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. 2013 May;43(5):911-20.
doi: 10.1017/S0033291712001870. Epub 2012 Sep 7.

Anxiety is related to Alzheimer cerebrospinal fluid markers in subjects with mild cognitive impairment

I H G B Ramakers  1 , F R J Verhey, P Scheltens, H Hampel, H Soininen, P Aalten, M Olde Rikkert, M M Verbeek, L Spiru, K Blennow, J Q Trojanowski, L M Shaw, P J Visser; Alzheimer's Disease Neuroimaging Initiative and DESCRIPA Investigators
Affiliations

Anxiety is related to Alzheimer cerebrospinal fluid markers in subjects with mild cognitive impairment

I H G B Ramakers et al. Psychol Med. 2013 May.

Abstract

Background: Anxiety, apathy and depression are common in subjects with mild cognitive impairment (MCI) and may herald Alzheimer's disease (AD). We investigated whether these symptoms correlated with cerebrospinal fluid (CSF) markers for AD in subjects with MCI. Method Subjects with MCI (n=268) were selected from the 'Development of screening guidelines and criteria for pre-dementia Alzheimer's disease' (DESCRIPA) and Alzheimer's Disease Neuroimaging Initiative (ADNI) studies. We measured amyloid β(1-42) protein (Aβ42) and total tau (t-tau) in CSF. Neuropsychiatric symptoms were measured with the Neuropsychiatric Inventory.

Results: Depressive symptoms were reported by 55 subjects (21%), anxiety by 35 subjects (13%) and apathy by 49 subjects (18%). The presence of anxiety was associated with abnormal CSF Aβ42 [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.6-3.3] and t-tau (OR 2.6, 95% CI 1.9-3.6) concentrations and with the combination of abnormal concentrations of both Aβ42 and t-tau (OR 3.1, 95% CI 2.0-4.7). The presence of agitation and irritability was associated with abnormal concentrations of Aβ42 (agitation: OR 1.6, 95% CI 1.1-2.3; irritability: OR 2.2, 95% CI 1.5-3.3). Symptoms of depression and apathy were not related to any of the CSF markers.

Conclusions: In subjects with MCI, symptoms of anxiety, agitation and irritability may reflect underlying AD pathology, whereas symptoms of depression and apathy do not.

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Conflict of interest statement

Declaration of Interest

I.H.G.B.R. receives research support from the Center for Translational Molecular Medicine, project LeARN (grant no. 02N-01). P.S. serves/has served on the advisory boards of: Genentech, Novartis, Roche, Danone, Nutricia, Baxter and Lundbeck. He has been a speaker at symposia organized by Lundbeck, Merz, Danone, Novartis, Roche and Genentech. For all his activities he receives no personal compensation. He serves on the editorial board of Alzheimer’s Research and Therapy and Alzheimer’s Disease and Associated Disorders, is a member of the scientific advisory board of the European Union Joint Programming Initiative and the French National Plan Alzheimer. The Alzheimer Center receives unrestricted funding from various sources through the VUmc Fonds. M.M.V. was a consultant for Schering Plough Research Institute until 2009. He received grants from the American Alzheimer Association, the Alzheimer Drug Discovery Foundation, the Stichting International Parkinson Fonds, the Internationale Stichting Alzheimer Onderzoek, the Center for Translational Molecular Medicine, project LeARN (grant no. 02N-01), and the Hersentichting Nederland. K.B. has served on advisory boards for Innogenetics, Ghent, Belgium. L.M.S. receives grants from the NIA for ADNI 1, ADNI GO, and ADNI 2, Pfizer/Upenn rbm studies. He has served as a technical advisory board member/consultant of Innogenetics, Fujirebio, Janssen AI R&D. P.J.V. has served as an advisory board member of Myriad, Guidage study Ipsen, and Bristol-Myers Squibb. He receives/received research grants from Bristol-Myers Squibb, European Commission 6th and 7th Framework programme, Life Sciences, Genomics and Biotechnology for Health, Diagenic, Norway, and Innogenetics, Belgium.

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