Benefits of Pilates in Parkinson's Disease: A Systematic Review and Meta-Analysis.

Pilates may be a beneficial method of exercise for people with Parkinson's disease (PD). However, no studies have critically reviewed the scientific evidence in this regard. The purpose of this study was to conduct a systematic review and meta-analysis on the effectiveness of Pilates as a rehabilitation strategy for PD. A systematic search of the electronic databases PubMed, PEDro, Scopus, and SPORTDiscus was conducted to identify studies related to the effect of Pilates on PD. The search timeframe ranged from the inception of each database to March 2019. The search resulted in the identification of four randomized controlled trials (RCTs) and four non-RCT studies. The methodological quality of the investigations ranged from poor to fair. The descriptive analysis of the eight investigations showed that Pilates resulted in beneficial effects on fitness, balance and functional autonomy. A subsequent meta-analysis on the four RCTs indicated that Pilates was more effective than traditional training programmes in improving lower limb function. Pilates can be safely prescribed for people with mild-to-moderate PD. Preliminary evidence indicates that its practice could have a positive impact on fitness, balance and physical function. Its benefits on lower-body function appear to be superior to those of other conventional exercises. Future randomized studies with greater samples are needed to confirm these observations.

Self-Paced Cycling Improves Cognition on Institutionalized Older Adults Without Known Cognitive Impairment: A 15-Month Randomized Controlled Trial.

This study aimed at identifying the effects of self-paced cycling on the cognitive and functional status and fall risk on institutionalized older adults without cognitive impairment. A total of 39 individuals were randomly assigned to an exercise group or to a control group. The exercise group participants cycled at their self-selected intensity at least for 15 min daily during 15 months. The control group participants performed recreational activities. The Mini-Mental State Examination, Fuld object memory evaluation, and symbol digit modality test were used for cognitive assessments. The Katz index, the timed "Up & Go" test, and the World Health Organization questionnaire were used to assess functional independence, mobility, and fall risk. Significant improvements were observed in the exercise group for global cognition and attention, visual scanning, and processing speed. Long-term self-paced cycling training seems to have a protective effect on cognitive status and attention, visual scanning, and processing speed in older institutionalized individuals.

A protective personal factor against disability and dependence in the elderly: an ordinal regression analysis with nine geographically-defined samples from Spain.

BACKGROUND: Sense of Coherence (SOC) is defined as a tendency to perceive life experiences as comprehensible, manageable and meaningful. The construct is split in three major domains: Comprehensibility, Manageability, and Meaningfulness. SOC has been associated with successful coping strategies in the face of illness and traumatic events and is a predictor of self-reported and objective health in a variety of contexts. In the present study we aim to evaluate the association of SOC with disability and dependence in Spanish elders. METHODS: A total of 377 participants aged 75 years or over from nine locations across Spain participated in the study (Mean age: 80.9 years; 65.3% women). SOC levels were considered independent variables in two ordinal logistic models on disability and dependence, respectively. Disability was established with the World health Organization-Disability Assessment Schedule 2.0 (36-item version), while dependence was measured with the Extended Katz Index on personal and instrumental activities of daily living. The models included personal (sex, age, social contacts, availability of an intimate confidant), environmental (municipality size, access to social resources) and health-related covariates (morbidity). RESULTS: High Meaningfulness was a strong protective factor against both disability (Odds Ratio [OR] = 0.50; 95% Confidence Interval [CI] = 0.29-0.87) and dependence (OR = 0.33; 95% CI = 0.19-0.58) while moderate and high Comprehensibility was protective for disability (OR = 0.40; 95% CI = 0.22-0.70 and OR = 0.39; 95%CI = 0.21-0.74), but not for dependence. Easy access to social and health resources was also highly protective against both disability and dependence. CONCLUSIONS: Our results are consistent with the view that high levels of SOC are protective against disability and dependence in the elderly. Elderly individuals with limited access to social and health resources and with low SOC may be a group at risk for dependence and disability in Spain.

Prevalence of disability in a composite ≥75 year-old population in Spain: a screening survey based on the International Classification of Functioning.

BACKGROUND: The prevalence and predictors of functional status and disability of elderly people have been studied in several European countries including Spain. However, there has been no population-based study incorporating the International Classification of Functioning, Disability and Health (ICF) framework as the basis for assessing disability. The present study reports prevalence rates for mild, moderate, and severe/extreme disability by the domains of activities and participation of the ICF. METHODS: Nine populations surveyed in previous prevalence studies contributed probabilistic and geographically defined samples in June 2005. The study sample was composed of 503 subjects aged ≥75 years. We implemented a two-phase screening design using the MMSE and the World Health Organization-Disability Assessment Schedule 2nd edition (WHO-DAS II, 12 items) as cognitive and disability screening tools, respectively. Participants scoring within the positive range of the disability screening were administered the full WHO-DAS II (36 items; score range: 0-100) assessing the following areas: Understanding and communication, Getting along with people, Life activities, Getting around, Participation in society, and Self-care. Each disability area assessed by WHO-DAS II (36 items) was reported according to the ICF severity ranges (No problem, 0-4; Mild disability, 5-24; Moderate disability, 25-49; Severe/Extreme disability, 50-100). RESULTS: The age-adjusted disability prevalence figures were: 39.17 ± 2.18%, 15.31 ± 1.61%, and 10.14 ± 1.35% for mild, moderate, and severe/extreme disability, respectively. Severe and extreme disability prevalence in mobility and life activities was three times higher than the average, and highest among women. Sex variations were minimal, although life activities for women of 85 years and over had more severe/extreme disability as compared to men (OR = 5.15 95% CI 3.19-8.32). CONCLUSIONS: Disability is highly prevalent among the Spanish elderly. Sex- and age-specific variations of disability are associated with particular disability domains.

An overview of L-2-hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype-phenotype study.

L-2-Hydroxyglutaric aciduria (L2HGA) is a rare, neurometabolic disorder with an autosomal recessive mode of inheritance. Affected individuals only have neurological manifestations, including psychomotor retardation, cerebellar ataxia, and more variably macrocephaly, or epilepsy. The diagnosis of L2HGA can be made based on magnetic resonance imaging (MRI), biochemical analysis, and mutational analysis of L2HGDH. About 200 patients with elevated concentrations of 2-hydroxyglutarate (2HG) in the urine were referred for chiral determination of 2HG and L2HGDH mutational analysis. All patients with increased L2HG (n=106; 83 families) were included. Clinical information on 61 patients was obtained via questionnaires. In 82 families the mutations were detected by direct sequence analysis and/or multiplex ligation dependent probe amplification (MLPA), including one case where MLPA was essential to detect the second allele. In another case RT-PCR followed by deep intronic sequencing was needed to detect the mutation. Thirty-five novel mutations as well as 35 reported mutations and 14 nondisease-related variants are reviewed and included in a novel Leiden Open source Variation Database (LOVD) for L2HGDH variants (http://www.LOVD.nl/L2HGDH). Every user can access the database and submit variants/patients. Furthermore, we report on the phenotype, including neurological manifestations and urinary levels of L2HG, and we evaluate the phenotype-genotype relationship.

Pathogenic cysteine mutations affect progranulin function and production of mature granulins.

Frontotemporal dementia with ubiquitin-positive inclusions (FTLD-U) can be caused by mutations in the progranulin gene (GRN). Progranulin (PGRN) is a cysteine-rich growth factor, which is proteolytically cleaved by elastase to produce several granulins (GRNs). All FTLD-U mutations in GRN characterized to date result in reduced secreted PGRN protein. We recently reported a Spanish family with progressive non-fluent aphasia and dementia in which a novel C521Y mutation segregates with disease. A second cysteine mutation (C139R) has also been reported to be disease specific. Allele-specific mRNA expression assays in brain reveal that the C521Y mutant allele is expressed at similar levels to the wild-type allele. Furthermore, plasma PGRN levels in C521Y carriers are comparable with non-carrier family relatives, suggesting that the mutation does not affect PGRN protein expression and secretion in vivo. Despite normal PGRN levels C521Y and C139R mutant GRNs show reduced neurite growth-stimulating activity in vitro. Further study revealed that these mutations also cause impaired cleavage of PGRN by elastase. Our data suggest that these mutations affect the function of full-length PGRN as well as elastase cleavage of PGRN into GRNs, leading to neurodegeneration.

Cortical atrophy and language network reorganization associated with a novel progranulin mutation.

Progressive nonfluent aphasia (PNFA) is an early stage of frontotemporal degeneration. We identified a novel Cys521Tyr progranulin gene variant in a PNFA family that potentially disrupts disulphide bridging causing protein misfolding. To identify early neurodegeneration changes, we performed neuropsychological and neuroimaging studies in 6 family members (MRI [magnetic resonance imaging], fMRI [functional MRI], and 18f-fluorodeoxygenlucose positron emission tomography, including 4 mutation carriers, and in 9 unrelated controls. Voxel-based morphometry (VBM) of the carriers compared with controls showed significant cortical atrophy in language areas. Grey matter loss was distributed mainly in frontal lobes, being more prominent on the left. Clusters were located in the superior frontal gyri, left inferior frontal gyrus, left middle frontal gyrus, left middle temporal gyri and left posterior parietal areas, concordant with (18)FDG-PET hypometabolic areas. fMRI during semantic and phonemic covert word generation (CWGTs) and word listening tasks (WLTs) showed recruitment of attentional and working memory networks in the carriers indicative of functional reorganization. During CWGTs, activation in left prefrontal cortex and bilateral anterior insulae was present whereas WLT recruited mesial prefrontal and anterior temporal cortex. These findings suggest that Cys521Tyr could be associated with early brain impairment not limited to language areas and compensated by recruitment of bilateral auxiliary cortical areas.

Nordic walking for people with relapsing-remittent multiple sclerosis: A case series study.

BACKGROUND: Patients with multiple sclerosis (MS) show fatigue, impaired gait and decreased functional mobility, which lead to a low quality of life (QoL). Low-cost and easy to perform exercise modalities having a positive impact on the aforementioned symptoms are needed. The performance of Nordic Walking (NW) could be a useful rehabilitation strategy but, to our knowledge, no study has been published in this regard as yet. This case series study aims at providing information regarding the usefulness and impact of a three-month NW program on self-perceived fatigue, functional mobility, physical fitness and QoL on a group of people with mild relapsing-remitting MS. METHODS: A case series study with multiple assessments was performed. Three data collection points at 1-week intervals for three weeks were done at baseline. The intervention consisted of a 12-weeks NW program with a total of four measurement occasions, one every three weeks. The Fatigue Severity Scale (FSS), the Timed up and Go test (TUG), the 6-Minute Walk test (6MWT) and the Multiple Sclerosis Impact Scale (MSIS-29), were used to assess the outcomes of the program on the participants' self-perceived fatigue, functional mobility, physical fitness and QoL, respectively. RESULTS: Of the 14 participants who volunteered for the study, five completed at least 80% of the planned sessions and were included in the final analysis. The intervention did not have a clinical significant impact on the participants' fatigue while its impact on their QoL showed mixed results. Positive trends were found for all the participants in their functional mobility and physical fitness. Regarding functional mobility, clinically important changes were observed in three participants. None of the observed changes in physical fitness achieved clinical significance. CONCLUSION: A 12-week Nordic walking program did not appear to be particularly feasible and had little impact on the functional levels on a group of people with mild relapsing-remitting MS. Given that beneficial effects were seen in some participants, and taken into account the low adherence rate observed, future studies should explore the feasibility of NW programs performed under different environmental conditions (i.e. outdoors) and including motivational strategies aimed at increasing participation.

Prevalence of dementia and major dementia subtypes in Spanish populations: a reanalysis of dementia prevalence surveys, 1990-2008.

BACKGROUND: This study describes the prevalence of dementia and major dementia subtypes in Spanish elderly. METHODS: We identified screening surveys, both published and unpublished, in Spanish populations, which fulfilled specific quality criteria and targeted prevalence of dementia in populations aged 70 years and above. Surveys covering 13 geographically different populations were selected (prevalence period: 1990-2008). Authors of original surveys provided methodological details of their studies through a systematic questionnaire and also raw age-specific data. Prevalence data were compared using direct adjustment and logistic regression. RESULTS: The reanalyzed study population (aged 70 year and above) was composed of Central and North-Eastern Spanish sub-populations obtained from 9 surveys and totaled 12,232 persons and 1,194 cases of dementia (707 of Alzheimer's disease, 238 of vascular dementia). Results showed high variation in age- and sex-specific prevalence across studies. The reanalyzed prevalence of dementia was significantly higher in women; increased with age, particularly for Alzheimer's disease; and displayed a significant geographical variation among men. Prevalence was lowest in surveys reporting participation below 85%, studies referred to urban-mixed populations and populations diagnosed by psychiatrists. CONCLUSION: Prevalence of dementia and Alzheimer's disease in Central and North-Eastern Spain is higher in females, increases with age, and displays considerable geographic variation that may be method-related. People suffering from dementia and Alzheimer's disease in Spain may approach 600,000 and 400,000 respectively. However, existing studies may not be completely appropriate to infer prevalence of dementia and its subtypes in Spain until surveys in Southern Spain are conducted.

Treadmill training combined with water and land-based exercise programs: Effects on Parkinson's disease patients.

BACKGROUND: There is a need for studies about the effects of treadmill training (TT) on Parkinson's disease (PD) patients when combined with other exercise training modalities. OBJECTIVE: To identify the effects of a multicomponent rehabilitation program on the illness impact, quality of life and fitness level in Parkinson's disease. METHODS: Participants were assigned to two exercise groups: water and land-based exercise (WL) or water and land-based exercise plus treadmill training (TWL). The water and land-based exercise group performed one water-based exercise and one land-based exercise session per week for 15 weeks. Participants in the water and land-based exercise plus treadmill training added two sessions of treadmill training to this schedule. The Senior Fitness Test (SFT) was used to assess the sample's fitness level. RESULTS: Participants in the water and land-based exercise Group experienced significant benefits in the disease impact (UPDRS t = 3.083; p = 0.029) and quality of life (PDQ-39 t = 2.942; p = 0.036). The addition of treadmill training did not have any significant effect on these variables. Both programs showed similar effects on the fitness components evaluated. CONCLUSION: Adding treadmill training to a combination of water and land-based exercise programs may have limited effects on quality of life and the impact on the disease.

L-2-hydroxyglutaric aciduria: clinical, neuroimaging, and neuropathological findings.

BACKGROUND: l-2-Hydroxyglutaric aciduria is a rare, infantile-onset, autosomal recessive organic aciduria affecting exclusively the central nervous system. To our knowledge, only 1 complete report of the neuropathological findings in an adult has been published. OBJECTIVE: To present the clinical, neuroimaging, and neuropathological findings of l-2-hydroxyglutaric aciduria. DESIGN: Case report. SETTING: Complexo Hospitalario de Pontevedra, Pontevedra, Spain. PATIENT: A 15-year-old boy who had early infantile-onset progressive psychomotor regression, mild choreodystonia affecting the distal part of the upper limbs, pyramidal signs, and epilepsy. RESULTS: The diagnosis of l-2-hydroxyglutaric aciduria was confirmed by the finding of highly elevated levels of l-2-hydroxyglutaric acid in the serum, urine, and cerebrospinal fluid. The neuroimaging findings showed striking confluent subcortical white matter lesions and minimal basal ganglia (pallidum, thalamic, and putaminal) abnormalities. The patient died of a spontaneous mesenteric thrombosis. The postmortem neuropathological findings showed spongiosis and cystic cavitations in subcortical white matter, with minimal abnormalities of the basal ganglia. The dentate nucleus, a structure usually affected in neuroimaging studies, showed minimal neuronal loss but was surrounded by important spongiosis and microvacuolation with astrocytic proliferation. CONCLUSIONS: This case reaffirms that l-2-hydroxyglutaric aciduria is a spongiform type of leukoencephalopathy with cystic cavitations predominating in the subcortical areas. Although the neuroimaging findings are highly characteristic of the disease, in this patient cerebellar abnormalities were minimal and dentate signal abnormalities were not present.

Unusual clinical findings and Complex III deficiency in a family with myotonic dystrophy.

Myotonic dystrophy type 1 (DM1), an autosomal dominant disease characterized by a CTG expansion in the 3' region of the DMPK gene in chromosome 19, is a highly heterogeneous disease. In this study, we present a family with early onset-classical type DM, and a homogeneous phenotype highlighted by severe neuromuscular symptoms and mental dysfunction with subcortical-type dementia. Neuroradiological abnormalities included brain atrophy, white matter lesions, and basal ganglia calcifications. A very large CTG triplet expansion was present in the DMPK locus in leukocytes in the three patients. One patient showed ragged-red fibers (RRF) and a defect complex III of the respiratory chain, but no mutations were found in the cytochrome b gene of mtDNA.

Investigation of the role of rare TREM2 variants in frontotemporal dementia subtypes.

Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous disorder. Rare TREM2 variants have been recently identified in families affected by FTD-like phenotype. However, genetic studies of the role of rare TREM2 variants in FTD have generated conflicting results possibly because of difficulties on diagnostic accuracy. The aim of the present study was to investigate associations between rare TREM2 variants and specific FTD subtypes (FTD-S). The entire coding sequence of TREM2 was sequenced in FTD-S patients of Spanish (n = 539) and German (n = 63) origin. Genetic association was calculated using Fisher exact test. The minor allele frequency for controls was derived from in-house genotyping data and publicly available databases. Seven previously reported rare coding variants (p.A28V, p.W44X, p.R47H, p.R62H, p.T66M, p.T96K, and p.L211P) and 1 novel missense variant (p.A105T) were identified. The p.R47H variant was found in 4 patients with FTD-S. Two of these patients showed cerebrospinal fluid pattern of amyloid beta, tau, and phosphorylated-tau suggesting underlying Alzheimer's disease (AD) pathology. No association was found between p.R47H and FTD-S. A genetic association was found between p.T96K and FTD-S (p = 0.013, odds ratio = 4.23, 95% Confidence Interval [1.17-14.77]). All 6 p.T96K patients also carried the TREM2 variant p.L211P, suggesting linkage disequilibrium. The remaining TREM2 variants were found in 1 patient, respectively, and were absent in controls. The present findings provide evidence that p.T96K is associated with FTD-S and that p.L211P may contribute to its pathogenic effect. The data also suggest that p.R47H is associated with an FTD phenotype that is characterized by the presence of underlying AD pathology.

[Effects of aquatic physical exercise on the kinematic gait pattern in patients with Parkinson's disease: a pilot study]. / Efecto del ejercicio acuatico sobre la cinematica del patron de marcha en pacientes con enfermedad de Parkinson: un estudio piloto.

AIM. To determine the effects of an aquatic-based physical exercise program on gait parameters of patients with Parkinson's disease (PD). PATIENTS AND METHODS. A total of nine patients diagnosed with idiopathic PD (stages I-III according to the Hoehn and Yahr scale) carried out an aquatic physical exercise program which lasted for five months, with one session per week. A three-dimensional biomechanical analysis was used to determine the effects of the program on several kinematic variables (walking speed, cadence, stride length, step time, single and double support time, angles of the hip, knee and ankle joints) which were assessed by a treadmill-walking test. RESULTS. At the end of the program, significant improvement in walking speed, stride length and on the relationship between single and double support time (p < 0,05). Although improvements in all tested ranges of motion were obtained, these did not reach statistical significance. CONCLUSIONS. Aquatic-based physical exercise seems to have positive effects in some aspects of the gait kinematics parameters present in the typical gait pattern of patients with PD.

Prevalence of Essential Tremor on Arosa Island, Spain: a Community-based, Door-to-Door Survey.

BACKGROUND: The prevalence of essential tremor (ET) is still not well understood and the various studies performed to date have generated highly variable results. Few epidemiologic studies on the prevalence of ET have been reported from Spain. METHODS: A one-stage door-to-door survey was conducted on Arosa Island, northwestern Spain, to determine the prevalence of ET in the population aged 65 years and older. The diagnostic criteria for ET were the presence of non-dystonic head tremor or moderate- to severe-amplitude tremor on at least four tests of the revised Washington Heights-Inwood Genetic Study of Essential Tremor (WHIGET) Scale. RESULTS: A total of 65 individuals with ET (28 males, 37 females) were identified, resulting in a crude prevalence of 8.63% (adjusted rate 8.42%). Prevalence increased with advancing age. There were no significant differences in prevalence between sexes in any of the age groups. Among the prevalent cases, 12.3% (n = 8) had been previously diagnosed. Only 29.2% (n = 19) reported functional disability caused by tremor. A family history of tremor was reported in 35.4% (n = 23). DISCUSSION: The prevalence of ET was higher than that seen in similar populations in Spain and other countries. A high proportion of those with ET were previously undiagnosed. Since Arosa Island has been a relatively isolated area, these results might indicate a predominant role, at least in the elderly, for genetic factors in the development of ET.

C9ORF72 repeat expansion in Australian and Spanish frontotemporal dementia patients.

A hexanucleotide repeat expansion in C9ORF72 has been established as a common cause of frontotemporal dementia (FTD). However, the minimum repeat number necessary for disease pathogenesis is not known. The aims of our study were to determine the frequency of the C9ORF72 repeat expansion in two FTD patient collections (one Australian and one Spanish, combined n = 190), to examine C9ORF72 expansion allele length in a subset of FTD patients, and to examine C9ORF72 allele length in 'non-expansion' patients (those with <30 repeats). The C9ORF72 repeat expansion was detected in 5-17% of patients (21-41% of familial FTD patients). For one family, the expansion was present in the proband but absent in the mother, who was diagnosed with dementia at age 68. No association was found between C9ORF72 non-expanded allele length and age of onset and in the Spanish sample mean allele length was shorter in cases than in controls. Southern blotting analysis revealed that one of the nine 'expansion-positive' patients examined, who had neuropathologically confirmed frontotemporal lobar degeneration with TDP-43 pathology, harboured an 'intermediate' allele with a mean size of only ∼65 repeats. Our study indicates that the C9ORF72 repeat expansion accounts for a significant proportion of Australian and Spanish FTD cases. However, C9ORF72 allele length does not influence the age at onset of 'non-expansion' FTD patients in the series examined. Expansion of the C9ORF72 allele to as little as ∼65 repeats may be sufficient to cause disease.

Medical, environmental and personal factors of disability in the elderly in Spain: a screening survey based on the International Classification of Functioning.

OBJECTIVES: The International Classification of Functioning, Disability and Health (ICF) advocates a multifactorial and multifaceted conceptualization of disability. The objective of this study was to ascertain major medical, environmental and personal determinants of severe/extreme disability among the elderly population in Spain. The assessment scheme was consistent with the ICF model of disability. METHODS: Nine populations contributed probabilistic or geographically-defined samples following a two-phase screening design. The Mini-Mental State Examination and the 12-item version of the World Health Organization-Disability Assessment Schedule, 2(nd) ed. (WHO-DAS II), were used as cognitive and disability screening tools, respectively. Positively screened individuals underwent clinical work-up for dementia and were administered the 36-item version of the WHO-DAS II to estimate ICF disability levels. We used logistic regression for the purposes of data combination, adjusted for age and sex in all analyses. RESULTS: The sample was composed of 503 participants aged ≥ 75 years. Alzheimers disease and depression were highly predictive of severe/extreme disability (OR: 17.40, 3.71). Good access to social services was strongly associated with a low level or absence of disability (OR: 0.05 to 0.18). Very difficult access to services and having dementia or another psychiatric disorder were associated with an increase in disability (OR: 66.06). There was also a significant interaction effect between access to services and neurological disorders (OR: 12.74). CONCLUSIONS: Disability is highly prevalent among the Spanish elderly and is influenced by medical, social and personal factors. Disability could potentially be reduced by ensuring access to social services, preventing dementia and stroke, and treating depression.