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    Cognitive impairment in tension-type headache is associated with altered hippocampal functional connectivity
    (Cell Press, 2025) Yulug, Burak; Yalcinkaya, Ali; Safa, Shair Shah; Karakus, Ayse; Sayman, Dila; Cankaya, Seyda; Sayman, Ceyhun
    Tension-type headache (TTH) is a widespread primary headache disorder that causes mild to moderate pain, which may be seen together with cognitive deficits. It is unclear if TTH-linked cognitive impairment is associated with functional alterations. Seventy-five participants were enrolled in the study. Mini Mental State Evaluation (MMSE) and Montreal Cognition Assessment (MoCA) tests were applied to evaluate cognitive impairment. A neuroimaging analysis was applied to determine whether the hippocampus responsible for pain and cognition was affected in TTH patients. Our functional data revealed significant alterations in the connectivity of the subiculum, hippocampal fissure, and left whole hippocampus. Among the significant functional brain alterations observed, the right subiculum consistently interacted with MoCA scores and increased pain intensity. Our findings suggest that TTH patients with cognitive impairment may exhibit unique functional alterations in the hippocampus. This suggests a potential negative association between pain modulation and cognitive processes in the hippocampus that may be responsible for the increased risk of dementia in these patients.
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    Depression is an independent risk factor for stroke reccurence and cognitive impairment in stroke patients
    (Springernature, 2025) Cankaya, Seyda; Safa, Shair Shah; Karakus, Ayse; Savcili, Mehmet; Hanoglu, Lutfu; Mardinoglu, Adil; Cetin, Fatma Ece
    Post-stroke depression (PSD) is a significant sequela of cerebrovascular accidents, affecting a substantial proportion of stroke survivors. However, it is still unclear whether the existence of depression after stroke is an independent risk factor for stroke recurrence and if the increased risk of cognitive impairment in PSD is related to the location of stroke. We aimed to compare the role of cortical, subcortical and cortico-subcortical infarcts in the development of PSD and cognitive impairment, as well as the role of the existence of depression in stroke recurrence. In this study, a 52-week, randomised, double-blind study consisted of 1059 stroke patients (866 non-depressive and 193 untreated depressive persons) who were matched in terms of demographic and clinical parameters. The Mini Mental State Examination Test (MMSE), Executive function (Trail Making Test Part A), processing speed (colour naming condition of the Stroop test), episodic memory (Rey Auditory Verbal Learning Test [RAVLT], including delayed free recall), semantic memory (verbal fluency test [animal naming]), language processing (Boston Naming Test [(number correct]), visuospatial perception (the bells test) was assessed at the baseline. The lesion sites are subdivided as cortical, subcortical, and cortico-subcortical territory infarcts on MRI. The stroke recurrence ratio was also recorded after a year. In results, we observed a higher rate of depression associated with lesions affecting the cortico-subcortical structures in patients with PSD compared to non-depressive patients (p < 0.05). Our results further indicated impaired cognitive scores in patients with PSD compared to those with non-depressive individuals (p < 0.05). Regarding the risk of stroke recurrence, we also found an increased rate of stroke recurrence in PSD after 12 months (p < 0.05). In detail, binomial logistic regression analyses using the backward Wald method determined that patients with depression (p = 007; odds ratio (OR) = 1.64; CI 1.14-2.35), hypertension (p = 0.004; OR = 1.74; CI 1.19-2.55), atrial fibrillation (p = 0.007; OR = 1.61; CI 1.14-2.28) and older age (p = 0.019; OR = 1.02; CI 1.003-1.03) were significantly predictors for stroke recurrency. Our regression analysis further revealed that PSD was a predictive factor for disabling cognitive test scores (impaired executive function [p < 0.001; OR = 4.51; CI 3.24-6.27], reduced processing speed [p < 0.001; OR = 4.29; CI 3.12-5.91], episodic memory [p < 0.001; OR = 4.65; CI 3.37-6.42), semantic memory [p < 0.001; OR = 4.79; 3.47-6.61], visuospatial [p < 0.001; OR = 6.10; CI 4.36-8.55], and language function [p < 0.001; OR = 5.086; CI 3.67-7.05]) after adjusting for age and education. In conclusion, the present study provides strong evidence confirming the importance of depression in predicting cognitive impairment and recurrence in stroke patients. Despite these positive findings, our findings warrant the performance of further research to demonstrate the efficacy of treatment on stroke recurrence, together with other vascular risk factors and cognitive disorders.
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    Subjective cognitive decline in major depressive patients is associated with altered entropy and connectivity changes of temporal and insular region
    (Springernature, 2025) Yulug, Burak; Yalcinkaya, Ali; Safa, Shair Shah; Sayman, Dila; Cankaya, Seyda; Karakus, Ayse; Sayman, Ceyhun
    Depressive cognitive impairment is seen in a significant number of patients with depression. However, it remains challenging to differentiate between patients with amnestic (those with subjective cognitive impairment complaints) and non-amnestic major depressive disorder, highlighting the urgent need for additional objective tools to help classify these patients more accurately. We analyzed cognitive state, alterations in regional entropy and functional connectivity measures of the brain between patients with major depression and healthy controls. The depressed cohort was categorized as either amnestic or non-amnestic, depending on self-reported experiences of forgetfulness. The superior temporal region and insula exhibited altered entropy and connectivity measures in individuals with depression and subjective cognitive impairment, which was correlated with impaired executive functions, a pattern not being evident in the control group. Our findings support the notion that insular and superior temporal entropic alterations are linked to subjective cognitive changes in the pathology of depression. These regions also hold potential as biomarkers for determining the underlying objective cognitive deficits in subjective cognitive complaints in patients with major depressive disorder (MDD). This underscores the need for improved diagnostic approaches and the implementation of practical dynamic neuroimaging modalities capable of addressing the current challenges in diagnosing subjective cognitive impairment in MDD, offering promise for the future management of patients with depression.
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    Targeting the parietal memory network with tDCS in MCI: study protocol for a randomized controlled trial
    (Frontiers Media Sa, 2025) Cankaya, Seyda; Akturk, Aynur; Karakus, Ayse; Hanoglu, Lutfu; Mardinoglu, Adil; Yulug, Burak
    Background: Mild cognitive impairment (MCI) is a critical transitional stage in dementia related disorders. In that context, dorsolateral prefrontal cortex (DLPFC), and lateral parietal cortex (LPC) are subjected to neuropathological changes in MCI. Furthermore, alterations in parietal memory network (PMN) integrity and default mode network (DMN) also occur in MCI. Transcranial direct current stimulation (tDCS) is a promising neuroprotective tool that might interfere with cognitive decline in Alzheimer's disease-MCI (aMCI) and Parkinson's disease-MCI (PD-MCI) when applied to DLPFC or LPC separately. Methods: This is a randomized and controlled study evaluating the effectiveness of tDCS in 120 patients (60 aMCI and 60 PD-MCI). Firstly, all patients will be randomly (1:1) divided into two groups: DLPFC (30 aMCI; 30 PD-MCI) and LPC (30 aMCI, 30 PD-MCI) for tDCS stimulation. Secondly, they will classify randomly (2:1) real and sham groups for tDCS applied to once a day for 10 days over 2 weeks. The stimulation will be delivered with a 2-mA current frequency and will last 20 min. The primary outcome assessment for this study will be the change in score from baseline to the end of (14-days and 90 days follow-up) the tDCS application for the neurocognitive tests. Potential outcome parameters will be discussed in the light of current literature to contribute to the new area of personalized non-invasive brain stimulation research in neurodegenerative diseases at early stages. The results of this study are expected to shed light on the neural underpinnings and pro-cognitive outcomes of tDCS. Potential outcome parameters will be discussed in the light of current literature to contribute to the new area of personalized non-invasive brain stimulation research in neurodegenerative diseases at early stages.