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Yayın 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, EsinParkinson'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.Yayın 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, EsinObjective: 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.Yayın 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, HakanDuring 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.Yayın Dijital nöropsikoloji: yaşlı bireylerin bilişsel işlevlerinin değerlendirilmesinde kullanılan teknolojik yaklaşımlar(İ.Ü. EDEBİYAT FAKÜLTESİ, 2022-04-12) Yıldırım, ElifNüfusun yaşlanması ile paralel olarak demans tanılı kişilerin sayısı artmaktadır. Demans seyrinin iyileştirilmesi için kritik bir öneme sahip olan bilişsel bozuklukların erken saptanmasında nöropsikolojik değerlendirmenin büyük bir rolü olduğu kabul edilmektedir. Sıklıkla klasik kâğıt- kalem testleri ile uygulanan nöropsikolojik değerlendirme, günümüzde gelişen teknoloji ile birlikte dijitalleşmeye başlamıştır. Özellikle de Covid–19 pandemisi ile birlikle bu dijitalleşme ivme kazanmıştır. Bu çalışmada, yaşlı bireylerin nöropsikolojik değerlendirmelerinde kullanılan dijital yaklaşımların incelenmesi amaçlanmaktadır. Bu kapsamda, telenöropsikoloji, bilgisayarlı nöropsikolojik değerlendirme bataryaları, mobil teknoloji ya da web temelli değerlendirme araçları ve sanal gerçeklik, arttırılmış gerçeklik gibi yenilikçi teknolojik yöntemlere dayanan ölçümleri içeren dijital yaklaşımların eleştirel bir değerlendirmesi yapılmıştır. Sıklıkla videokonferans aracılığı ile nöropsikolojik testlerin uzaktan uygulanmasına odaklanan telenöropsikoloji çalışmaları ile ilgili sonuçlar bu yöntemin güvenilir ve geçerli olduğunu belirtmektedir. Bilgisayarlı bataryalar ve mobil teknolojiye dayanan yöntemler, klinik dışı bireysel uygulamaya olanak sağlamakta ve geniş örneklemli takip çalışmaları için altyapı hazırlamaktadır. Sanal gerçeklik gibi yeni teknolojilerin kullanıldığı değerlendirme yöntemler ise henüz emekleme aşamasında olsa da daha hassas ölçümlerin yapılması için büyük potansiyel taşımaktadır. Ulaşılabilirliğin artması ve ölçümlerin standartlaşması gibi avantajlar taşıyan dijital yaklaşımlar içinde sıklıkla kullanılan yöntemlerin büyük bir kısmının klasik kağıt-kalem testleri ve hastaların tanıları ile tutarlı olduğu gösterilmiştir. Fakat dijital yaklaşımların detaylı psikometrik analizlerinin yapılması ve iyi uygulama rehberlerinin geliştirmesi konusunda çeşitli eksiklikler bulunmaktadır. Buna ek olarak, dijital yaklaşımların uzman-hasta ilişkisinde zorluk yaratabileceği ve hastanın test sırasında gözlemlenmesi konusunda kısıtlılıklar taşıdığı belirtilmektedir. Her ne kadar dijital nöropsikoloji uygulamalarının yarattığı kısıtlılıklar mevcut olsa da, dijital yaklaşımlar hastalar, alandaki uzmanlar ve sağlık sistemi açısından önemli faydalar sağlama potansiyeline sahiptir. Bu nedenle, tüm taraflar açısından fayda sağlayacak akademik ve klinik çalışmaların yapılması önem taşımaktadır.Yayın White-matter changes in early and late stages of mild cognitive impairment(Churchill Livingstone, 2020-08) Femir Gürtuna, Banu; Kurt, Elif; Ulaşoğlu Yıldız, Çiğdem; Bayram, Ali; Yıldırım, Elif; Soncu Büyükişcan, Ezgi; Bilgiç, BaşarMild Cognitive Impairment (MCI) is characterized by cognitive deficits that exceed age-related decline, but not interfering with daily living activities. Amnestic type of the disorder (aMCI) is known to have a high risk to progress to Alzheimer's Disease (AD), the most common type of dementia. Identification of very early structural changes in the brain related to the cognitive decline in MCI patients would further contribute to the understanding of the dementias. In the current study, we target to investigate whether the white-matter changes are related to structural changes, as well as the cognitive performance of MCI patients. Forty-nine MCI patients were classified as Early MCI (E-MCI, n = 24) and Late MCI (L-MCI, n = 25) due to their performance on The Free and Cued Selective Reminding Test (FCSRT). Age-Related White-Matter Changes (ARWMC) scale was used to evaluate the white-matter changes in the brain. Volumes of specific brain regions were calculated with the FreeSurfer program. Both group and correlation analyses were conducted to show if there was any association between white-matter hyperintensities (WMHs) and structural changes and cognitive performance. Our results indicate that, L-MCI patients had significantly more WMHs not in all but only in the frontal regions compared to E-MCI patients. Besides, ARWMC scores were not correlated with total hippocampal and white-matter volumes. It can be concluded that WMHs play an important role in MCI and cognitive functions are affected by white-matter changes of MCI patients, especially in the frontal regions.Yayın Investigation of symptom-specific functional connectivity patterns in Parkinson’s disease(Springer-Verlag Italia S.R.L., 2025-06-14) Kıçik, Ani; Bayram, Ali; Erdoğdu, Emel; Kurt, Elif; Sarıdede, Dilek Betül; Cengiz, Sevim; Bilgiç, Başar; Hanağası, Haşmet; Öztürk Işık, Esin; Gürvit, Hakan; Tüzün, Erdem; Demiralp, TamerParkinson’s disease (PD) is a complex neurodegenerative disease, characterized by pronounced heterogeneity in symptoms. This study investigates the functional connectivity (FC) patterns associated with distinct symptom clusters, aiming to elucidate the heterogeneity in PD and uncover the neural mechanisms underlying its motor and cognitive symptoms. Resting-state functional MRI (rs-fMRI) data from 55 non-demented PD patients and 24 healthy controls (HC) were used to perform seed-to-seed FC analyses. A clustering algorithm was applied to the cognitive and motor scores of all PD patients to generate relatively homogeneous symptomatic subgroups. PD patients exhibited a general decrease in FC within a network comprising the sensorimotor network (SMN) and the visual network (VN) regions. Symptom-based clustering revealed three relatively homogeneous subgroups, exhibiting a gradient pattern: patients with greater motor deficits showed significant disconnection within the SMN, whereas patients with greater visuospatial deficits exhibited reduced FC in an extended subnetwork, with pronounced disconnections between the VN and SMN areas. Our study demonstrated a notable disconnection between the SMN and VN, indicating impaired visual-motor integration in PD. Stronger disconnection within the SMN was associated with greater motor dysfunction, and stronger visual-sensorimotor disconnections were associated with greater visuospatial deficits. These findings suggest that at least two separate routes of functional disconnection may be responsible for the inhomogeneous symptom distribution in PD.Yayın Automated diagnosis of Alzheimer’s Disease using OCT and OCTA: a systematic review(Institute of Electrical and Electronics Engineers Inc., 2024-08-06) Turkan, Yasemin; Tek, Faik Boray; Arpacı, Fatih; Arslan, Ozan; Toslak, Devrim; Bulut, Mehmet; Yaman, AylinRetinal optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) have emerged as promising, non-invasive, and cost-effective modalities for the early diagnosis of Alzheimer's disease (AD). However, a comprehensive review of automated deep learning techniques for diagnosing AD or mild cognitive impairment (MCI) using OCT/OCTA data is lacking. We addressed this gap by conducting a systematic review using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. We systematically searched databases, including Scopus, PubMed, and Web of Science, and identified 16 important studies from an initial set of 4006 references. We then analyzed these studies through a structured framework, focusing on the key aspects of deep learning workflows for AD/MCI diagnosis using OCT-OCTA. This included dataset curation, model training, and validation methodologies. Our findings indicate a shift towards employing end-to-end deep learning models to directly analyze OCT/OCTA images in diagnosing AD/MCI, moving away from traditional machine learning approaches. However, we identified inconsistencies in the data collection methods across studies, leading to varied outcomes. We emphasize the need for longitudinal studies on early AD and MCI diagnosis, along with further research on interpretability tools to enhance model accuracy and reliability for clinical translation.
