I am a behavioral neurologist and a movement disorders specialist with research interests in cognitive neuroscience and intellectual interests in psychoanalysis, particularly Lacanian.
Background and purpose: To evaluate the phenotype and the frequencies of mutations in PRKN, DJ1 a... more Background and purpose: To evaluate the phenotype and the frequencies of mutations in PRKN, DJ1 and PINK1 genes in patients with Parkinson disease (PD) in Turkey. Methods: Eighty-six patients from 77 PD families participated in the study. Seventyfour families were originating from Turkey, two families from Greece and one family from Bulgaria. All patients underwent detailed neurological examination. PRKN, PINK1 and DJ1 genes were sequenced, and dosage analysis was performed by multiplex ligation-dependent probe amplification. Results: Sixteen patients with PD were found to carry homozygous (n = 14) or compound heterozygous (n = 2) PRKN mutations. We identified exon rearrangements, three point mutations and one new point mutation in exon 2 (p.K27del). In two families, two new PINK1 point mutations (L31X and P416L) were identified. No pathogenic mutations were found in DJ1 gene. Clinical phenotypes of PRKN patients were comparable to previously described features, but only in four of 13 families, the pedigree structure was clearly consistent with an autosomal recessive (AR) mode of inheritance in comparison with nine families where also different pattern of transmission could have been possible. Conclusions: Our data suggest that the PRKN gene mutation is the most frequent form of ARPD in Turkey. The proportion of mutations with regard to the age of onset in our population is in the range of those previously described, but our pedigrees are characterized by high rate of consanguinity, which might explain the high proportion of families with homozygous mutations and of patients in more than one generation. Pathogenic DJ1 mutations do not seem to play a major role in Turkey.
Turkish Journal of Anaesthesiology and Reanimation
Objective: The present study aimed to compare the effects of two different fresh gas flows (FGFs)... more Objective: The present study aimed to compare the effects of two different fresh gas flows (FGFs) (0.5 L min-1 and 2 L min-1) applied during maintenance of anaesthesia on recovery from anaesthesia and early cognitive functions in geriatric patients. Methods: In this prospective, randomised, double-blind study, sixty patients were divided into two groups according to the amount of FGF. Minimal-flow anaesthesia (0.5 L min-1 FGF) was applied to group I and medium-flow anaesthesia (2 L min-1 FGF) was applied to group II during maintenance of anaesthesia. Following the termination of inhalation anaesthesia, recovery times were recorded. The evaluation of cognitive functions was performed using the Addenbrooke's Cognitive Examination (ACE-R). Results: There was no significant difference between the two groups in terms of demographic characteristics and recovery (P > 0.05). There was no significant difference between the two groups in terms of the preoperative day, the first postoperative day, and the third postoperative day; ACE-R scores (P > 0.05). In group II, on the third postoperative day ACE-R scores were found to be significantly lower than the preoperative ACE-R scores (P=0.04). In group II, third postoperative day ACE-R memory sub-scores (14.53 ± 3.34) were found to be significantly lower than preoperative ACE-R memory sub-scores (15.03 ± 3.57) (P=0.04). Conclusion: In geriatric patients, minimal-flow anaesthesia was not superior to medium-flow anaesthesia in terms of recovery properties and cognitive functions. Keeping in mind that hypoxaemia and changes in anaesthesia levels may occur with the reduction of FGF, both minimal-and medium-flow anaesthesia can be applied with appropriate monitoring without adverse effects on recovery and cognitive functions.
Background In preclinical Alzheimer’s disease, it is unclear why some individuals with amyloid pa... more Background In preclinical Alzheimer’s disease, it is unclear why some individuals with amyloid pathologic change are asymptomatic (stage 1), whereas others experience subjective cognitive decline (SCD, stage 2). Here, we examined the association of stage 1 vs. stage 2 with structural brain reserve in memory-related brain regions. Methods We tested whether the volumes of hippocampal subfields and parahippocampal regions were larger in individuals at stage 1 compared to asymptomatic amyloid-negative older adults (healthy controls, HCs). We also tested whether individuals with stage 2 would show the opposite pattern, namely smaller brain volumes than in amyloid-negative individuals with SCD. Participants with cerebrospinal fluid (CSF) biomarker data and bilateral volumetric MRI data from the observational, multi-centric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study were included. The sample comprised 95 amyloid-negative and 26 amyloid-positive asymptomatic p...
AIM In this study, we aimed to establish Turkish normative data for two versions of The Pyramids ... more AIM In this study, we aimed to establish Turkish normative data for two versions of The Pyramids and Palm Trees Test (PPTT), pictorial (PPTT-P), and verbal (PPTT-V) using Turkish culture-specific items. METHODS The study sample involves 181 participants stratified into three age groups and further stratified into three education levels and gender. The participants were given the PPTT versions along with a neuropsychological battery. Participants in the aged group were further screened for cognition and depression. The internal consistency, the convergent and discriminant validity of the PPTT versions, and predictors of the performance in the PPTT versions are statistically analyzed. RESULTS The Cronbach's alpha coefficients for PPTT-P and PPTT-V were found as 0.48. and 0.42, respectively. Among the demographic variables, only education had an effect on the performances of both versions. Education level explained 21.2% of the variance in PPTT-P performance and 13.7% of the variance in PPTT-V performance. A cutoff score of 45 is proposed for the individuals with primary school education and 47 for those with higher education. Results suggested that both versions had moderate convergent but no discriminant validity. CONCLUSIONS Present findings suggest that PPTT is a useful neuropsychological instrument for assessing semantic memory in the Turkish population.
Giriş Tipik Alzheimer hastalığı (AH), merkezini progresif amnestik bozukluğun oluşturduğu, diğer ... more Giriş Tipik Alzheimer hastalığı (AH), merkezini progresif amnestik bozukluğun oluşturduğu, diğer kognitif fonksiyonlardaki bozulma ve kişilik değişikliğinin sıklıkla sonradan eklendiği, kronik nörodejeneratif bir hastalıktır. Bununla birlikte, etkilenen beyin alanlarına bağlı olarak diğer fokal kortikal demans sendromlarının çeşitli amnestik olmayan klinik profilleri ile atipik olarak ortaya çıkabilir. Ulusal Yaşlılık Enstitüsü-Alzheimer Derneği'nin (NIA-AA) 2011 yılında ve Uluslararası Çalışma Grubu-2'nin (IWG-2) 2014 yılında yayınladığı Alzheimer Hastalığı Tanı Kriterleri'nde tipik amnestik AH dışında, dil bozuklukları (logopenik varyant primer progresif afazi-lvPPA), vizyospasyal bozuklular (posterior kortikal atrofi-PKA), davranışsal/yürütücü işlev bozuklukları (frontal varyant-fvAH) ve Down sendromu ile sunulan atipik AH grupları da kendilerine yer bulmuşlardır (1,2). Ancak klinik pratikte BOS biyobelirteçleri ve literatürde post-mortem incelemeler ile AH patolojisi taşıyabileceği gösterilen diğer bir klinik profil ise kortikobazal sendromdur (KBS) ve NIA-AA ve IWG-2 tanı kriterleri kapsamında atipik AH sunumları arasında yer almamaktadır (3). KBS sinsi başlangıçlı, korteks ve ekstrapiramidal alanları tutan ve klinik olarak asimetrik ekstrapiramidal bulgular ile apraksi, yabancı el fenomeni, kortikal duyu kusuru, miyokloni gibi kortikal bulgular gösteren, sıklıkla 50-70 yaşları arasında ortaya çıkan, nispeten nadir bir sendromdur. Hastaların birçoğunda yürütücü bozukluk olarak da adlandırılan frontal tipte bir demans oluşur. En sık kortikobazal dejenerasyon (KBD) patolojisi görülen bu sendromda yapılan otopsi serilerinde ikinci sırada %23-50 arasında değişen oranlarda AH patolojisi olabileceği gösterilmiştir (3, 4). Dahası, Cambridge'den 34 olguluk bir atipik AH otopsi serisinde grubun %18'ini KBS oluştururken, fvAH sadece %6'sını oluşturmuştur (5). fvAH gibi çok daha nadir görülen atipik AH varyantları tanı kriterlerinde kendilerine yer bulurken, KBS'nin bir alttip olarak tanımlanmamış olması KBS
Objective: In this case report, we aimed to examine the effects of an intensive voice treatment (... more Objective: In this case report, we aimed to examine the effects of an intensive voice treatment (the Lee Silverman Voice Treatment [LSVT®LOUD]) for Wilson's disease (WD), and adult cerebral palsy (CP), and dysarthria.Method: The participants received LSVT®LOUD four times a week for 4 weeks. Acoustic, perceptual (GRBAS) analyses were performed and data from the Voice Handicap Index (VHI) were obtained before and after treatment.Results: Besides the Harmonics-to Noise Ratio (HNR) value (dB) of the participant with WD, for both participants' fundamental frequencies (Hz), jitter (%), and shimmer (%) values showed significant differences (p < .05) after therapy. Both participants showed significant improvements (p < .05) in the duration (s) and the sound pressure level (dB, SPL) of sustained vowel phonation (/a/), in SPL (dB) of pitch range (high and low /a/) and reading and conversation (p < .01). There was a positive improvement in the high-frequency values (Hz) of both participants but not in the low-frequency values (Hz) in the participant with WD. Perceptual analysis with GRBAS judgements of sustained vowel (/a/) and paragraph reading of two participants also showed improvement. After therapy, perceived loudness of the participants' voice increased.Conclusions: The findings provide some preliminary observations that the individuals with WD and the adult individuals with CP can respond positively to intensive speech treatment such as LSVT®LOUD. Further studies are needed to investigate speech treatments specific to WD and adult CP.
Re cei ved/Ge lifl Ta ri hi: 09.06.2020 Ac cep ted/Ka bul Ta ri hi: 01.02.2021 Objective: Mutatio... more Re cei ved/Ge lifl Ta ri hi: 09.06.2020 Ac cep ted/Ka bul Ta ri hi: 01.02.2021 Objective: Mutations in the Presenilin-1 (PSEN1) gene have been associated with early-onset familial Alzheimer disease (AD) and these mutations usually exhibit full penetrance. However, the p.E318G variant located at exon 9 of PSEN1 is an exception. This variant is also seen in non-demented controls other than patients with AD suggesting that it may be a rare polymorphism or a mutation with low penetrance. In addition, results from studies conducted in different populations investigating the role of p.E318G variant in AD were conflicting. In this study, we aimed to determine the frequency of the PSEN1 p.E318G variant and APOE genotypes in a Turkish cohort and to investigate whether they were associated with the risk of AD. Materials and Methods: The study included 217 patients with familial AD, 153 patients with sporadic AD, and 402 controls. The PSEN1 p.E318G and APOE genotypes were determined using real-time polymerase chain reaction with hydrolysis probes. Results: The p.E318G variant was found in five patients with familial AD, three patients with sporadic AD, and 11 control subjects. There was no significant difference in the distribution of the p.E318G variant between patients and controls in familial and sporadic forms. APOE ε4 allele carriers had an increased risk for AD compared with non-carriers both in familial [odds ratio (OR): 3.67, 95% confidence interval (CI): (2.69-4.99); p<0.001] and sporadic cases [OR: 2.91, 95% CI: (2.06-4.10); p<0.001]. No significant difference was found in the distribution of the p.E318G variant with either the absence or presence of the APOE ε4 allele. Conclusion: Our results showed that PSEN1 p.E318G variation, either alone or together with the APOE ε4 allele, is not associated with AD risk in Turkish patients with AD. However, the APOE ε4 allele constitutes a significant risk factor for AD both in familial and sporadic forms.
Objective: To explore the underlying genetic variations and mechanisms in a family affected by is... more Objective: To explore the underlying genetic variations and mechanisms in a family affected by isolated dystonia. Material and Method: We employed whole genome Single Nucleotide Polymorphism (SNP) based linkage analysis along with whole exome sequencing (WES) in a consanguineous family presenting with isolated dystonia. An in-house pipeline compiled for WES analysis along with in-depth in silico prediction algorithms were used to assess the associated data produced in this study. Sanger sequencing was used for variant confirmation and segregation. Results: Data analysis included locus oriented WES variant prioritization and cryptic splicing predictions. We detected a homozygous and synonymous variation rs748449895 (NM_015125.4: c.4143C>T; p.(Thr1381=)) in the capicua transcriptional repressor, CIC. This variation disrupts the YB-1 RNA recognition motif and creates an alternative SRp20 RNA recognition motif. Conclusion: The resulting variant might cause the dystonia phenotype by ...
Re cei ved / Ge lifl Ta ri hi: 08.12.2020 Ac cep ted / Ka bul Ta ri hi: 17.05.2021 Amaç: Laküner ... more Re cei ved / Ge lifl Ta ri hi: 08.12.2020 Ac cep ted / Ka bul Ta ri hi: 17.05.2021 Amaç: Laküner inmelerin çoğu sporadik olup, hipertansiyon, diyabet, sigara ve kardiyovasküler hastalıklar önemli risk faktörleri arasındadır. Küçük damar hastalıklarının yol açtığı inmeler ise genel olarak ailevi özellik taşıyan dominant ve resesif kalıtım modelleriyle gözlenen tek gen hastalıklarıyla ilişkilidir. En yaygın bilineni NOTCH3 genindeki patojenik varyantlarla ortaya çıkan subkortikal enfarkt ve lökoensefalopati ile giden otozomal dominant serebral arteriyopati (CADASIL) hastalığıdır. Bu hastalığın çok daha nadir bir kliniği ise patojenik HTRA1 gen değişimleri ile gözlenen resesif (CARASIL) formudur. Nörolojik ve kraniyal manyetik rezonans görüntüleme (MRG) bulguları CADASIL'e çok benzer olan CARASIL, moleküler patolojik yolakların farklı olması, hafıza disfonksiyonunun daha ağır seyretmesi, özellikle erkeklerde beklenenden daha erken yaşta başlayan yaygın alopesi görülmesi, bağ dokusunun etkilenmesi ve Objective: Most lacunar strokes are sporadic, and hypertension, diabetes, smoking, and cardiovascular diseases are among its main risk factors. Strokes caused by small vessel diseases are generally associated with single-gene disorders with familial dominant and recessive inheritance. The most common condition is cerebral autosomal dominant arteriopathy, with subcortical infarcts and leukoencephalopathy (CADASIL), associated with the NOTCH3 gene. An infrequent form of this disease is the cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), revealed with pathogenic HTRA1 gene variants related to distinct molecular pathways. The neurological and cranial magnetic resonance imaging (MRI) findings are very similar to CADASIL; however, earlier than expected onset of common alopecia in man, low back pain, and more severe memory impairment are the differences in terms of clinical presentations. Clinical findings of 22 patients from 16 families with widespread white matter lesions in the periventricular field in the brain were investigated with molecular genetic findings. Materials and Methods: Clinical examination results and cranial MRI findings are reported, and NOTCH3 and HTRA1 genes are sequenced stepwise by Sanger and next-generation sequencing techniques. Results: Missense changes in epidermal growth factor (EGF)-like domain in the NOTCH3 are found in 18 cases from 14 families. Two different homozygous pathogenic missense and nonsense variants, in the HTRA1 gene, were detected in four patients from two families. The disease onset age was approximately 16 years earlier in cases carrying pathogenic variants located in the encoding region of EGF-like domains 1-6 of NOTCH3. Conclusion: In the NOTCH3 gene with c.382T>C (p.C128R), c.555T>G (p.C185W), and c.1903C>T (p.R635C) and in the HTRA1 gene c.235C>T (p.Q79*) are presented for the first time in this study. Molecular genetic investigation of CADASIL and CARASIL is important to support the clinical diagnosis, determine the inheritance model, provide patient and family counseling, manage disease process, and evaluate possible treatment strategies.
Diagnosis of comorbid psychiatric conditions are a significant determinant for the prognosis of n... more Diagnosis of comorbid psychiatric conditions are a significant determinant for the prognosis of neurodegenerative diseases. Apathy, which is a behavioral executive dysfunction, frequently accompanies Alzheimer's disease (AD) and leads to higher daily functional loss. We assume that frontal lobe hypofunction in apathetic AD patients are more apparent than the AD patients without apathy. This study aims to address the neuroanatomical correlates of apathy in the early stage of AD using task-free functional magnetic resonance imaging (MRI). METHODS Patients (n=20) were recruited from the Neurology and Psychiatry Departments of İstanbul University, İstanbul School of Medicine whose first referrals were 6-to 12-month history of progressive cognitive decline. Patients with clinical dementia rating 0.5 and 1 were included in the study. The patient group was divided into two subgroups as apathetic and non-apathetic AD according to their psychiatric examination and assessment scores. A healthy control group was also included (n=10). All subjects underwent structural and functional MRI. The resting-state condition was recorded eyes open for 5 minutes. RESULTS The difference between the three groups came up in the pregenual anterior cingulate cortex (pgACC) at the trend level (P = 0.056). Apathetic AD group showed the most constricted activation area at pgACC. CONCLUSION The region in and around anterior default mode network (pgACC) seems to mediate motivation to initiate behavior, and this function appears to weaken as the apathy becomes more severe in AD.
Purpose/aim of the study: Parkinson's disease (PD) is the second most common neurodegenerative di... more Purpose/aim of the study: Parkinson's disease (PD) is the second most common neurodegenerative disorder. Vitamin D deficiency is suggested to be related to PD. A genome-wide association study indicated that genes involved in vitamin D metabolism affect vitamin D levels. Among these genes, single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) and vitamin D binding protein (VDBP/GC) genes have also been demonstrated to be associated with PD risk. Our aim was to investigate the relevance of SNPs within the 7-dehydrocholesterol reductase/nicotinamide adenine dinucleotide synthetase 1 (DHCR7/NADSYN1) locus and vitamin D 25-hydroxylase (CYP2R1) gene, which encode important enzymes that play a role in the vitamin D synthesis pathway, with PD and its clinical features. Materials and methods: Genotypes of 382 PD patients and 240 cognitively healthy individuals were evaluated by a LightSNiP assay for a total of 10 SNPs within the DHCR7/NADSYN1 locus and CYP2R1 gene. Results: There were no significant differences in the allele and genotype distributions of any of the SNPs between any patient groups and healthy subjects. However, our results indicated that all of the SNPs within the DHCR7/NADSYN1 locus and CYP2R1 gene, except rs1993116, were associated with clinical motor features of PD including initial predominant symptom, freezing of gait (FoG) and falls as well as disease stage and duration of the disease. Conclusions: In conclusion, genetic variants of the DHCR7/NADSYN1 locus and the CYP2R1 gene might be related to the inefficient utilization of vitamin D independent from vitamin D levels, and it might result in differences in the clinical features of PD patients.
AimSports activities provide social interaction for humans. Commitment to a given team is a salie... more AimSports activities provide social interaction for humans. Commitment to a given team is a salient feature of being a sports fan and becomes a prominent part of self‐identification for fanatics. Emotion, subjective hedonic experience, and non‐romantic love are related to fan behaviors. Few studies have evaluated the neural basis of sports fanaticism.MethodsThirty men, including 16 football fanatics and 14 non‐fanatics, with a mean age of 27.4 ± 6.4 years (range, 20–48 years) were enrolled. Subjects underwent functional MRI while watching a set of goals scored by favorite, rival, and neutral teams.ResultsThe analysis of variance in a general linear model revealed a significant Group × Condition interaction effect in the bilateral dorsal anterior cingulate cortex (dACC) that was more prominent in the left hemisphere. In the post‐hoc comparisons, fanatics showed increased activation in bilateral dACC, supplementary motor area, superior frontal cortex, right dorsolateral prefrontal cor...
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
*Yazarın editörlüğünde halen yazımı sürmekte olan "Kognitif Bozukluklar" isimli kitabın II. Kısmı... more *Yazarın editörlüğünde halen yazımı sürmekte olan "Kognitif Bozukluklar" isimli kitabın II. Kısmı'ndan modifiye edilmiştir.
Perspectives on Neurophysiology and Neurogenic Speech and Language Disorders, 2014
Frontotemporal dementia (FTD) is a progressive, neurodegenerative syndrome that results in change... more Frontotemporal dementia (FTD) is a progressive, neurodegenerative syndrome that results in changes in personality, behavior, and language. The right temporal variant, a relatively under-studied and perhaps under-diagnosed clinical subtype of FTD, manifests as behavioral changes, loss of person-specific knowledge, and eventual deficits in word-finding and semantic knowledge. Thorough assessment is necessary in order to distinguish right temporal variant FTD from other dementias. Speech-language pathologists (SLPs) play an essential role in accurate diagnosis, provision of appropriate resources and referrals, and administration of effective treatments.
Background and purpose: To evaluate the phenotype and the frequencies of mutations in PRKN, DJ1 a... more Background and purpose: To evaluate the phenotype and the frequencies of mutations in PRKN, DJ1 and PINK1 genes in patients with Parkinson disease (PD) in Turkey. Methods: Eighty-six patients from 77 PD families participated in the study. Seventyfour families were originating from Turkey, two families from Greece and one family from Bulgaria. All patients underwent detailed neurological examination. PRKN, PINK1 and DJ1 genes were sequenced, and dosage analysis was performed by multiplex ligation-dependent probe amplification. Results: Sixteen patients with PD were found to carry homozygous (n = 14) or compound heterozygous (n = 2) PRKN mutations. We identified exon rearrangements, three point mutations and one new point mutation in exon 2 (p.K27del). In two families, two new PINK1 point mutations (L31X and P416L) were identified. No pathogenic mutations were found in DJ1 gene. Clinical phenotypes of PRKN patients were comparable to previously described features, but only in four of 13 families, the pedigree structure was clearly consistent with an autosomal recessive (AR) mode of inheritance in comparison with nine families where also different pattern of transmission could have been possible. Conclusions: Our data suggest that the PRKN gene mutation is the most frequent form of ARPD in Turkey. The proportion of mutations with regard to the age of onset in our population is in the range of those previously described, but our pedigrees are characterized by high rate of consanguinity, which might explain the high proportion of families with homozygous mutations and of patients in more than one generation. Pathogenic DJ1 mutations do not seem to play a major role in Turkey.
Turkish Journal of Anaesthesiology and Reanimation
Objective: The present study aimed to compare the effects of two different fresh gas flows (FGFs)... more Objective: The present study aimed to compare the effects of two different fresh gas flows (FGFs) (0.5 L min-1 and 2 L min-1) applied during maintenance of anaesthesia on recovery from anaesthesia and early cognitive functions in geriatric patients. Methods: In this prospective, randomised, double-blind study, sixty patients were divided into two groups according to the amount of FGF. Minimal-flow anaesthesia (0.5 L min-1 FGF) was applied to group I and medium-flow anaesthesia (2 L min-1 FGF) was applied to group II during maintenance of anaesthesia. Following the termination of inhalation anaesthesia, recovery times were recorded. The evaluation of cognitive functions was performed using the Addenbrooke's Cognitive Examination (ACE-R). Results: There was no significant difference between the two groups in terms of demographic characteristics and recovery (P > 0.05). There was no significant difference between the two groups in terms of the preoperative day, the first postoperative day, and the third postoperative day; ACE-R scores (P > 0.05). In group II, on the third postoperative day ACE-R scores were found to be significantly lower than the preoperative ACE-R scores (P=0.04). In group II, third postoperative day ACE-R memory sub-scores (14.53 ± 3.34) were found to be significantly lower than preoperative ACE-R memory sub-scores (15.03 ± 3.57) (P=0.04). Conclusion: In geriatric patients, minimal-flow anaesthesia was not superior to medium-flow anaesthesia in terms of recovery properties and cognitive functions. Keeping in mind that hypoxaemia and changes in anaesthesia levels may occur with the reduction of FGF, both minimal-and medium-flow anaesthesia can be applied with appropriate monitoring without adverse effects on recovery and cognitive functions.
Background In preclinical Alzheimer’s disease, it is unclear why some individuals with amyloid pa... more Background In preclinical Alzheimer’s disease, it is unclear why some individuals with amyloid pathologic change are asymptomatic (stage 1), whereas others experience subjective cognitive decline (SCD, stage 2). Here, we examined the association of stage 1 vs. stage 2 with structural brain reserve in memory-related brain regions. Methods We tested whether the volumes of hippocampal subfields and parahippocampal regions were larger in individuals at stage 1 compared to asymptomatic amyloid-negative older adults (healthy controls, HCs). We also tested whether individuals with stage 2 would show the opposite pattern, namely smaller brain volumes than in amyloid-negative individuals with SCD. Participants with cerebrospinal fluid (CSF) biomarker data and bilateral volumetric MRI data from the observational, multi-centric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study were included. The sample comprised 95 amyloid-negative and 26 amyloid-positive asymptomatic p...
AIM In this study, we aimed to establish Turkish normative data for two versions of The Pyramids ... more AIM In this study, we aimed to establish Turkish normative data for two versions of The Pyramids and Palm Trees Test (PPTT), pictorial (PPTT-P), and verbal (PPTT-V) using Turkish culture-specific items. METHODS The study sample involves 181 participants stratified into three age groups and further stratified into three education levels and gender. The participants were given the PPTT versions along with a neuropsychological battery. Participants in the aged group were further screened for cognition and depression. The internal consistency, the convergent and discriminant validity of the PPTT versions, and predictors of the performance in the PPTT versions are statistically analyzed. RESULTS The Cronbach's alpha coefficients for PPTT-P and PPTT-V were found as 0.48. and 0.42, respectively. Among the demographic variables, only education had an effect on the performances of both versions. Education level explained 21.2% of the variance in PPTT-P performance and 13.7% of the variance in PPTT-V performance. A cutoff score of 45 is proposed for the individuals with primary school education and 47 for those with higher education. Results suggested that both versions had moderate convergent but no discriminant validity. CONCLUSIONS Present findings suggest that PPTT is a useful neuropsychological instrument for assessing semantic memory in the Turkish population.
Giriş Tipik Alzheimer hastalığı (AH), merkezini progresif amnestik bozukluğun oluşturduğu, diğer ... more Giriş Tipik Alzheimer hastalığı (AH), merkezini progresif amnestik bozukluğun oluşturduğu, diğer kognitif fonksiyonlardaki bozulma ve kişilik değişikliğinin sıklıkla sonradan eklendiği, kronik nörodejeneratif bir hastalıktır. Bununla birlikte, etkilenen beyin alanlarına bağlı olarak diğer fokal kortikal demans sendromlarının çeşitli amnestik olmayan klinik profilleri ile atipik olarak ortaya çıkabilir. Ulusal Yaşlılık Enstitüsü-Alzheimer Derneği'nin (NIA-AA) 2011 yılında ve Uluslararası Çalışma Grubu-2'nin (IWG-2) 2014 yılında yayınladığı Alzheimer Hastalığı Tanı Kriterleri'nde tipik amnestik AH dışında, dil bozuklukları (logopenik varyant primer progresif afazi-lvPPA), vizyospasyal bozuklular (posterior kortikal atrofi-PKA), davranışsal/yürütücü işlev bozuklukları (frontal varyant-fvAH) ve Down sendromu ile sunulan atipik AH grupları da kendilerine yer bulmuşlardır (1,2). Ancak klinik pratikte BOS biyobelirteçleri ve literatürde post-mortem incelemeler ile AH patolojisi taşıyabileceği gösterilen diğer bir klinik profil ise kortikobazal sendromdur (KBS) ve NIA-AA ve IWG-2 tanı kriterleri kapsamında atipik AH sunumları arasında yer almamaktadır (3). KBS sinsi başlangıçlı, korteks ve ekstrapiramidal alanları tutan ve klinik olarak asimetrik ekstrapiramidal bulgular ile apraksi, yabancı el fenomeni, kortikal duyu kusuru, miyokloni gibi kortikal bulgular gösteren, sıklıkla 50-70 yaşları arasında ortaya çıkan, nispeten nadir bir sendromdur. Hastaların birçoğunda yürütücü bozukluk olarak da adlandırılan frontal tipte bir demans oluşur. En sık kortikobazal dejenerasyon (KBD) patolojisi görülen bu sendromda yapılan otopsi serilerinde ikinci sırada %23-50 arasında değişen oranlarda AH patolojisi olabileceği gösterilmiştir (3, 4). Dahası, Cambridge'den 34 olguluk bir atipik AH otopsi serisinde grubun %18'ini KBS oluştururken, fvAH sadece %6'sını oluşturmuştur (5). fvAH gibi çok daha nadir görülen atipik AH varyantları tanı kriterlerinde kendilerine yer bulurken, KBS'nin bir alttip olarak tanımlanmamış olması KBS
Objective: In this case report, we aimed to examine the effects of an intensive voice treatment (... more Objective: In this case report, we aimed to examine the effects of an intensive voice treatment (the Lee Silverman Voice Treatment [LSVT®LOUD]) for Wilson's disease (WD), and adult cerebral palsy (CP), and dysarthria.Method: The participants received LSVT®LOUD four times a week for 4 weeks. Acoustic, perceptual (GRBAS) analyses were performed and data from the Voice Handicap Index (VHI) were obtained before and after treatment.Results: Besides the Harmonics-to Noise Ratio (HNR) value (dB) of the participant with WD, for both participants' fundamental frequencies (Hz), jitter (%), and shimmer (%) values showed significant differences (p < .05) after therapy. Both participants showed significant improvements (p < .05) in the duration (s) and the sound pressure level (dB, SPL) of sustained vowel phonation (/a/), in SPL (dB) of pitch range (high and low /a/) and reading and conversation (p < .01). There was a positive improvement in the high-frequency values (Hz) of both participants but not in the low-frequency values (Hz) in the participant with WD. Perceptual analysis with GRBAS judgements of sustained vowel (/a/) and paragraph reading of two participants also showed improvement. After therapy, perceived loudness of the participants' voice increased.Conclusions: The findings provide some preliminary observations that the individuals with WD and the adult individuals with CP can respond positively to intensive speech treatment such as LSVT®LOUD. Further studies are needed to investigate speech treatments specific to WD and adult CP.
Re cei ved/Ge lifl Ta ri hi: 09.06.2020 Ac cep ted/Ka bul Ta ri hi: 01.02.2021 Objective: Mutatio... more Re cei ved/Ge lifl Ta ri hi: 09.06.2020 Ac cep ted/Ka bul Ta ri hi: 01.02.2021 Objective: Mutations in the Presenilin-1 (PSEN1) gene have been associated with early-onset familial Alzheimer disease (AD) and these mutations usually exhibit full penetrance. However, the p.E318G variant located at exon 9 of PSEN1 is an exception. This variant is also seen in non-demented controls other than patients with AD suggesting that it may be a rare polymorphism or a mutation with low penetrance. In addition, results from studies conducted in different populations investigating the role of p.E318G variant in AD were conflicting. In this study, we aimed to determine the frequency of the PSEN1 p.E318G variant and APOE genotypes in a Turkish cohort and to investigate whether they were associated with the risk of AD. Materials and Methods: The study included 217 patients with familial AD, 153 patients with sporadic AD, and 402 controls. The PSEN1 p.E318G and APOE genotypes were determined using real-time polymerase chain reaction with hydrolysis probes. Results: The p.E318G variant was found in five patients with familial AD, three patients with sporadic AD, and 11 control subjects. There was no significant difference in the distribution of the p.E318G variant between patients and controls in familial and sporadic forms. APOE ε4 allele carriers had an increased risk for AD compared with non-carriers both in familial [odds ratio (OR): 3.67, 95% confidence interval (CI): (2.69-4.99); p<0.001] and sporadic cases [OR: 2.91, 95% CI: (2.06-4.10); p<0.001]. No significant difference was found in the distribution of the p.E318G variant with either the absence or presence of the APOE ε4 allele. Conclusion: Our results showed that PSEN1 p.E318G variation, either alone or together with the APOE ε4 allele, is not associated with AD risk in Turkish patients with AD. However, the APOE ε4 allele constitutes a significant risk factor for AD both in familial and sporadic forms.
Objective: To explore the underlying genetic variations and mechanisms in a family affected by is... more Objective: To explore the underlying genetic variations and mechanisms in a family affected by isolated dystonia. Material and Method: We employed whole genome Single Nucleotide Polymorphism (SNP) based linkage analysis along with whole exome sequencing (WES) in a consanguineous family presenting with isolated dystonia. An in-house pipeline compiled for WES analysis along with in-depth in silico prediction algorithms were used to assess the associated data produced in this study. Sanger sequencing was used for variant confirmation and segregation. Results: Data analysis included locus oriented WES variant prioritization and cryptic splicing predictions. We detected a homozygous and synonymous variation rs748449895 (NM_015125.4: c.4143C>T; p.(Thr1381=)) in the capicua transcriptional repressor, CIC. This variation disrupts the YB-1 RNA recognition motif and creates an alternative SRp20 RNA recognition motif. Conclusion: The resulting variant might cause the dystonia phenotype by ...
Re cei ved / Ge lifl Ta ri hi: 08.12.2020 Ac cep ted / Ka bul Ta ri hi: 17.05.2021 Amaç: Laküner ... more Re cei ved / Ge lifl Ta ri hi: 08.12.2020 Ac cep ted / Ka bul Ta ri hi: 17.05.2021 Amaç: Laküner inmelerin çoğu sporadik olup, hipertansiyon, diyabet, sigara ve kardiyovasküler hastalıklar önemli risk faktörleri arasındadır. Küçük damar hastalıklarının yol açtığı inmeler ise genel olarak ailevi özellik taşıyan dominant ve resesif kalıtım modelleriyle gözlenen tek gen hastalıklarıyla ilişkilidir. En yaygın bilineni NOTCH3 genindeki patojenik varyantlarla ortaya çıkan subkortikal enfarkt ve lökoensefalopati ile giden otozomal dominant serebral arteriyopati (CADASIL) hastalığıdır. Bu hastalığın çok daha nadir bir kliniği ise patojenik HTRA1 gen değişimleri ile gözlenen resesif (CARASIL) formudur. Nörolojik ve kraniyal manyetik rezonans görüntüleme (MRG) bulguları CADASIL'e çok benzer olan CARASIL, moleküler patolojik yolakların farklı olması, hafıza disfonksiyonunun daha ağır seyretmesi, özellikle erkeklerde beklenenden daha erken yaşta başlayan yaygın alopesi görülmesi, bağ dokusunun etkilenmesi ve Objective: Most lacunar strokes are sporadic, and hypertension, diabetes, smoking, and cardiovascular diseases are among its main risk factors. Strokes caused by small vessel diseases are generally associated with single-gene disorders with familial dominant and recessive inheritance. The most common condition is cerebral autosomal dominant arteriopathy, with subcortical infarcts and leukoencephalopathy (CADASIL), associated with the NOTCH3 gene. An infrequent form of this disease is the cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), revealed with pathogenic HTRA1 gene variants related to distinct molecular pathways. The neurological and cranial magnetic resonance imaging (MRI) findings are very similar to CADASIL; however, earlier than expected onset of common alopecia in man, low back pain, and more severe memory impairment are the differences in terms of clinical presentations. Clinical findings of 22 patients from 16 families with widespread white matter lesions in the periventricular field in the brain were investigated with molecular genetic findings. Materials and Methods: Clinical examination results and cranial MRI findings are reported, and NOTCH3 and HTRA1 genes are sequenced stepwise by Sanger and next-generation sequencing techniques. Results: Missense changes in epidermal growth factor (EGF)-like domain in the NOTCH3 are found in 18 cases from 14 families. Two different homozygous pathogenic missense and nonsense variants, in the HTRA1 gene, were detected in four patients from two families. The disease onset age was approximately 16 years earlier in cases carrying pathogenic variants located in the encoding region of EGF-like domains 1-6 of NOTCH3. Conclusion: In the NOTCH3 gene with c.382T>C (p.C128R), c.555T>G (p.C185W), and c.1903C>T (p.R635C) and in the HTRA1 gene c.235C>T (p.Q79*) are presented for the first time in this study. Molecular genetic investigation of CADASIL and CARASIL is important to support the clinical diagnosis, determine the inheritance model, provide patient and family counseling, manage disease process, and evaluate possible treatment strategies.
Diagnosis of comorbid psychiatric conditions are a significant determinant for the prognosis of n... more Diagnosis of comorbid psychiatric conditions are a significant determinant for the prognosis of neurodegenerative diseases. Apathy, which is a behavioral executive dysfunction, frequently accompanies Alzheimer's disease (AD) and leads to higher daily functional loss. We assume that frontal lobe hypofunction in apathetic AD patients are more apparent than the AD patients without apathy. This study aims to address the neuroanatomical correlates of apathy in the early stage of AD using task-free functional magnetic resonance imaging (MRI). METHODS Patients (n=20) were recruited from the Neurology and Psychiatry Departments of İstanbul University, İstanbul School of Medicine whose first referrals were 6-to 12-month history of progressive cognitive decline. Patients with clinical dementia rating 0.5 and 1 were included in the study. The patient group was divided into two subgroups as apathetic and non-apathetic AD according to their psychiatric examination and assessment scores. A healthy control group was also included (n=10). All subjects underwent structural and functional MRI. The resting-state condition was recorded eyes open for 5 minutes. RESULTS The difference between the three groups came up in the pregenual anterior cingulate cortex (pgACC) at the trend level (P = 0.056). Apathetic AD group showed the most constricted activation area at pgACC. CONCLUSION The region in and around anterior default mode network (pgACC) seems to mediate motivation to initiate behavior, and this function appears to weaken as the apathy becomes more severe in AD.
Purpose/aim of the study: Parkinson's disease (PD) is the second most common neurodegenerative di... more Purpose/aim of the study: Parkinson's disease (PD) is the second most common neurodegenerative disorder. Vitamin D deficiency is suggested to be related to PD. A genome-wide association study indicated that genes involved in vitamin D metabolism affect vitamin D levels. Among these genes, single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) and vitamin D binding protein (VDBP/GC) genes have also been demonstrated to be associated with PD risk. Our aim was to investigate the relevance of SNPs within the 7-dehydrocholesterol reductase/nicotinamide adenine dinucleotide synthetase 1 (DHCR7/NADSYN1) locus and vitamin D 25-hydroxylase (CYP2R1) gene, which encode important enzymes that play a role in the vitamin D synthesis pathway, with PD and its clinical features. Materials and methods: Genotypes of 382 PD patients and 240 cognitively healthy individuals were evaluated by a LightSNiP assay for a total of 10 SNPs within the DHCR7/NADSYN1 locus and CYP2R1 gene. Results: There were no significant differences in the allele and genotype distributions of any of the SNPs between any patient groups and healthy subjects. However, our results indicated that all of the SNPs within the DHCR7/NADSYN1 locus and CYP2R1 gene, except rs1993116, were associated with clinical motor features of PD including initial predominant symptom, freezing of gait (FoG) and falls as well as disease stage and duration of the disease. Conclusions: In conclusion, genetic variants of the DHCR7/NADSYN1 locus and the CYP2R1 gene might be related to the inefficient utilization of vitamin D independent from vitamin D levels, and it might result in differences in the clinical features of PD patients.
AimSports activities provide social interaction for humans. Commitment to a given team is a salie... more AimSports activities provide social interaction for humans. Commitment to a given team is a salient feature of being a sports fan and becomes a prominent part of self‐identification for fanatics. Emotion, subjective hedonic experience, and non‐romantic love are related to fan behaviors. Few studies have evaluated the neural basis of sports fanaticism.MethodsThirty men, including 16 football fanatics and 14 non‐fanatics, with a mean age of 27.4 ± 6.4 years (range, 20–48 years) were enrolled. Subjects underwent functional MRI while watching a set of goals scored by favorite, rival, and neutral teams.ResultsThe analysis of variance in a general linear model revealed a significant Group × Condition interaction effect in the bilateral dorsal anterior cingulate cortex (dACC) that was more prominent in the left hemisphere. In the post‐hoc comparisons, fanatics showed increased activation in bilateral dACC, supplementary motor area, superior frontal cortex, right dorsolateral prefrontal cor...
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
*Yazarın editörlüğünde halen yazımı sürmekte olan "Kognitif Bozukluklar" isimli kitabın II. Kısmı... more *Yazarın editörlüğünde halen yazımı sürmekte olan "Kognitif Bozukluklar" isimli kitabın II. Kısmı'ndan modifiye edilmiştir.
Perspectives on Neurophysiology and Neurogenic Speech and Language Disorders, 2014
Frontotemporal dementia (FTD) is a progressive, neurodegenerative syndrome that results in change... more Frontotemporal dementia (FTD) is a progressive, neurodegenerative syndrome that results in changes in personality, behavior, and language. The right temporal variant, a relatively under-studied and perhaps under-diagnosed clinical subtype of FTD, manifests as behavioral changes, loss of person-specific knowledge, and eventual deficits in word-finding and semantic knowledge. Thorough assessment is necessary in order to distinguish right temporal variant FTD from other dementias. Speech-language pathologists (SLPs) play an essential role in accurate diagnosis, provision of appropriate resources and referrals, and administration of effective treatments.
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Papers by Hakan Gurvit