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Principal Investigator  
Principal Investigator's Name: Leonie Banning
Institution: Maastricht University
Department: Psychiatry and Neuropsychology
Proposed Analysis: Neuropsychiatric symptoms (NPS) such as depression, anxiety and apathy are highly prevalent among persons with mild cognitive impairment (MCI), and Alzheimer’s disease (AD) and often form a heavy burden for the patient and caregivers. The presence of NPS in MCI has been reported to increase risk of conversion to AD (Rosenberg et al., 2013), although findings have been inconsistent (Tan et al., submitted; Cooper et al., 2015). Further, NPS have been shown to be chronically present, with individual symptoms having their own specific course (Aalten et al., 2005). The grouping of certain symptoms together, as for example depression and apathy are often seen together, suggests that there is an overlapping underlying neurobiological mechanism. The main focus of prior research has been on associating (individual) NPS with single AD biomarkers, within one specific disease stage. For example, Ramakers et al. (2013) reported in patients with MCI an association between anxiety and abnormal CSF AB42 and t-tau concentrations and between agitation and CSF AB42; but not between depression, apathy and CSF biomarkers. Additionally, the focus has been on predicting (rates of) cognitive decline or conversion to AD, whereas our main interest is to predict the expression and course of NPS. An important limiting factor of prior research is the limited power to study (inter)relations of biomarkers or to make stratifications based on diagnosis. The aim of this study is to examine: (1) The relationship (cross-sectional) between a more complete profile of AD biomarkers and NPS. More specifically, the association between amyloid (B-amyloid 1-42 in CSF) and neuronal injury (t-tau and p-tau in CSF; medial temporal lobe atrophy (MTA) and white matter hyperintensities (WMH)) markers, APOE genotype and NPS (depression, anxiety, apathy, irritability, agitation and night-time behavior disturbances). (2) The AD biomarker – NPS relationship over the spectrum of cognitive decline. More specifically, per syndromal diagnosis of subjective cognitive decline (SCD), MCI and dementia. (3) The predictive value of AD biomarkers on the presence and course of NPS. Data will be analyzed in SPSS version 24 using multilevel analyses. Next to the ADNI data, we aim to run the same analyses in a second, independent Dutch cohort study (the Parelsnoer Institute – Neurodegenerative diseases (Aalten et al., 2014)) to increase power and validity of results. Strengths will be the use of well-characterized cohorts; the use of both cross-sectional and longitudinal data of NPS over the whole spectrum of AD; and the use of specific, well-validated AD biomarkers. This study will add to our understanding of mechanisms linking NPS with AD. References Aalten, P., de Vugt, M. E., Jaspers, N., Jolles, J., & Verhey, F. R. (2005). The course of neuropsychiatric symptoms in dementia. Part I: findings from the two‐year longitudinal Maasbed study. International Journal of Geriatric Psychiatry, 20(6), 523-530. Aalten, P., Ramakers, I. H., Biessels, G. J., de Deyn, P. P., Koek, H. L., OldeRikkert, M. G., . . . van der Flier, W. M. (2014). The Dutch Parelsnoer Institute-Neurodegenerative diseases; methods, design and baseline results. BMC Neurology, 14, 254. doi: 10.1186/s12883-014-0254-4 Cooper, C., Sommerlad, A., Lyketsos, C. G., & Livingston, G. (2015). Modifiable predictors of dementia in mild cognitive impairment: a systematic review and meta-analysis. American Journal of Psychiatry. Ramakers, I. H., Verhey, F. R., Scheltens, P., Hampel, H., Soininen, H., Aalten, P., . . . Visser, P. J. (2013). Anxiety is Related to Alzheimer Cerebrospinal Fluid Markers in Subjects with Mild Cognitive Impairment. Psychological Medicine, 43(5), 911-920. doi: 10.1017/s0033291712001870 Rosenberg, P. B., Mielke, M. M., Appleby, B. S., Oh, E. S., Geda, Y. E., & Lyketsos, C. G. (2013). The association of neuropsychiatric symptoms in MCI with incident dementia and Alzheimer disease. American Jouranl of Psychiatry, 21(7), 685-695. doi: 10.1016/j.jagp.2013.01.006 Tan, E., Hamel, R., Köhler, S., Munoz, J., Verhey, F. & Ramakers, I. (Submitted). The predictive accuracy of depressive symptoms for the development of dementia in people with mild cognitive impairment: a systematic review and meta-analysis
Additional Investigators