Lisa Bransby1, Yen Ying Lim1, David Ames2,3, Christopher Fowler1, Joanne Roberston1, Karra Harrington1,4, Peter J Snyder5, Victor L Villemagne1,6,7, Olivier Salvado8, Colin L Masters1, Paul Maruff1,9. 1. a The Florey Institute of Neuroscience and Mental Health , The University of Melbourne , Melbourne , VIC , Australia. 2. b National Ageing Research Institute , Melbourne , VIC , Australia. 3. c Academic Unit for Psychiatry of Old Age, St. Vincent's Health , The University of Melbourne , Melbourne , VIC , Australia. 4. d Cooperative Research Centre for Mental Health , Parkville , Australia. 5. e Ryan Institute for Neuroscience , University of Rhode Island , Kingston , RI , USA. 6. f Department of Nuclear Medicine and Centre for PET , Austin Health , Melbourne , VIC , Australia. 7. g Department of Medicine, Austin Health , The University of Melbourne , Melbourne , VIC , Australia. 8. h Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship , Australian e-Health Research Centre-BiaMedIA , Brisbane , QLD , Australia. 9. i CogState Ltd ., Melbourne , VIC , Australia.
Abstract
Introduction: Preclinical Alzheimer's disease (AD) is characterized by amyloid-related cognitive decline. Reduction in this decline is used to determine the efficacy of drug therapies designed to forestall the disease in preclinical AD clinical trials, measured by a Preclinical Alzheimer's Cognitive Composite (PACC). Most studies estimate rates of cognitive change by comparing cognitively normal (CN) older adults with abnormally high beta-amyloid (Aβ+) to those with low levels (Aβ-). However, participants of preclinical AD clinical trials must be Aβ+ for entry. Therefore, we estimated the effect of very high amyloid (Aβ++) and Aβ+ on cognitive change over three years measured by different versions of the PACC in individuals with preclinical AD. Method: CN older adults underwent Aβ neuroimaging and neuropsychological assessments over three years as part of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Three cognitive composite scores were computed: the Alzheimer's Disease Cooperative Study (ADCS)-PACC, the ADCS-PACC with no Mini-Mental State Examination (MMSE), and the z-scores of Attention, Verbal Fluency and Episodic Memory for Nondemented Older Adults (ZAVEN) composite. Results: Compared to the Aβ++ group, the Aβ+ group showed a slower rate of cognitive decline with the largest magnitude of difference reflected by the ADCS-PACC (d = 0.85). The ADCS-PACC excluding the MMSE and the ZAVEN also reflected a moderate to large magnitude of difference between groups (d = 0.62, d = 0.72, respectively). Conclusions: When all individuals have abnormal Aβ, the level of Aβ at baseline is associated with the rate of subsequent decline. The ADCS-PACC was the most sensitive composite score in showing that lower Aβ is associated with a slower rate of cognitive decline; however, there are limitations to the use of the MMSE. These results provide a benchmark of comparison for preclinical AD clinical trials aiming to slow cognitive deterioration.
Introduction: Preclinical Alzheimer's disease (AD) is characterized by amyloid-related cognitive decline. Reduction in this decline is used to determine the efficacy of drug therapies designed to forestall the disease in preclinical AD clinical trials, measured by a Preclinical Alzheimer's Cognitive Composite (PACC). Most studies estimate rates of cognitive change by comparing cognitively normal (CN) older adults with abnormally high beta-amyloid (Aβ+) to those with low levels (Aβ-). However, participants of preclinical AD clinical trials must be Aβ+ for entry. Therefore, we estimated the effect of very high amyloid (Aβ++) and Aβ+ on cognitive change over three years measured by different versions of the PACC in individuals with preclinical AD. Method: CN older adults underwent Aβ neuroimaging and neuropsychological assessments over three years as part of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Three cognitive composite scores were computed: the Alzheimer's Disease Cooperative Study (ADCS)-PACC, the ADCS-PACC with no Mini-Mental State Examination (MMSE), and the z-scores of Attention, Verbal Fluency and Episodic Memory for Nondemented Older Adults (ZAVEN) composite. Results: Compared to the Aβ++ group, the Aβ+ group showed a slower rate of cognitive decline with the largest magnitude of difference reflected by the ADCS-PACC (d = 0.85). The ADCS-PACC excluding the MMSE and the ZAVEN also reflected a moderate to large magnitude of difference between groups (d = 0.62, d = 0.72, respectively). Conclusions: When all individuals have abnormal Aβ, the level of Aβ at baseline is associated with the rate of subsequent decline. The ADCS-PACC was the most sensitive composite score in showing that lower Aβ is associated with a slower rate of cognitive decline; however, there are limitations to the use of the MMSE. These results provide a benchmark of comparison for preclinical AD clinical trials aiming to slow cognitive deterioration.
Authors: J K Longhurst; J L Cummings; S E John; B Poston; J V Rider; A M Salazar; V R Mishra; A Ritter; J Z Caldwell; J B Miller; J W Kinney; M R Landers Journal: J Prev Alzheimers Dis Date: 2022
Authors: Helen Brooker; Gareth Williams; Adam Hampshire; Anne Corbett; Dag Aarsland; Jeffrey Cummings; Jose Luis Molinuevo; Alireza Atri; Zahinoor Ismail; Byron Creese; Tormod Fladby; Charlotte Thim-Hansen; Keith Wesnes; Clive Ballard Journal: Alzheimers Dement (Amst) Date: 2020-10-14
Authors: Matthew Calamia; Daniel S Weitzner; Alyssa N De Vito; John P K Bernstein; Ray Allen; Jeffrey N Keller Journal: PLoS One Date: 2021-01-19 Impact factor: 3.240
Authors: Christopher Fowler; Stephanie R Rainey-Smith; Sabine Bird; Julia Bomke; Pierrick Bourgeat; Belinda M Brown; Samantha C Burnham; Ashley I Bush; Carolyn Chadunow; Steven Collins; James Doecke; Vincent Doré; Kathryn A Ellis; Lis Evered; Amir Fazlollahi; Jurgen Fripp; Samantha L Gardener; Simon Gibson; Robert Grenfell; Elise Harrison; Richard Head; Liang Jin; Adrian Kamer; Fiona Lamb; Nicola T Lautenschlager; Simon M Laws; Qiao-Xin Li; Lucy Lim; Yen Ying Lim; Andrea Louey; S Lance Macaulay; Lucy Mackintosh; Ralph N Martins; Paul Maruff; Colin L Masters; Simon McBride; Lidija Milicic; Madeline Peretti; Kelly Pertile; Tenielle Porter; Morgan Radler; Alan Rembach; Joanne Robertson; Mark Rodrigues; Christopher C Rowe; Rebecca Rumble; Olivier Salvado; Greg Savage; Brendan Silbert; Magdalene Soh; Hamid R Sohrabi; Kevin Taddei; Tania Taddei; Christine Thai; Brett Trounson; Regan Tyrrell; Michael Vacher; Shiji Varghese; Victor L Villemagne; Michael Weinborn; Michael Woodward; Ying Xia; David Ames Journal: J Alzheimers Dis Rep Date: 2021-06-03