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Amyloid-β, Anxiety, and Cognitive Decline in Preclinical Alzheimer Disease: A Multicenter, Prospective Cohort Study
Open accessAbstract
IMPORTANCE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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.
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Cites
The validity of the Hospital Anxiety and Depression Scale
Bjelland, I., Dahl, A. A., Haug, T. T., & Neckelmann, D. (2002) · Journal of Psychosomatic Research · doi:10.1016/s0022-3999(01)00296-3 · Cited by 9,779
Anxiety and cognitive performance: Attentional control theory
Eysenck, M. W., Derakshan, N., Santos, R., & Calvo, M. G. (2007) · Emotion · doi:10.1037/1528-3542.7.2.336 · Cited by 5,289
Villemagne, V. L., Burnham, S., Bourgeat, P., Brown, B., Ellis, K. A., Salvado, O., Szoeke, C., Macaulay, S. L., Martins, R., Maruff, P., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70044-9 · Cited by 2,279
Self-citationBrain on stress: how the social environment gets under the skin
McEwen, B. S. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1121254109 · Cited by 1,200
Use of Florbetapir-PET for Imaging β-Amyloid Pathology
Clark, C. M. (2011) · JAMA · doi:10.1001/jama.2010.2008 · Cited by 1,117
Ellis, K. A., Bush, A. I., Darby, D., Fazio, D. D., Foster, J. K., Hudson, P. J., Lautenschlager, N. T., Lenzo, N. P., Martins, R. N., Maruff, P. T., et al. (2009) · International Psychogeriatrics · doi:10.1017/s1041610209009405 · Cited by 1,005
Self-citationAmyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging
Rowe, C. C., Ellis, K. A., Rimajova, M., Bourgeat, P., Pike, K. E., Jones, G., Fripp, J., Tochon-Danguy, H., Morandeau, L., O'Keefe, G., et al. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.04.007 · Cited by 986
Self-citationAntidepressants increase neural progenitor cells in the human hippocampus
Boldrini, M., Underwood, M. D., Hen, R., Rosoklija, G. B., Dwork, A. J., John Mann, J., & Arango, V. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.75 · Cited by 686
Vandenberghe, R. R., Laere, K. V., Ivanoiu, A., Salmon, É., Bastin, C., Triau, E., Hasselbalch, S. G., Law, I. G., Andersen, A., Kørner, A., et al. (2010) · Annals of Neurology · doi:10.1002/ana.22068 · Cited by 664
Assessment of Memory Complaint in Age-Associated Memory Impairment: The MAC-Q
Crook, T. H., Feher, E. P., & Larrabee, G. J. (1992) · International Psychogeriatrics · doi:10.1017/s1041610292000991 · Cited by 434
van Zoonen, K., Buntrock, C., Ebert, D. D., Smit, F., Reynolds, C. F., Beekman, A. T., & Cuijpers, P. (2014) · International Journal of Epidemiology · doi:10.1093/ije/dyt175 · Cited by 425
Geda, Y. E., Roberts, R. O., Mielke, M. M., Knopman, D. S., Christianson, T. J. H., Pankratz, V. S., Boeve, B. F., Sochor, O., Tangalos, E. G., Petersen, R. C., et al. (2014) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2014.13060821 · Cited by 352
Boldrini, M., Hen, R., Underwood, M. D., Rosoklija, G. B., Dwork, A. J., Mann, J. J., & Arango, V. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.04.024 · Cited by 348
Stepped-Care Prevention of Anxiety and Depression in Late Life
Veer-Tazelaar, P. J. V., van Marwijk, H., van Oppen, P., van Hout, H. P. J., van der Horst, H. E., Cuijpers, P. J., Smit, F., & Beekman, A. T. F. (2009) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2008.555 · Cited by 320
Late-Life Anxiety and Cognitive Impairment: A Review
Beaudreau, S. A., & O'Hara, R. M. (2008) · American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e31817945c3 · Cited by 307
Cognitive dysfunction in depression: Neurocircuitry and new therapeutic strategies
Murrough, J. W., Iacoviello, B., Neumeister, A., Charney, D. S., & Iosifescu, D. V. (2011) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2011.06.006 · Cited by 307
Self-citationVillain, N., Chételat, G., Grassiot, B., Bourgeat, P., Jones, G., Ellis, K. A., Ames, D., Martins, R. N., Eustache, F., Salvado, O., et al. (2012) · Brain · doi:10.1093/brain/aws125 · Cited by 255
Self-citationAn Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice
Sheline, Y. I., West, T., Yarasheski, K., Swarm, R., Jasielec, M. S., Fisher, J. R., Ficker, W. D., Yan, P., Xiong, C., Frederiksen, C., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008169 · Cited by 223
Effect of amyloid on memory and non-memory decline from preclinical to clinical Alzheimer’s disease
Lim, Y. Y., Maruff, P. T., Pietrzak, R. H., Ames, D. J., Ellis, K. A., Harrington, K., Lautenschlager, N. T., Szoeke, C. E. I., Martins, R. N., Masters, C. L., et al. (2013) · Brain · doi:10.1093/brain/awt286 · Cited by 219
Self-citationPsychological treatments for depression and anxiety in dementia and mild cognitive impairment
Orgeta, V., Qazi, A., Spector, A. E., & Orrell, M. W. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009125.pub2 · Cited by 218
Beaudreau, S. A., & O'Hara, R. M. (2009) · Psychology and Aging · doi:10.1037/a0016035 · Cited by 201
Effects of Anxiety Versus Depression on Cognition in Later Life
Bierman, E. J. M., Comijs, H. C., Jonker, C., & Beekman, A. T. F. (2005) · American Journal of Geriatric Psychiatry · doi:10.1097/00019442-200508000-00007 · Cited by 201
Florbetapir F 18 amyloid PET and 36-month cognitive decline:a prospective multicenter study
AV45-A11 Study Group, Doraiswamy, P. M., Sperling, R. A., Johnson, K., Reiman, E. M., Wong, T. Z., Sabbagh, M. N., Sadowsky, C. H., Fleisher, A. S., Carpenter, A., et al. (2014) · Molecular Psychiatry · doi:10.1038/mp.2014.9 · Cited by 195
España, J., Giménez‐Llort, L., Valero, J., Miñano-Molina, A. J., Rábano, A., Rodrı́guez-Álvarez, J., LaFerla, F. M., & Saura, C. A. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.06.015 · Cited by 191
Serfaty, M. A., Haworth, D., Blanchard, M., Buszewicz, M., Murad, S., & King, M. (2009) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.165 · Cited by 190
Yochim, B. P., Mueller, A. E., & Segal, D. L. (2012) · Journal of Anxiety Disorders · doi:10.1016/j.janxdis.2012.10.010 · Cited by 164
Chételat, G., Villemagne, V. L., Pike, K. E., Ellis, K. A., Bourgeat, P., Jones, G. R., O'Keefe, G. J., Salvado, O., Szoeke, C. E. I., Martins, R. N., et al. (2011) · Brain · doi:10.1093/brain/awq383 · Cited by 159
Self-citationIncidence of cerebral microbleeds in preclinical Alzheimer disease
Yates, P. A., Desmond, P. M., Phal, P. M., Steward, C., Szoeke, C., Salvado, O., Ellis, K. A., Martins, R. N., Masters, C. L., Ames, D., et al. (2014) · Neurology · doi:10.1212/wnl.0000000000000285 · Cited by 150
Self-citationUshering in the study and treatment of preclinical Alzheimer disease
Langbaum, J. B. S., Fleisher, A., Chen, K., Ayutyanont, N., Lopera, F. J., Quiroz, Y. T., Caselli, R. J., Tariot, P. N., & Reiman, E. M. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.107 · Cited by 149
Does Fluoxetine Have Any Effect on the Cognition of Patients With Mild Cognitive Impairment?
Mowla, A., Mosavinasab, M., & Pani, A. (2007) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e31802e0002 · Cited by 141
Does Anxiety Affect Risk of Dementia? Findings From the Caerphilly Prospective Study
Gallacher, J., Bayer, A., Fish, M., Pickering, J., Pedro, S., Dunstan, F., Ebrahim, S., & Ben-Shlomo, Y. (2009) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3181a6177c · Cited by 137
Ramakers, I. H. G. B., Verhey, F. R. J., Scheltens, P., Hampel, H. J., Soininen, H. S., Aalten, P., Rikkert, M. G. M. O., Verbeek, M. M., Spiru, L., Blennow, K., et al. (2012) · Psychological Medicine · doi:10.1017/s0033291712001870 · Cited by 122
Mowla, A., Mosavinasab, M., Haghshenas, H., & Haghighi, A. B. (2007) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e31814b98c1 · Cited by 116
Deregulation of hypothalamic-pituitary-adrenal axis functions in an Alzheimer's disease rat model
Brureau, A., Zussy, C., Delair, B., Ogier, C., IXART, G., Maurice, T., & Givalois, L. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.11.015 · Cited by 112
Caselli, R. J., & Reiman, E. M. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-129026 · Cited by 111
Anxiety, Depression, and 1‐Year Incident Cognitive Impairment in Community‐Dwelling Older Adults
Potvin, O., Forget, H., Grenier, S., Préville, M., & Hudon, C. (2011) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2011.03521.x · Cited by 110
Stronger effect of amyloid load than APOE genotype on cognitive decline in healthy older adults
Lim, Y. Y., Ellis, K. A., Pietrzak, R. H., Ames, D. J., Darby, D., Harrington, K., Martins, R. N., Masters, C. L., Rowe, C. C., Savage, G. R., et al. (2012) · Neurology · doi:10.1212/wnl.0b013e31826e9ae6 · Cited by 109
Self-citationLavretsky, H., Siddarth, P., Kepe, V., Ercoli, L. M., Miller, K. J., Burggren, A. C., Bookheimer, S. Y., Huang, S., Barrio, J. R., & Small, G. W. (2009) · American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e3181953b82 · Cited by 108
Biringer, E., Mykletun, A., Dahl, A. A., Smith, A. D., Engedal, K., Nygaard, H. A., & Lund, A. (2005) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.1390 · Cited by 108
Human anterior and posterior hippocampus respond distinctly to state and trait anxiety.
Satpute, A. B., Mumford, J. A., Naliboff, B. D., & Poldrack, R. A. (2012) · Emotion · doi:10.1037/a0026517 · Cited by 102
Amyloid Deposition Is Linked to Aberrant Entorhinal Activity among Cognitively Normal Older Adults
Huijbers, W., Mormino, E. C., Wigman, S. E., Ward, A. M., Vannini, P., McLaren, D. G., Becker, J. A., Schultz, A. P., Hedden, T., Johnson, K. A., et al. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.3579-13.2014 · Cited by 91
Aβ and cognitive change: Examining the preclinical and prodromal stages of Alzheimer's disease
Lim, Y. Y., Maruff, P. T., Pietrzak, R. H., Ellis, K. A., Darby, D., Ames, D. J., Harrington, K., Martins, R. N., Masters, C. L., Szoeke, C. E. I., et al. (2014) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2013.11.005 · Cited by 84
Self-citationBierman, E. J. M., Comijs, H. C., Rijmen, F., Jonker, C., & Beekman, A. T. F. (2008) · Aging & Mental Health · doi:10.1080/13607860802224276 · Cited by 76
Decline in Cognitive Function over 18 Months in Healthy Older Adults with High Amyloid-β
Ellis, K. A., Lim, Y. Y., Harrington, K., Ames, D. J., Bush, A. I., Darby, D., Martins, R. N., Masters, C. L., Rowe, C. C., Savage, G. R., et al. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-122170 · Cited by 52
Self-citationState Anxiety and Cognitive Functioning in Older Adults
Potvin, O., Bergua, V., Meillon, C., Goff, M. L., Bouisson, J., Dartigues, J., & Amieva, H. (2013) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2013.01.029 · Cited by 48
Pietrzak, R. H., Scott, J. C., Neumeister, A., Lim, Y. Y., Ames, D. J., Ellis, K. A., Harrington, K., Lautenschlager, N. T., Szoeke, C. E. I., Martins, R. N., et al. (2014) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.113.134239 · Cited by 45
Self-citationPotvin, O., Hudon, C., Dion, M., Grenier, S., & Préville, M. (2010) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2647 · Cited by 44
The association of Aβ amyloid and composite cognitive measures in healthy older adults and MCI
Harrington, K., Lim, Y. Y., Ellis, K. A., Copolov, C., Darby, D., Weinborn, M., Ames, D. J., Martins, R. N., Savage, G. R., Szoeke, C. E. I., et al. (2013) · International Psychogeriatrics · doi:10.1017/s1041610213001087 · Cited by 36
Self-citationVascular Risk Factors and Cognitive Functions in Nondemented Elderly Individuals
Wiederkehr, S., Laurin, D., Simard, M., Verreault, R., & Lindsay, J. (2009) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/0891988709335797 · Cited by 24
Beaudreau, S. A., Fairchild, J. K., Spira, A. P., Lazzeroni, L. C., & O'Hara, R. M. (2012) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.3868 · Cited by 17
Ellis, K. A., Rainey‐Smith, S. R., Rembach, A., Macaulay, S. L., Villemagne, V. L., & Aibl research group (2013) · International Review of Psychiatry · doi:10.3109/09540261.2013.870136 · Cited by 17
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Rabin, L. A., Smart, C. M., & Amariglio, R. E. (2017) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-032816-045136 · Cited by 590
Luo, R., Su, L.-Y., Li, G., Yang, J., Liu, Q., Yang, L.-X., Zhang, D.-F., Zhou, H., Xu, M., Fan, Y., et al. (2020) · Autophagy · doi:10.1080/15548627.2019.1596488 · Cited by 364
Liu, Q., Xi, Y., Wang, Q., Liu, J., Li, P., Meng, X., Liu, K., Chen, W., Liu, X., & Liu, Z. (2021) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2021.04.005 · Cited by 241
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Mortamais, M., Ash, J. A., Harrison, J., Kaye, J. A., Kramer, J. H., RANDOLPH, C. C., Pose, C., Albala, B., Ropacki, M. T., Ritchie, C. W., et al. (2016) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2016.06.2365 · Cited by 212
Metadata
- Authors
- Pietrzak, R. H., Lim, Y. Y., Neumeister, A., Ames, D., Ellis, K. A., Harrington, K., Lautenschlager, N. T., Restrepo, C., Martins, R. N., Masters, C. L., Villemagne, V. L., Rowe, C. C., & Maruff, P.
- Affiliations
- United States Department of Veterans Affairs (US)
- The University of Melbourne (AU)
- New York University (US)
- Edith Cowan University (AU)
- Corresponding author
- Pietrzak, Robert H.
- ORCID
- Venue
- JAMA Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2015-03-01
- Volume
- 72
- Issue
- 3
- Pages
- 284
- ISSN
- 2168-622X (ISSN-L)
- OpenAlex
- W2049932209
- Cited by
- 214
- References
- 51
- Citations by year
- 2026: 13 · 2025: 16 · 2024: 24 · 2023: 17 · 2022: 22 · 2021: 27 · 2020: 19 · 2019: 15 · 2018: 15 · 2017: 20 · 2016: 15 · 2015: 10
- FWCI
- 16.22
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- JAMA Psychiatry (publishedVersion)
- UWA Profiles and Research Repository (UWA) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Australasian Journal of Paramedicine (submittedVersion)
- Swinburne figshare (Swinburne University of Technology) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Oncology › Cancer-related cognitive impairment studies
- Keywords
- amyloid-beta, preclinical Alzheimer's disease, anxiety, cognitive decline, depressive symptoms, moderating effect, amyloid PET, Pittsburgh compound B, florbetapir, verbal memory, executive function, language, global cognition, older adults, subjective memory complaints, APOE genotype, mild cognitive impairment, dementia risk
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Anxiety, Depression, Female, Genotype, Humans, Male, Middle Aged, Neuropsychological Tests, Prospective Studies, Amyloid beta-Peptides, Disease Progression, Positron-Emission Tomography, Prodromal Symptoms
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