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Purpose: To translate and cross-culturally adapt the King's Parkinson's Disease Pain Scale (KPPS) into Spanish., Methods: The English KPPS was forward translated into Spanish, back translated, and revised by the original developers. Cross-cultural adaptation of relevant target groups was conducted following COSMIN standards. Cognitive pretesting in Spanish people with Parkinson's Disease (PD) and pain was performed via three semi-structured focus group meetings. Changes were implemented based on qualitative and quantitative analyses. A Delphi study (two rounds) of individual assessments by Spanish experts was conducted. Changes were implemented based on the Content Validity Index (CVI) at item and scale levels (I-CVI/S-CVI)., Results: Five Spanish professionals performed the initial translation. Thirty-eight inter-translation inconsistencies were identified, and consensus was reached for a unified version. After back translation and confirmation with scale developers, the pre-final Spanish KPPS was obtained. Cognitive pretesting in 30 people with PD-related pain identified 5 items where terminology changes were made to assure comprehensibility. The Delphi study in 14 Spanish experts underlined the necessity to further modify two items. After the second round, all experts agreed on the modifications and I-CVI and S-CVI were satisfactory., Conclusions: The KPPS was successfully translated and cross-culturally adapted into Spanish.

Background: The evaluation of motor impairment in Parkinson's disease (PD) is mainly assessed with the motor subdomain of the Unified Parkinson's Disease Rating scale (UPDRS part III) and, lately, with the MDS-UPDRS part III. To optimize efforts and special needs during specific circumstances in clinical practice, we sought to identify the most sensitive items to assess motor impairment in PD., Methods: We included the COPPADIS-PD cohort and collected the UPDRS part III at baseline (V0), 12 months (V1), and 24 months (V2). Factor analysis and effect size using Cohen's d formula were performed in the Off and On states at V0, V1, and V2., Results: We included 667 patients with PD, mean age of 62.59 ± 8.91 years, 410 (60.2%) males, with a median HY stage of 2.00 (1.00; 4.00) at baseline. Over time, the most discriminating items were postural stability and body bradykinesia ("arise from chair" and "gait") in the Off state, right and left upper extremity bradykinesia ("finger tap", "hand movements" and "prono/supination") in the On state. Body bradykinesia and right-left finger tapping were the items with the largest effect size (0.93, 0.84, 0.83, respectively) to assess motor improvement after receiving antiparkinsonian medications over time., Conclusion: Under specific circumstances, selecting a few items of the UPDRS part III, including postural stability, body bradykinesia, and upper extremity bradykinesia, could be used to create a quick clinical judgment of motor status and improvement in PD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The Movement Disorder Society-sponsored Non-motor Rating Scale (MDS-NMS) assess the severity and disability caused by non-motor symptoms (NMS) in Parkinson's disease (PD)., Objective: This article encapsulates the formal process for completing this program and the data on the first officially approved non-English version of the MDS-NMS (Spanish)., Methods: The MDS-NMS translation program involves four steps: translation and back-translation; cognitive pre-testing to ensure that raters and patients understand the scale and are comfortable with its content; field testing of the finalized version; analysis of the factor structure of the tested version against the original English language version for the nine domains that could be analyzed in a confirmatory factor analysis. To be designated an "Official MDS translation," the confirmatory factor analysis Comparative Fit Index had to be ≥0.90., Results: The Spanish MDS-NMS was tested in 364 native-Spanish-speaking patients with PD from seven countries. For all subjects with fully computable data with all domains of the MDS-NMS ( n  = 349), the Comparative Fit Index was ≥0.90 for the nine eligible domains. Missing data were negligible and moderate floor effect (42.90%) was found for the Non-Motor Fluctuations subscale. Item homogeneity coefficient was adequate, and the correlation of the MDS-NMS domains with other measures for related constructs was acceptable ( r s ≥ 0.50)., Conclusions: The Spanish version of the MDS-NMS followed the IPMDS Translation Program protocol, reached the criterion to be designated as an Official Translation, and is now available on the MDS website., (© 2023 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background 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., (© 2022 European Academy of Neurology.)

Background: Blood homocysteine appears to be increased in Parkinson's disease (PD) and may play a role in the development and progression of this disorder. However, the specific contribution of abnormal homocysteine levels to cortical degeneration in PD remains elusive., Objective: To characterize the cortical structural correlates of homocysteine levels in PD., Methods: From the COPPADIS cohort, we identified a subset of PD patients and healthy controls (HC) with available homocysteine and imaging data. Surface-based vertex-wise multiple regression analyses were performed to investigate the cortical macrostructural (cortical thinning) and microstructural (increased intracortical diffusivity) correlates of homocysteine levels in this sample., Results: A total of 137 PD patients and 43 HC were included. Homocysteine levels were increased in the PD group (t = -2.2, p = 0.03), correlating in turn with cognitive performance (r = -0.2, p = 0.03). Homocysteine in PD was also associated with frontal cortical thinning and, in a subset of patients with available DTI data, with microstructural damage in frontal and posterior-cortical regions (p < 0.05 Monte-Carlo corrected)., Conclusions: Homocysteine in PD appears to be associated with cognitive performance and structural damage in the cerebral cortex. These findings not only reinforce the presence and importance of cortical degeneration in PD, but also suggest that homocysteine plays a role among the multiple pathological processes thought to be involved in its development., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Levodopa-carbidopa intestinal gel (LCIG) has shown to be efficacious in motor and non-motor symptoms (NMS). Nevertheless, studies with patient Quality of Life (QoL) as a primary endpoint are scarce. To assess the effect of LCIG on Advanced Parkinson's Disease (APD) patients QoL. Secondarily, the impact on motor symptoms and NMS, emotional well-being, treatment satisfaction, and caregiver QoL, stress, disease burden, anxiety, depression, and work impairment were also investigated. In this prospective, 6-month multicenter postmarketing observational study, LCIG was administered to 59 patients with APD. Endpoints were assessed using validated scales and questionnaires. LCIG significantly improved patient QoL (PDQ-39 mean change ± standard deviation from baseline, -12.8 ± 14.6; P < 0.0001), motor symptoms (UPDRS-III in "On," -6.5 ± 11.8; P = 0.0002), NMS (NMSS, -35.7 ± 31.1; P < 0.0001), mood (Norris/Bond-Lader VAS, -6.6 ± 21.1; P = 0.0297), fatigue (PFS-16, -0.6 ± 1.0; P = 0.0003), depression (BDI-II, -5.1 ± 9.4; P = 0.0002), anxiety (BAI, -6.2 ± 9.6; P < 0.0001), and patient treatment satisfaction (SATMED-Q, 16.1 ± 16.8; P < 0.0001). There were significant correlations between the change from baseline to 6 months between PDQ-39 and UPDRS-IV, NMSS, BAI, BDI-II, AS, and PFS-16 scores, and Norris/Bond-Lader alertness/sedation factor. Caregiver anxiety also improved (Goldberg anxiety scale, -1.1 ± 1.0; P = 0.0234), but the clinical relevance of this finding is questionable. The serious adverse events reported were similar to those previously described for LCIG. In patients with APD, LCIG improves QoL, motor symptoms and NMS, emotional well-being, and satisfaction with the treatment. Improvement in patient QoL is associated with improvements in motor complications, NMS, anxiety, depression, apathy and fatigue. Improvements in patients' QoL does not correspond with improvements in caregivers' QoL or burden., (© 2021. The Author(s).)

Background: Advanced Parkinson's disease (APD) has been recently defined as a stage in which certain symptoms and complications are present, with a detrimental influence on the overall patient's health conditions and with a poor response to conventional treatments. However, historically, the term APD has been controversial, thus consequently, APD prevalence has not been previously studied., Objectives: The main objective was to determine the prevalence of APD in patients diagnosed with idiopathic PD in hospitals of the Spanish National Healthcare System. Secondary objectives were the prevalence and incidence of PD and the clinical and sociodemographic characteristics and quality of life of patients with APD or non-APD., Methods: This was a non-interventional, cross-sectional, multicenter, national study in the hospital setting., Results: The study population included 929 patients with PD (mean age 71.8 ± 10.1 years; 53.8% male) and a mean time since diagnosis of 6.6 ± 5.4 years. At the time of diagnosis, 613 patients (66.06%) reported having had premotor symptoms. The Hoehn and Yahr stage was 1 in 15.7% of the patients, 2 in 42.8%, 3 in 30.1%, 4 in 9.9%, and 5 in 1.4%; 46.9% of the patients had comorbidities (mean age-adjusted Charlson comorbidity index 3.5 ± 1.7; median 10-year survival 77%) and the mean 8-item Parkinson's Disease Quality of Life Questionnaire was 27.8 ± 20.5. We found an APD prevalence of 38.21% (95%CI: 35.08-41.42%), a PD prevalence of 118.4 (95%CI: 117.3-119.6), and a PD incidence of 9.4 (95%CI: 5.42-13.4) all per 100,000 population. Among the APD population, a 15.2% were receiving some form of therapy for advanced stages of the disease (deep brain stimulation, levodopa/carbidopa intestinal gel, or apomorphine subcutaneous infusion)., Conclusions: The percentage of patients with APD in the hospitals of the Spanish National Healthcare System was 38.2%.

Background: Non-motor symptoms (NMS) are integral to Parkinson's Disease (PD) and management remains a challenge. Safinamide is a novel molecule in relation to addressing NMS due to its multifocal mechanism of action with both dopaminergic and non-dopaminergic properties., Objective: To investigate the efficacy of safinamide on NMS and its burden in PD patients with motor fluctuations after 6 months of treatment., Methods: This observational, multicenter, open-label, pilot study assessed a wide range of NMS using the following rating scales, NMSS (non-motor symptom scale), KPPS (King's PD pain scale), HADS (hospital anxiety and depression scale), PDQ-8 (Parkinson's disease quality of life questionnaire), and PDSS-2 (Parkinson's disease sleep scale), EuroQol-5D 3 level version (EQ-5D-3L), CGI-I (clinical global impression of improvement), and PGI-C (patient global impression of change). Motor examination using UPDRS part III (Unified Parkinson's disease rating scale, motor examination), UPDRS IV (complications of therapy) and Hoehn and Yahr staging were also obtained., Results: 27 patients were included in the analysis and were evaluated at baseline and ≥ 6 months after safinamide treatment. 26 patients had a daily maintenance dose of 100 mg and 1 patient a daily dose of 50 mg. Significant improvements in UPDRS IV, KPPS item 5 (region-specific "off" dystonia), KPPS domain 3 (items 4-6, fluctuation related pain) and KPPS total score were observed after treatment with safinamide, while maintaining stable dopaminergic medication. No statistically significant differences were found in NMSS, HADS, PDSS-2, EQ-5D-3L, and PDQ-8 after treatment., Conclusions: Our results suggest that safinamide may have a beneficial effect on pain, a key unmet need in fluctuating PD patients., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Introduction: We aimed to assess associations between multimodal neuroimaging measures of cholinergic basal forebrain (CBF) integrity and cognition in Parkinson's disease (PD) without dementia., Methods: The study included a total of 180 non-demented PD patients and 45 healthy controls, who underwent structural MRI acquisitions and standardized neurocognitive assessment through the PD-Cognitive Rating Scale (PD-CRS) within the multicentric COPPADIS-2015 study. A subset of 73 patients also had Diffusion Tensor Imaging (DTI) acquisitions. Volumetric and microstructural (mean diffusivity, MD) indices of CBF degeneration were automatically extracted using a stereotactic CBF atlas. For comparison, we also assessed multimodal indices of hippocampal degeneration. Associations between imaging measures and cognitive performance were assessed using linear models., Results: Compared to controls, CBF volume was not significantly reduced in PD patients as a group. However, across PD patients lower CBF volume was significantly associated with lower global cognition (PD-CRS total : r = 0.37, p < 0.001), and this association remained significant after controlling for several potential confounding variables (p = 0.004). Analysis of individual item scores showed that this association spanned executive and memory domains. No analogue cognition associations were observed for CBF MD. In covariate-controlled models, hippocampal volume was not associated with cognition in PD, but there was a significant association for hippocampal MD (p = 0.02)., Conclusions: Early cognitive deficits in PD without dementia are more closely related to structural MRI measures of CBF degeneration than hippocampal degeneration. In our multicentric imaging acquisitions, DTI-based diffusion measures in the CBF were inferior to standard volumetric assessments for capturing cognition-relevant changes in non-demented PD., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Parkinson's disease is the second most prevalent progressive neurodegenerative disease and causes considerable disability in patients. We conducted a cross-sectional analytical study to examine the metric properties of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS-2); the 12-item World Health Organization Disability Assessment Schedule (WHODAS-S) and the Rapid Assessment of Disability Scale (RADS) in assessing disability in Parkinsonian patients., Patients and Methods: Patients with cognitive impairment, neurological disorder, or disability due to any condition other than PD were excluded. One hundred sixty-eight consecutive patients were assessed in ON state. The following attributes were evaluated: data quality and acceptability, reliability, and construct (convergent and known-groups) validity. Testretest reliability was analyzed in fifty-six patients., Results: Out of 168 patients, 65.4% were men's, 96 (57.1%) at stage III of Hoehn and Yahr. One hundred fifty-one patients lived independently in the community, 102 lived with their spouses, 108 were retired, and 48 were still working. Cronbach's alpha exceeded the minimum requirement of 0.70 for the three scales. The SEM obtained was, also for the three scales, higher than the ½ of the standard deviation value. The validity for known groups showed that all domains were significantly different in both WHODAS-S and RADS. The stability of the scale was evaluated with the test-retest (ICC). The results for the WHODAS-2 ≤ 0.002; for the WHODAS-S were p ≤ 0.000]; and for the RADS were p ≤ 0.000]., Conclusion: The RADS is by far the fastest scale to use. All three scales showed suitable metric properties., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We would like to submit the following erratum to our recently published paper [...].

Objectives: To assess the association between having suffered a fall in the month prior to interview and long-term overall survival in nursing-home residents., Methods: Retrospective cohort study conducting an overall survival follow-up of 689 representative nursing-home residents from Madrid, Spain. Residents lived in three types of facilities: public, subsidized and private and its information was collected by interviewing the residents, caregivers and/or facility physicians. Residents contributed to follow-up time from their baseline interviews until death or being censored at the end of the 5-year follow-up period. The association between suffering a fall during the month prior to interview and long-term overall survival was analyzed using Cox proportional hazards models. To adjust for potential confounders we used progressive adjusted models. We then repeated the analyses with severity of the fall (no fall, non-severe, severe) as the main independent variable., Results: After a 2408 person-year follow-up (median 4.5 years), 372 participants had died. In fully-adjusted models, residents who had suffered any kind of fall in the previous month showed virtually the same survival rates compared to non-fallers (hazard ratio (HR) = 1.03; 95% CI = 0.75-1.40). There was a weak graded relationship between increased fall severity and survival rates for the non-severe fall group (HR = 0.92; 95% CI = 0.58-1.45) and the severe fall group (HR = 1.36; 95% CI = 0.73-2.53) compared with residents who had not suffered any kind of fall. The hazard ratios for severe falls were higher in men, residents with less comorbidity, fewer medications, and those functionally independent., Conclusion: We found no associations between having suffered a fall in the month prior to interview and long-term survival; neither did we find a marked association when severity of fall was accounted for in the whole population. In some subgroups, however, the results merit further scrutiny., Competing Interests: The authors have declared that no competing interests exist.

Safinamide is an approved drug for the treatment of fluctuations in Parkinson's disease (PD). Scarce data are available on its use in clinical practice. A group of Spanish movement disorders specialists was convened to review the use of safinamide across different clinical scenarios that may guide neurologists in clinical practice. Eight specialists with recognized expertise in PD management elaborated the statements based on available evidence in the literature and on their clinical experience. The RAND/UCLA method was carried, with final conclusions accepted after a 2-round modified Delphi process. Higher level of agreement between panellists was reached for the following statements. Safinamide significantly improves mean daily ON time without troublesome dyskinesias [corrected]. Adjunctive treatment with safinamide is associated with motor improvements in patients with mid-to-late PD. The efficacy of safinamide on motor fluctuations is maintained at long-term, with no increase over time in dyskinesias severity. The clinical benefits of safinamide on pain and depression remain unclear. Safinamide presents a similar incidence of adverse events compared with placebo. The efficacy and safety of safinamide shown in the pivotal clinical trials are reproduced in clinical practice, with improvement of parkinsonian symptoms, decrease of daily OFF time, control of dyskinesias at the long term, and good tolerability and safety.

Background: The Unified Dyskinesia Rating Scale (UDysRS) is a well-established tool for producing comprehensive assessments of severity and disability associated with dyskinesia in patients with Parkinson's disease (PD). The scale was originally developed in English, and a broad international effort has been undertaken to develop and validate versions in additional languages. Our aim was to validate the Hebrew version of the UDysRS., Methods: We translated the UDysRS into Hebrew, back-translated it into English, and carried out cognitive pretesting. We then administered the scale to non-demented native Hebrew-speaking patients who fulfilled the Brain Bank diagnostic criteria for probable PD (n = 250). Data were compared to the Reference Standard data used for validating UDysRS translations., Results: The different portions of the Hebrew UDysRS showed high internal consistency (α ≥ 0.92). A confirmatory factor analysis in which we compared the Hebrew UDysRS to the Reference Standard version produced a comparative fit index (CFI) of 0.98, exceeding the threshold criterion of CFI > 0.9 indicating factor validity. A secondary exploratory factor analysis provided further support to the consistency between the factor structures of the Hebrew and Reference Standard versions of the UDysRS., Conclusion: The UDysRS Hebrew version shows strong clinimetric properties and fulfills the criteria for designation as an official International Parkinson and Movement Disorder Society-approved translation for use in clinical and research settings., (© 2020 S. Karger AG, Basel.)

Background: The asymmetry of motor manifestations present in Parkinson's disease (PD) suggests the existence of differences between both hemispheres. As a consequence, this asymmetry might contribute to different PD clinical phenotypes., Objective: To study the relationship between motor symptom laterality with motor, non-motor symptoms (NMS), freezing of gait (FOG), and quality of life (QoL) impairment in PD., Methods: In this cross-sectional study, we measured motor symptoms severity and complications with the Unified Parkinsons' disease Rating Scale (UPDRS), FOG with the FOG questionnaire, QoL with the 39-item PD Quality of Life Questionnaire Summary Index, and NMS with the NMS, Visual Analogue Scales for Pain and Fatigue, Beck Depression Inventory-II, Impulsive-Compulsive Disorders, and PD Sleep and Cognitive Rating scales. We defined left and right motor laterality using the UPDRS part III. We used comparative, regression, and effect size analyses to evaluate the impact of asymmetry on motor and NMS, FOG, and QoL., Results: 342 left (LPD) and 310 right (RPD) patients, with a mean age of 62.0±8.8 years, were included. In multivariate regression analysis, LPD was associated with a greater motor (OR = 1,50, 95% CI 1.02-2.21), FOG (OR = 1.56, 95% CI 1.01-2.41), and overall NMS impairment (OR = 1.43, 95% CI 1.001-2.06), and better QoL (OR = 0.52 95% CI 0.32-0.85). Overall, only a mild effect size was found for all comparisons in which significant differences were present., Conclusion: In this large multicenter study, motor symptom laterality seems to carry a mild but significant impact on PD clinical manifestations, and QoL.

Objective: The recent advances in technology are opening a new opportunity to remotely evaluate motor features in people with Parkinson's disease (PD). We hypothesized that typing on an electronic device, a habitual behavior facilitated by the nigrostriatal dopaminergic pathway, could allow for objectively and nonobtrusively monitoring parkinsonian features and response to medication in an at-home setting., Methods: We enrolled 31 participants recently diagnosed with PD who were due to start dopaminergic treatment and 30 age-matched controls. We remotely monitored their typing pattern during a 6-month (24 weeks) follow-up period before and while dopaminergic medications were being titrated. The typing data were used to develop a novel algorithm based on recursive neural networks and detect participants' responses to medication. The latter were defined by the Unified Parkinson's Disease Rating Scale-III (UPDRS-III) minimal clinically important difference. Furthermore, we tested the accuracy of the algorithm to predict the final response to medication as early as 21 weeks prior to the final 6-month clinical outcome., Results: The score on the novel algorithm based on recursive neural networks had an overall moderate kappa agreement and fair area under the receiver operating characteristic (ROC) curve with the time-coincident UPDRS-III minimal clinically important difference. The participants classified as responders at the final visit (based on the UPDRS-III minimal clinically important difference) had higher scores on the novel algorithm based on recursive neural networks when compared with the participants with stable UPDRS-III, from the third week of the study onward., Conclusions: This preliminary study suggests that remotely gathered unsupervised typing data allows for the accurate detection and prediction of drug response in PD. © 2019 International Parkinson and Movement Disorder Society., (© 2019 International Parkinson and Movement Disorder Society.)

Background: Self-rated health (SRH) is a health measure used in studies of older adults. The objective of this study is to analyze SRH as a predictor of mortality in the institutionalized older population and the characteristics of those who do not provide information about their SRH on health questionnaires., Methods: This is a 15-year follow-up study of older adult residents in nursing or care homes in of Madrid, Spain. SRH was measured on a 5-point Likert type scale. The association between answering the SRH question and socio-demographic and health characteristics was evaluated through prevalence ratio (PR), estimated by Poisson regression models. Survival rates associated with SRH were studied through a multivariate Cox regression., Results: The sample has a mean age of 83.4 (standard deviation, SD = 7.3), with 75.7% women. Twelve percent did not answer the SRH item. Those who did not answer showed a higher probability of disability (Barthel index, PR = 0.76, 95% confidence interval = 0.67-0.86) and/or dementia (PR = 8.03, 3.38-19.03). A trend for higher mortality was observed in those persons who did not respond (adjusted hazard ratio HR = 1.26, 0.75-2.11). The mortality rate was 32% higher for those who declared poor SRH in comparison with those who reported good SRH (adjusted HR = 1.32, 1.08-1.6)., Conclusions: There is an elevated number of people who do not respond to the SRH item, mainly those with disabilities and cognitive deterioration. Lack of response to SRH is a good indicator of 15-year mortality for persons institutionalized in care or nursing homes.

Background and Objectives: Nursing or care home characteristics may have a long-term impact on the residents' mortality risks that has not been studied previously. The study's main objective was to assess the association between facility ownership and long-term, all-cause mortality., Research Design and Methods: We conducted a mortality follow-up study on a cohort of 611 nursing-home residents in the city Madrid, Spain, from their 1998-1999 baseline interviews up to September 2013. Residents lived in three types of facilities: public, subsidized and private, which were also sub-classified according to size (number of beds). Residents' information was collected by interviewing the residents themselves, their caregivers and facility physicians. We used time-to-event multivariable models and inverse probability weighting to estimate standardized mortality risk differences., Results: After a 3728 person-year follow-up (median/maximum of 4.8/15.2 years), 519 participants had died. In fully-adjusted models, the standardized mortality risk difference at 5 years of follow-up between medium-sized private facilities and large-sized public facilities was -18.9% (95% confidence interval [CI]: -33.4 to -4.5%), with a median survival (95% CI) of 3.6 (0.5 to 6.8) additional years. The fully-standardized 5-year mortality difference (95% CIs) between for-profit private facilities and not-for-profit public institutions was -15.1% (-31.1% to 0.9%), and the fully-standardized median survival difference (95% CIs) was 3.0 (-1.7 to 7.7) years., Discussion and Implications: These results are compatible with an association between factors related with the ownership of facilities and the long-term mortality risk of their residents. One of these factors, the facility size, could partly explain this association., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Current rehabilitation models emphasize therapy that attempts to return to "normal" the lives of persons who are disabled. An opportunity is available to scrutinize whether this recovery orientation of rehabilitation is necessarily optimal., Method: This conceptual article uses reasoning, informed by experience and a nonsystematic review of literature across diverse disciplines., Results: For some persons with disability, optimizing recovery might be unwanted or insufficient. To expand rehabilitation, we append the Latin "ultra", beyond, to "habilitare", make fit. The resulting term, "ultrabilitate", commits to human flourishing that moves persons toward, around or beyond recovery of particular functioning., Conclusions: By expanding the scope of disability management, ultrabilitation could inform therapy selection and facilitate human flourishing. Empirical research is needed to test our ideas. Implications for rehabilitation Despite significant progress, rehabilitation limits some people with disabilities. Modern health systems still benchmark therapy for rehabilitation against "normal" or species-typical standards to aid recovery. "Ultrabilitation", meaning "beyond fitness", promotes flourishing, either without an interest in recovery or in moving toward, beyond or around recovery. Biological, social and technological conditions are needed to support ultrabilitation. Ultrabilitation complements rehabilitation when rehabilitation is not sufficient to optimize functioning and personal growth.

Objective: To analyse whether there is a short-term association between road traffic noise in the city of Madrid and Parkinson's disease (PD)-related demand for healthcare., Methods: Time-series analysis (2008-2009) using variables of analysis linked to emergency and daily PD-related demand for healthcare (ICD-10: G20-G21), namely, PD-hospital admissions (HAs), PD-outpatient visits (OVs) and PD-emergency medical calls in Madrid. The noise pollution measurements used were Leqd, equivalent sound level for the daytime hours (from 8 a.m. to 10 p.m.), and Leqn, equivalent sound level for night time hours (from 10 p.m. to 8 a.m.) in dB(A). We controlled for temperature, pollution, trends and seasons, and used the Poisson regression model to calculate relative risk (RR)., Results: The association between Leqd and HAs was found to be linear. Leqd and Leqn at lag 0.1 and temperature at lags 1 and 5 were the only environmental variables associated with increased PD-related healthcare demand. The RR (lag 0) for Leqd and HA was 1.07 (1.04-1.09), the RR (lag 0) for Leqd and OV was 1.28 (1.12-1.45), and the RR (lags 0.1) for Leqn and emergency medical calls was 1.46 (1.06-2.01)., Conclusion: The above results indicate that road traffic noise is a risk factor for PD exacerbation. Measures to reduce noise-exposure levels could result in a lower PD-related healthcare demand., (Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Pantothenate kinase-associated neurodegeneration is a progressive neurological disorder occurring in both childhood and adulthood. The objective of this study was to design and pilot-test a disease-specific clinical rating scale for the assessment of patients with pantothenate kinase-associated neurodegeneration., Methods: In this international cross-sectional study, patients were examined at the referral centers following a standardized protocol. The motor examination was filmed, allowing 3 independent specialists in movement disorders to analyze 28 patients for interrater reliability assessment. The scale included 34 items (maximal score, 135) encompassing 6 subscales for cognition, behavior, disability, parkinsonism, dystonia, and other neurological signs., Results: Forty-seven genetically confirmed patients (30 ± 17 years; range, 6-77 years) were examined with the scale (mean score, 62 ± 21; range, 20-106). Dystonia with prominent cranial involvement and atypical parkinsonian features were present in all patients. Other common signs were cognitive impairment, psychiatric features, and slow and hypometric saccades. Dystonia, parkinsonism, and other neurological features had a moderate to strong correlation with disability. The scale showed good internal consistency for the total scale (Cronbach's α = 0.87). On interrater analysis, weighted kappa values (0.30-0.93) showed substantial or excellent agreement in 85% of the items. The scale also discriminated a subgroup of homozygous c.1583C>T patients with lower scores, supporting construct validity for the scale., Conclusions: The proposed scale seems to be a reliable and valid instrument for the assessment of pediatric and adult patients with pantothenate kinase-associated neurodegeneration. Additional validation studies with a larger sample size will be required to confirm the present results and to complete the scale validation testing. © 2017 International Parkinson and Movement Disorder Society., (© 2017 International Parkinson and Movement Disorder Society.)

Objective: The aim of this study is to present a predictive model of Parkinson's disease (PD) global severity, measured with the Clinical Impression of Severity Index for Parkinson's Disease (CISI-PD)., Methods: This is an observational, longitudinal study with annual follow-up assessments over 3 years (four time points). A multilevel analysis and multiple imputation techniques were performed to generate a predictive model that estimates changes in the CISI-PD at 1, 2, and 3 years., Results: The clinical state of patients (CISI-PD) significantly worsened in the 3-year follow-up. However, this change was of small magnitude (effect size: 0.44). The following baseline variables were significant predictors of the global severity change: baseline global severity of disease, levodopa equivalent dose, depression and anxiety symptoms, autonomic dysfunction, and cognitive state. The goodness-of-fit of the model was adequate, and the sensitive analysis showed that the data imputation method applied was suitable., Conclusion: Disease progression depends more on the individual's baseline characteristics than on the 3-year time period. Results may contribute to a better understanding of the evolution of PD including the non-motor manifestations of the disease.

Falls can injure, even kill. No one with Parkinson's disease (PD) wants to fall by accident. However, the potential nastiness of falls does not preclude a more nuanced understanding of the personal meaning that falls can have. Rather than view falls as a problem to fear and manage solely by preventing and repairing harm, people with PD and those who care for them may recast falls as a mixed blessing. Falls may be a resource, skill, and catalyst for personal growth. We discuss how falls may give rise to opportunities in interrelated domains: capabilities, credo, character, creativity, chronemics, and connectedness. Clinicians could incorporate a positive focus across these domains to help people with PD to 'fall upward' in the sense of flourish.

Background: Parkinson's disease (PD) is characterized by motor and nonmotor symptoms that progress with time, causing disability. The performance of a disease-specific, self-applied tool for assessing disability, the MDS-UPDRS Part II, is tested against generic and rater-based rating scales., Methods: An international, cross-sectional, observational study was performed. Patients were assessed with the Hoehn and Yahr (HY) and five disability measures: MDS-UPDRS Part II, Schwab and England Scale (S&E), Clinical Impression of Severity Index-PD (CISI-PD) Disability item, Barthel Index (BI), and Rapid Assessment of Disability Scale (RADS). Data analysis included correlation coefficients, Mann-Whitney and Kruskal-Wallis tests, and intraclass-correlation coefficient for concordance., Results: The sample was composed of 451 patients, 55.2% men, with a mean age of 65.06 years (SD = 10.71). Disability rating scales correlated from |0.75| (CISI-PD Disability with BI) to 0.87 (MDS-UPDRS Part II with RADS). In general, MDS-UPDRS Part II showed high correlation coefficients with clinical variables and satisfactory concordance with the rest of disability measures, with ICC ranging from 0.83 (with BI) to 0.93 (with RADS). All disability rating scales showed statistical significant differences in the sample grouped by sex, age, disease duration, and severity level., Conclusions: The MDS-UPDRS Part II showed an appropriate performance to assess disability in PD, even better than some rater-based, generic or specific, scales applied in this study.

Introduction: Understanding how a person lives with chronic illness is necessary to provide care according to the individual's needs. Nowadays, there is no validated scale to measure how the person is living with a chronic condition, such as Parkinson's disease., Objectives: The objectives were to: 1) define the concept of Living with a chronic illness; 2) design a measuring scale of the degree of Living with a chronic illness, in particular with Parkinson's disease., Methodology: Two methodological steps were carried out. Regarding the first methodological step, a concept analysis of Living with a chronic illness was done using Rodgers' evolutionary method. the second methodological step was the design of the scale, following DeVellis guideline., Results: Through the concept analysis it was identified that Living with a chronic illness is a complex, dynamic, cyclic and multidimensional process, involving the attributes of Acceptance, Coping, Self-management, Integration and Adjustment. In relation to the design of the scale, it was developed a self-reported measure, with five Likert response options and 27 items., Conclusions: The designed scale, is an innovative measure with a high potential interest in clinical community to identify with are the factor(s) that make the person have a positive or negative living with the disease. Consequently, nurses could intervene in a holistic way, according to the patient individual needs.

Understanding how a person lives with a chronic illness, such as Parkinson's disease (PD), is necessary to provide individualized care and professionals role in person-centered care at clinical and community levels is paramount. The present study was aimed to analyze the psychometric properties of the Living with Chronic Illness-PD Scale (EC-PC) in a wide Spanish-speaking population with PD. International cross-sectional study with retest was carried out with 324 patients from four Latin American countries and Spain. Feasibility, acceptability, scaling assumptions, reliability, precision, and construct validity were tested. The study included 324 patients, with age (mean±s.d.) 66.67±10.68 years. None of the EC-PC items had missing values and all acceptability parameters fulfilled the standard criteria. Around two-third of the items (61.54%) met scaling assumptions standards. Concerning internal consistency, Cronbach's alpha values were 0.68-0.88; item-total correlation was >0.30, except for two items; item homogeneity index was >0.30, and inter-item correlation values 0.14-0.76. Intraclass correlation coefficient for EC-PC stability was 0.76 and standard error of measurement (s.e.m.) for precision was 8.60 (for a EC-PC s.d.=18.57). EC-PC presented strong correlation with social support ( r S =0.61) and moderate correlation with life satisfaction ( r S =0.46). Weak and negligible correlations were found with the other scales. Internal validity correlations ranged from 0.46 to 0.78. EC-PC total scores were significantly different for each severity level based on Hoehn and Yahr and Clinical Impression of Severity Index, but not for Patient Global Impression of Severity. The EC-PC has satisfactory acceptability, reliability, precision, and validity to evaluate living with PD., Competing Interests: The authors declare no conflict of interest.

Objectives: To analyse the relationships between chronic conditions, body functions, activity limitations and participation restrictions in the International Classification of Functioning, Disability and Health (ICF) framework., Design: A cross-sectional study., Setting: 2 geographical areas in the Autonomous Region of Aragon, Spain, namely, a rural area, Cinco Villas, and an urban area in the city of Zaragoza., Participants: 864 individuals selected by simple random sampling from the register of Social Security card holders, aged 50 years and over, positive to disability screening., Main Outcome Measures: ICF Checklist-body function domains, WHO Disability Assessment Schedule 2.0 (WHODAS 2.0, 36-item (WHODAS-36)) global scores and medical diagnoses (chronic conditions) from primary care records., Results: Mild disability (WHODAS-36 level 5-24%) was present in 51.5% of the sample. In the adjusted ordinal regression model with WHODAS-36 as the dependent variable, disability was substantially associated with moderate-to-complete impairment in the following functions: mental, OR 212.8 (95% CI 72 to 628.9); neuromusculoskeletal, OR 44.8 (24.2 to 82.8); and sensory and pain, OR 6.3 (3.5 to 11.2). In the relationship between health conditions and body function impairments, the strongest links were seen for: dementia with mental functions, OR 50.6 (25.1 to 102.1); cerebrovascular disease with neuromusculoskeletal function, OR 5.8 (3.5 to 9.7); and chronic renal failure with sensory function and pain, OR 3.0 (1.49 to 6.4). Dementia, OR 8.1 (4.4 to 14.7) and cerebrovascular disease, OR 4.1 (2.7 to 6.4) were associated with WHODAS-36 scores., Conclusions: Body functions are heterogeneously linked to limitations in activities and restrictions on participation, with the highest impact being due to mental and musculoskeletal functions. This may be relevant for disability assessment and intervention design, particularly if defined on a body function basis. Control of specific health conditions, such as dementia and cerebrovascular disease, appears to be paramount in reducing disability among persons aged 50 years and over., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: During the last two decades, protein aggregation at all organismal levels, from viruses to humans, has emerged from a neglected area of protein science to become a central issue in biology and biomedicine. This article constitutes a risk-based review aimed at supporting an etiologic scenario of selected, sporadic, protein-associated, i.e., conformational, neurodegenerative disorders (NDDs), and their vascular- and metabolic-associated ailments., Methods: A rationale is adopted, to incorporate selected clinical data and results from animal-model research, complementing epidemiologic evidences reported in two prior articles., Findings: Theory is formulated assuming an underlying conformational transmission mechanism, mediated either by horizontal transfer of mammalian genes coding for specific aggregation-prone proteins, or by xeno-templating between bacterial and host proteins. We build a few population-based and experimentally-testable hypotheses focusing on: (1) non-disposable surgical instruments for sporadic Creutzfeldt-Jakob disease (sCJD) and other rapid progressive neurodegenerative dementia (sRPNDd), multiple system atrophy (MSA), and motor neuron disease (MND); and (2) specific bacterial infections such as B. pertussis and E. coli for all forms, but particularly for late-life sporadic conformational, NDDs, type 2 diabetes mellitus (T2DM), and atherosclerosis where natural protein fibrils present in such organisms as a result of adaptation to the human host induce prion-like mechanisms., Conclusion: Implications for cohort alignment and experimental animal research are discussed and research lines proposed.

Global evaluations of Parkinson's disease (PD) severity are available, but their concordance and accuracy have not been previously tested. The present international, cross-sectional study was aimed at determining the agreement level among four global scales for PD (Hoehn and Yahr, HY; Clinical Global Impression of Severity, CGIS; Clinical Impression of Severity Index, CISI-PD; and Patient Global Impression of Severity, PGIS) and identifying which of them better correlates with itemized PD assessments. Assessments included additional scales for evaluation of the movement impairment, disability, affective disorders, and quality of life. Spearman correlation coefficients, weighted and generalized kappa, and Kendall's concordance coefficient were used. Four hundred thirty three PD patients, 66% in HY stages 2 or 3, mean disease duration 8.8 years, were analyzed. Correlation between the global scales ranged from 0.60 (HY with PGIS) to 0.91 (CGIS with CISI-PD). Kendall's coefficient of concordance resulted 0.76 ( P <0.0001). HY and CISI-PD showed the highest association with age, disease duration, and levodopa-equivalent daily dose, and CISI-PD with measures of PD manifestations, disability, and quality of life. PGIS and CISI-PD correlated similarly with anxiety and depression scores. The lowest agreement in classifying patients as mild, moderate, or severe was observed between PGIS and HY or CISI-PD (58%) and the highest between CGIS and CISI-PD (84.3%). The four PD global severity scales agree moderately to strongly among them; clinician-based ratings estimate PD severity, as established by other measures, better than PGIS; and the CISI-PD showed the highest association with measures of impairment, disability, and quality of life., Competing Interests: P.M.-M. has received honorarium from AbbVie as speaker for a symposium, Editorial Viguera for a master course, UCB for lecturing in a summer course of the International University Menendez Pelayo, and honorarium from AbbVie for participating in the Advisory Board (epidemiological study). He has received Research grants from Parkinson’s UK, Parkinson’s Disease Non-Motor Group. M.R-V. has received honoraria from Boehringer-Ingelheim, Ever Neuro Pharma, UCB, Vanquish and MedLearning, and has participated in Advisory Boards for UCB Latin America. He has received grant from Boehringer Ingelheim for a workshop. J.C.M.-C. has received research support from Allergan, Lundbeck, and Abbvie, and speaking honoraria from Abbvie, Italfarmaco, Lundbeck, UCB, Allergan, Ipsen and Merz. N.G. has received honorarium from Allergan and Bago as speaker and director of a workshop. V.C.A. has received honorarium for speaking engagements at scientific meetings of Abbvie, and UCB Pharma, Allergan and Merz. W.F. is an associated editor of the IPMDS Website, Financial Committe, and Public Relationships Committee. He has received honoraria from Novartis for organizing Continued Medical Education Courses and has received research grants from Colciencias and the Universidad Nacional de Colombia. K.R.C. has received honorarium from UCB, Abbvie, Britannia, US Worldmeds, Mundipharma, Medtronic, Napp, Otsuka pharmaceuticals in the last 3 years and acted as a consultant for UCB, Abbvie, Britannia, Medtronic and Mundipharma. He has received funding from Parkinson’s UK, NIHR, European Commission, as well as educational grants from UCB, Britannia, Abbvie and Medtronic. M.M. received honoraria from speaking engagements at scientific meetings of Lundbeck and GSK. He has received grant support from Allergan and Pfizer and honoraria as consultant for Medtronic. The remaining authors declare no conflict of interest.

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder causing motor and non-motor symptoms that can affect independence, social adjustment and the quality of life (QoL) of both patients and caregivers. Studies designed to find diagnostic and/or progression biomarkers of PD are needed. We describe here the study protocol of COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015), an integral PD project based on four aspects/concepts: 1) PD as a global disease (motor and non-motor symptoms); 2) QoL and caregiver issues; 3) Biomarkers; 4) Disease progression., Methods/design: Observational, descriptive, non-interventional, 5-year follow-up, national (Spain), multicenter (45 centers from 15 autonomous communities), evaluation study. Specific goals: (1) detailed study (clinical evaluations, serum biomarkers, genetic studies and neuroimaging) of a population of PD patients from different areas of Spain, (2) comparison with a control group and (3) follow-up for 5 years. COPPADIS-2015 has been specifically designed to assess 17 proposed objectives., Study Population: approximately 800 non-dementia PD patients, 600 principal caregivers and 400 control subjects. Study evaluations: (1) baseline includes motor assessment (e.g., Unified Parkinson's Disease Rating Scale part III), non-motor symptoms (e.g., Non-Motor Symptoms Scale), cognition (e.g., Parkinson's Disease Cognitive Rating Scale), mood and neuropsychiatric symptoms (e.g., Neuropsychiatric Inventory), disability, QoL (e.g., 39-item Parkinson's disease Quality of Life Questionnaire Summary-Index) and caregiver status (e.g., Zarit Caregiver Burden Inventory); (2) follow-up includes annual (patients) or biannual (caregivers and controls) evaluations. Serum biomarkers (S-100b protein, TNF-α, IL-1, IL-2, IL-6, vitamin B12, methylmalonic acid, homocysteine, uric acid, C-reactive protein, ferritin, iron) and brain MRI (volumetry, tractography and MTAi [Medial Temporal Atrophy Index]), at baseline and at the end of follow-up, and genetic studies (DNA and RNA) at baseline will be performed in a subgroup of subjects (300 PD patients and 100 control subjects). Study periods: (1) recruitment period, from November, 2015 to February, 2017 (basal assessment); (2) follow-up period, 5 years; (3) closing date of clinical follow-up, May, 2022., Funding: Public/Private., Discussion: COPPADIS-2015 is a challenging initiative. This project will provide important information on the natural history of PD and the value of various biomarkers.

Background: Sutherland et al. (2011) suggested that, instead of risk factors for single neurodegenerative disorders (NDDs), there was a need to identify specific "drivers", i.e., risk factors with impact on specific deposits, such as amyloid-β, tau, or α-synuclein, acting across entities., Objectives and Methods: Redefining drivers as "neither protein/gene- nor entity-specific features identifiable in the clinical and general epidemiology of conformational NDDs (CNDDs) as potential footprints of templating/spread/transfer mechanisms", we conducted an analysis of the epidemiology of ten CNDDs, searching for patterns., Results: We identified seven potential drivers, each of which was shared by at least two CNDDs: 1) an age-at-exposure-related susceptibility to Creutzfeldt-Jakob disease (CJD) and several late-life CNDDs; 2) a relationship between age at onset, survival, and incidence; 3) shared genetic risk factors for CJD and late-life CNNDs; 4) partly shared personal (diagnostic, educational, behavioral, and social risk factors) predating clinical onset of late-life CNDDs; 5) two environmental risk factors, namely, surgery for sporadic CJD and amyotrophic lateral sclerosis, and Bordetella pertussis infection for Parkinson's disease; 6) reticulo-endothelial system stressors or general drivers (andropause or premenopausal estrogen deficiency, APOEɛ4, and vascular risk factors) for late-life CNDDs such as dementia/Alzheimer's disease, type-2 diabetes mellitus, and some sporadic cardiac and vascular degenerative diseases; and 7) a high, invariant incidence ratio of sporadic to genetic forms of mid- and late-life CNDDs, and type-2 diabetes mellitus., Conclusion: There might be a systematic epidemiologic pattern induced by specific proteins (PrP, TDP-43, SOD1, α-synuclein, amyloid-β, tau, Langerhans islet peptide, and transthyretin) or established combinations of these.

This study analyzes the relationship between gender and self-perceived health status in Spanish retirees and housewives from a sample of 1,106 community-dwelling older adults. A multivariate linear regression model was used in which self-perceived health status was measured by the EQ-5D visual analogue scale and gender according to work status (retired men and women and housewives). Retired males reported a significantly better health status than housewives. Self-perceived health status was closely associated with physical, mental, and functional health and leisure activities. Finally, being a woman with complete dedication to domestic work is associated with a worse state of self-perceived health.

Introduction: To be able to provide patients with a chronic illness personalised care, it is necessary to know how they live with their disorder. Today, there is no validated scale that assesses this aspect., Aim: To present the pilot study of the preliminary version of the living with a chronic process scale (EC-PC, from the name in Spanish) carried out in patients with Parkinson's disease (PD) in Spain., Patients and Methods: A preliminary version of the scale was produced from a literature review and the participation of experts in chronic processes and in PD. Fifteen patients, in all the different stages of PD, answered the preliminary version of the EC-PC (39 items) and a questionnaire about the EC-PC. The viability/acceptability and preliminary aspects of internal consistency were analysed., Results: No domain showed any floor or ceiling effects, but 43.6% of the items had a ceiling effect. The corrected item-total correlation was satisfactory, except in five items. The internal consistency of the five domains was satisfactory, with alpha indexes of 0.81-0.92 and item homogeneity coefficients of 0.19-0.43. The patients identified three items as ambiguous and difficult to answer. Based on these results, 12 items were eliminated and the final version of the EC-PC was drafted, its content being considered satisfactory following its evaluation by expert professionals., Conclusions: The EC-PC, pending validation, is a viable scale of potential interest in the clinical and community healthcare setting for assessing the ability to live with a chronic process like PD.

Introduction: Alzheimer's disease (AD) is a major threat for the well-being of an increasingly aged world population. The physiopathological mechanisms of late-onset AD are multiple, possibly heterogeneous, and not well understood. Different combinations of variables from several domains (i.e., clinical, neuropsychological, structural, and biochemical markers) may predict dementia conversion, according to distinct physiopathological pathways, in different groups of subjects., Methods: We launched the Vallecas Project (VP), a cohort study of non-demented people aged 70-85, to characterize the social, clinical, neuropsychological, structural, and biochemical underpinnings of AD inception. Given the exploratory nature of the VP, multidimensional and machine learning techniques will be applied, in addition to the traditional multivariate statistical methods., Results: A total of 1169 subjects were recruited between October 2011 and December 2013. Mean age was 74.4 years (SD 3.9), 63.5% of the subjects were women, and 17.9% of the subjects were carriers of at least one ε4 allele of the apolipoprotein E gene. Cognitive diagnoses at inclusion were as follows: normal cognition 93.0% and mild cognitive impairment (MCI) 7.0% (3.1% amnestic MCI, 0.1% non-amnestic MCI, 3.8% mixed MCI). Blood samples were obtained and stored for future determinations in 99.9% of the subjects and 3T magnetic resonance imaging study was conducted in 89.9% of the volunteers. The cohort is being followed up annually for 4 years after the baseline., Conclusion: We have established a valuable homogeneous single-center cohort which, by identifying groups of variables associated with high risk of MCI or dementia conversion, should help to clarify the early physiopathological mechanisms of AD and should provide avenues for prompt diagnosis and AD prevention.

Aims: Pilot studies applying a humanoid robot (NAO), a pet robot (PARO) and a real animal (DOG) in therapy sessions of patients with dementia in a nursing home and a day care center., Methods: In the nursing home, patients were assigned by living units, based on dementia severity, to one of the three parallel therapeutic arms to compare: CONTROL, PARO and NAO (Phase 1) and CONTROL, PARO, and DOG (Phase 2). In the day care center, all patients received therapy with NAO (Phase 1) and PARO (Phase 2). Therapy sessions were held 2 days per week during 3 months. Evaluation, at baseline and follow-up, was carried out by blind raters using: the Global Deterioration Scale (GDS), the Severe Mini Mental State Examination (sMMSE), the Mini Mental State Examination (MMSE), the Neuropsychiatric Inventory (NPI), the Apathy Scale for Institutionalized Patients with Dementia Nursing Home version (APADEM-NH), the Apathy Inventory (AI) and the Quality of Life Scale (QUALID). Statistical analysis included descriptive statistics and non-parametric tests performed by a blinded investigator., Results: In the nursing home, 101 patients (Phase 1) and 110 patients (Phase 2) were included. There were no significant differences at baseline. The relevant changes at follow-up were: (Phase 1) patients in the robot groups showed an improvement in apathy; patients in NAO group showed a decline in cognition as measured by the MMSE scores, but not the sMMSE; the robot groups showed no significant changes between them; (Phase 2) QUALID scores increased in the PARO group. In the day care center, 20 patients (Phase 1) and 17 patients (Phase 2) were included. The main findings were: (Phase 1) improvement in the NPI irritability and the NPI total score; (Phase 2) no differences were observed at follow-up.

Background: The purpose of this study was to identify incidence and survival patterns in conformational neurodegenerative disorders (CNDDs)., Methods: We identified 2563 reports on the incidence of eight conditions representing sporadic, acquired and genetic, protein-associated, i.e., conformational, NDD groups and age-related macular degeneration (AMD). We selected 245 papers for full-text examination and application of quality criteria. Additionally, data-collection was completed with detailed information from British, Swedish, and Spanish registries on Creutzfeldt-Jakob disease (CJD) forms, amyotrophic lateral sclerosis (ALS), and sporadic rapidly progressing neurodegenerative dementia (sRPNDd). For each condition, age-specific incidence curves, age-adjusted figures, and reported or calculated median survival were plotted and examined., Findings: Based on 51 valid reported and seven new incidence data sets, nine out of eleven conditions shared specific features. Age-adjusted incidence per million person-years increased from ≤1.5 for sRPNDd, different CJD forms and Huntington's disease (HD), to 1589 and 2589 for AMD and Alzheimer's disease (AD) respectively. Age-specific profiles varied from (a) symmetrical, inverted V-shaped curves for low incidences to (b) those increasing with age for late-life sporadic CNDDs and for sRPNDd, with (c) a suggested, intermediate, non-symmetrical inverted V-shape for fronto-temporal dementia and Parkinson's disease. Frequently, peak age-specific incidences from 20-24 to ≥90 years increased with age at onset and survival. Distinct patterns were seen: for HD, with a low incidence, levelling off at middle age, and long median survival, 20 years; and for sRPNDd which displayed the lowest incidence, increasing with age, and a short median disease duration., Interpretation: These results call for a unified population view of NDDs, with an age-at-onset-related pattern for acquired and sporadic CNDDs. The pattern linking age at onset to incidence magnitude and survival might be explained by differential pathophysiological mechanisms associated with specific misfolded protein deposits.

In our efforts to develop hybrid compounds of curcumin and melatonin as potential disease-modifying agents for Alzheimer's disease (AD), a potent lead hybrid compound, Z-CM-I-1, has been recently identified and biologically characterized in vitro. In this work, we report the in vivo effects of Z-CM-I-1 on AD pathologies in an APP/PS1 transgenic AD model. Our studies demonstrated that Z-CM-I-1 significantly decreased the accumulation of Aβ in the hippocampus and cortex regions of the brain and reduced inflammatory responses and oxidative stress after treatment for 12 weeks at 50 mg/kg per dose via oral administration. Furthermore, Z-CM-I-1 significantly improved synaptic dysfunction evidenced by the increased expression of synaptic marker proteins, PSD95 and synaptophysin, indicating its protective effects on synaptic degeneration. Lastly, we demonstrated that Z-CM-I-1 significantly increased the expression level of complexes I, II, and IV of the mitochondria electron transport chain in the brain tissue of APP/PS1 mice. Collectively, these results clearly suggest that Z-CM-I-1 is orally available and exhibits multifunctional properties in vivo on AD pathologies, thus strongly encouraging further development of this lead compound as a potential disease-modifying agent for AD patients.

Background: Health-related quality of life (HRQOL) in older adults is determined by personal conditions, as well as by the social and physical environment. The purpose of the present study was to describe the factors related to health conditions and residential environment that influence HRQOL of older adults., Methods: Data from 1815 cases came from three cross-sectional surveys on quality of life in older adults in Spain: non-institutionalized older adults (n = 1106), institutionalized older adults without dementia (n = 234) and institutionalized older adults with dementia (n = 475). Assessment instruments used were: Barthel Index, Short Portable Mental Status Questionnaire, Comorbidity Index, EQ-5D-3L (5 dimensions, EQ-index and EQ-VAS), and information about sociodemographic characteristics and social networks. Partial correlation and multivariate logistic regression analyses were carried out., Results: In group comparisons, institutionalized older adults showed a higher percentage of problems in the EQ-5D-3L dimensions than the non-institutionalized ones. Also, older adults with dementia presented less pain/discomfort and anxiety/depression than the other groups, but showed more problems in mobility, self-care and usual activities. EQ-Index showed a high association with functional independence, perceived health status and comorbidity. According to the logistic regression models, the Barthel Index was the most common determinant for most of EQ-5D-3L dimensions in all groups., Conclusion: Institutionalized older adults with dementia presented lower HRQOL than the other groups. Functional independence, comorbidity and cognitive status were the main HRQOL determinants in all groups. Maintenance and improvement of the functional condition might be translated into a higher HRQOL of older adults., (© 2014 Japan Geriatrics Society.)

The multimodal assessment of capacities in severe dementia (MAC-SD), a novel cognitive and functional assessment, was developed for use with patients with severe dementia. Its psychometric attributes were examined in a unicenter, open, observational study. The MAC-SD along with the Spanish language Severe Mini Mental Exam were administered to 103 patients with a diagnosis of severe dementia. Psychometric analyses were performed to determine acceptability, reliability, validity, and responsiveness. As a whole, the MAC-SD sections showed no floor effects, satisfactory internal consistency, reproducibility, construct validity, precision, and sensitivity to change. The MAC-SD performed as a useful, valid, and potentially responsive tool to measure cognition and functioning in the most advanced stages of dementia.

Objective: Apathy is one of the most frequent symptoms of dementia, still needing better measurement methods. The objective of this study was to validate a new scale for apathy in institutionalized persons with dementia (APADEM-NH)., Methods: The scale includes 26 items distributed in three dimensions: Deficit of Thinking and Self-Generated behaviors (DT): 13 items, Emotional Blunting (EB): 7 items, and Cognitive Inertia (CI): 6 items. The sample included 100 institutionalized patients (90% female) with probable Alzheimer disease (AD) (57%), possible AD (13%), AD + cerebral vascular disease (17%), Lewy body dementia (11%), and Parkinson associated to dementia (2%), covering all stages of dementia severity according to the Global Deterioration Scale and Clinical Dementia Rating. Additional assessments were the Apathy Inventory, Neuropsychiatric Inventory, Cornell Scale for Depression, and the tested scale. Re-test and inter-rater reliability were carried out in 50 patients., Results: All subscales lacked relevant floor and ceiling effects (<15%). Internal consistency for each dimension was (Cronbach's α): DT = 0.88, EB = 0.83, CI = 0.88; item-total correlations were >0.40; and item homogeneity 0.36-0.51. Test-retest reliability for the items was kW = 0.48-0.92; for the subscales, intraclass correlation coefficient (ICC) = 0.80-0.88; and for the total score, ICC = 0.90. Inter-rater reliability reached kW values of 0.84-1.00; subscales ICC, 0.97-0.99, and total score ICC, 0.99. Standard error of measurement for total score was 6.41 and internal validity ranged from rS = 0.69-0.80., Conclusions: APADEM-NH proved to be feasible, reliable, and valid for apathy assessment in institutionalized patients suffering mild to severe dementia, discerning well between apathy and depression., (Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Severity of PD is usually assessed by means of the motor and disability-based Hoehn and Yahr staging (HY), or clinician and patient global perceptions. Scores of more detailed assessments, as the MDS-UPDRS, have not been translated to a grading that allows assignment of score sections to severity levels. The objective of the present study is to determine cut-off points for PD severity levels based on the MDS-UPDRS., Methods: International, observational study. Applied assessments were: HY, MDS-UPDRS, Clinical Impression for Severity Index, and Clinical and Patient Global Impression of Severity. The coincidence in severity level (mild, moderate, severe) of at least two clinical classifications plus the patient's gradation was considered "the criterion of severity". Cut-off values for each MDS-UPDRS subscale was determined by triangulation of: 1) percentile 90 of the subscale total score; 2) receiver operating characteristic (ROC) analysis; and 3) ordinal logistic regression (OLR) model., Results: Sample was composed of 452 consecutive PD patients without dementia, 55.3% males, age 65.1 ± 10.7 years and PD duration 8.7 ± 6.3 years. All HY stages were represented. The "criterion", classified 275 patients (60.8% of the sample) as: mild PD, 149 (54.2%); moderate, 82 (29.8%); and severe, 44 (16%). The following MDS-UPDRS cut-off points between mild/moderate and moderate/severe levels were found: Part 1: 10/11 and 21/22; Part 2: 12/13 and 29/30; Part 3: 32/33 and 58/59; and Part 4: 4/5 and 12/13., Conclusion: Cut-off points to classify PD patients as mild, moderate, or severe on the basis of their MDS-UPDRS scores are proposed., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objectives: Active ageing, considered from the perspective of participation in leisure activities, promotes life satisfaction and personal well-being. The aims of this work are to define and explain leisure activity profiles among institutionalized older adults, considering their sociodemographic characteristics and objective and subjective conditions in relation to their quality of life., Methods: Two samples of institutionalized people aged 60 and over were analysed together: 234 older adults without dementia and 525 with dementia. Sociodemographic, economic, family and social network, and health and functioning variables were selected. Cluster analysis was applied to obtain activity profiles according to the leisure activities, and ordinal regression models were performed to analyse factors associated to activity level., Results: The sample was clustered into three groups of people: active (27%), moderately active (35%) and inactive people (38%). In the final regression model (Nagelkerke pseudo R(2) = 0.500), a higher level of activity was associated with better cognitive function (Pfeiffer scale), self-perceived health status and functional ability, as well as with a higher frequency of gathering with family and friends, and higher educational level., Conclusion: The decline in physical and mental health, the loss of functional capabilities and the weakening of family and social ties represent a significant barrier to active ageing in a context of institutionalization.

Introduction: People with progressive dementia evolve into a state where traditional neuropsychological tests are not effective. Severe Impairment Battery (SIB) and short form (SIB-s) were developed for evaluating the cognitive status in patients with severe dementia., Aim: To evaluate the psychometric attributes of the SIB-s in patients with severe dementia., Patients and Methods: 127 institutionalized patients (female: 86.6%; mean age: 82.6 ± 7.5 years-old) with dementia were assessed with the SIB-s, the Global Deterioration Scale (GDS), Mini-Mental State Examination (MMSE), Severe Mini-Mental State Examination (sMMSE), Barthel Index and FAST., Results: SIB-s acceptability, reliability, validity and precision were analyzed. The mean total score for scale was 19.1 ± 15.34 (range: 0-48). Floor effect was 18.1%, only marginally higher than the desirable 15%. Factor analysis identified a single factor explaining 68% of the total variance of the scale. Cronbach's alpha coefficient was 0.96 and the item-total corrected correlation ranged from 0.27 to 0.83. The item homogeneity value was 0.43. Test-retest and inter-rater reliability for the total score was satisfactory (ICC: 0.96 and 0.95, respectively). The SIB-s showed moderate correlation with functional dependency scales (Barthel Index: 0.48, FAST: -0.74). Standard error of measurement was 3.07 for the total score., Conclusions: The SIB-s is a reliable and valid instrument for evaluating patients with severe dementia in the Spanish population of relatively brief instruments.

Aim: This study aimed at analyzing the effect of quality of life (QoL) on mortality in older adults with dementia living in long-term care facilities., Methods: A prospective observational cohort study was carried out on 412 residents aged older than 60 years, diagnosed with dementia according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition. Besides assessment of QoL (EQ-5D index by proxy) and perceived health status (EQ-VAS), baseline measurements included severity of dementia (Clinical Dementia Rating Scale [CDR]), comorbidity (number of self-reported chronic conditions), disability evaluation (Barthel Index), cognitive state (Mini Examen Cognoscitivo, a validated and modified Spanish version of the Mini-Mental State Examination) and depression (Cornell Depression Scale for Dementia). Sociodemographic and clinical variables were analyzed as potential effect modifiers and confounders in the relationship between QoL and mortality using a multivariate logistic regression analysis., Results: After an 18-month follow up, 138 residents had died. Adjusting for CDR and Barthel Index, the odds of mortality were multiplied by 0.25 (95% CI 0.09-0.70) and 0.79 (95% CI 0.26-2.42) for every unit of change in the EQ-5D index in the residents with Cornell score <6 and ≥ 6, respectively., Conclusion: The present study suggests that the effect of QoL on mortality in institutionalized adults with dementia should take into account the presence or absence of depression. In addition, residents with a greater disability and more advanced dementia should be a target for interventions in rehabilitation care., (© 2014 Japan Geriatrics Society.)

Parkinson's disease (PD) is a progressive, neurodegenerative disorder whose symptoms and manifestations greatly deteriorate the health, functional status and quality of life of patients, has severe consequences on their families and caregivers and supposes a challenge for the healthcare system and society. The aim of this paper is to comprehensively and descriptively review studies on the economic impact of the disease and interventions, analyzing major contributing factors to direct and indirect costs in PD. Cost-of-illness studies have shown that costs of PD are high, mainly due to drug, hospitalization and productivity loss, and tend to increase as the disease progresses. Studies on PD treatment have suggested that therapies for advanced PD (levodopa/carbidopa intestinal gel and apomorphine) and surgical procedures are cost-effective and cost saving, despite their high expenditures; however, further research such as on the economic impact of non-motor manifestations or on the cost-effectiveness of non-medical interventions is still needed.