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

  • I. H. G. B. Ramakers (a1), F. R. J. Verhey (a1), P. Scheltens (a2), H. Hampel (a3), H. Soininen (a4), P. Aalten (a1), M. Olde Rikkert (a5), M. M. Verbeek (a6), L. Spiru (a7), K. Blennow (a8), J. Q. Trojanowski (a9), L. M. Shaw (a9) and P. J. Visser (a1) (a2)
  • DOI:
  • Published online: 07 September 2012

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.


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.


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.


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

Corresponding author
*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:
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