title: Amyloid-β, anxiety, and cognitive decline in preclinical Alzheimer disease: a multicenter, prospective cohort study.
abstract: OBJECTIVE
  Alzheimer disease (AD) is now known to have a long preclinical phase in which pathophysiologic processes develop many years, even decades, before the onset of clinical symptoms. Although the presence of abnormal levels of amyloid-β (Aβ) is associated with higher rates of progression to clinically classified mild cognitive impairment or dementia, little research has evaluated potentially modifiable moderators of Aβ-related cognitive decline, such as anxiety and depressive symptoms.
  
  
  OBJECTIVE
  To evaluate the association between Aβ status and cognitive changes, and the role of anxiety and depressive symptoms in moderating Aβ-related cognitive changes in the preclinical phase of AD.
  
  
  METHODS
  In this multicenter, prospective cohort study with baseline and 18-, 36-, and 54-month follow-up assessments, we studied 333 healthy, older adults at hospital-based research clinics.
  
  
  METHODS
  Carbon 11-labeled Pittsburgh Compound B (PiB)-, florbetapir F 18-, or flutemetamol F 18-derived measures of Aβ, Hospital Anxiety and Depression Scale scores, and comprehensive neuropsychological evaluation that yielded measures of global cognition, verbal memory, visual memory, attention, language, executive function, and visuospatial ability.
  
  
  RESULTS
  A positive Aβ (Aβ+) status at baseline was associated with a significant decline in global cognition, verbal memory, language, and executive function, and elevated anxiety symptoms moderated these associations. Compared with the Aβ+, low-anxiety group, slopes of cognitive decline were significantly more pronounced in the Aβ+, high-anxiety group, with Cohen d values of 0.78 (95% CI, 0.33-1.23) for global cognition, 0.54 (95% CI, 0.10-0.98) for verbal memory, 0.51 (95% CI, 0.07-0.96) for language, and 0.39 (95% CI, 0.05-0.83) for executive function. These effects were independent of age, educational level, IQ, APOE genotype, subjective memory complaints, vascular risk factors, and depressive symptoms; furthermore, depressive symptoms and subjective memory complaints did not moderate the association between Aβ and cognitive decline.
  
  
  CONCLUSIONS
  These results provide additional support for the deleterious effect of elevated Aβ levels on cognitive function in preclinical AD. They further suggest that elevated anxiety symptoms moderate the effect of Aβ on cognitive decline in preclinical AD, resulting in more rapid decline in several cognitive domains. Given that there is currently no standard antiamyloid therapy and that anxiety symptoms are amenable to treatment, these findings may help inform risk stratification and management of the preclinical phase of AD.
authors: Veterans Affairs Connecticut Healthcare System, Clinical Neurosciences Division, US Department of Veterans Affairs, West Haven2Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut.
authors: Robert H
authors: RH
authors: Pietrzak
authors: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia4Department of Neurology, Warren Alpert School of Medicine, Brown University, Providence, Rhode Island.
authors: Yen Ying
authors: YY
authors: Lim
authors: Departments of Psychiatry and Radiology, New York University School of Medicine, New York.
authors: Alexander
authors: A
authors: Neumeister
authors: Academic Unit for Psychiatry of Old Age, St. Vincent's Health, Department of Psychiatry, The University of Melbourne, Kew, Victoria, Australia7School of Psychiatry and Clinical Neurosciences and Western Australia Centre for Health and Ageing, University o.
authors: David
authors: D
authors: Ames
authors: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia6Academic Unit for Psychiatry of Old Age, St. Vincent's Health, Department of Psychiatry, The University of Melbourne, Kew, Victoria, Austra.
authors: Kathryn A
authors: KA
authors: Ellis
authors: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
authors: Karra
authors: K
authors: Harrington
authors: Academic Unit for Psychiatry of Old Age, St. Vincent's Health, Department of Psychiatry, The University of Melbourne, Kew, Victoria, Australia7School of Psychiatry and Clinical Neurosciences and Western Australia Centre for Health and Ageing, University o.
authors: Nicola T
authors: NT
authors: Lautenschlager
authors: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
authors: Carolina
authors: C
authors: Restrepo
authors: Centre of Excellence for Alzheimer's Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia.
authors: Ralph N
authors: RN
authors: Martins
authors: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
authors: Colin L
authors: CL
authors: Masters
authors: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia9Department of Nuclear Medicine and Centre for Positron Emission Tomography, Austin Health, Heidelberg, Victoria, Australia10Department of M.
authors: Victor L
authors: VL
authors: Villemagne
authors: Department of Nuclear Medicine and Centre for Positron Emission Tomography, Austin Health, Heidelberg, Victoria, Australia10Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
authors: Christopher C
authors: CC
authors: Rowe
authors: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia11Cogstate Ltd, Melbourne, Victoria, Australia.
authors: Paul
authors: P
authors: Maruff
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001007:Anxiety / Q000503:physiopathology*; D003863:Depression / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D062706:Prodromal Symptoms; D011446:Prospective Studies
chemical_list: D016229:Amyloid beta-Peptides