Objective Sleep Function is Associated with Hippocampal Subfield Volumes in Community-Dwelling Adults.

BACKGROUND: Sleep patterns often shift as people age, a phenomenon frequently associated with the onset of neurodegenerative conditions. Additionally, distinct alterations occur in brain structure as individuals grow older, particularly within the hippocampus, a region known for its role in cognition and sleep regulation. Yet, how exactly do changes in sleep relate to specific subfields within the hippocampus is still unclear. METHODS: We conducted a study involving non-demented healthy adults from the Aiginition Longitudinal Biomarker Investigation Of Neurodegeneration (ALBION) cohort. Participants underwent objective sleep measurements using wrist Actiwatch and WatchPAT devices. Further, all participants underwent the same Magnetic Resonance Imaging (MRI) protocol, including a 3D high resolution T1-weighted sequence, on the same 3.0 Tesla MRI scanner using an eight-channel head coil. The study aimed to examine the relationship between objectively measured sleep metrics and the morphology of twenty-two distinct hippocampal subregions. RESULTS: In total, 75 non-demented participants with 63 mean years of age were included in the study. Results indicated that a higher frequency of awakenings during sleep was associated with increased volume in the right presubiculum body (beta = 0.630, p False Discovery Rate (FDR) <0.036). Longer sleep duration showed a tendency to be associated with smaller volumes of the right presubiculum body, hinting at a possible negative impact of prolonged sleep on this brain region. Similar trends were observed regarding sleep apnea and the presubiculum body volume. Further analysis based on age stratification revealed that in younger participants, longer sleep duration was linked to decreased volume of the presubiculum body, while a greater number of awakenings was correlated with increased volume of the same region. Among older participants, higher frequencies of awakenings were associated with larger volumes in various hippocampal subfields. CONCLUSIONS: These findings shed light on the complex relationship between sleep characteristics and brain structure, highlighting potential age-related differences. The study provides valuable insights into how sleep disruptions may impact hippocampal morphology and cognitive function of cognitively healthy adults. Further research is warranted to elucidate the underlying mechanisms and implications for neurodegenerative diseases.

A Multicomponent Home-Based Intervention for Neuropsychiatric Symptoms in People With Dementia and Caregivers' Burden and Depression: A 6-Month Longitudinal Study.

OBJECTIVES: Many people with dementia live in their home and require ongoing care, which is often provided by informal family caregivers. Thus, we examined the effectiveness of a multicomponent home-based intervention by evaluating its impact on a) neuropsychiatric symptoms of people with dementia and b) burden and depression of their caregivers. METHODS: During the first 6 months of this prospective single-center study, we applied a home-based multicomponent intervention in 205 dyads of care-recipients and caregivers. In further analyzes, we included only dyads of caregivers and care-recipients with available data both at baseline and 6-month follow-up (N = 144). All assessments were conducted at home and included sociodemographic features, care-recipients' clinical data, cognitive status (Mini-Mental State Examination), activities of daily living (Instrumental Activities of Daily Living; Katz Index of Independence in Activities of Daily Living), neuropsychiatric symptoms (Neuropsychiatric Inventory), and caregivers' burden (Zarit Burden Inventory) and depression (Center for Epidemiological Studies-Depression). RESULTS: We found significant decreases in the severity (pFDR = 0.002) and associated distress (pFDR = 0.001) of neuropsychiatric symptoms, as well as caregivers' burden (pFDR = 0.004) and depressive symptoms (pFDR = 0.001). As expected, there was significant deterioration in care-recipients' cognitive status (pFDR = 0.005) and measures of activities of daily living (pFDR < 0.005). CONCLUSION: Despite the progressive course of dementia, the home-based multicomponent intervention was effective in decreasing caregivers' burden and depression and minimizing care-recipients' neuropsychiatric symptoms' severity and associated distress after 6 months. Our study highlights the establishment of home-based care units as an advantageous solution, specifically for family members seen to have a "taken-for-granted" role in dementia caring.

Structural and functional brain changes in X-linked Charcot-Marie-Tooth disease: insights from a multimodal neuroimaging study.

PURPOSE: Brain involvement in X-linked Charcot-Marie-Tooth disease (CMTX) has been previously reported. We studied the brain structural and functional integrity using a multimodal neuroimaging approach in patients with no current central nervous system (CNS) symptoms, in order to further delineate the disease's phenotype. METHODS: Seventeen CMTX patients with no current CNS symptoms and 24 matched healthy controls underwent brain magnetic resonance imaging (MRI). Structural integrity was evaluated performing Gray matter analysis with voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) of diffusion tensor imaging (DTI). Functional integrity was evaluated with resting-state functional MRI (rs-fMRI). RESULTS: Decreased gray matter density was detected in CMTX patients compared to healthy controls in bilateral hippocampus, left thalamus, left postcentral gyrus, left superior parietal lobule, left cerebellum crus I and II, and vermis VI. DTI analysis showed increased fractional anisotropy and radial diffusivity in the right anterior insula and increased axial diffusivity in right cerebellum crus I in CMTX patients. rs-fMRI revealed decreased spontaneous neural activity on left precentral gyrus in patients compared to healthy controls. CONCLUSION: Advanced magnetic resonance (MR) neuroimaging techniques in CMTX patients revealed structural and functional involvement of multiple motor and extra-motor brain areas. MR neuroimaging techniques have the potential to delineate the CNS phenotype of a peripheral neuropathy like CMTX.

Executive Dysfunction, Social Cognition Impairment, and Gray Matter Pathology in Myotonic Dystrophy Type 2: A Pilot Study.

BACKGROUND: In contrast to myotonic dystrophy type 1, the cognitive and radiologic profile of myotonic dystrophy type 2 (DM2) is relatively poorly characterized. OBJECTIVE: To conduct a pilot study to systematically evaluate cognitive and radiologic features in a cohort of Greek individuals with DM2. METHOD: Eleven genetically confirmed individuals with DM2 and 26 age- and education-matched healthy controls were administered the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS) to screen for impairment in multiple cognitive domains. MRI data were evaluated by morphometric analyses to identify disease-specific gray and white matter alterations. The following statistical thresholds were used for cognitive comparisons: PFDR < 0.05 and Bayes factor (BF 10 ) >10. RESULTS: The DM2 group exhibited cognitive impairment (ECAS Total score; PFDR = 0.001; BF 10 = 108.887), which was dominated by executive impairment ( PFDR = 0.003; BF 10 = 25.330). A trend toward verbal fluency impairment was also identified. No significant impairments in memory, language, or visuospatial function were captured. The analysis of subscores revealed severe impairments in social cognition and alternation. Voxel-based morphometry identified widespread frontal, occipital, and subcortical gray matter atrophy, including the left superior medial frontal gyrus, right medial orbitofrontal gyrus, right operculum, right precuneus, bilateral fusiform gyri, and bilateral thalami. CONCLUSION: DM2 may be associated with multifocal cortical and thalamic atrophy, which is likely to underpin the range of cognitive manifestations mostly characterized by executive impairment and specifically by impaired social cognition.

Neurometabolic Alterations in Motor Neuron Disease: Insights from Magnetic Resonance Spectroscopy.

Magnetic resonance spectroscopy (MRS) has contributed important academic insights in motor neuron diseases (MNDs), particularly in amyotrophic lateral sclerosis (ALS). Over the past three decades momentous methodological advances took place, including the emergence of high-field magnetic resonance imaging (MRI) platforms, multi-voxel techniques, whole-brain protocols, novel head-coil designs, and a multitude of open-source imaging suites. Technological advances in MRS are complemented by important conceptual developments in MND, such as the recognition of the importance of extra-motor brain regions, multi-timepoint longitudinal study designs, assessment of asymptomatic mutation carriers, description of genotype-associated signatures, and the gradual characterisation of non-ALS MND phenotypes. We have conducted a systematic review of published MRS studies in MND to identify important emerging research trends, key lessons from pioneering studies, and stereotyped shortcomings. We also sought to highlight notable gaps in the current literature so that research priorities for future studies can be outlined. While MRS remains relatively underutilised in MND compared to other structural, diffusivity and functional imaging modalities, our review suggests that MRS can not only advance our academic understanding of MND biology, but has a multitude of practical benefits for clinical and pharmaceutical trial applications.

Genotype-associated cerebellar profiles in ALS: focal cerebellar pathology and cerebro-cerebellar connectivity alterations.

OBJECTIVE: Cerebellar disease burden and cerebro-cerebellar connectivity alterations are poorly characterised in amyotrophic lateral sclerosis (ALS) despite the likely contribution of cerebellar pathology to the clinical heterogeneity of the condition. METHODS: A prospective imaging study has been undertaken with 271 participants to systematically evaluate cerebellar grey and white matter alterations, cerebellar peduncle integrity and cerebro-cerebellar connectivity in ALS. Participants were stratified into four groups: (1) patients testing positive for GGGGCC repeat expansions in C9orf72, (2) patients carrying an intermediate-length repeat expansion in ATXN2, (3) patients without established ALS-associated mutations and (4) healthy controls. Additionally, the cerebellar profile of a single patient with ALS who had an ATXN2 allele length of 62 was evaluated. Cortical thickness, grey matter and white matter volumes were calculated in each cerebellar lobule complemented by morphometric analyses to characterise genotype-associated atrophy patterns. A Bayesian segmentation algorithm was used for superior cerebellar peduncle volumetry. White matter diffusivity parameters were appraised both within the cerebellum and in the cerebellar peduncles. Cerebro-cerebellar connectivity was assessed using deterministic tractography. RESULTS: Cerebellar pathology was confined to lobules I-V of the anterior lobe in patients with sporadic ALS in contrast to the considerable posterior lobe and vermis disease burden identified in C9orf72 mutation carriers. Patients with intermediate ATXN2 expansions did not exhibit significant cerebellar pathology. CONCLUSIONS: Focal rather than global cerebellar degeneration characterises ALS. Pathognomonic ALS symptoms which are typically attributed to other anatomical regions, such as dysarthria, dysphagia, pseudobulbar affect, eye movement abnormalities and cognitive deficits, may be modulated, exacerbated or partially driven by cerebellar changes in ALS.

Neuropsychological Assessment Should Always be Considered in Myotonic Dystrophy Type 2.

Myotonic dystrophies (DMs) are hereditary, multisystem, slowly progressive myopathies. One of the systems they affect is the CNS. In contrast to the well-established cognitive profile of myotonic dystrophy type 1 (DM1), only a few studies have investigated cognitive dysfunction in individuals with myotonic dystrophy type 2 (DM2), and their findings have been inconsistent. To identify the most commonly affected cognitive domains in individuals with DM2, we performed a formal comprehensive review of published DM2 studies. Using the terms "myotonic dystrophy type 2" AND "cognitive deficits," "cognitive," "cognition," "neuropsychological," "neurocognitive," and "neurobehavioral" in all fields, we conducted an advanced search on PubMed. We read and evaluated all of the available original research articles (13) and one case study, 14 in total, and included them in our review. Most of the research studies of DM2 reported primary cognitive deficits in executive functions (dysexecutive syndrome), memory (short-term nonverbal, verbal episodic memory), visuospatial/constructive-motor functions, and attention and processing speed; language was rarely reported to be affected. Based on the few neuroimaging and/or multimodal DM2 studies we could find, the cognitive profile of DM2 is associated with brain abnormalities in several secondary and high-order cortical and subcortical regions and associative white matter tracts. The limited sample size of individuals with DM2 was the most prominent limitation of these studies. The multifaceted profile of cognitive deficits found in individuals with DM2 highlights the need for routine neuropsychological assessment at both baseline and follow-up, which could unveil these individuals' cognitive strengths and deficits.

Multimodal Neurophysiological and Neuroimaging Evidence of Genetic Influence on Motor Control: A Case Report of Monozygotic Twins.

Considering genetic influence on brain structure and function, including motor control, we report a case of right-handed monozygotic twins with atypical organization of fine motor movement control that might imply genetic influence. Structural and functional organization of the twins' motor function was assessed using transcranial magnetic stimulation (TMS), fMRI with a motor-task paradigm, and diffusion tensor imaging (DTI) tractography. TMS revealed that both twins presented the same unexpected activation and inhibition of both motor cortices during volitional unilateral fine hand movement. The right ipsilateral corticospinal tract was weaker than the left contralateral one. The motor-task fMRI identified activation in the left primary motor cortex and bilateral secondary motor areas during right-hand (dominant) movement and activation in the bilateral primary motor cortex and secondary motor areas during left-hand movement. Based on DTI tractography, both twins showed a significantly lower streamline count (number of fibers) in the right corticospinal tract compared with a control group, which was not the case for the left corticospinal tract. Neither twin reported any difficulty in conducting fine motor movements during their activities of daily living. The combination of TMS and advanced neuroimaging techniques identified an atypical motor control organization that might be influenced by genetic factors. This combination emphasizes that activation of the unilateral uncrossed pyramidal tract represents an alternative scheme to a "failure" of building a standard pattern but may not necessarily lead to disability.

Assessing the efficacy of a structured stress management program in reducing stress and climacteric symptoms in peri- and postmenopausal women.

To evaluate the effectiveness of a structured education program on lifestyle habits, which is also incorporating teaching on deep breathing, progressive muscle relaxation, and guided visualization, in the control of various components of the climacteric symptomatology in peri- and postmenopausal women. Sixty-one women aged 40-65 years with varying climacteric and stress symptoms were included in this study. Women were randomly assigned to the intervention group (31) or the control group (30). The intervention group followed an 8-week stress management program. The following parameters were assessed at baseline and at the end of the 8-week follow-up period in both groups: climacteric symptoms (Green Climacteric Scale (GCS)), sleep quality (Pittsburg Sleep Quality Index (PSQI)), mood status (Depression-Anxiety-Stress Scale), self-esteem (Rosenberg Self-esteem Scale), and health-related control (health locus of control (HLC)). A mixed-model ANOVA showed significant time × group × GCS interaction (within subjects: F = 23.830, p value<0.001; between subjects: F = 39.078, p value<0.001). With regard to HLC, there was a non-significant between subjects but a significant within-subjects effect (HLC × group × time, F = 3.848, p value = 0.024). Regarding DASS scores, there was a significant between-subjects' effect (F = 10.258, p value = 0.003) but a non-significant within-subjects' effect. With regard to PSQI, the analysis showed significant within-subjects' effects (PSQI × group × time: F = 4.691, p value = 0.003) and non-significant between-subjects' effects (F = 0.022, p = 0.883). Finally, regarding RSS, there was a significant within-subjects' (RSS × group × time, F = 4.183, p value = 0.029) but non-significant between-subjects' effect (F = 1.582, p value = 0.213). Stress management may offer an alternative approach to the management of climacteric symptoms.

A Comparison of the Greek ACE-III, M-ACE, ACE-R, MMSE, and ECAS in the Assessment and Identification of Alzheimer's Disease.

OBJECTIVE: This study aimed to adapt the Addenbrooke's Cognitive Examination-III (ACE-III) and Mini-Addenbrooke's Cognitive Examination (M-ACE) into Greek and then to examine the convergent validity against their predecessors Addenbrooke's Cognitive Examination-Revised (ACE-R) and Mini-Mental State Examination (MMSE) in a Greek population. Moreover, a primary aim was to appraise the utility of each screen by conducting a comparison of the psychometric properties of ACE-III, M-ACE, ACE-R, MMSE, and the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis (ALS) Screen (ECAS) in detecting Alzheimer's disease (AD). METHODS: Forty patients with AD were recruited and matched with 38 controls. Bayesian Pearson's correlation analysis was conducted to examine the convergent validity. Receiver operating characteristic curve analysis was implemented to appraise the sensitivity and specificity of the tests in detecting AD. RESULTS: The ACE-III, M-ACE, and the ECAS scores robustly correlated with ACE-R and MMSE. The ACE-III and the ECAS-ALS Non-Specific score were the most sensitive and specific tools in detecting AD, closely followed by ECAS Total score and M-ACE. Only ECAS Total score correlated with the duration of disease. The ECAS scores were more resilient to ceiling effects than the other screens. M-ACE produced fewer ceiling effects than MMSE. CONCLUSION: The Greek ACE-III and M-ACE were successfully adapted and showed good convergent validity against their predecessors. They showed very good psychometric properties in detecting AD and may be considered in hectic clinical settings. ECAS Total score and ECAS-ALS Non-Specific showed comparable psychometric properties in the detection of AD and may be considered in polypathological clinics where motor impairments are common.

Mini-Mental State Examination: Greek Normative Data Stratified by Age and Education in a Large Sample of 925 Community-Dwelling Healthy Participants.

BACKGROUND: Cognitive screening measures are widely administered in everyday clinical practice in different geriatric settings. Despite the presence of several extended-like screening tests, Mini-Mental State Examination (MMSE) continues to be largely used not only by neuropsychologists, neurologists, and psychiatrists but also by general practitioners and other health-related specialties. AIM: We herein provide normative data for the MMSE in a large sample of community-dwelling healthy participants aged over 50 years old stratified by age and education. MATERIAL AND METHODS: The sample included 925 community-dwelling healthy participants (age range: 50-91 years) of both genders (231 males/694 females) with different educational level (range: 1-16 years). Demographic-related effects were examined for the total MMSE score using hierarchical regression analysis; normative data are presented in mean ± standard deviation and percentile ranks and divided into seven overlapping age tables with different midpoints at 55, 60, 65, 70, 75, 80, and 85 years using the overlapping cell procedure. RESULTS: Initial analysis did not show any effect of gender but revealed significant correlation between age, education, and total MMSE. Hierarchical regression analysis revealed that education significantly accounted for 17.3% of the total variance in the MMSE with age adding a significant 7.4% to the final model (adjusted R2 = 0.246, F = 151.872, p < 0.001; age: ß = -0.286, p < 0.001; education: ß = 0.332, p < 0.001). The sample was stratified according to the overlapping cell procedure with regard to age (age groups: 50-60, 55-65, 60-70, 65-75, 70-80, 75-85, 80-91); four educational levels were considered: 1-5, 6-9, 10-12, and 13-16 years. CONCLUSIONS: Current normative data for the Greek version of the MMSE are provided as a useful set of norms for clinical and research practice.

A New Preprocedural Score to Predict Bleeding Complications of Endovascular Interventions for Peripheral Artery Disease.

Purpose: To investigate the bleeding complications associated with endovascular therapy (EVT) for peripheral artery disease (PAD) and develop a dedicated peripheral bleeding score (PBS). Materials and Methods: This prospective, single-center study enrolled 530 patients (mean age 67.6±9.8 years; 396 men) undergoing endovascular procedures between August 2016 and July 2018 for chronic PAD. Primary endpoints were the incidence of 30-day bleeding complications [minor and major (prolonging hospitalization, causing permanent sequelae, or resulting in death)], the identification of factors associated with bleeding events, and the development of a dedicated PBS based on univariate and multivariate analysis. Hazard ratios (HR) and 95% confidence intervals (CI) are reported. The HAS-BLED score was compared with the PBS. Results: The overall peripheral bleeding complication rate was 3.8% (20/530), of which 3.2% (17/530) were major and included 4 (0.7%) active retroperitoneal bleeding events and 13 (2.4%) pseudoaneurysms. The annualized incidences of overall bleeding and major bleeding complications were 1.9% and 1.6%, respectively. Multivariable regression analysis identified age ≥75 as a correlate of significantly increased bleeding risk (HR 3.32, 95% CI 1.12 to 9.80, p<0.02). Male gender (HR 0.193, 95% CI 0.49 to 0.75, p<0.001) and statin therapy (HR 0.245, 95% CI 0.08 to 0.71, p=0.01) were correlated with a significantly decreased bleeding risk. Based on the regression analysis findings an 8-point PBS was developed, demonstrating 75.0% sensitivity and 78.4% specificity in detecting bleeding complications. The HAS-BLED score failed to identify 30-day bleeding events. Conclusion: The annualized incidence of bleeding complications associated with peripheral EVT was low. Advanced age and female sex were correlated with increased bleeding risk. The PBS demonstrated satisfactory statistical performance and could be considered for inclusion in the preprocedural endovascular checklist to help optimize intra- and postprocedural care.

Differential Effect of Demographics, Processing Speed, and Depression on Cognitive Function in 755 Non-demented Community-dwelling Elderly Individuals.

BACKGROUND: Several factors may account for inter- and intra-individual variability in cognitive functions, including age, gender, education level, information processing speed, and mood. OBJECTIVE: To evaluate the combined contribution of demographic factors, information processing speed, and depressive symptoms to scores on several diagnostic cognitive measures that are commonly used in geriatric neuropsychological practice in Greece. METHODS: Using a cross-sectional study, we established a multivariate general linear model and analyzed the predictive role of age, gender, education, information processing speed (Trail Making Test-Part A), and depressive symptoms (Geriatric Depression Scale-15 Items) on measures of general cognitive status (Mini-Mental State Examination), verbal memory (Rey Auditory Verbal Learning Test), language (Confrontation Naming), and executive functions (Category and Phonemic Fluency, Trail Making Test-Part B) for a sample of 755 healthy, community-dwelling Greek individuals aged 50 to 90 years. RESULTS: Participant factors significantly but differentially contributed to cognitive measures. Demographic factors and information processing speed emerged as the significant predictors for the majority of the cognitive measures (Mini-Mental State Examination; Rey Auditory Verbal Learning Test; Confrontation Naming; Category and Phonemic Fluency; Trail Making Test-Part B), whereas depressive symptoms significantly predicted verbal memory and semantic fluency measures (Rey Auditory Verbal Learning Test and Category Fluency). CONCLUSIONS: Clinicians should consider participant demographics, underlying slowing of processing speed, and depressive symptoms as potential confounding factors in cognitive measures. Our findings may explain the observed inter- and intra-individual variability in cognitive functions in the elderly population.

Ipsilateral and contralateral cerebro-cerebellar white matter connections: A diffusion tensor imaging study in healthy adults.

BACKGROUND AND PURPOSE: The cerebellum has a pivotal role in regulating human behavior; yet whether this function is mediated only through contralateral cerebro-cerebellar pathways is under-investigated. Thus, we examined feed-backward and feed-forward ipsilateral and contralateral cerebro-cerebellar connections using a detereministic diffusion tensor imaging (DTI) algorithm, the robustness of which was also estimated using phantom DTI data. MATERIALS AND METHODS: Fifty-one healthy controls (22-60 years old; 15 males/36 females) were scanned in a 3T MRI scanner with a 30-direction DTI sequence. Multiple region-of-interest (ROI) method was applied for the reconstruction of the ipsilateral and contralateral (based on cerebellar seed ROI) fronto-ponto-cerebellar (FPC), parieto-ponto-cerebellar (PPC), temporo-ponto-cerebellar (TPC), occipito-ponto-cerebellar (OPC) and dentate-rubro-thalamo-cortical (DRTC) tract bilaterally using the Brainance DTI Suite. A realistic diffusion MR phantom was used to evaluate the fiber tracking methodology for 16 fibers containing crossing, kissing, splitting and bending configurations. RESULTS: Both contralateral and ipsilateral FPC, PPC, OPC and ipsilateral DRTC tracts were successfully reconstructed; the contralateral DRTC tract was not reconstructed in all subjects. Also, the TPC tract was not reproduced in several subjects mostly regarding the contralateral connection. Descriptive DTI measures (number of fibers, fractional anisotropy, radial and axial diffusivity) are presented for each tract. Regarding phantom data, Brainance DTI Suite returned a dataset of 16 fibers that almost perfectly matched the 16 ground truth fibers. CONCLUSIONS: We identified ipsilateral and contralateral connections using a clinically applicable DTI sequence, a robust deterministic algorithm and an unbiased methodology, which can be applied in daily practice in different brain pathologies.

Endogenous sex hormones and memory performance in middle-aged Greek women with subjective memory complaints.

The changing hormonal milieu during the menopausal transition may contribute to the development of memory disorders. We aimed to assess the association of sex hormones with memory function in a sample of Greek middle-aged women. This pilot study included 44 women with subjective memory complaints. Memory performance was evaluated using the Hopkins Verbal Learning Test (HVLT), the Brief Visuospatial Memory test (BVMT), and the verbal digits backwards test (VSPAN), to assess verbal, visuospatial, and working memory performance, respectively. Menopausal symptoms were assessed using the Green Climacteric Scale. VSPAN backwards scores were positively associated with log-transformed free androgen index (logFAI), in models adjusted for age, education, log-transformed free estrogen index (logFEI), hypertension, and the intensity of menopausal symptoms. BVMT total scores were predicted by logFAI (b-coefficient = 0.424, p value = 0.002), education, and combined climacteric symptomatology, in a model adjusted for age, logFEI, and hypertension. Women with circulating estradiol above the median value of 10 pg/mL had better total HTLV total scores compared to women with estradiol values below the median (HTLV total scores, estradiol ≤ 10 pg/mL vs. > 10 pg/mL: 24.2 ± 3.6 vs. 30.0 ± 7.9, p value = 0.007 unadjusted). This association was affected by education and remained independent of menopausal symptoms and testosterone levels, education, and hypertension (model R 2 = 22.3%; b-coefficient = 0.318, p value = 0.024). Endogenous total estradiol is associated with verbal episodic memory, while logFAI is associated with working memory performance and visuospatial episodic memory in this sample of postmenopausal women. These associations were not influenced by age, education, or menopausal symptoms. Larger studies are necessary to evaluate the significance of our findings.

Pain modulation is affected differently in medication-overuse headache and chronic myofascial pain - A multimodal MRI study.

Background Neuroimaging studies revealed structural and functional changes in medication-overuse headache (MOH), but it remains unclear whether similar changes could be observed in other chronic pain disorders. Methods In this cross-sectional study, we investigated functional connectivity (FC) with resting-state functional magnetic resonance imaging (fMRI) and white matter integrity using diffusion tensor imaging (DTI) to measure fractional anisotropy (FA) and mean diffusivity (MD) in patients with MOH ( N = 12) relative to two control groups: patients with chronic myofascial pain (MYO; N = 11) and healthy controls (CN; N = 16). Results In a data-driven approach we found hypoconnectivity in the fronto-parietal attention network in both pain groups relative to CN (i.e. MOH < CN and MYO < CN). In contrast, hyperconnectivity in the saliency network (SN) was detected only in MOH, which correlated with FA in the insula. In a seed-based analysis we investigated FC between the periaqueductal grey (PAG) and all other brain regions. In addition to overlapping hyperconnectivity seen in patient groups (relative to CN), MOH had a distinct connectivity pattern with lower FC to parieto-occipital regions and higher FC to orbitofrontal regions compared to controls. FA and MD abnormalities were mostly observed in MOH, involving the insula. Conclusions Hyperconnectivity within the SN along with associated white matter changes therein suggest a particular role of this network in MOH. In addition, abnormal connectivity between the PAG and other pain modulatory (frontal) regions in MOH are consistent with dysfunctional central pain control.

Verbal and Figural Fluency in Temporal Lobe Epilepsy: Does Hippocampal Sclerosis Affect Performance?

BACKGROUND AND OBJECTIVES: Clinicians commonly use verbal and nonverbal measures to test fluency in patients with epilepsy, either during routine cognitive assessment or as part of pre- and postsurgical evaluation. We hypothesized that patients with mesial temporal lobe epilepsy (TLE) with hippocampal sclerosis would perform worse than patients with lateral TLE in both verbal and design fluency. METHODS: We assessed semantic, phonemic, and nonverbal fluency in 49 patients with TLE: 31 with lateral TLE and 18 with mesial TLE plus hippocampal sclerosis. We also gave non-fluency cognitive measures: psychomotor speed, attentional set shifting, selective attention, abstract reasoning, verbal and visual episodic memory, and incidental memory. RESULTS: Patients with mesial TLE performed significantly worse on figural fluency than patients with lateral TLE. Even though group differences on verbal fluency measures were not significant, the patients with mesial TLE had a pattern of poorer performance. The patients with mesial TLE scored significantly worse on measures of selective attention, verbal episodic memory, and incidental memory. CONCLUSIONS: Our study underlines differences in cognitive function between patients with mesial and lateral TLE, particularly in figural fluency. Although we cannot directly assess the role of the hippocampus in cognitive aspects of creative and divergent thinking related to figural fluency, the cognitive discrepancies between these two TLE groups could be ascribed to the mesial TLE hippocampal pathology shown in our study and addressed in the literature on hippocampal involvement in divergent thinking. Our findings could benefit cognitive rehabilitation programs tailored to the needs of patients with TLE.

Clinical and cognitive implications of cerebrospinal fluid oligoclonal bands in multiple sclerosis patients.

The presence of cerebrospinal fluid oligoclonal bands (CSF-OCB) in Caucasian patients with multiple sclerosis (MS) is supportive of diagnosis, though the relation with patients' clinical and specifically cognitive features has never been established or thoroughly examined. Thus, we investigated the clinical and for the first time the cognitive profile of MS patients in relation to CSF-OCB. We studied 108 patients with and without OCB and recorded demographic characteristics and detailed clinical data. A comprehensive neuropsychological battery covering different cognitive domains (attention/processing speed, memory, perception/constructions, reasoning, executive functions) was administered to MS patients and 142 demographically related healthy controls (HC). We did not find any significant differences between patients with and without OCB on demographic and clinical parameters (p > 0.05), including subtype and brain neuroimaging findings. Results revealed significantly higher cognitive scores in HC compared to both OCB subgroups, with more widespread cognitive changes in patients with OCB. Analysis between OCB subgroups showed significantly worse performance in patients with OCB on visual memory (Rey's complex figure test-recall; p = 0.006). Concluding, the presence of CSF-OCB in our MS patients tends to be related to more widespread cognitive changes, specifically worse visual memory. Future longitudinal studies in different populations are warranted to better clarify the clinical and cognitive characteristics related to CSF-OCB which could serve as early biomarker in disease monitoring.

Neurocognitive impairment in Whipple disease with central nervous system involvement.

Young-onset dementias pose a major challenge to both clinicians and researchers. Cognitive decline may be accompanied by systemic features, leading to a diagnosis of "dementia plus" syndromes. Whipple disease is a rare systemic illness characterized by arthralgias, chronic diarrhea, weight loss, fever, and abdominal pain. Central nervous system involvement, including severe cognitive deterioration, may precede systemic manifestations, appear during the course of the disease, or even be the only symptom. We report a previously highly functional 48-year-old man whom we first suspected of having early-onset neurodegenerative dementia but then diagnosed with Whipple disease based on a detailed clinical and laboratory evaluation. Initial neuropsychological evaluation revealed marked impairment in the patient's fluid intelligence and severe cognitive deficits in his information processing speed, complex attention, memory, visuomotor and construction dexterities, problem solving, and executive functions. At neuropsychological follow-up 21 months later, his information processing speed had improved only slightly and deficits persisted in his other cognitive functions. Repeat brain magnetic resonance imaging at that time showed that he had responded to antibiotic treatment. Because Whipple disease can cause young-onset "dementia plus" syndromes that may leave patients with neurocognitive deficits even after apparently successful treatment, we recommend comprehensive neuropsychological assessment for early detection of residual and reversible cognitive processes and evaluation of treatment response.