Journal ArticleDOI
Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study.
Victor L. Villemagne,Samantha C. Burnham,Pierrick Bourgeat,Belinda M. Brown,Kathryn A. Ellis,Olivier Salvado,Cassandra Szoeke,S. Lance Macaulay,Ralph N. Martins,Paul Maruff,David Ames,Christopher C. Rowe,Colin L. Masters +12 more
Reads0
Chats0
TLDR
These projections suggest a prolonged preclinical phase of AD in which Aβ deposition reaches the authors' threshold of positivity at 17·0 (95% CI 14·9-19·9) years, hippocampal atrophy at 4·2 (3·6-5·1] years, and memory impairment at 3·3 (2·5-4·5) years before the onset of dementia (clinical dementia rating score 1).Abstract:
Summary Background Similar to most chronic diseases, Alzheimer's disease (AD) develops slowly from a preclinical phase into a fully expressed clinical syndrome. We aimed to use longitudinal data to calculate the rates of amyloid β (Aβ) deposition, cerebral atrophy, and cognitive decline. Methods In this prospective cohort study, healthy controls, patients with mild cognitive impairment (MCI), and patients with AD were assessed at enrolment and every 18 months. At every visit, participants underwent neuropsychological examination, MRI, and a carbon-11-labelled Pittsburgh compound B ( 11 C-PiB) PET scan. We included participants with three or more 11 C-PiB PET follow-up assessments. Aβ burden was expressed as 11 C-PiB standardised uptake value ratio (SUVR) with the cerebellar cortex as reference region. An SUVR of 1·5 was used to discriminate high from low Aβ burdens. The slope of the regression plots over 3–5 years was used to estimate rates of change for Aβ deposition, MRI volumetrics, and cognition. We included those participants with a positive rate of Aβ deposition to calculate the trajectory of each variable over time. Findings 200 participants (145 healthy controls, 36 participants with MCI, and 19 participants with AD) were assessed at enrolment and every 18 months for a mean follow-up of 3·8 (95% CI CI 3·6–3·9) years. At baseline, significantly higher Aβ burdens were noted in patients with AD (2·27, SD 0·43) and those with MCI (1·94, 0·64) than in healthy controls (1·38, 0·39). At follow-up, 163 (82%) of the 200 participants showed positive rates of Aβ accumulation. Aβ deposition was estimated to take 19·2 (95% CI 16·8–22·5) years in an almost linear fashion—with a mean increase of 0·043 (95% CI 0·037–0·049) SUVR per year—to go from the threshold of 11 C-PiB positivity (1·5 SUVR) to the levels observed in AD. It was estimated to take 12·0 (95% CI 10·1–14·9) years from the levels observed in healthy controls with low Aβ deposition (1·2 [SD 0·1] SUVR) to the threshold of 11 C-PiB positivity. As AD progressed, the rate of Aβ deposition slowed towards a plateau. Our projections suggest a prolonged preclinical phase of AD in which Aβ deposition reaches our threshold of positivity at 17·0 (95% CI 14·9–19·9) years, hippocampal atrophy at 4·2 (3·6–5·1) years, and memory impairment at 3·3 (2·5–4·5) years before the onset of dementia (clinical dementia rating score 1). Interpretation Aβ deposition is slow and protracted, likely to extend for more than two decades. Such predictions of the rate of preclinical changes and the onset of the clinical phase of AD will facilitate the design and timing of therapeutic interventions aimed at modifying the course of this illness. Funding Science and Industry Endowment Fund (Australia), The Commonwealth Scientific and Industrial Research Organisation (Australia), The National Health and Medical Research Council of Australia Program and Project Grants, the Austin Hospital Medical Research Foundation, Victorian State Government, The Alzheimer's Drug Discovery Foundation, and the Alzheimer's Association.read more
Citations
More filters
Journal ArticleDOI
NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease
Clifford R. Jack,David A. Bennett,Kaj Blennow,Maria C. Carrillo,Billy Dunn,Samantha Budd Haeberlein,David M. Holtzman,William J. Jagust,Frank Jessen,Jason Karlawish,Enchi Liu,José Luis Molinuevo,Thomas J. Montine,Creighton H. Phelps,Katherine P. Rankin,Christopher C. Rowe,Philip Scheltens,Eric Siemers,Heather M. Snyder,Reisa A. Sperling,Cerise L Elliott,Eliezer Masliah,Laurie M. Ryan,Nina Silverberg +23 more
TL;DR: This research framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms and envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD.
Journal ArticleDOI
2016 Alzheimer's disease facts and figures
Journal ArticleDOI
Dementia prevention, intervention, and care
Gill Livingston,Gill Livingston,Andrew Sommerlad,Vasiliki Orgeta,Sergi G. Costafreda,Sergi G. Costafreda,Jonathan Huntley,Jonathan Huntley,David Ames,Clive Ballard,Sube Banerjee,Alistair Burns,Jiska Cohen-Mansfield,Claudia Cooper,Claudia Cooper,Nick C. Fox,Laura N. Gitlin,Robert Howard,Robert Howard,Helen C. Kales,Eric B. Larson,Eric B. Larson,Karen Ritchie,Karen Ritchie,Kenneth Rockwood,Elizabeth L Sampson,Quincy M. Samus,Lon S. Schneider,Geir Selbæk,Geir Selbæk,Linda Teri,Naaheed Mukadam +31 more
TL;DR: The Lancet Commission on Dementia Prevention, Intervention, and Care met to consolidate the huge strides that have been made and the emerging knowledge as to what the authors should do to prevent and manage dementia.
Journal ArticleDOI
The amyloid hypothesis of Alzheimer's disease at 25 years
Dennis J. Selkoe,John Hardy +1 more
TL;DR: In a recent study, this article showed that low cerebrospinal fluid (CSF) Aβ42 and amyloid-PET positivity precede other AD manifestations by many years.
Journal ArticleDOI
The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease
Jeff Sevigny,Ping Chiao,Thierry Bussiere,Paul H. Weinreb,Leslie Williams,Marcel Maier,Robert Dunstan,Stephen Salloway,Tianle Chen,Yan Ling,John O'Gorman,Fang Qian,Mahin Arastu,Mingwei Li,Sowmya Chollate,Melanie S. Brennan,Omar Quintero-Monzon,Robert H. Scannevin,H. Moore Arnold,Thomas Engber,Kenneth J. Rhodes,James Ferrero,Yaming Hang,Alvydas Mikulskis,Jan Grimm,Christoph Hock,Roger M. Nitsch,Alfred Sandrock +27 more
TL;DR: In patients with prodromal or mild AD, one year of monthly intravenous infusions of aducanumab reduces brain Aβ in a dose- and time-dependent manner, accompanied by a slowing of clinical decline measured by Clinical Dementia Rating—Sum of Boxes and Mini Mental State Examination scores.
References
More filters
Journal ArticleDOI
Longitudinal Assessment of Aβ and Cognition in Aging and Alzheimer Disease
Victor L. Villemagne,Kerryn E. Pike,Gaël Chételat,Kathryn A. Ellis,Rachel S. Mulligan,Pierrick Bourgeat,Uwe Ackermann,Gareth Jones,Cassandra Szoeke,Olivier Salvado,Ralph N. Martins,Graeme O'Keefe,Chester A. Mathis,William E. Klunk,David Ames,Colin L. Masters,Christopher C. Rowe +16 more
TL;DR: Assess Aβ deposition longitudinally and explore its relationship with cognition and disease progression.
Journal ArticleDOI
The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging: Methodology and baseline characteristics of 1112 individuals recruited for a longitudinal study of Alzheimer's disease
Kathryn A. Ellis,Ashley I. Bush,David Darby,Daniela De Fazio,Jonathan K. Foster,Peter Hudson,Nicola T. Lautenschlager,Nat Lenzo,Ralph N. Martins,Paul Maruff,Colin L. Masters,Andrew Milner,Kerryn E. Pike,Christopher C. Rowe,Greg Savage,Cassandra Szoeke,Kevin Taddei,Victor L. Villemagne,Michael Woodward,David Ames +19 more
TL;DR: The participants comprising the AIBL cohort represent a group of highly motivated and well-characterized individuals who represent a unique resource for the study of AD.
Journal ArticleDOI
C-11-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer's disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study
Juha O. Rinne,David J. Brooks,Martin N. Rossor,Nick C. Fox,Roger Bullock,William E. Klunk,Chester A. Mathis,Kaj Blennow,Jerome Barakos,A Okello,Sofia Rodriguez Martinez de Liano,Enchi Liu,Martin Koller,Gregg Keith M,Dale Schenk,Ronald Black,Michael Grundman +16 more
TL;DR: Treatment with bapineuzumab for 78 weeks reduced cortical (11)C-PiB retention compared with both baseline and placebo and seems to be useful in assessing the effects of potential Alzheimer's disease treatments on cortical fibrillar amyloid-beta load in vivo.
Journal ArticleDOI
Neuropathology of nondemented aging: Presumptive evidence for preclinical Alzheimer disease
Joseph L. Price,Daniel W. McKeel,Virginia Buckles,Catherine M. Roe,Chengjie Xiong,Michael Grundman,Lawrence A. Hansen,Ronald C. Petersen,Joseph E. Parisi,Dennis W. Dickson,Charles D. Smith,Daron G. Davis,Frederick A. Schmitt,William R. Markesbery,Jeffrey Kaye,Roger Kurlan,Christine M. Hulette,Brenda F. Kurland,Roger Higdon,Walter A. Kukull,John C. Morris +20 more
TL;DR: Cognitive function in nondemented aging appears to be degraded by the presence of NFTs and SPs, and neuropathological processes related to AD in persons without dementia appear to be associated with subtle cognitive dysfunction and may represent a preclinical stage of the illness.
Journal ArticleDOI
An operational approach to National Institute on Aging–Alzheimer's Association criteria for preclinical Alzheimer disease
Clifford R. Jack,David S. Knopman,Stephen D. Weigand,Heather J. Wiste,Prashanthi Vemuri,Val J. Lowe,Kejal Kantarci,Jeffrey L. Gunter,Matthew L. Senjem,Robert J. Ivnik,Rosebud O. Roberts,Walter A. Rocca,Bradley F. Boeve,Ronald C. Petersen +13 more
TL;DR: A workgroup commissioned by the Alzheimer's Association and the National Institute on Aging recently published research criteria for preclinical Alzheimer disease (AD) performed a preliminary assessment of these guidelines.
Related Papers (5)
Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease
Reisa A. Sperling,Paul S. Aisen,Laurel A. Beckett,David A. Bennett,Suzanne Craft,Anne M. Fagan,Takeshi Iwatsubo,Clifford R. Jack,Jeffrey Kaye,Thomas J. Montine,Denise C. Park,Eric M. Reiman,Christopher C. Rowe,Eric Siemers,Yaakov Stern,Kristine Yaffe,Maria C. Carrillo,Bill Thies,Marcelle Morrison-Bogorad,Molly V. Wagster,Creighton H. Phelps +20 more
The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease
Guy M. McKhann,Guy M. McKhann,David S. Knopman,Howard Chertkow,Bradley T. Hyman,Clifford R. Jack,Claudia H. Kawas,William E. Klunk,Walter J. Koroshetz,Jennifer J. Manly,Richard Mayeux,Richard C. Mohs,John C. Morris,Martin N. Rossor,Philip Scheltens,Maria C. Carrillo,Bill Thies,Sandra Weintraub,Creighton H. Phelps +18 more
Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B.
William E. Klunk,Henry Engler,Agneta Nordberg,Yanming Wang,G. Blomqvist,Daniel P. Holt,Mats Bergström,Irina Savitcheva,Guo Feng Huang,Sergio Estrada,Birgitta Ausén,Manik L. Debnath,Julien Barletta,Julie C. Price,Johan Sandell,Brian J. Lopresti,Anders Wall,Pernilla Koivisto,Gunnar Antoni,Chester A. Mathis,Bengt Långström +20 more