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Principal Investigator  
Principal Investigator's Name: Alina Ruge
Institution: Carl von Ossietzky University of Oldenburg
Department: Department für Psychologie
Proposed Analysis: I request access to the ADNI data to investigate potential associations between intra-cerebellar structural connectivity and the progression of cognitive and neuropsychiatric symptoms (NPS) over the course of three years. These associations should be explored in an Alzheimer’s disease (AD) diagnosed, a mild cognitively impaired (MCI), and a healthy control sample. NPS are common in AD (Lawlor, 2002 [1]; American Psychiatric Association, 1994 [2]), vary in their severity over time (Vik-Mo, Giil, Borda, Ballard, & Aarsland, D., 2020 [3]; Feldman, H. H., & Woodward, M., 2005 [4]), and are associated with structural decline in cortical areas (PFC, OFC, ACC; Spalletta, Girardi, Caltagirone, & Orfei, 2012 [5]), as well as in pathways connecting the cerebral cortex with the cerebellum (Vermeiren, Van Dam, Aerts, Engelborghs, & De Deyn, 2014 [6]). Implicated in these pathways are the middle cerebellar peduncle (MCP) and the superior cerebellar peduncle (SCP). The MCP is part of the descending cortico-cerebellar pathway, and the SCP intercepts the ascending cortico-cerebellar pathway (Palesi et al., 2017 [7]). A third peduncle, the inferior cerebellar peduncle (ICP), connects with the vestibular nucleus, the reticular formation, the pontine tegmentum, and the posterior cerebellum (Jang & Kwon, 2016 [8]) of the olivocerebellar and the dorsal spinocerebellar tracts (Jang & Do Lee, 2020 [9]). These cerebellar peduncles may play a role in the neuronal pathogenesis of NPS in AD. Research on AD however does not yet include sufficient studies on the intra-cerebellar structural connectivity and AD related cognitive and neuropsychiatric symptoms. Research goal: I aim to analyse the diffusor tensor imaging (DTI) ADNI data over the course of three years (baseline, and two consecutive time points with available DTI data) in terms of changes in structural connectivity (white matter microstructural properties) within the ICP, MCP, and SCP. I will use growth cure modelling to study the relationship between microstructural connectivity in these peduncles and cognitive symptoms (e.g. Neuropsychological Battery, Functional Assessment Questionnaire) and neuropsychiatric symptoms (e.g. Geriatric Depression Scale) in three groups of individuals. The repeated measures will comprise three time points, each separated by one year. To characterize the microstructural properties in the cerebellar peduncles, I will apply common DTI diffusivity measures, such as mean diffusivity, axial diffusivity, radial diffusivity, and fractional anisotropy as the independent variables, to predict cognitive impairment and neuropsychiatric symptoms progression over time. Literature: [1] Lawlor, B. (2002). Managing behavioural and psychological symptoms in dementia. The British Journal of Psychiatry, 181(6), 463-465. [2] APA Diagnostic (1994). Statistical Manual of mental disorders. [3] Vik-Mo, A. O., Giil, L. M., Borda, M. G., Ballard, C., & Aarsland, D. (2020). The individual course of neuropsychiatric symptoms in people with Alzheimer's and Lewy body dementia: 12-year longitudinal cohort study. The British Journal of Psychiatry, 216(1), 43-48. [4] Feldman, H. H., & Woodward, M. (2005). The staging and assessment of moderate to severe Alzheimer disease. Neurology, 65(6 suppl 3), S10-S17. [5] Spalletta, G., Girardi, P., Caltagirone, C., & Orfei, M. D. (2012). Anosognosia and neuropsychiatric symptoms and disorders in mild Alzheimer disease and mild cognitive impairment. Journal of Alzheimer's disease, 29(4), 761-772. [6] Vermeiren, Y., Van Dam, D., Aerts, T., Engelborghs, S., & De Deyn, P. P. (2014). Brain region-specific monoaminergic correlates of neuropsychiatric symptoms in Alzheimer's disease. Journal of Alzheimer's Disease, 41(3), 819-833. [7] Palesi, F., De Rinaldis, A., Castellazzi, G., Calamante, F., Muhlert, N., Chard, D., ... & Gandini Wheeler-Kingshott, C. A. (2017). Contralateral cortico-ponto-cerebellar pathways reconstruction in humans in vivo: implications for reciprocal cerebro-cerebellar structural connectivity in motor and non-motor areas. Scientific reports, 7(1), 1-13. [8] Jang, S. H., & Kwon, H. G. (2016). Connectivity of inferior cerebellar peduncle in the human brain: a diffusion tensor imaging study. Neural Network World, 26(5), 439. [9] Jang, S. H., & Do Lee, H. (2020). Relationship between ataxia and inferior cerebellar peduncle injury in patients with cerebral infarct. Medicine, 99(9).
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