Publications by authors named "Firat Kara"

Objective: To assess the association of systolic and diastolic blood pressure (SBP and DBP) in recently menopausal women with white matter hyperintensity (WMH) volume later in life and determine whether short-term menopausal hormone therapy (mHT) modifies these associations.

Methods: Kronos Early Estrogen Prevention Study (KEEPS) was a multicenter, randomized, double-blinded, placebo-controlled 4-year mHT trial (oral conjugated equine estrogens or transdermal 17β-estradiol). KEEPS continuation was an observational follow-up of the participants 10 years after the end of mHT.

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Introduction: Premenopausal bilateral oophorectomy (PBO) before the age of 46 years is associated with an increased risk of dementia. We investigated the long-term effects of PBO performed before age 50 years on amyloid beta (Aβ), tau, and neurodegeneration imaging biomarkers of Alzheimer's disease (AD).

Methods: Mayo Clinic Cohort Study of Oophorectomy and Aging-2 participants were divided into early PBO (< 46 years; n = 61), and late PBO (46-49 years; n = 51) groups and were compared to referent women who did not undergo PBO (n = 119).

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Background: Findings from Kronos Early Estrogen Prevention Study (KEEPS)-Cog trial suggested no cognitive benefit or harm after 48 months of menopausal hormone therapy (mHT) initiated within 3 years of final menstrual period. To clarify the long-term effects of mHT initiated in early postmenopause, the observational KEEPS Continuation Study reevaluated cognition, mood, and neuroimaging effects in participants enrolled in the KEEPS-Cog and its parent study the KEEPS approximately 10 years after trial completion. We hypothesized that women randomized to transdermal estradiol (tE2) during early postmenopause would show cognitive benefits, while oral conjugated equine estrogens (oCEE) would show no effect, compared to placebo over the 10 years following randomization in the KEEPS trial.

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Article Synopsis
  • * The review highlights how H MRS metabolites correlate with other AD detection methods, such as biofluid analysis and PET scans, while also examining the impact of apolipoprotein 4 allele status on brain chemistry.
  • * Understanding these biochemical changes through H MRS could provide insights into AD progression and aid in developing new treatments.
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Introduction: Premenopausal bilateral oophorectomy (PBO) is associated with later-life cognition, but the underlying brain changes remain unclear. We assessed the impact of PBO and PBO age on white matter integrity.

Methods: Female participants with regional diffusion tensor imaging (DTI) metrics of fractional anisotropy (FA) and mean diffusivity (MD) were included (22 with PBO < 40 years; 43 with PBO 40-45 years; 39 with PBO 46-49 years; 907 referents without PBO < 50 years).

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Objective: To evaluate the associations between prescription opioid exposures in community-dwelling older adults and gray and white matter structure by magnetic resonance imaging.

Methods: Secondary analysis was conducted of a prospective, longitudinal population-based cohort study employing cross-sectional imaging of older adult (≥65 years) enrollees between November 1, 2004, and December 31, 2017. Gray matter outcomes included cortical thickness in 41 structures and subcortical volumes in 6 structures.

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Objective: To investigate the associations of glenohumeral internal (IR) and external rotation (ER), horizontal adduction (HA), and thoracic spine rotation ranges of motion (ROM), isometric muscle strength of the shoulder rotators, and trunk muscle endurance with the Closed Kinetic Chain Upper Extremity Stability Test (CKCUEST), the Upper Quarter Y Balance Test (YBT-UQ), and the Upper Limb Rotation Test (ULRT) in overhead athletes.

Design: Cross-sectional study.

Settings: Laboratory.

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Objective: This study aimed to determine long-term cardiometabolic effects of hormone therapies initiated within 3 years of onset of menopause after a 14-year follow-up study of participants of the Kronos Early Estrogen Prevention Study (KEEPS).

Methods: KEEPS was a multisite clinical trial that recruited recently menopausal women with good cardiovascular health for randomization to oral conjugated equine estrogens (Premarin, 0.45 mg/d) or transdermal 17β-estradiol (Climara, 50 μg/d) both with micronized progesterone (Prometrium, 200 mg/d) for 12 d/mo, or placebo pills and patch for 4 years.

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Few proton magnetic resonance spectroscopy studies have explored chemotherapy-related biochemical changes in brain regions. This observational study aimed to longitudinally assess short-term cognitive changes and brain metabolite concentrations in women undergoing chemotherapy for breast cancer. We analyzed 11 women with newly diagnosed stage 1 to 3 breast cancer.

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The aim of this cross-sectional study was to examine whether a history of selective estrogen receptor modifiers (SERMs), tamoxifen and raloxifene, use was associated with cognitive performance, odds of mild cognitive impairment (MCI), or magnetic resonance imaging (MRI) markers of neurodegeneration associated with Alzheimer's disease. We included women with prior history of breast cancer or no prior history of any cancer at enrollment in the Mayo Clinic Study of Aging (MCSA). This information was abstracted using the Rochester Epidemiology Project medical-linkage system.

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Purpose: Advanced MRS protocols improve data quality and reproducibility relative to vendor-provided protocols; however, they are challenging to incorporate into the clinical workflow and require local MRS expertise for successful implementation. Here, we developed an automated advanced MRS acquisition protocol at 3T to facilitate acquisition of high-quality spectroscopic data without local MRS expertise.

Methods: First, a B shimming protocol was selected for automation by comparing 3 widely used B algorithms (2 vendor protocols and FAST(EST)MAP).

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Proton magnetic resonance spectroscopy (H MRS) may provide information on pathophysiological changes associated with tau deposition in cognitively unimpaired older adults. In this study, the associations of posterior cingulate gyrus tau and amyloid beta (Aβ) deposition on PET with H MRS metabolite ratios acquired from bilateral posterior cingulate gyri were investigated in cognitively unimpaired older adults. Participants (n = 40) from the Mayo Clinic Study of Aging underwent single-voxel sLASER H MRS from the posterior cingulate gyrus at 3 Tesla, F-flortaucipir, and C- Pittsburgh Compound B (PiB) PET.

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Article Synopsis
  • Premenopausal bilateral ovariectomy is linked to a higher risk of Alzheimer's disease, but the reasons behind this connection are not fully understood.
  • In a study using rodent models of Alzheimer's, it was found that ovariectomized transgenic mice exhibited changes like increased hypothalamic energy metabolism and reduced brain connectivity compared to their sham-operated counterparts.
  • The research showed that both the genetic type of the mice and the ovariectomy procedure influenced brain imaging markers related to Alzheimer's, but no significant interaction between the type of surgery and genotype was found regarding specific protein levels linked to the disease.
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In vivo MRS is a non-invasive measurement technique used not only in humans, but also in animal models using high-field magnets. MRS enables the measurement of metabolite concentrations as well as metabolic rates and their modifications in healthy animals and disease models. Such data open the way to a deeper understanding of the underlying biochemistry, related disturbances and mechanisms taking place during or prior to symptoms and tissue changes.

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Glutamate is the principal excitatory neurotransmitter in the brain and is at the base of a wide variety of neuropathologies, including epilepsy, autism, Fragile X, and obsessive compulsive disorder. Glutamate has also become the target for novel drugs in treatment and in fundamental research settings. However, much remains unknown on the working mechanisms of these drugs and the effects of chronic administration on the glutamatergic system.

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A large proportion of the population suffers from endocrine disruption, e.g., menopausal women, which might result in accelerated aging and a higher risk for developing cognitive disorders.

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The benefit of small animal imaging is directly linked to the validity and reliability of the collected data. If the data (regardless of the modality used) are not reproducible and/or reliable, then the outcome of the data is rather questionable. Therefore, standardization of the use of small animal imaging equipment, as well as of animal handling in general, is of paramount importance.

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Article Synopsis
  • Inflammatory responses in the central nervous system significantly contribute to brain injuries and diseases.
  • The study indicates that using IL-13 through lentiviral vectors helps activate microglia and macrophages, providing protection against cell loss and demyelination in a mouse model of multiple sclerosis.
  • Results show that IL-13 not only alters inflammatory responses to a more protective state but also limits damage in already inflamed environments, suggesting its potential therapeutic role in MS.
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Resting-state functional MRI (rsfMRI) is a widely implemented technique used to investigate large-scale topology in the human brain during health and disease. Studies in mice provide additional advantages, including the possibility to flexibly modulate the brain by pharmacological or genetic manipulations in combination with high-throughput functional connectivity (FC) investigations. Pharmacological modulations that target specific neurotransmitter systems, partly mimicking the effect of pathological events, could allow discriminating the effect of specific systems on functional network disruptions.

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Non-invasive measures of well-known pathological hallmarks of multiple sclerosis (MS) such as demyelination, inflammation and axonal injury would serve as useful markers to monitor disease progression and evaluate potential therapies. To this end, in vivo localized proton magnetic resonance spectroscopy ((1)H-MRS) provides a powerful means to monitor metabolic changes in the brain and may be sensitive to these pathological hallmarks. In our study, we used the cuprizone mouse model to study pathological features of MS, such as inflammation, de- and remyelination, in a highly reproducible manner.

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Conventional MRI is frequently used during the diagnosis of multiple sclerosis but provides only little additional pathological information. Proton MRS ((1) H-MRS), however, provides biochemical information on the lesion pathology by visualization of a spectrum of metabolites. In this study we aimed to better understand the changes in metabolite concentrations following demyelination of the white matter.

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Purpose: To establish regional T1 and T2 values of the healthy mouse brain at ultra-high magnetic field strength of 17.6 T and to follow regional brain T1 and T2 changes with age.

Methods: In vivo T1 and T2 values in the C57BL/6J mouse brain were followed with age using multislice-multiecho sequence and multiple spin echo saturation recovery with variable repetition time sequence, respectively, at 9.

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T2-family acidic endoribonucleases are represented in all genomes. A physiological role for RNase T2 has yet to be defined for metazoa. RNASET2 mutation in humans is linked with a leukoencephalopathy that arises in infancy characterized by cortical cysts and multifocal white matter lesions.

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The present study was designed to examine which kind of memory: reference or working, better correlates with individual variation in rats' spatial learning abilities. To answer this question two groups of rats were trained to an arbitrary criterion in a partially baited 12-arm radial maze under two different experimental conditions: with or without allothetic cues. After 10 days break, rats were examined under the same conditions for memory retention.

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