury is associated with elevated rates of neurodegenerative diseases such as Alzheimer's disease and chronic traumatic encephalopathy. In experimental models, diffuse axonal injury triggers post-traumatic neurodegeneration, with axonal damage leading to Wallerian degeneration and toxic proteinopathies of amyloid and hyperphosphorylated tau. However, in humans the link between diffuse ... Read more >>

Brain (Brain : a journal of neurology)
[2020, 143(12):3685-3698]

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Reply: Concentric demyelination pattern in COVID-19-associated acute haemorrhagic leukoencephalitis: a lurking catastrophe?

Ross W Paterson, Rachel L Brown, Vinojini Vivekanandam, Alexander J M Foulkes, Maria Thom, Sarah Wiethoff, Laura Benjamin, Gerry Christofi, Patricia McNamara, Jasper Morrow, Thomas D Miller, Ross Nortley, Ruth Geraldes, David Attwell, Guru Kumar, Alex D Everitt, Nicholas W S Davies, S Anand Trip, Eli Silber, Robin Howard, Richard J Perry, David J Werring, Anna Checkley, Nicky Longley, Jennifer Spillane, Michael P Lunn, Chandrashekar Hoskote, Hans Rolf Jäger, Hadi Manji, Michael S Zandi, ,

Brain (Brain : a journal of neurology)
[2020, 143(12):e101]

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Genetic testing in dementia - utility and clinical strategies.

Carolin A M Koriath, Joanna Kenny, Natalie S Ryan, Jonathan D Rohrer, Jonathan M Schott, Henry Houlden, Nick C Fox, Sarah J Tabrizi, Simon Mead,

Techniques for clinical genetic testing in dementia disorders have advanced rapidly but remain to be more widely implemented in practice. A positive genetic test offers a precise molecular diagnosis, can help members of an affected family to determine personal risk, provides a basis for reproductive choices and can offer options ... Read more >>

Nat Rev Neurol (Nature reviews. Neurology)
[2021, 17(1):23-36]

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Augmenting Dementia Cognitive Assessment With Instruction-Less Eye-Tracking Tests.

Kyriaki Mengoudi, Daniele Ravi, Keir X X Yong, Silvia Primativo, Ivanna M Pavisic, Emilie Brotherhood, Kirsty Lu, Jonathan M Schott, Sebastian J Crutch, Daniel C Alexander,

Eye-tracking technology is an innovative tool that holds promise for enhancing dementia screening. In this work, we introduce a novel way of extracting salient features directly from the raw eye-tracking data of a mixed sample of dementia patients during a novel instruction-less cognitive test. Our approach is based on self-supervised ... Read more >>

IEEE J Biomed Health Inform (IEEE journal of biomedical and health informatics)
[2020, 24(11):3066-3075]

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A Clinicopathologic Study of Movement Disorders in Frontotemporal Lobar Degeneration.

Eduardo de Pablo-Fernández, Belén González-Herrero, Debora Cerdán Santacruz, Martin N Rossor, Jonathan M Schott, Tammaryn Lashley, Janice L Holton, Nick C Fox, Tamas Revesz, Jason D Warren, Zane Jaunmuktane, Jonathan D Rohrer, Thomas T Warner,

<h4>Background</h4>Despite the considerable overlap with atypical parkinsonism, a systematic characterization of the movement disorders associated with frontotemporal lobar degeneration (FTLD) is lacking.<h4>Objective</h4>The aim of this study is to provide a detailed description of the phenomenology and neuropathologic correlations of movement disorders in FTLD.<h4>Methods</h4>In this cohort study, movement disorder clinical data ... Read more >>

Mov Disord (Movement disorders : official journal of the Movement Disorder Society)
[2020, :]

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Functional cognitive disorder: dementia's blind spot.

Harriet A Ball, Laura McWhirter, Clive Ballard, Rohan Bhome, Daniel J Blackburn, Mark J Edwards, Stephen M Fleming, Nick C Fox, Robert Howard, Jonathan Huntley, Jeremy D Isaacs, Andrew J Larner, Timothy R Nicholson, Catherine M Pennington, Norman Poole, Gary Price, Jason P Price, Markus Reuber, Craig Ritchie, Martin N Rossor, Jonathan M Schott, Tiago Teodoro, Annalena Venneri, Jon Stone, Alan J Carson,

An increasing proportion of cognitive difficulties are recognized to have a functional cause, the chief clinical indicator of which is internal inconsistency. When these symptoms are impairing or distressing, and not better explained by other disorders, this can be conceptualized as a cognitive variant of functional neurological disorder, termed functional ... Read more >>

Brain (Brain : a journal of neurology)
[2020, 143(10):2895-2903]

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The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings.

Ross W Paterson, Rachel L Brown, Laura Benjamin, Ross Nortley, Sarah Wiethoff, Tehmina Bharucha, Dipa L Jayaseelan, Guru Kumar, Rhian E Raftopoulos, Laura Zambreanu, Vinojini Vivekanandam, Anthony Khoo, Ruth Geraldes, Krishna Chinthapalli, Elena Boyd, Hatice Tuzlali, Gary Price, Gerry Christofi, Jasper Morrow, Patricia McNamara, Benjamin McLoughlin, Soon Tjin Lim, Puja R Mehta, Viva Levee, Stephen Keddie, Wisdom Yong, S Anand Trip, Alexander J M Foulkes, Gary Hotton, Thomas D Miller, Alex D Everitt, Christopher Carswell, Nicholas W S Davies, Michael Yoong, David Attwell, Jemeen Sreedharan, Eli Silber, Jonathan M Schott, Arvind Chandratheva, Richard J Perry, Robert Simister, Anna Checkley, Nicky Longley, Simon F Farmer, Francesco Carletti, Catherine Houlihan, Maria Thom, Michael P Lunn, Jennifer Spillane, Robin Howard, Angela Vincent, David J Werring, Chandrashekar Hoskote, Hans Rolf Jäger, Hadi Manji, Michael S Zandi,

Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and ... Read more >>

Brain (Brain : a journal of neurology)
[2020, 143(10):3104-3120]

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Altered DNA methylation profiles in blood from patients with sporadic Creutzfeldt-Jakob disease.

Luke C Dabin, Fernando Guntoro, Tracy Campbell, Tony Bélicard, Adam R Smith, Rebecca G Smith, Rachel Raybould, Jonathan M Schott, Katie Lunnon, Peter Sarkies, John Collinge, Simon Mead, Emmanuelle Viré,

Prion diseases are fatal and transmissible neurodegenerative disorders caused by the misfolding and aggregation of prion protein. Although recent studies have implicated epigenetic variation in common neurodegenerative disorders, no study has yet explored their role in human prion diseases. Here we profiled genome-wide blood DNA methylation in the most common ... Read more >>

Acta Neuropathol (Acta neuropathologica)
[2020, 140(6):863-879]

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Concordance of CSF measures of Alzheimer's pathology with amyloid PET status in a preclinical cohort: A comparison of Lumipulse and established immunoassays.

Ashvini Keshavan, Henrietta Wellington, Zhongbo Chen, Ayesha Khatun, Miles Chapman, Melanie Hart, David M Cash, William Coath, Thomas D Parker, Sarah M Buchanan, Sarah E Keuss, Matthew J Harris, Heidi Murray-Smith, Amanda Heslegrave, Nick C Fox, Henrik Zetterberg, Jonathan M Schott,

<h4>Introduction</h4>We assessed the concordance of cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau measured on the fully automated Lumipulse platform with pre-symptomatic Alzheimer's disease (AD) pathology on amyloid positron emission tomography (PET).<h4>Methods</h4>In 72 individuals from the Insight 46 study, CSF Aβ40, Aβ42, total tau (t-tau), and phosphorylated tau at site ... Read more >>

Alzheimers Dement (Amst) (Alzheimer's & dementia (Amsterdam, Netherlands))
[2020, 12(1):e12097]

Cited: 1 time

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Measuring cortical mean diffusivity to assess early microstructural cortical change in presymptomatic familial Alzheimer's disease.

Philip S J Weston, Teresa Poole, Jennifer M Nicholas, Nicolas Toussaint, Ivor J A Simpson, Marc Modat, Natalie S Ryan, Yuying Liang, Martin N Rossor, Jonathan M Schott, Sebastien Ourselin, Hui Zhang, Nick C Fox,

<h4>Background</h4>There is increasing interest in improving understanding of the timing and nature of early neurodegeneration in Alzheimer's disease (AD) and developing methods to measure this in vivo. Autosomal dominant familial Alzheimer's disease (FAD) provides the opportunity for investigation of presymptomatic change. We assessed early microstructural breakdown of cortical grey matter ... Read more >>

Alzheimers Res Ther (Alzheimer's research & therapy)
[2020, 12(1):112]

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Increased variability in reaction time is associated with amyloid beta pathology at age 70.

Kirsty Lu, Jennifer M Nicholas, Sarah-Naomi James, Christopher A Lane, Thomas D Parker, Ashvini Keshavan, Sarah E Keuss, Sarah M Buchanan, Heidi Murray-Smith, David M Cash, Carole H Sudre, Ian B Malone, William Coath, Andrew Wong, Susie M D Henley, Nick C Fox, Marcus Richards, Jonathan M Schott, Sebastian J Crutch,

<h4>Introduction</h4>We investigated whether life-course factors and neuroimaging biomarkers of Alzheimer's disease pathology predict reaction time (RT) performance in older adults.<h4>Methods</h4>Insight 46 study participants, all born in the same week in 1946 (n = 501; ages at assessment = 69 to 71 years), completed a 2-choice RT task and amyloid beta ... Read more >>

Alzheimers Dement (Amst) (Alzheimer's & dementia (Amsterdam, Netherlands))
[2020, 12(1):e12076]

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Precision prevention of Alzheimer's and other dementias: Anticipating future needs in the control of risk factors and implementation of disease-modifying therapies.

Giovanni B Frisoni, José Luis Molinuevo, Daniele Altomare, Emmanuel Carrera, Frederik Barkhof, Johannes Berkhof, Julien Delrieu, Bruno Dubois, Miia Kivipelto, Agneta Nordberg, Jonathan M Schott, Wiesje M van der Flier, Bruno Vellas, Frank Jessen, Philip Scheltens, Craig Ritchie,

Empirical evidence suggests that a fair proportion of dementia cases are preventable, that some preventive actions can be taken immediately, and others may soon be implemented. Primary prevention may target cognitively normal persons with modifiable risk factors through lifestyle and multiple domain interventions (including general cardiovascular health). While the effect ... Read more >>

Alzheimers Dement (Alzheimer's & dementia : the journal of the Alzheimer's Association)
[2020, 16(10):1457-1468]

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A blood miRNA signature associates with sporadic Creutzfeldt-Jakob disease diagnosis.

Penny J Norsworthy, Andrew G B Thompson, Tze H Mok, Fernando Guntoro, Luke C Dabin, Akin Nihat, Ross W Paterson, Jonathan M Schott, John Collinge, Simon Mead, Emmanuelle A Viré,

Sporadic Creutzfeldt-Jakob disease (sCJD) presents as a rapidly progressive dementia which is usually fatal within six months. No clinical blood tests are available for diagnosis or disease monitoring. Here, we profile blood microRNA (miRNA) expression in sCJD. Sequencing of 57 sCJD patients, and healthy controls reveals differential expression of hsa-let-7i-5p, ... Read more >>

Nat Commun (Nature communications)
[2020, 11(1):3960]

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Olfactory testing does not predict β-amyloid, MRI measures of neurodegeneration or vascular pathology in the British 1946 birth cohort.

Sarah M Buchanan, Thomas D Parker, Christopher A Lane, Ashvini Keshavan, Sarah E Keuss, Kirsty Lu, Sarah-Naomi James, Heidi Murray-Smith, Andrew Wong, Jennifer Nicholas, David M Cash, Ian B Malone, William Coath, David L Thomas, Carole Sudre, Nick C Fox, Marcus Richards, Jonathan M Schott,

<h4>Objective</h4>To explore the value of olfactory identification deficits as a predictor of cerebral β-amyloid status and other markers of brain health in cognitively normal adults aged ~ 70 years.<h4>Methods</h4>Cross-sectional observational cohort study. 389 largely healthy and cognitively normal older adults were recruited from the MRC National Survey of Health and Development (1946 British ... Read more >>

J Neurol (Journal of neurology)
[2020, 267(11):3329-3336]

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How to diagnose difficult white matter disorders.

Thomas Williams, Henry Houlden, Elaine Murphy, Nevin John, Nick C Fox, Jonathan M Schott, Matthew Adams, Indran Davagananam, Jeremy Chataway, David S Lynch,

Genetic and acquired disorders of white matter comprise a diverse group of conditions, with often overlapping clinical and radiological findings. Patients present with a variable combination of cognitive impairment, ataxia, spasticity or movement disorders, among others. There are many genetic causes, and the route to diagnosis involves comprehensive clinical assessment, ... Read more >>

Pract Neurol (Practical neurology)
[2020, 20(4):280-286]

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Longitudinal Changes in Diet Quality over Adulthood and Physical Function in Older Life: Findings from a British Birth Cohort

Thanasis Tektonidis, Shelly Coe, Patrick Esser, Jane Maddock, Sarah Buchanan, Foteini Mavrommati, Hooshang Izadi, Jonathan M Schott, Marcus Richards, Helen Dawes,

Abstract Objectives A healthy diet has been linked to better physical function in older adults but evidence on the role of cumulative dietary exposure is scarce. Sex differences in the relationship are also underexplored. The objective was to explore the longitudinal association of diet quality in adulthood (from 36–64 y), ... Read more >>

Curr Dev Nutr (Current developments in nutrition)
[2020, 4(Suppl 2):1495-1495]

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Cerebrospinal Fluid YKL-40 and Chitotriosidase Levels in Frontotemporal Dementia Vary by Clinical, Genetic and Pathological Subtype.

Ione O C Woollacott, Jennifer M Nicholas, Carolin Heller, Martha S Foiani, Katrina M Moore, Lucy L Russell, Ross W Paterson, Ashvini Keshavan, Jonathan M Schott, Jason D Warren, Amanda Heslegrave, Henrik Zetterberg, Jonathan D Rohrer,

<h4>Background</h4>Chronic glial dysfunction may contribute to the pathogenesis of frontotemporal dementia (FTD). Cerebrospinal fluid (CSF) levels of glia-derived proteins YKL-40 and chitotriosidase are increased in Alzheimer's disease (AD) but have not been explored in detail across the spectrum of FTD.<h4>Methods</h4>We investigated whether CSF YKL-40 and chitotriosidase levels differed between FTD ... Read more >>

Dement Geriatr Cogn Disord (Dementia and geriatric cognitive disorders)
[2020, 49(1):56-76]

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Bilateral nucleus basalis of Meynert deep brain stimulation for dementia with Lewy bodies: A randomised clinical trial.

James Gratwicke, Ludvic Zrinzo, Joshua Kahan, Amy Peters, Una Brechany, Ann McNichol, Mazda Beigi, Harith Akram, Jonathan Hyam, Ashwini Oswal, Brian Day, Laura Mancini, John Thornton, Tarek Yousry, Sebastian J Crutch, John-Paul Taylor, Ian McKeith, Lynn Rochester, Jonathan M Schott, Patricia Limousin, David Burn, Martin N Rossor, Marwan Hariz, Marjan Jahanshahi, Thomas Foltynie,

<h4>Background</h4>Dementia with Lewy bodies (DLB) is the second most common form of dementia. Current symptomatic treatment with medications remains inadequate. Deep brain stimulation of the nucleus basalis of Meynert (NBM DBS) has been proposed as a potential new treatment option in dementias.<h4>Objective</h4>To assess the safety and tolerability of low frequency ... Read more >>

Brain Stimul (Brain stimulation)
[2020, 13(4):1031-1039]

Cited: 2 times

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