Yen Ying Lim1, Jenalle E Baker2, Loren Bruns2, Andrea Mills2, Christopher Fowler2, Jurgen Fripp2, Stephanie R Rainey-Smith2, David Ames2, Colin L Masters2, Paul Maruff2. 1. From Florey Institute of Neuroscience and Mental Health (Y.Y.L., J.E.B., A.M., C.F., C.L.M., P.M.), Parkville; Turner Institute for Brain and Mental Health (Y.Y.L., A.M.), School of Psychological Sciences, Monash University, Clayton; School of Computing and Information Systems (L.B.), The University of Melbourne, Parkville, Victoria; CSIRO Health and Biosecurity (J.F.), Australian e-Health Research Centre, Brisbane; Centre of Excellence for Alzheimer's Disease Research and Care (S.R.R.-S.), School of Medical Sciences, Edith Cowan University; Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital) (S.R.R.-S.), Perth; National Ageing Research Institute (D.A.), Parkville, Victoria; Academic Unit for Psychiatry of Old Age, Department of Psychiatry (D.A.), The University of Melbourne, St. George's Hospital, Kew; and Cogstate Ltd. (P.M.), Melbourne, Victoria, Australia. yenying.lim@monash.edu. 2. From Florey Institute of Neuroscience and Mental Health (Y.Y.L., J.E.B., A.M., C.F., C.L.M., P.M.), Parkville; Turner Institute for Brain and Mental Health (Y.Y.L., A.M.), School of Psychological Sciences, Monash University, Clayton; School of Computing and Information Systems (L.B.), The University of Melbourne, Parkville, Victoria; CSIRO Health and Biosecurity (J.F.), Australian e-Health Research Centre, Brisbane; Centre of Excellence for Alzheimer's Disease Research and Care (S.R.R.-S.), School of Medical Sciences, Edith Cowan University; Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital) (S.R.R.-S.), Perth; National Ageing Research Institute (D.A.), Parkville, Victoria; Academic Unit for Psychiatry of Old Age, Department of Psychiatry (D.A.), The University of Melbourne, St. George's Hospital, Kew; and Cogstate Ltd. (P.M.), Melbourne, Victoria, Australia.
Abstract
OBJECTIVE: To determine the extent to which deficits in learning over 6 days are associated with β-amyloid-positive (Aβ+) and hippocampal volume in cognitively normal (CN) adults. METHODS: Eighty CN older adults who had undergone PET neuroimaging to determine Aβ status (n = 42 Aβ- and 38 Aβ+), MRI to determine hippocampal and ventricular volume, and repeated assessment of memory were recruited from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Participants completed the Online Repeatable Cognitive Assessment-Language Learning Test (ORCA-LLT), which required they learn associations between 50 Chinese characters and their English language equivalents over 6 days. ORCA-LLT assessments were supervised on the first day and were completed remotely online for all remaining days. RESULTS: Learning curves in the Aβ+ CN participants were significantly worse than those in matched Aβ- CN participants, with the magnitude of this difference very large (d [95% confidence interval (CI)] 2.22 [1.64-2.75], p < 0.001), and greater than differences between these groups for memory decline since their enrollment in AIBL (d [95% CI] 0.52 [0.07-0.96], p = 0.021), or memory impairment at their most recent visit. In Aβ+ CN adults, slower rates of learning were associated with smaller hippocampal and larger ventricular volumes. CONCLUSIONS: These results suggest that in CN participants, Aβ+ is associated more strongly with a deficit in learning than any aspect of memory dysfunction. Slower rates of learning in Aβ+ CN participants were associated with hippocampal volume loss. Considered together, these data suggest that the primary cognitive consequence of Aβ+ is a failure to benefit from experience when exposed to novel stimuli, even over very short periods.
OBJECTIVE: To determine the extent to which deficits in learning over 6 days are associated with β-amyloid-positive (Aβ+) and hippocampal volume in cognitively normal (CN) adults. METHODS: Eighty CN older adults who had undergone PET neuroimaging to determine Aβ status (n = 42 Aβ- and 38 Aβ+), MRI to determine hippocampal and ventricular volume, and repeated assessment of memory were recruited from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Participants completed the Online Repeatable Cognitive Assessment-Language Learning Test (ORCA-LLT), which required they learn associations between 50 Chinese characters and their English language equivalents over 6 days. ORCA-LLT assessments were supervised on the first day and were completed remotely online for all remaining days. RESULTS: Learning curves in the Aβ+ CN participants were significantly worse than those in matched Aβ- CN participants, with the magnitude of this difference very large (d [95% confidence interval (CI)] 2.22 [1.64-2.75], p < 0.001), and greater than differences between these groups for memory decline since their enrollment in AIBL (d [95% CI] 0.52 [0.07-0.96], p = 0.021), or memory impairment at their most recent visit. In Aβ+ CN adults, slower rates of learning were associated with smaller hippocampal and larger ventricular volumes. CONCLUSIONS: These results suggest that in CN participants, Aβ+ is associated more strongly with a deficit in learning than any aspect of memory dysfunction. Slower rates of learning in Aβ+ CN participants were associated with hippocampal volume loss. Considered together, these data suggest that the primary cognitive consequence of Aβ+ is a failure to benefit from experience when exposed to novel stimuli, even over very short periods.
Authors: Michelle E Farrell; Kathryn V Papp; Rachel F Buckley; Heidi I L Jacobs; Aaron P Schultz; Michael J Properzi; Patrizia Vannini; Bernard J Hanseeuw; Dorene M Rentz; Keith A Johnson; Reisa A Sperling Journal: Neurology Date: 2022-03-25 Impact factor: 11.800
Authors: Yen Ying Lim; Jenalle E Baker; Andrea Mills; Loren Bruns; Christopher Fowler; Jurgen Fripp; Stephanie R Rainey-Smith; David Ames; Colin L Masters; Paul Maruff Journal: Alzheimers Dement (Amst) Date: 2021-03-16
Authors: Aubryn Samaroo; Rebecca E Amariglio; Samantha Burnham; Paige Sparks; Michael Properzi; Aaron P Schultz; Rachel Buckley; Keith A Johnson; Reisa A Sperling; Dorene M Rentz; Kathryn V Papp Journal: Alzheimers Dement (Amst) Date: 2021-01-05
Authors: Roos J Jutten; Dorene M Rentz; Jessie F Fu; Danielle V Mayblyum; Rebecca E Amariglio; Rachel F Buckley; Michael J Properzi; Paul Maruff; Craig E Stark; Michael A Yassa; Keith A Johnson; Reisa A Sperling; Kathryn V Papp Journal: Front Aging Neurosci Date: 2022-01-13 Impact factor: 5.750
Authors: Shehroo B Pudumjee; Emily S Lundt; Sabrina M Albertson; Mary M Machulda; Walter K Kremers; Clifford R Jack; David S Knopman; Ronald C Petersen; Michelle M Mielke; Nikki H Stricker Journal: J Alzheimers Dis Date: 2021 Impact factor: 4.472
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
Authors: Esther C McWilliams; Florentine M Barbey; John F Dyer; Md Nurul Islam; Bernadette McGuinness; Brian Murphy; Hugh Nolan; Peter Passmore; Laura M Rueda-Delgado; Alison R Buick Journal: Front Psychiatry Date: 2021-06-25 Impact factor: 4.157