BACKGROUND: Little is known about the association of cortical Aβ with depression and anxiety among cognitively normal (CN) elderly persons. METHODS: We conducted a cross-sectional study derived from the population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota; involving CN persons aged ≥ 60 years that underwent PiB-PET scans and completed Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI). Cognitive diagnosis was made by an expert consensus panel. Participants were classified as having abnormal (≥1.4; PiB+) or normal PiB-PET (<1.4; PiB-) using a global cortical to cerebellar ratio. Multi-variable logistic regression analyses were performed to calculate odds ratios (OR) and 95% confidence intervals (95% CI) after adjusting for age and sex. RESULTS: Of 1,038 CN participants (53.1% males), 379 were PiB+. Each one point symptom increase in the BDI (OR = 1.03; 1.00-1.06) and BAI (OR = 1.04; 1.01-1.08) was associated with increased odds of PiB-PET+. The number of participants with BDI > 13 (clinical depression) was greater in the PiB-PET+ than PiB-PET- group but the difference was not significant (OR = 1.42; 0.83-2.43). Similarly, the number of participants with BAI > 10 (clinical anxiety) was greater in the PiB-PET+ than PiB-PET- group but the difference was not significant (OR = 1.77; 0.97-3.22). CONCLUSIONS: As expected, depression and anxiety levels were low in this community-dwelling sample, which likely reduced our statistical power. However, we observed an informative albeit weak association between increased BDI and BAI scores and elevated cortical amyloid deposition. This observation needs to be tested in a longitudinal cohort study.

Department of Health Sciences Research Mayo Clinic Rochester Minnesota USA

Department of Neurology Mayo Clinic Rochester Minnesota USA

Department of Radiology Mayo Clinic Rochester Minnesota USA

International Clinical Research Center St Anne's University Hospital Brno Czech Republic

Paracelsus Medical University Salzburg Austria

Translational neuroscience and Aging Program Mayo Clinic Scottsdale Arizona USA

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Altman DG, Royston P. The cost of dichotomising continuous variables. BMJ. 2006;332:1080. PubMed PMC

Beck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: psychometric properties. Journal of Consulting and Clinical Psychology. 1988;56:893–897. PubMed

Beck AT, Steer RA, Brown GK. BDI–II, Beck Depression Inventory: Manual. San Antonio, TX; Boston, MA: Psychological Corp.; Harcourt Brace; 1996.

Bjelland I, Lie SA, Dahl AA, Mykletun A, Stordal E, Kraemer HC. A dimensional versus a categorical approach to diagnosis: anxiety and depression in the HUNT 2 study. International Journal of Methods in Psychiatric Research. 2009;18:128–137. PubMed PMC

Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathologica. 1991;82:239–259. PubMed

Brendel M, Pogarell O, Xiong G, Delker A, Bartenstein P, Rominger A. Depressive symptoms accelerate cognitive decline in amyloid-positive MCI patients. European Journal of Nuclear Medicine and Molecular Imaging. 2015;42:716–724. PubMed PMC

Butters MA, et al. Imaging Alzheimer pathology in late-life depression with PET and Pittsburgh Compound-B. Alzheimer Disease and Associated Disorders. 2008;22:261–268. PubMed PMC

Chetelat G, et al. Relationship between memory performance and beta-amyloid deposition at different stages of Alzheimer's disease. Neurodegenerative Diseases. 2012;10:141–144. PubMed

Choi SH, et al. A three-dimensional human neural cell culture model of Alzheimer's disease. Nature. 2014;515:274–278. PubMed PMC

Chung JK, et al. Cortical Amyloid beta Deposition and Current Depressive Symptoms in Alzheimer Disease and Mild Cognitive Impairment. Journal of Geriatric Psychiatry and Neurology. 2016;29:149–159. PubMed PMC

Cole GB, et al. Specific estrogen sulfotransferase (SULT1E1) substrates and molecular imaging probe candidates. Proceedings of the National Academy of Sciences of the United States of America. 2010;107:6222–6227. PubMed PMC

Donovan NJ, et al. Depressive Symptoms and Biomarkers of Alzheimer's Disease in Cognitively Normal Older Adults. Journal of Alzheimer's Disease. 2015;46:63–73. PubMed PMC

Dubois B, et al. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurology. 2007;6:734–746. PubMed

Geda YE, et al. Depression, apolipoprotein E genotype, and the incidence of mild cognitive impairment: a prospective cohort study. Archives of Neurology. 2006;63:435–440. PubMed

Geda YE, et al. Prevalence of neuropsychiatric symptoms in mild cognitive impairment and normal cognitive aging: population-based study. Archives of General Psychiatry. 2008;65:1193–1198. PubMed PMC

Geda YE, et al. Baseline neuropsychiatric symptoms and the risk of incident mild cognitive impairment: a population-based study. American Journal of Psychiatry. 2014;171:572–581. PubMed PMC

Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science. 2002;297:353–356. PubMed

Harrington KD, et al. Amyloid burden and incident depressive symptoms in cognitively normal older adults. International Journal of Geriatric Psychiatry. 2017;32:455–463. PubMed

Harrington KD, Lim YY, Gould E, Maruff P. Amyloid-beta and depression in healthy older adults: A systematic review. Australian and New Zealand Journal of Psychiatry. 2015;49:36–46. PubMed

Holmes SE, et al. beta-Amyloid, APOE and BDNF Genotype, and Depressive and Anxiety Symptoms in Cognitively Normal Older Women and Men. The American Journal of Geriatric Psychiatry. 2016;24:1191–1195. PubMed

Ismail Z, et al. Neuropsychiatric symptoms as early manifestations of emergent dementia: Provisional diagnostic criteria for mild behavioral impairment. Alzheimer's and Dementia. 2016;12:195–202. PubMed PMC

Ivnik R, et al. Mayo's Older Americans Normative Studies: WAIS-R, WMS-R, and AVLT norms for ages 56 through 97. Clinical Neuropsychologist. 1992a;6:1–104.

Ivnik RJ, et al. Mayo's Older Americans Normative Studies: Updated AVLT norms for ages 56 to 97. Clinical Neuropsychologist. 1992b;6:83–104.

Ivnik RJ, et al. Mayo's Older Americans Normative Studies: WAIS-R norms for ages 56 to 97. Clinical Neuropsychologist. 1992c;6:1–30.

Ivnik RJ, et al. Mayo's Older Americans Normative Studies: WMS-R norms for ages 56 to 94. Clinical Neuropsychologist. 1992d;6:49–82. PubMed

Jack CR, Jr, Barrio JR, Kepe V. Cerebral amyloid PET imaging in Alzheimer's disease. Acta Neuropathologica. 2013;126:643–657. PubMed PMC

Jack CR, Jr, et al. Brain beta-amyloid measures and magnetic resonance imaging atrophy both predict time-to-progression from mild cognitive impairment to Alzheimer's disease. Brain. 2010;133:3336–3348. PubMed PMC

Jagust WJ, et al. The Alzheimer's Disease Neuroimaging Initiative positron emission tomography core. Alzheimer's & Dementia. 2010;6:221–229. PubMed PMC

Knopman DS, et al. Short-term clinical outcomes for stages of NIA-AA preclinical Alzheimer disease. Neurology. 2012;78:1576–1582. PubMed PMC

Krell-Roesch J, et al. FDG-PET and Neuropsychiatric Symptoms among Cognitively Normal Elderly Persons: The Mayo Clinic Study of Aging. Journal of Alzheimer's disease. 2016;53:1609–1616. PubMed PMC

Laborde-Lahoz P, et al. Subsyndromal depression among older adults in the USA: prevalence, comorbidity, and risk for new-onset psychiatric disorders in late life. International Journal of Geriatric Psychiatry. 2014;30:677–685. PubMed

Malec JF, et al. Mayo's Older Americans Normative Studies: Utility of corrections for age and education for the WAIS-R. Clinical Neuropsychologist. 1992;6:31–47.

Morris JC, et al. Pittsburgh compound B imaging and prediction of progression from cognitive normality to symptomatic Alzheimer disease. Archives of Neurology. 2009;66:1469–1475. PubMed PMC

Murray ME, et al. Clinicopathologic and 11C-Pittsburgh compound B implications of Thal amyloid phase across the Alzheimer's disease spectrum. Brain. 2015;138:1370–1381. PubMed PMC

Petersen RC. Mild cognitive impairment as a diagnostic entity. Journal of Internal Medicine. 2004;256:183–194. PubMed

Petersen RC, et al. Association of Elevated Amyloid Levels With Cognition and Biomarkers in Cognitively Normal People From the Community. JAMA Neurology. 2016;73:85–92. PubMed PMC

Pietrzak RH, et al. Amyloid-beta, anxiety, and cognitive decline in preclinical Alzheimer disease: a multicenter, prospective cohort study. JAMA Psychiatry. 2015;72:284–291. PubMed

Pietrzak RH, et al. Anxiety symptoms, cerebral amyloid burden and memory decline in healthy older adults without dementia: 3-year prospective cohort study. British Journal of Psychiatry. 2014;204:400–401. PubMed

Pink A, et al. Cortical Thickness and Anxiety Symptoms Among Cognitively Normal Elderly Persons: The Mayo Clinic Study of Aging. The Journal of Neuropsychiatry and Clinical Neurosciences. 2017;29:60–66. PubMed PMC

Pink A, et al. Neuropsychiatric symptoms, APOE epsilon4, and the risk of incident dementia: a population-based study. Neurology. 2015;84:935–943. PubMed PMC

Roberts RO, et al. The Mayo Clinic Study of Aging: design and sampling, participation, baseline measures and sample characteristics. Neuroepidemiology. 2008;30:58–69. PubMed PMC

Shaw LM, Korecka M, Clark CM, Lee VM, Trojanowski JQ. Biomarkers of neurodegeneration for diagnosis and monitoring therapeutics. Nature Reviews. Drug Discovery. 2007;6:295–303. PubMed

Sperling RA, et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's and Dementia. 2011;7:280–292. PubMed PMC

Winblad B, et al. Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. Journal of Internal Medicine. 2004;256:240–246. PubMed

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