title: Trajectories of memory decline in preclinical Alzheimer's disease: results from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of ageing.
abstract: Memory changes in preclinical Alzheimer's disease (AD) are often characterized by heterogenous trajectories. However, data regarding the nature and determinants of predominant trajectories of memory changes in preclinical AD are lacking. We analyzed data from 333 cognitively healthy older adults who participated in a multicenter prospective cohort study with baseline and 18-, 36-, and 54-month follow-up assessments. Latent growth mixture modeling revealed 3 predominant trajectories of memory change: a below average, subtly declining memory trajectory (30.9%); a below average, rapidly declining memory trajectory (3.6%); and an above average, stable memory trajectory (65.5%). Compared with the stable memory trajectory, high Αβ (relative risk ratio [RRR] = 2.1), and lower Mini-Mental State Examination (RRR = 0.6) and full-scale IQ (RRR = 0.9) scores were independently associated with the subtly declining memory trajectory; and high Αβ (RRR = 8.3), APOE ε4 carriage (RRR = 6.1), and greater subjective memory impairment (RRR = 1.2) were independently associated with the rapidly declining memory trajectory. Compared with the subtly declining memory trajectory group, APOE ε4 carriage (RRR = 8.4), and subjective memory complaints (RRR = 1.2) were associated with a rapidly declining memory trajectory. These results suggest that the preclinical phase of AD may be characterized by 2 predominant trajectories of memory decline that have common (e.g., high Αβ) and unique (e.g., APOE ε4 genotype) determinants.
authors.affiliation: United States Department of Veterans Affairs, National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA. Electronic address: robert.pietrzak@yale.edu.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Pietrzak
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia; Department of Neurology, Warren Alpert School of Medicine, Brown University, Providence, RI, USA.
authors.forename: Yen Ying
authors.initials: YY
authors.lastname: Lim
authors.affiliation: Academic Unit for Psychiatry of Old Age, St. Vincent's Health, Department of Psychiatry, The University of Melbourne, Kew, Victoria, Australia; National Ageing Research Institute, Parkville, Victoria, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Karra
authors.initials: K
authors.lastname: Harrington
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Carolina
authors.initials: C
authors.lastname: Restrepo
authors.affiliation: Centre of Excellence for Alzheimer's Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia; Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Nedlands, Western Australia, Australia.
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Rembach
authors.affiliation: Centre of Excellence for Alzheimer's Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia; Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Nedlands, Western Australia, Australia.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Laws
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia; Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia; Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.affiliation: Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia; Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Rowe
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia; Cogstate Ltd, Melbourne, Victoria, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Maruff
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D061212:Memory, Episodic; D057054:Molecular Imaging; D015337:Multicenter Studies as Topic; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D012306:Risk; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4
keywords: APOE; Alzheimer's disease; Aβ; Memory; Trajectories