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    The cerebral blood flow deficits in Parkinson’s disease with mild cognitive impairment using arterial spin labeling MRI
    (Springer, 2020-09) Arslan, Dilek Betül; Gürvit, İbrahim Hakan; Genç, Ozan; Kıçik, Ani; Eryürek, Kardelen; Cengiz, Sevim; Erdoğdu, Emel; Yıldırım, Zerrin; Tüfekçioğlu, Zeynep; Uluğ, Aziz Müfit; Bilgiç, Başar; Hanağası, Haşmet Ayhan; Tüzün, Erdem; Demiralp, Tamer; Öztürk Işık, Esin
    Parkinson's disease (PD) with mild cognitive impairment (PD-MCI) is currently diagnosed based on an arbitrarily predefined standard deviation of neuropsychological test scores, and more objective biomarkers for PD-MCI diagnosis are needed. The purpose of this study was to define possible brain perfusion-based biomarkers of not only mild cognitive impairment, but also risky gene carriers in PD using arterial spin labeling magnetic resonance imaging (ASL-MRI). Fifteen healthy controls (HC), 26 cognitively normal PD (PD-CN), and 27 PD-MCI subjects participated in this study. ASL-MRI data were acquired by signal targeting with alternating radio-frequency labeling with Look-Locker sequence at 3 T. Single nucleotide polymorphism genotyping for rs9468 [microtubule-associated protein tau (MAPT) H1/H1 versus H1/H2 haplotype] was performed using a Stratagene Mx3005p real-time polymerase chain-reaction system (Agilent Technologies, USA). There were 15 subjects withMAPTH1/H1 and 11 subjects withMAPTH1/H2 within PD-MCI, and 33 subjects withMAPTH1/H1 and 19 subjects withMAPTH1/H2 within all PD. Voxel-wise differences of cerebral blood flow (CBF) values between HC, PD-CN and PD-MCI were assessed by one-way analysis of variance followed by pairwise post hoc comparisons. Further, the subgroup of PD patients carrying the riskyMAPTH1/H1 haplotype was compared with noncarriers (MAPTH1/H2 haplotype) in terms of CBF by a two-samplettest. A pattern that could be summarized as "posterior hypoperfusion" (PH) differentiated the PD-MCI group from the HC group with an accuracy of 92.6% (sensitivity = 93%, specificity = 93%). Additionally, the PD patients withMAPTH1/H1 haplotype had decreased perfusion than the ones with H1/H2 haplotype at the posterior areas of the visual network (VN), default mode network (DMN), and dorsal attention network (DAN). The PH-type pattern in ASL-MRI could be employed as a biomarker of both current cognitive impairment and future cognitive decline in PD.
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    Corrigendum to “Detection of visual and frontoparietal network perfusion deficits in Parkinson’s disease dementia” [Eur. J. Radiol. 144 (2021) 109985]
    (Elsevier Ireland Ltd, 2022-10-28) Azamat, Sena; Arslan, Dilek Betül; Erdoğdu, Emel; Kıçik, Ani; Cengiz, Sevim; Eryürek, Kardelen; Tüfekçioğlu, Zeynep; Bilgiç, Başar; Hanagasi, Haşmet; Demiralp, Tamer; Gürvit, Hakan; Öztürk Işık, Esin
    The authors would like to add the following grant support that was accidentally not included in the original article. Acknowledgements: This study was supported by TUBITAK 1001 project #115S219, Istanbul University Scientific Research Projects Unit project #1567/42362 and Bogazici University Scientific Research Projects Unit project #15222. The authors would like to apologize for any inconvenience caused.
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    Detection of visual and frontoparietal network perfusion deficits in Parkinson's disease dementia
    (Elsevier Ireland Ltd, 2021-11) Azamat, Sena; Arslan, Dilek Betül; Erdoğdu, Emel; Kıçik, Ani; Cengiz, Sevim; Eryürek, Kardelen; Tüfekçioğlu, Zeynep; Bilgiç, Başar; Hanagasi, Haşmet; Demiralp, Tamer; Gürvit, Hakan; Öztürk Işık, Esin
    Mild cognitive impairment of Parkinson's disease (PD) may be an early manifestation that may progressively worsen to dementia. Cognitive decline has been associated with changes in the brain perfusion pattern. This study aimed to evaluate cerebral blood flow (CBF) deficits specific to different stages of cognitive decline. Seventeen patients with cognitively normal PD (PD-CN), 18 patients with PD with mild cognitive impairment (PD-MCI), and 16 patients with PD with dementia (PDD) were included in this study. The participants were scanned using a 3 T Philips MRI scanner. Arterial spin labelling magnetic resonance (ASL-MR) images were acquired, followed by calculation of the CBF maps, and registration onto the MNI152 brain atlas. A whole-brain voxel-based CBF comparison was performed among the patient groups using age as a covariate. The mean age of patients with PDD was significantly higher than that of patients with PD-MCI (P = 0.015) and PD-CN (P = 0.001). The CBF values of the three groups were significantly different in the left cuneus of the visual network (VN), left inferior frontal gyrus of the frontoparietal network (FPN), and left dorsomedial nucleus of the thalamus. PDD had lower perfusion values than PD-MCI group in the same regions detected in the main group analysis. Additionally, comparison of PDD with PD-CN and non-demented groups revealed that the perfusion reduction extended into the bilateral cuneus of the VN, bilateral thalami, and left inferior frontal gyrus of the FPN. PDD could be separated from PD-MCI and PD-CN stages with CBF deficits in non-dopaminergically mediated posterior and dopaminergically mediated frontal networks.
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    Identification of metabolic correlates of mild cognitive impairment in Parkinson's disease using magnetic resonance spectroscopic imaging and machine learning
    (Springer Science and Business Media Deutschland GmbH, 2022-12) Cengiz, Sevim; Arslan, Dilek Betül; Kıçik, Ani; Erdoğdu, Emel; Yıldırım, Muhammed; Hatay, Gökçe Hale; Tüfekçioğlu, Zeynep; Uluğ, Aziz Müfit; Bilgiç, Başar; Hanagasi, Haşmet; Demiralp, Tamer; Gürvit, Hakan; Öztürk Işıkk, Esin
    Objective: To investigate metabolic changes of mild cognitive impairment in Parkinson’s disease (PD-MCI) using proton magnetic resonance spectroscopic imaging (1H-MRSI). Methods: Sixteen healthy controls (HC), 26 cognitively normal Parkinson’s disease (PD-CN) patients, and 34 PD-MCI patients were scanned in this prospective study. Neuropsychological tests were performed, and three-dimensional 1H-MRSI was obtained at 3 T. Metabolic parameters and neuropsychological test scores were compared between PD-MCI, PD-CN, and HC. The correlations between neuropsychological test scores and metabolic intensities were also assessed. Supervised machine learning algorithms were applied to classify HC, PD-CN, and PD-MCI groups based on metabolite levels. Results: PD-MCI had a lower corrected total N-acetylaspartate over total creatine ratio (tNAA/tCr) in the right precentral gyrus, corresponding to the sensorimotor network (p = 0.01), and a lower tNAA over myoinositol ratio (tNAA/mI) at a part of the default mode network, corresponding to the retrosplenial cortex (p = 0.04) than PD-CN. The HC and PD-MCI patients were classified with an accuracy of 86.4% (sensitivity = 72.7% and specificity = 81.8%) using bagged trees. Conclusion: 1H-MRSI revealed metabolic changes in the default mode, ventral attention/salience, and sensorimotor networks of PD-MCI patients, which could be summarized mainly as ‘posterior cortical metabolic changes’ related with cognitive dysfunction.
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    Shrinkage of olfactory amygdala connotes cognitive impairment in patients with Parkinson’s disease
    (Springer, 2023-10) Ay, Ulaş; Yıldırım, Zerrin; Erdoğdu, Emel; Kıçik, Ani; Öztürk Işık, Esin; Demiralp, Tamer; Gürvit, Hakan
    During the caudo-rostral progression of Lewy pathology, the amygdala is involved relatively early in Parkinson’s disease (PD). However, lesser is known about the volumetric differences at the amygdala subdivisions, although the evidence mainly implicates the olfactory amygdala. We aimed to investigate the volumetric differences between the amygdala’s nuclear and sectoral subdivisions in the PD cognitive impairment continuum compared to healthy controls (HC). The volumes of nine nuclei of the amygdala were estimated with FreeSurfer (nuclear parcellation-NP) from T1-weighted images of PD patients with normal cognition (PD-CN), PD with mild cognitive impairment (PD-MCI), PD with dementia (PD-D), and HC. The appropriate nuclei were then merged to obtain three sectors of the amygdala (sectoral parcellation-SP). The nuclear and sectoral volumes were compared among the four groups and between the hyposmic and normosmic PD patients. There was a significant difference in the total amygdala volume among the four groups. In terms of nuclei, the bilateral cortico-amygdaloid transition area (CAT) and sectors superficial cortex-like region (sCLR) volumes of PD-MCI and PD-D were less than those of the PD-CN and HC. A linear discriminant analysis revealed that left CAT and left sCLR volumes classified the PD-CN and cognitively impaired PD (PD-CI: PD-MCI plus PD-D) with 90.7% accuracy according to NP and 85.2% accuracy to SP. Similarly, left CAT and sCLR volumes correctly identified the hyposmic and normosmic PD with 64.8% and 61.1% accuracies. Notably, the left olfactory amygdala volume successfully discriminated cognitive impairment in PD and could be used as neuroimaging-based support for PD-CI diagnosis.