Psychological Medicine

Original Articles

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

I. H. G. B. Ramakersa1 c1, F. R. J. Verheya1, P. Scheltensa2, H. Hampela3, H. Soininena4, P. Aaltena1, M. Olde Rikkerta5, M. M. Verbeeka6, L. Spirua7, K. Blennowa8, J. Q. Trojanowskia9, L. M. Shawa9, P. J. Vissera1a2 and the Alzheimer's Disease Neuroimaging Initiative and DESCRIPA Investigators

a1 Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht, The Netherlands

a2 Department of Neurology, Alzheimer Center, VU Medical Center, Amsterdam, The Netherlands

a3 Department of Psychiatry, Psychosomatic Medicine, and Psychotherapy, University of Frankfurt, Frankfurt am Main, Germany

a4 Department of Neurology, University and University Hospital of Kuopio, Kuopio, Finland

a5 Department of Geriatrics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

a6 Department of Neurology and Laboratory Medicine, Alzheimer Center Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

a7 ‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania

a8 Clinical Neurochemistry Laboratory, Göteborg University, Sahlgren's University Hospital, Mölndal, Sweden

a9 Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

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.

(Received December 14 2011)

(Revised June 22 2012)

(Accepted July 12 2012)

(Online publication September 07 2012)

Key words

  • Alzheimer's disease;
  • anxiety;
  • apathy;
  • biomarkers;
  • cerebrospinal fluid;
  • depression;
  • mild cognitive impairment;
  • neuropsychiatric symptoms


c1 Address for correspondence: I. H. G. B. Ramakers, Ph.D., Maastricht University, Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, School for Mental Health and Neuroscience, PO Box 616, 6200 MD Maastricht, The Netherlands. (Email: