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
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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
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Journal ArticleDOI
Longitudinal evaluation of surrogates of regional cerebral blood flow computed from dynamic amyloid PET imaging.
TL;DR: Regional PiB-based measures, in particular R1, can be suitable surrogates of rCBF and may obviate the need for a separate scan to measure neuronal activity, thereby reducing patient burden, radioactivity exposure, and cost.
Journal ArticleDOI
Amyloid burden, cortical thickness, and cognitive function in the wisconsin registry for alzheimer's prevention
Benjamin M. Doherty,Jennifer M. Oh,Stephanie A. Schultz,Rebecca L. Koscik,N. Maritza Dowling,Todd E. Barnhart,Dhanabalan Murali,Catherine L. Gallagher,Cynthia M. Carlsson,Barbara B. Bendlin,Asenath LaRue,Bruce P. Hermann,Howard A. Rowley,Sanjay Asthana,Mark A. Sager,Brad T. Christian,Sterling C. Johnson,Ozioma C. Okonkwo +17 more
TL;DR: The findings suggest that early Aβ aggregation is associated with deleterious changes in brain structure and cognitive function, even in midlife, and that the temporal lag between Aβ deposition and the inception of neurodegenerative/cognitive changes might be narrower than currently thought.
Journal ArticleDOI
Resistance Exercise-Induced Responses in Physiological Factors Linked with Cognitive Health.
Kieran J. Marston,Belinda M. Brown,Stephanie R. Rainey-Smith,Stephanie R. Rainey-Smith,Jeremiah J. Peiffer +4 more
TL;DR: Vascular and neuronal degeneration as a cause or consequence of dementia and Alzheimer's disease, and the biological markers of neurogenesis and blood vessel growth, function, and regulation are discussed.
Journal ArticleDOI
Association of amyloid-β CSF/PET discordance and tau load 5 years later.
Juhan Reimand,Lyduine Collij,Philip Scheltens,Femke Bouwman,Rik Ossenkoppele,Alzheimer’s Disease Neuroimaging Initiative +5 more
TL;DR: Aβ load detectable by both CSF and PET seems to precede substantial tau deposition, and compared to participants with abnormal Aβ levels on both PET and CSF, the CSF+/PET− group has a distinctly better prognosis.
Journal ArticleDOI
Online assessment of risk factors for dementia and cognitive function in healthy adults
Jonathan Huntley,Anne Corbett,Keith Wesnes,Helen Brooker,Robert Stenton,Adam Hampshire,Clive Ballard +6 more
TL;DR: Several potentially modifiable risk factors for cognitive decline and dementia have been identified, including low educational attainment, smoking, diabetes, physical inactivity, hypertension, midlife obesity, depression, and perceived social isolation.
References
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Journal ArticleDOI
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Guy M. McKhann,David A. Drachman,Marshall F. Folstein,Robert Katzman,Donald L. Price,Emanuel M. Stadlan +5 more
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Information Theory and an Extension of the Maximum Likelihood Principle
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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
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