Risk of Cognitive Impairment in Patients With Parkinson’s Disease With Visual Hallucinations and Subjective Cognitive Complaints

Cognitive impairment; Parkinson's disease; Visual hallucinationsDeterioro cognitivo; Enfermedad de Parkinson; Alucinaciones visualesDeteriorament cognitiu; Malaltia de Parkinson; Al·lucinacions visualsBackground and Purpose Visual hallucinations (VH) and subjective cognitive complaints (SCC) are associated with cognitive impairment (CI) in Parkinson’s disease. Our aims were to determine the association between VH and SCC and the risk of CI development in a cohort of patients with Parkinson’s disease and normal cognition (PD-NC). Methods Patients with PD-NC (total score of >80 on the Parkinson’s Disease Cognitive Rating Scale [PD-CRS]) recruited from the Spanish COPPADIS cohort from January 2016 to November 2017 were followed up after 2 years. Subjects with a score of ≥1 on domain 5 and item 13 of the Non-Motor Symptoms Scale at baseline (V0) were considered as “with SCC” and “with VH,” respectively. CI at the 2-year follow-up (plus or minus 1 month) (V2) was defined as a PD-CRS total score of <81. Results At V0 (n=376, 58.2% males, age 61.14±8.73 years [mean±SD]), the frequencies of VH and SCC were 13.6% and 62.2%, respectively. VH were more frequent in patients with SCC than in those without: 18.8% (44/234) vs 4.9% (7/142), p<0.0001. At V2, 15.2% (57/376) of the patients had developed CI. VH presenting at V0 was associated with a higher risk of CI at V2 (odds ratio [OR]=2.68, 95% confidence interval=1.05–6.83, p=0.0.039) after controlling for the effects of age, disease duration, education, medication, motor and nonmotor status, mood, and PD-CRS total score at V0. Although SCC were not associated with CI at V2, presenting both VH and SCC at V0 increased the probability of having CI at V2 (OR=3.71, 95% confidence interval=1.36–10.17, p=0.011). Conclusions VH were associated with the development of SCC and CI at the 2-year follow-up in patients with PD-NC.The resources obtained for the development of this project have been obtained by the Degen Foundation (https://fundaciondegen.org/). A part of the Project is financed with grants from the Spanish Ministry of Economy and Competitiveness [PI16/01575] co-founded by ISCIII (Concesión de subvenciones de Proyectos de Investigación en Salud de la convocatoria 2020 de la Acción Estratégica en Salud 2017-2020 por el proyecto “PROGRESIÓN NO MOTORA E IMPACTO EN LA CALIDAD DE VIDA EN LA ENFERMEDAD DE PARKINSON”)

Ileal apparent and standardized amino acid digestibility of soybean and colza meal in diets for finishing pigs

Agri-food chains generate by-products such as soybean and colza meal for animal feed. Their nutritional value is variable and should be analysed for better quality control before their inclusion in balanced diets. The objective was to determine the content and ileal apparent and standardized digestibility of protein and amino acids (AA) of soybean (PS) and colza meal (PC) as a source of protein in diets for finishing pigs. The experimental units were arranged in a 3×3 Latin square design repeated. The treatments (T) were T1: PS+corn starch, T2: PC+corn starch, and T3: corn starch (Control), which were randomly assigned to six pigs cannulated in distal ileum (PV 75±1.2 kg). The variables were contents and apparent ileal and standardized ileal digestibility of amino acids in soybean and colza meal. To determine digestibility, chromic oxide was added to the diets. The protein and fat contents were higher in the soybean meal. Ash, crude fibre, neutral detergent fibre, acid detergent fibre, phosphorus and calcium contents were higher in the colza meal. Essential amino acid content was higher in soybean meal, but methionine was higher in colza meal. Apparent ileal digestibility (DIA) of total amino acids was similar (p > 0.05) among protein ingredients; but for lysine and threonine it was higher (p ≤ 0.05) in soybean meal, except methionine. Methionine DIA was 89.78 %, 3.88 % higher (p ≤ 0.05) in colza meal. Standardized ileal digestibility (DIE) of total amino acids was similar (p > 0.05) among ingredients, but lysine and threonine were higher (p ≤ 0.05) in soybean meal. DIE was different (p ≤ 0.05) among ingredients for all amino acids except methionine. Ileal and standardized digestibility of all amino acids were higher in soybean meal, except methionine, which was higher in colza meal. The DIA of total amino acids was similar in both protein ingredients, except lysine and threonine in soybean meal and methionine in colza meal

Sporadic Fatal Insomnia in Europe:Phenotypic features and diagnostic challenges

[Objective] Comprehensively describe the phenotypic spectrum of sporadic fatal insomnia (sFI) to facilitate diagnosis and management of this rare and peculiar prion disorder.[Methods] A survey among major prion disease reference centers in Europe identified 13 patients diagnosed with sFI in the past 20 years. We undertook a detailed analysis of clinical and histopathological features and the results of diagnostic investigations.[Results] Mean age at onset was 43 years, and mean disease duration 30 months. Early clinical findings included psychiatric, sleep, and oculomotor disturbances, followed by cognitive decline and postural instability. In all tested patients, video‐polysomnography demonstrated a severe reduction of total sleep time and/or a disorganized sleep. Cerebrospinal fluid (CSF) levels of proteins 14‐3‐3 and t‐tau were unrevealing, the concentration of neurofilament light protein (NfL) was more consistently increased, and the real‐time quaking‐induced conversion assay (RT‐QuIC) revealed a positive prion seeding activity in 60% of cases. Electroencephalography and magnetic resonance imaging showed nonspecific findings, whereas fluorodeoxyglucose positron emission tomography (FDG‐PET) demonstrated a profound bilateral thalamic hypometabolism in 71% of cases. Molecular analyses revealed PrPSc type 2 and methionine homozygosity at PRNP codon 129 in all cases.[Interpretation] sFI is a disease of young or middle‐aged adults, which is difficult to reconcile with the hypothesis of a spontaneous etiology related to stochastic, age‐related PrP misfolding. The combination of psychiatric and/or sleep‐related symptoms with oculomotor abnormalities represents an early peculiar clinical feature of sFI to be valued in the differential diagnosis. Video‐polysomnography, FDG‐PET, and especially CSF prion RT‐QuIC and NfL constitute the most promising supportive diagnostic tests in vivo.Peer reviewe

Clinical and structural brain correlates of hypomimia in early-stage Parkinson's disease

Altres ajuts: acord transformatiu CRUE-CSICBackground and purpose: Reduced facial expression of emotions is a very frequent symptom of Parkinson's disease (PD) and has been considered part of the motor features of the disease. However, the neural correlates of hypomimia and the relationship between hypomimia and other non-motor symptoms of PD are poorly understood. Methods: The clinical and structural brain correlates of hypomimia were studied. For this purpose, cross-sectional data from the COPPADIS study database were used. Age, disease duration, levodopa equivalent daily dose, Unified Parkinson's Disease Rating Scale part III (UPDRS-III), severity of apathy and depression and global cognitive status were collected. At the imaging level, analyses based on gray matter volume and cortical thickness were used. Results: After controlling for multiple confounding variables such as age or disease duration, the severity of hypomimia was shown to be indissociable from the UPDRS-III speech and bradykinesia items and was significantly related to the severity of apathy (β = 0.595; p < 0.0001). At the level of neural correlates, hypomimia was related to motor regions brodmann area 8 (BA 8) and to multiple fronto-temporo-parietal regions involved in the decoding, recognition and production of facial expression of emotions. Conclusion: Reduced facial expressivity in PD is related to the severity of symptoms of apathy and is mediated by the dysfunction of brain systems involved in motor control and in the recognition, integration and expression of emotions. Therefore, hypomimia in PD may be conceptualized not exclusively as a motor symptom but as a consequence of a multidimensional deficit leading to a symptom where motor and non-motor aspects converge

Nonmotor Symptoms in LRRK2 G2019S Associated Parkinson's Disease

BACKGROUND: Idiopathic Parkinson's disease (IPD) and LRRK2-associated PD (LRRK2-PD) might be expected to differ clinically since the neuropathological substrate of LRRK2-PD is heterogeneous. The range and severity of extra-nigral nonmotor features associated with LRRK2 mutations is also not well-defined. OBJECTIVE: To evaluate the prevalence and time of onset of nonmotor symptoms (NMS) in LRRK2-PD patients. METHODS: The presence of hyposmia and of neuropsychiatric, dysautonomic and sleep disturbances was assessed in 33 LRRK2-G2019S-PD patients by standardized questionnaires and validated scales. Thirty-three IPD patients, matched for age, gender, duration of parkinsonism and disease severity and 33 healthy subjects were also evaluated. RESULTS: University of Pennsylvania Smell Identification Test (UPSIT) scores in LRRK2-G2019S-PD were higher than those in IPD (23.5±6.8 vs 18.4±6.0; p = 0.002), and hyposmia was less frequent in G2019S carriers than in IPD (39.4% vs 75.8%; p = 0.01). UPSIT scores were significantly higher in females than in males in LRRK2-PD patients (26.9±4.7 vs 19.4±6.8; p<0.01). The frequency of sleep and neuropsychiatric disturbances and of dysautonomic symptoms in LRRK2-G2019S-PD was not significantly different from that in IPD. Hyposmia, depression, constipation and excessive daytime sleepiness, were reported to occur before the onset of classical motor symptoms in more than 40% of LRRK2-PD patients in whom these symptoms were present at the time of examination. CONCLUSION: Neuropsychiatric, dysautonomic and sleep disturbances occur as frequently in patients with LRRK2-G2019S-PD as in IPD but smell loss was less frequent in LRRK2-PD. Like in IPD, disturbances such as hyposmia, depression, constipation and excessive daytime sleepiness may antedate the onset of classical motor symptoms in LRRK2-G2019S-PD

General demographic data and parkinsonian motor symptoms in patients with <i>LRRK2</i> G2019S associated Parkinson’s disease, idiopathic Parkinson’s disease and healthy subjects.

<p><i>LRRK2</i> G2019S PD: <i>LRRK2</i> G2019S related Parkinson’s disease; IPD: Idiopathic Parkinson’s disease; HS: healthy subjects.</p>1<p>Mean ± Standard deviation (Range).</p>¶<p>Kruskal-Wallis analysis;</p>§<p>Mann-Whitney U test;</p>#<p>Chi-square test;</p>±<p>Fisher’s exact test.</p><p>General demographic data and parkinsonian motor symptoms in patients with <i>LRRK2</i> G2019S associated Parkinson’s disease, idiopathic Parkinson’s disease and healthy subjects.</p

Estimated presence of nonmotor symptoms in <i>LRRK2</i> G2019S Parkinson’s disease patients and idiopathic Parkinson’s disease patients in relation to onset of motor symptoms.

<p><i>LRRK2</i> G2019S PD: <i>LRRK2</i> G2019S related Parkinson’s disease; IPD: Idiopathic Parkinson’s disease, OMS: onset of motor symptoms, RBD: REM sleep behavior disorder, EDS: excessive daytime sleepiness.</p><p>Estimated presence of nonmotor symptoms in <i>LRRK2</i> G2019S Parkinson’s disease patients and idiopathic Parkinson’s disease patients in relation to onset of motor symptoms.</p

University of Pennsylvania Smell Identification Test (UPSIT) scores.

<p>UPSIT scores in LRRK2 G2019S Parkinson’s disease patients, idiopathic Parkinson’s disease patients and healthy controls (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108982#pone-0108982-g001" target="_blank">Figure 1</a>.A). UPSIT score in each group separated by sex (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108982#pone-0108982-g001" target="_blank">Figure 1</a>.B). Circles represent individual values, while the bar refers to the mean UPSIT score in each group. IPD: idiopathic Parkinson’s disease; LRRK2-PD: LRRK2 associated Parkinson’s disease, HS: healthy subjects.</p

Nonmotor symptoms in patients with <i>LRRK2</i> G2019S associated Parkinson’s disease, idiopathic Parkinson’s disease and healthy subjects.

<p><i>LRRK2</i> G2019S PD: <i>LRRK2</i> G2019S-related Parkinson’s disease; IPD: Idiopathic Parkinson’s disease; HS: healthy subjects. G-I: Gastro-intestinal; RBD: REM behavior disorder; EDS: excessive daytime sleepiness.</p>#<p>Chi-square test;</p>±<p>Fisher’s exact test;</p>¶<p>Kruskal-Wallis analysis;</p>§<p>Mann-Whitney <i>U</i> test;</p><p>*Statistically significant: <i>P<</i>0.05;</p>1<p>Mean ± Standard deviation (Range);</p>2<p>Hyposmia was arbitrarily defined as an UPSIT score lower than the mean–2 SD UPSIT score obtained in a subset of healthy subjects of the same gender and similar age.</p><p>Nonmotor symptoms in patients with <i>LRRK2</i> G2019S associated Parkinson’s disease, idiopathic Parkinson’s disease and healthy subjects.</p