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
Light-Induced Pupillary Responses in Alzheimer's Disease.
TL;DR: Current knowledge on pupillometric features in AD and other neurodegenerative diseases are synopsized, potential roles of pupillometry in AD detection, diagnosis and monitoring are discussed, alone or in combination with additional biomarkers.
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The NGF Metabolic Pathway in the CNS and its Dysregulation in Down Syndrome and Alzheimer’s Disease
TL;DR: The physiological role of NGF and its biological significance to cholinergic neurons of the CNS is discussed, the evidence for a dysregulation of the NGF metabolism in Alzheimer's disease and Down syndrome is presented, and the trophic factor hypothesis is revived.
Journal ArticleDOI
Temporal evolution of biomarkers and cognitive markers in the asymptomatic, MCI, and dementia stage of Alzheimer's disease
TL;DR: The pattern of disease progression in the asymptomatic, mild cognitive impairment (MCI), and dementia stage of Alzheimer's disease (AD) is investigated.
Journal ArticleDOI
Partial-Volume Effect Correction Improves Quantitative Analysis of 18F-Florbetaben β-Amyloid PET Scans
Michael Rullmann,Juergen Dukart,Juergen Dukart,Karl-Titus Hoffmann,Julia Luthardt,Solveig Tiepolt,Marianne Patt,Hermann-Josef Gertz,Matthias L. Schroeter,Matthias L. Schroeter,John Seibyl,Walter J. Schulz-Schaeffer,Osama Sabri,Henryk Barthel +13 more
TL;DR: PVEC increases the ability of 18F-florbetaben PET to discriminate between AD patients and HCs, to detect Aβ plaques in the atrophic mesial temporal cortex, and potentially to evaluate changes in brain Aβ load over time.
Journal ArticleDOI
The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory.
TL;DR: It is found in 89 older individuals without dementia, that BIN1 rs744373 risk-allele carriers show higher AV1451 tau-PET across brain regions corresponding to Braak stages II–VI, suggesting that alterations in Bin1 may contribute to memory deficits via increased tau pathology.
References
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