The Association Between Biomarkers and Neuropsychiatric Symptoms Across the Alzheimer's Disease Spectrum

Leonie C.P. Banning, Inez H.G.B. Ramakers*, Sebastian Köhler, Esther E. Bron, Frans R.J. Verhey, Peter Paul de Deyn, Jurgen A.H.R. Claassen, Huiberdina L. Koek, Huub A.M. Middelkoop, Wiesje M. van der Flier, Aad van der Lugt, Pauline Aalten, The Alzheimer's Disease Neuroimaging Initiative, Parelsnoer Institute Neurodegenerative Diseases study group

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Objective: To investigate the relationship between Alzheimer's disease biomarkers and neuropsychiatric symptoms. Methods: Data from two large cohort studies, the Dutch Parelsnoer Institute – Neurodegenerative Diseases and the Alzheimer's Disease Neuroimaging Initiative was used, including subjects with subjective cognitive decline (N = 650), mild cognitive impairment (N = 887), and Alzheimer's disease dementia (N = 626). Cerebrospinal fluid (CSF) levels of Aβ42, t-tau, p-tau, and hippocampal volume were associated with neuropsychiatric symptoms (measured with the Neuropsychiatric Inventory) using multiple logistic regression analyses. The effect of the Mini-Mental State Examination (as proxy for cognitive functioning) on these relationships was assessed with mediation analyses. Results: Alzheimer's disease biomarkers were not associated with depression, agitation, irritability, and sleep disturbances. Lower levels of CSF Aβ42, higher levels of t- and p-tau were associated with presence of anxiety. Lower levels of CSF Aβ42 and smaller hippocampal volumes were associated with presence of apathy. All associations were mediated by cognitive functioning. Conclusion: The association between Alzheimer's disease pathology and anxiety and apathy is partly due to impairment in cognitive functioning.

Original languageEnglish
Pages (from-to)735-744
Number of pages10
JournalAmerican Journal of Geriatric Psychiatry
Issue number7
Early online date1 Jan 2020
Publication statusPublished - Jul 2020

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