Neuroinflammation is linked to dementia risk in Parkinson's disease.

The development of dementia is a devastating aspect of Parkinson's disease (PD), affecting nearly half of patients within 10 years post-diagnosis. For effective therapies to prevent and slow progression to PD dementia (PDD), the key mechanisms that determine why some people with PD develop early dementia, while others remain cognitively unaffected, need to be understood. Neuroinflammation and tau protein accumulation have been demonstrated in post-mortem PD brains, and in many other neurodegenerative disorders leading to dementia. However, whether these processes mediate dementia risk early on in the PD disease course is not established. To this end, we used PET neuroimaging with 11C-PK11195 to index neuroinflammation and 18F-AV-1451 for misfolded tau in early PD patients, stratified according to dementia risk in our 'Neuroinflammation and Tau Accumulation in Parkinson's Disease Dementia' (NET-PDD) study. The NET-PDD study longitudinally assesses newly-diagnosed PD patients in two subgroups at low and high dementia risk (stratified based on pentagon copying, semantic fluency, MAPT genotype), with comparison to age- and sex-matched controls. Non-displaceable binding potential (BPND) in 43 brain regions (Hammers' parcellation) was compared between groups (pairwise t-tests), and associations between BPND of the tracers tested (linear-mixed-effect models). We hypothesized that people with higher dementia risk have greater inflammation and/or tau accumulation in advance of significant cognitive decline. We found significantly elevated neuroinflammation (11C-PK11195 BPND) in multiple subcortical and restricted cortical regions in the high dementia risk group compared with controls, while in the low-risk group this was limited to two cortical areas. The high dementia risk group also showed significantly greater neuroinflammation than the low-risk group concentrated on subcortical and basal ganglia regions. Neuroinflammation in most of these regions was associated with worse cognitive performance (Addenbrooke's Cognitive Examination-III score). Overall neuroinflammation burden also correlated with serum levels of pro-inflammatory cytokines. In contrast, increases in 18F-AV-1451 (tau) BPND in PD versus controls were restricted to subcortical regions where off-target binding is typically seen, with no relationship to cognition found. Whole-brain 18F-AV-1451 burden correlated with serum phosphorylated tau181 levels. Although there was minimal regional tau accumulation in PD, regional neuroinflammation and tau burden correlated in PD participants, with the strongest association in the high dementia risk group, suggesting possible co-localization of these pathologies. In conclusion, our findings suggest that significant regional neuroinflammation in early PD might underpin higher risk for PDD development, indicating neuroinflammation as a putative early modifiable aetiopathological disease factor to prevent or slow dementia development using immunomodulatory strategies.

Attitudes toward uterus transplantation. An option for motherhood?

INTRODUCTION: Uterus transplantation is a novel surgical procedure that allows women with absolute uterine factor infertility to carry a pregnancy and give birth. While previous studies have explored the attitudes of women with absolute uterine factor infertility toward uterus transplantation, none have surveyed and compare their views with other groups of interest (Morris syndrome women, relatives of Morris syndrome and Rokitansky syndrome women, infertile women and women of childbearing age) in the same sociocultural setting. The objective of this study was to evaluate attitudes and insights regarding uterus transplantation among women with Rokitansky syndrome and other groups of interest. MATERIAL AND METHODS: We designed a cross-sectional study including five groups of women: women with Rokitansky syndrome, women with Morris syndrome, relatives of women with Morris and Rokitansky syndrome, infertile women, and childbearing-age women. We conducted an online survey through the REDCap platform. The link was distributed by mail, telephone and in hospital outpatient visits. Baseline demographic information was assessed and information regarding motherhood preferences, attitude toward uterus transplantation, preferred uterus graft and perception of risk of the procedure was collected. RESULTS: We obtained a total of 200 responses, with a mean participant age of 34.5 years (±9.8). Overall, 17.5% (n = 35) were women with Rokitansky syndrome, 5.5% (n = 11) Morris syndrome women, 21.5% (n = 43) infertile women, 26.5% (n = 53) relatives of Morris and Rokitansky syndrome women and 29% (n = 58) childbearing-age women. 71.5% of women with Rokitansky syndrome would undergo uterus transplantations ahead of adoption and surrogacy with no statistically significant differences found between groups. Overall, more than one-half (58%) would prefer deceased over living donor. CONCLUSIONS: The results of this survey indicate that uterus transplantation is desired by most women who would benefit from the procedure, including those with either Morris syndrome or absolute uterine factor infertility. This was also the preferred option for motherhood if absolute uterine factor infertility was diagnosed among surveyed infertility patients or women of childbearing age with no known reproductive difficulties. Overall, most respondents indicated a deceased donor was preferable to a living donor and that patients may not be sufficiently aware of potential risks of uterus transplantation, highlighting the importance of adequate counseling by medical providers.

The Endotoxin Hypothesis of Parkinson's Disease.

The endotoxin hypothesis of Parkinson's disease (PD) is the idea that lipopolysaccharide (LPS) endotoxins contribute to the pathogenesis of this disorder. LPS endotoxins are found in, and released from, the outer membrane of Gram-negative bacteria, for example in the gut. It is proposed that gut dysfunction in early PD leads to elevated LPS levels in the gut wall and blood, which promotes both α-synuclein aggregation in the enteric neurons and a peripheral inflammatory response. Communication to the brain via circulating LPS and cytokines in the blood and/or the gut-brain axis leads to neuroinflammation and spreading of α-synuclein pathology, exacerbating neurodegeneration in brainstem nuclei and loss of dopaminergic neurons in the substantia nigra, and manifesting in the clinical symptoms of PD. The evidence supporting this hypothesis includes: (1) gut dysfunction, permeability, and bacterial changes occur early in PD, (2) serum levels of LPS are increased in a proportion of PD patients, (3) LPS induces α-synuclein expression, aggregation, and neurotoxicity, (4) LPS causes activation of peripheral monocytes leading to inflammatory cytokine production, and (5) blood LPS causes brain inflammation and specific loss of midbrain dopaminergic neurons, mediated by microglia. If the hypothesis is correct, then treatment options might include: (1) changing the gut microbiome, (2) reducing gut permeability, (3) reducing circulating LPS levels, or (4) blocking the response of immune cells and microglia to LPS. However, the hypothesis has a number of limitations and requires further testing, in particular whether reducing LPS levels can reduce PD incidence, progression, or severity. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort.

BACKGROUND: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. OBJECTIVE: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. METHODS: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype-phenotype relationships were analyzed. RESULTS: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. CONCLUSIONS: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

GBA and APOE Impact Cognitive Decline in Parkinson's Disease: A 10-Year Population-Based Study.

BACKGROUND: Common genetic variance in apolipoprotein E (APOE), ß-glucocerebrosidase (GBA), microtubule-associated protein tau (MAPT), and α-synuclein (SNCA) has been linked to cognitive decline in Parkinson's disease (PD), although studies have yielded mixed results. OBJECTIVES: To evaluate the effect of genetic variants in APOE, GBA, MAPT, and SNCA on cognitive decline and risk of dementia in a pooled analysis of six longitudinal, non-selective, population-based cohorts of newly diagnosed PD patients. METHODS: 1002 PD patients, followed for up to 10 years (median 7.2 years), were genotyped for at least one of APOE-ε4, GBA mutations, MAPT H1/H2, or SNCA rs356219. We evaluated the effect of genotype on the rate of cognitive decline (Mini-Mental State Examanation, MMSE) using linear mixed models and the development of dementia (diagnosed using standardized criteria) using Cox regression; multiple comparisons were accounted for using Benjamini-Hochberg corrections. RESULTS: Carriers of APOE-ε4 (n = 281, 29.7%) and GBA mutations (n = 100, 10.3%) had faster cognitive decline and were at higher risk of progression to dementia (APOE-ε4, HR 3.57, P < 0.001; GBA mutations, HR 1.76, P = 0.001) than non-carriers. The risk of cognitive decline and dementia (HR 5.19, P < 0.001) was further increased in carriers of both risk genotypes (n = 23). No significant effects were observed for MAPT or SNCA rs356219. CONCLUSIONS: GBA and APOE genotyping could improve the prediction of cognitive decline in PD, which is important to inform the clinical trial selection and potentially to enable personalized treatment © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Black cohosh efficacy and safety for menopausal symptoms. The Spanish Menopause Society statement.

OBJECTIVE: The increasing interest in Western countries regarding phytotherapy use to treat menopause-related symptoms has led the Spanish Menopause Society (AEEM) to update its position statement performed in 2009 on the role of black cohosh (Cimicifuga racemosa) for the treatment of menopausal symptoms. MATERIAL AND METHODS: A panel of experts from both clinical and research backgrounds were assembled to investigate the best available evidence. Selected studies were obtained by an electronic search, including the Internet search engines MEDLINE-Pubmed (1997-December 2021) and the Cochrane Controlled Trials Register. RESULTS: Most of the well-designed studies published in recent years have been conducted with the isopropanolic extract of black cohosh/C. racemosa. The most common dose is 40 mg/day capable of achieving a significant reduction in hot flushes (particularly in women with intense hot flushes) and an improvement in mood. Used at the recommended doses, C. racemose produces no significant adverse reactions. CONCLUSION: Black cohosh is an effective and safe treatment option for the relieving of vasomotor symptoms. Finally, further clinical trials with sufficient patient enrollment and longer study follow-up are needed.

Impact of Severe Acute Respiratory Syndrome Coronavirus 2 Infection on Pregnancy Outcomes: A Population-based Study.

BACKGROUND: We performed a population-based study to describe the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on pregnancy outcomes. METHODS: This prospective, population-based study included pregnant women who consecutively presented at first/second trimester visits or at delivery at 3 hospitals in Barcelona, Spain. SARS-CoV-2 antibodies (immunoglobulin [Ig] G and IgM/IgA) were measured in all participants, and nasopharyngeal real-time polymerase chain reaction (RT-PCR) was performed at delivery. The primary outcome was a composite of pregnancy complications in SARS-CoV-2-positive vs negative women that included miscarriage, preeclampsia, preterm delivery, perinatal death, small-for-gestational-age newborn, or neonatal admission. Secondary outcomes were components of the primary outcome plus abnormal fetal growth, malformation, or intrapartum fetal distress. Outcomes were also compared between positive symptomatic and positive asymptomatic SARS-CoV-2 women. RESULTS: Of 2225 pregnant women, 317 (14.2%) were positive for SARS-CoV-2 antibodies (n = 314, 99.1%) and/or RT-PCR (n = 36, 11.4%). Among positive women, 217 (68.5%) were asymptomatic, 93 (29.3%) had mild coronavirus disease 2019 (COVID-19), and 7 (2.2%) had pneumonia, of whom 3 required intensive care unit admission. In women with and without SARS-CoV-2 infection, the primary outcome occurred in 43 (13.6%) and 268 (14%), respectively (risk difference, -0.4%; 95% confidence interval, -4.1% to 4.1). Compared with noninfected women, those with symptomatic COVID-19 had increased rates of preterm delivery (7.2% vs 16.9%, P = .003) and intrapartum fetal distress (9.1% vs 19.2%, P = .004), while asymptomatic women had rates that were similar to those of noninfected cases. Among 143 fetuses from infected mothers, none had anti-SARS-CoV-2 IgM/IgA in cord blood. CONCLUSIONS: The overall rate of pregnancy complications in women with SARS-CoV-2 infection was similar to that of noninfected women. However, symptomatic COVID-19 was associated with modest increases in preterm delivery and intrapartum fetal distress.

T lymphocyte senescence is attenuated in Parkinson's disease.

BACKGROUND: Immune involvement is well-described in Parkinson's disease (PD), including an adaptive T lymphocyte response. Given the increasing prevalence of Parkinson's disease in older age, age-related dysregulation of T lymphocytes may be relevant in this disorder, and we have previously observed changes in age-associated CD8+ T cell subsets in mid-stage PD. This study aimed to further characterise T cell immunosenescence in newly diagnosed PD patients, including shifts in CD4+ and CD8+ subpopulations, and changes in markers of cellular ageing in CD8+ T lymphocytes. METHODS: Peripheral blood mononuclear cells were extracted from the blood of 61 newly diagnosed PD patients and 63 age- and sex-matched controls. Flow cytometric analysis was used for immunophenotyping of CD8+ and CD4+ lymphocyte subsets, and analysis of recent thymic emigrant cells. Telomere length within CD8+ T lymphocytes was assessed, as well as the expression of the telomerase reverse transcriptase enzyme (hTERT), and the cell-ageing markers p16INK4a and p21CIP1/Waf1. RESULTS: The number of CD8+ TEMRA T cells was found to be significantly reduced in PD patients compared to controls. The expression of p16INK4a in CD8+ lymphocytes was also lower in patients versus controls. Chronic latent CMV infection was associated with increased senescent CD8+ lymphocytes in healthy controls, but this shift was less apparent in PD patients. CONCLUSIONS: Taken together, our data demonstrate a reduction in CD8+ T cell replicative senescence which is present at the earliest stages of Parkinson's disease.

The Gastrointestinal Dysfunction Scale for Parkinson's Disease.

BACKGROUND: Gastrointestinal dysfunction is an important feature of Parkinson's disease (PD), and there is increasing evidence that it may play a key role in the disease process. However, its assessment is limited by different tools and underlying differences in diagnostic criteria for gastrointestinal dysfunction. To date, there is no psychometric instrument for quantitative evaluation of gastrointestinal symptoms specifically designed for use in PD. OBJECTIVE: The objective of this study was to develop a self-report questionnaire-based instrument, the Gastrointestinal Dysfunction Scale for Parkinson's Disease, and to evaluate its psychometric properties. METHODS: We performed a literature review and conducted 3 focus groups to develop the Gastrointestinal Dysfunction Scale for Parkinson's Disease. Three hundred and sixteen patients with PD and 55 controls completed the Gastrointestinal Dysfunction Scale for Parkinson's Disease, the Non-Motor Symptom Scale, the Hospital Anxiety and Depression Scale, and a stool diary adapted from the Bristol Stool Chart. RESULTS: The Gastrointestinal Dysfunction Scale for Parkinson's Disease demonstrated good internal consistency (Cronbach's α = 0.82) and test-retest stability (0.79 < ICCs > 0.94). Correlation analyses supported good convergent and divergent validity. Receiver operating characteristic analysis demonstrated that a cutoff score of ≥9 on the Gastrointestinal Dysfunction Scale for Parkinson's Disease Constipation subscale discriminates between PD patients with and without constipation. CONCLUSIONS: The Gastrointestinal Dysfunction Scale for Parkinson's Disease is a novel disease-specific self-report tool to quantitatively assess the presence and severity of gastrointestinal dysfunction features in patients with PD, with strong reliability and validity. Further longitudinal studies are needed to demonstrate its utility in tracking gastrointestinal dysfunction in PD clinical cohorts. © 2021 International Parkinson and Movement Disorder Society.

Formation of Multicolor Nanogels Based on Cationic Polyfluorenes and Poly(methyl vinyl ether-alt-maleic monoethyl ester): Potential Use as pH-Responsive Fluorescent Drug Carriers.

In this study, we employed the copolymer poly(methyl vinyl ether-alt-maleic monoethyl ester) (PMVEMA-Es) and three fluorene-based cationic conjugated polyelectrolytes to develop fluorescent nanoparticles with emission in the blue, green and red spectral regions. The size, Zeta Potential, polydispersity, morphology, time-stability and fluorescent properties of these nanoparticles were characterized, as well as the nature of the interaction between both PMVEMA-Es and fluorescent polyelectrolytes. Because PMVEMA-Es contains a carboxylic acid group in its structure, the effects of pH and ionic strength on the nanoparticles were also evaluated, finding that the size is responsive to pH and ionic strength, largely swelling at physiological pH and returning to their initial size at acidic pHs. Thus, the developed fluorescent nanoparticles can be categorized as pH-sensitive fluorescent nanogels, since they possess the properties of both pH-responsive hydrogels and nanoparticulate systems. Doxorubicin (DOX) was used as a model drug to show the capacity of the blue-emitting nanogels to hold drugs in acidic media and release them at physiological pH, from changes in the fluorescence properties of both nanoparticles and DOX. In addition, preliminary studies by super-resolution confocal microscopy were performed, regarding their potential use as image probes.

Impact of GBA1 variants on long-term clinical progression and mortality in incident Parkinson's disease.

INTRODUCTION: Variants in the GBA1 gene have been identified as a common risk factor for Parkinson's disease (PD). In addition to pathogenic mutations (those associated with Gaucher disease), a number of 'non-pathogenic' variants also occur at increased frequency in PD. Previous studies have reported that pathogenic variants adversely affect the clinical course of PD. The role of 'non-pathogenic' GBA1 variants on PD course is less clear. In this study, we report the effect of GBA1 variants in incident PD patients with long-term follow-up. METHODS: The study population consisted of patients in the Cambridgeshire Incidence of Parkinson's disease from General Practice to Neurologist and Parkinsonism: Incidence, Cognition and Non-motor heterogeneity in Cambridgeshire cohorts. Patients were grouped into non-carriers, carriers of 'non-pathogenic' GBA1 variants and carriers of pathogenic GBA1 mutations. Survival analyses for time to development of dementia, postural instability and death were carried out. Cox regression analysis controlling for potential confounders were used to determine the impact of GBA1 variants on these outcome measures. RESULTS: GBA1 variants were identified in 14.4% of patients. Pathogenic and 'non-pathogenic' GBA1 variants were associated with the accelerated development of dementia and a more aggressive motor course. Pathogenic GBA1 variants were associated with earlier mortality in comparison with non-carriers, independent of the development of dementia. DISCUSSION: GBA1 variants, including those not associated with Gaucher disease, are common in PD and result in a more aggressive disease course.

Psychometric properties of the Portuguese version of the Yale Food Addiction Scale.

PURPOSE: Rising rates of obesity have been recently associated to the novel concept of food addiction (FA). The Yale Food Addiction Scale (YFAS) is the most widely used measure for examining FA (1) and analysis of its reliability and validity is expected to facilitate empirical research on the construct. Here, we tested the psychometric properties of a Portuguese version of the YFAS (P-YFAS), establishing its factor structure, reliability and construct validity. METHODS: Data were obtained from 468 Portuguese individuals, 278 sampled from non-clinical populations, and 190 among obese candidates for weight-loss surgery. A battery of self-report measures of eating behavior was applied. RESULTS: Confirmatory factor analysis verified a one-factor structure with acceptable fit, with item analysis suggesting the need to eliminate item 24 from the P-YFAS. Internal consistency (KR-20 = .82) and test-retest stability were adequate. Correlation analyses supported convergent and divergent validity of the P-YFAS, particularly in the clinical sample. Both FA symptom count and diagnosis, according to the P-YFAS, adequately discriminated between samples, with classification of FA met by 2.5 and 25.8% of the participants in the non-clinical and clinical samples, respectively. CONCLUSIONS: These findings reinforce the use of P-YFAS in non-clinical and clinical populations. Future directions for extending YFAS validation are discussed.

Approach to the management of pregnancy in patients with pseudoxanthoma elasticum: a review.

Management of pregnancy in patients with rare diseases is often guided by incomplete knowledge because of a lack of high-quality case control studies or single-centre experience. Pseudoxanthoma elasticum (PXE) is an autosomal recessive metabolic disorder that results in calcification of elastic fibres of the skin, retina, and arteries, leading to skin lesions, eventual central visual loss, and potential arterial insufficiency in most patients. It is due to mutations in ABCC6, which encodes the eponymous membrane transport protein. We review the literature on pregnancy in PXE, including the effects of the diseases on pregnancy and its complications, the effect of PXE on the foetus, and the effects of pregnancy on PXE, and conclude that in the majority of pregnancies in women with PXE, the outcome for mother, baby, and the disease is uneventful. We also provide recommendations for managing pregnancy in PXE.

The dilemma between milestones of progression versus clinical scales in Parkinson's disease.

There are significant challenges in accurately documenting the progression of Parkinson's disease (PD). The disease course is highly heterogeneous, there are no validated biomarkers, and we are reliant on repeated clinical measures to assess disease state over time. Yet, the ability to chart disease progression accurately is vital in both observational and interventional study designs, where reliable measures are critical to determine whether an outcome has been met. In this chapter, we first discuss the natural history of PD, including the spectrum of clinical presentation and expected developments through the course of the disease. We then explore in detail the current strategies for measuring disease progression, which can be broadly divided into: (i) the use of quantitative clinical scales; and (ii) determination of the onset time of key milestones. We discuss the strengths and limitations of these approaches for use in clinical trials, with a particular focus on disease modification trials. The selection of outcome measures for a particular study will depend on multiple factors, but trial duration is an important determinant. Milestones are reached over a course of years rather than months, and hence clinical scales with sensitivity to change are needed for short-term studies. However, milestones represent important markers of disease stage which are not confounded by symptomatic therapies and are of critical relevance to the patient. Prolonged but low intensity follow-up beyond a limited period of treatment with a putative disease-modifying agent may allow milestones to be incorporated into evaluation of efficacy in a practical and cost-effective way.

Criterion and construct validity of the Beck Depression Inventory (BDI-II) to measure depression in patients with cancer: The contribution of somatic items.

Background/Objective: Screening for depression in patients with cancer can be difficult due to overlap between symptoms of depression and cancer. We assessed validity of the Beck Depression Inventory (BDI-II) in this population. Method: Data was obtained in an outpatient neuropsychiatry unit treating patients with and without cancer. Psychometric properties of the BDI-II Portuguese version were assessed separately in 202 patients with cancer, and 376 outpatients with mental health complaints but without cancer. Results: Confirmatory factor analysis suggested a three-factor structure model (cognitive, affective and somatic) provided best fit to data in both samples. Criterion validity was good for detecting depression in oncological patients, with an area under the ROC curve (AUC) of 0.85 (95% confidence interval [CI], 0.76-0.91). A cut-off score of 14 had sensitivity of 87% and specificity of 73%. Excluding somatic items did not significantly change the ROC curve for BDI-II (difference AUCs = 0.002, p=0.9). A good criterion validity for BDI-II was also obtained in the non-oncological population (AUC = 0.87; 95% CI 0.81-0.91), with a cut-off of 18 (sensitivity=84%; specificity=73%). Conclusions: The BDI-II demonstrated good psychometric properties in patients with cancer, comparable to a population without cancer. Exclusion of somatic items did not affect screening accuracy.

Cognitive and Motor Decline in Dementia with Lewy Bodies and Parkinson's Disease Dementia.

Background: There is a need to better understand the rate of cognitive and motor decline of Dementia with Lewy bodies (DLB) and Parkinson's disease Dementia (PDD). Objectives: To compare the rate of cognitive and motor decline in patients with DLB and PDD from the E-DLB Consortium and the Parkinson's Incidence Cohorts Collaboration (PICC) Cohorts. Methods: The annual change in MMSE and MDS-UPDRS part III was estimated using linear mixed regression models in patients with at least one follow-up (DLB n = 837 and PDD n = 157). Results: When adjusting for confounders, we found no difference in the annual change in MMSE between DLB and PDD (-1.8 [95% CI -2.3, -1.3] vs. -1.9 [95% CI -2.6, -1.2] [P = 0.74]). MDS-UPDRS part III showed nearly identical annual changes (DLB 4.8 [95% CI 2.1, 7.5]) (PDD 4.8 [95% CI 2.7, 6.9], [P = 0.98]). Conclusions: DLB and PDD showed similar rates of cognitive and motor decline. This is relevant for future clinical trial designs.

Two Sisters with Kallmann Syndrome, Gonadal Dysgenesis, and Multiple Neuromuscular and Endocrine Disorders: Report of Two Cases with Description of an Unusual Association.

Kallmann syndrome (KS) is an uncommon genetic disorder characterized by isolated congenital hypogonadotropic hypogonadism (CHH) and anosmia/hyposmia. KS originates from abnormal embryonic migration of olfactory axons and gonadotropin-releasing hormone (GnRH)-synthesizing neurons. It can be challenging to diagnose due to its heterogeneous clinical presentation and genes implied. Herein, we report a rare phenotype of KS in two sisters accompanied by a variety of nonreproductive disorders such as hypoparathyroidism, hypercortisolism, atrophy of the cerebellum, intellectual disability, and remarkably, ovarian dysgenesis. Additionally, both subjects present muscle weakness, exercise intolerance, marked hypotonia and seizures, being suspected, although not fully confirmed, mitochondrial encephalomyopathy. These cases illustrate the heterogeneous clinical presentation and the diagnostic difficulties often found in patients suffering from this condition. These clinical features have never been described before as associated with KS; therefore, we decided to report this novel KS phenotype.

Enhanced sweet taste perception in obesity: Joint analysis of gustatory data from multiple studies.

Introduction: While sweet taste perception is a potential determinant of feeding behavior in obesity, the supporting evidence is inconsistent and is typically associated with methodological limitations. Notably, possible associations between sweet taste perception and measures of food reward remain undetermined. Materials and methods: We conducted a cross-sectional analysis comparing 246 individuals with severe obesity and 174 healthy volunteers using a validated method for taste perception assessment. We included gustatory variables, namely intensity and pleasantness ratings of sour, salt, sweet, and bitter tastants, and taste thresholds assessed by electrogustometry. Reward-related feeding behavior, including hedonic hunger, food addiction, feeding behavior traits, and acceptance of foods and alcohol, was evaluated using self-rated scales for comparison with gustatory measures. Result: In logistic regressions adjusted for age, gender, educational level, and research center, we found that a greater likelihood of belonging to the obesity group was associated with higher sweet intensity ratings (OR = 1.4, P = 0.01), hedonic hunger, food addiction symptoms, restrained and emotional eating (1.7 < OR ≤ 4.6, all P ≤ 0.001), and lower alcohol acceptance (OR = 0.6, P = 0.0002). Using principal component analysis, we found that while hedonic hunger, food addiction, and emotional eating were strongly interrelated, they were not associated with sweet intensity perception that, in turn, had a closer relationship with alcohol acceptance and restrained eating. Conclusion: We found that individuals with obesity report higher sweet taste intensity ratings than healthy controls. Furthermore, while psychological measures of reward-related feeding behavior assess a common construct, sweet intensity perception may represent a different obesity-related dimension.