Applying machine-learning algorithms to large datasets such as those available in Huntington's disease offers the opportunity to discover hidden patterns, often not discernible to clinical observation.

A computer model of Huntington's disease progression is missing.

Longitudinal data encompassing 2079 assessment measures from four observational studies were integrated and machine-learning methods were applied to develop a probabilistic model of disease progression. The model was validated using a separate Enroll-HD dataset and compared with existing clinical reference assessments and CAG-age product.

Nine disease states were discovered based on 44 motor, cognitive, and functional measures, which correlated with reference assessments.

The validation set included 3158 participants of whom 61.5% had manifest disease. Analysis of transition times showed that "early-disease" states 1 and 2, which occur before motor diagnosis, lasted ~16 years.

Increasing numbers of participants had motor onset during "transition" states 3 to 5, which collectively lasted ~10 years, and the "late-disease" states 6 to 9 also lasted ~10 years. The annual probability of conversion from one of the nine identified disease states to the next ranged from 5% to 27%.

The natural history of Huntington's disease can be described by nine disease states of increasing severity. The ability to derive characteristics of disease states and probabilities for progression through these states will improve trial design and participant selection. © 2021 International Parkinson and Movement Disorder Society.

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To determine the long-term prognosis of the cognitive deficits progression in elderly people with amnestic mild cognitive impairment based on the analysis of the initial clinical and immunological parameters.

This study is based on a clinical and follow-up study of 252 outpatients with aMCI, who were observed in the Federal State Budgetary Scientific Institution «Mental Health Research Center» from 2018 to 2020.

The psychometric assessment complex included the following scales and tests: MMSE, MoCA, The 10 words test, BNT, David Wechsler's Scale, subtest 6, CDT, Memory test of 5 geometric shapes, BVRT Test, DRS - Mattis Dementia Rating Scale: Verbal fluency, DRS - Mattis Dementia Rating Scale, The Munsterberg Test.

As part of the study, the level of cytokines in the blood serum was determined in all patients by enzyme immunoassay, using diagnostic kits manufactured by Cytokine LLC.

In patients with a progression of aMCI syndrome, an increase in proinflammatory cytokines IL-1, IL-6, IL-8, TNF-α is initially detected, which may reflect the level of systemic inflammation or functional insufficiency of anti-inflammatory mechanisms.

In turn, the group with a subsequent improvement in cognitive functioning, on the contrary, is distinguished by an initially increased level of the anti-inflammatory interleukin system.

The scientists here provide new data on the presence of systemic inflammation and immune disturbances and their association with clinical course of disease in the majority of elderly patients with aMCI.

Signs of a chronic low-level systemic inflammatory response in patients with aMCI is the unfavorable prognosis criterion: in such patients, cognitive deficit significantly progresses or dementia due to Alzheimer disease develops within three years.

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Pramipexole or levodopa treatment has been suggested as a therapeutic method for Parkinson disease. Nonetheless, the combined effects of 2 drugs for Parkinson disease patients are not completely understood.The aim of this systematic review was to evaluate the clinical efficacy and safety of Pramipexole plus levodopa combination therapy in the treatment of Parkinson disease compared to that of levodopaL monotherapy, in order to confer a reference for clinical practice.

Randomized controlled trials of Pramipexole plus levodopa for Parkinson disease published up to April, 2020 were retrieved. Standardized mean difference, odds ratio, and 95% confidence interval were calculated and heterogeneity was measured with the I2 test. Sensitivity analysis was also carried out. The outcomes of interest were as follows: the efficacy, unified Parkinson disease rating scale scores, Hamilton depression rating scale score or adverse events.

Twenty-four RCTs with 2171 participants were included. Clinical efficacy of Pramipexole plus levodopa combination therapy was significantly better than levodopa monotherapy.

The Hamilton depression rating scale score showed significant decrease in the Pramipexole plus levodopa combination therapy compared to L monotherapy. In contrast to levodopa monotherapy, Pramipexole plus levodopa combination therapy reduced the number of any adverse events obviously in Parkinson disease patients.

Moreover, the safety profile of Pramipexole plus levodopa combination therapy was found to be better than that of levodopa monotherapy. Further well-designed, multicenter RCTs are needed to confirm the findings of this systematic review of the literature of the field.

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Thermoregulatory dysfunction in Parkinson's disease.

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Thermoregulatory dysfunction is considered to be the least investigated among all the autonomic disorders in Parkinson disease. Pathophysiological mechanisms of this phenomena involve as central, as peripheric parts of nervous system.

Dopamine deficiency in combination with peripheric autonomic dysfunction leads to temperature balance disturbance, which may be expressed by various clinical symptoms. Dopaminergic innervation of preoptic-anterior hypothalamus area plays a crucial role in thermoregulation function of central nervous system.

Current thermoregulatory tests give possibility not only to reveal sudomotor and heat dissipation disorders in patients with Parkinson disease, but also to make differential diagnosis with other neurodegenerative disorders. Early detection and treatment of thermoregulatory dysfunction may improve quality of life in patients with Parkinson disease.

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The abnormal accumulation of copper ions is considered to be one of the pathological factors of Alzheimer's disease, but the internal relationship between Cu and Alzheimer's disease progression is still not fully clear.

In this work, a sensitive and selective near-infrared fluorescent copper ion probe was designed for quantification and visualization of Cu level in lysates, living cells, living zebrafish and brain tissues of drosophila and mice with Alzheimer's disease.

By using this probe, the authors demonstrated that the content of Cu in the brains of Alzheimer's disease mice and drosophila enhanced nearly 3.5-fold and 4-fold than that of normal mice and drosophila, respectively.

More importantly, pathogenesis analysis revealed that elevated Cu led to changes in factors closely associated with Alzheimer's disease, such as the increasing of reactive oxygen species, the aggregation of amyloid-β protein and nerve cell cytotoxicity.

These findings could promote the understanding of the roles between Cu and Alzheimer's disease.

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Prior studies have demonstrated that Lyme disease is frequently over-diagnosed. However, few studies describe which conditions are misdiagnosed as Lyme disease.

This retrospective observational cohort study evaluated patients referred for Lyme disease to a Maryland academic center between 2000-2013 who lacked evidence for Borrelia burgdorferi infection. The primary outcome is clinically described diagnoses contributing to symptoms. Secondary outcomes included symptom duration and determination whether diagnoses were new or attributed to existing medical conditions.

Of 1261 referred patients, 1061 had no findings of active Lyme disease, with 690 receiving other diagnoses.

Among the 690 patients, the median symptom duration was 796 days, and a total of 139 discrete diagnoses were made. Infectious disease diagnoses comprised only 3.2%. Leading diagnoses were anxiety/depression, fibromyalgia, chronic fatigue syndrome, migraine disorder, osteoarthritis and sleep disorder/apnea.

Examples of less frequent but non-syndromic diseases newly diagnosed included multiple sclerosis, malignancy, Parkinson's disease, sarcoidosis or amyotrophic lateral sclerosis.

Most patients with long-term symptoms have either new or pre-existing disorders accounting for their symptoms other than Lyme disease, suggesting overdiagnosis in this population. Patients referred for consideration of Lyme disease for chronic symptoms deserve careful assessment for diagnoses other than Borrelia burgdorferi infection.

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Impaired Color Discrimination in Alzheimer Disease Dementia.

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Patients with Alzheimer disease dementia often show impaired orientation and navigation. Signage offers an opportunity to compensate for these deficits, communicate information efficiently and facilitate way finding. Certain properties of signs such as colors and contrasts may beneficially affect the uptake and processing of information particularly in ADD patients.

Thirty-six healthy older adults and 30 ADD patients performed a computerized color perception task that required discriminating different color combinations. The effects of different contrast features on performance accuracy and speed in the 2 experimental groups were examined by nonparametric mixed analysis of variances.

Analyses revealed a significant effect of contrast polarity on reaction times, significant effects of group on reaction times and errors as well as a marginally significant interaction of group×color on errors. All participants benefited from positive contrast polarity as indicated by increased performance speed. Furthermore, ADD patients reacted slower and less accurate than healthy controls, but showed higher accuracy at black-white and red-yellow than at blue-green color combinations.

The authors' findings suggest the implementation of signs with positive contrast polarity to ensure faster reactions. In addition, certain color combinations may enhance accuracy, particularly in patients with ADD.

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Mevidalen is a selective positive allosteric modulator (PAM) of the dopamine D1 receptor subtype.

The scientists objective was to assess the safety and efficacy of mevidalen for treatment of cognition in patients with Lewy body dementia (LBD).

Mevidalen resulted in significant, dose-dependent improvements of MDS-UPDRS total score. The 30 mg and 75 mg mevidalen doses significantly improved ADCS-CGIC scores compared to placebo.

Increases in blood pressure, adverse events, and cardiovascular serious adverse events were most pronounced at the 75 mg dose.

Mevidalen harnesses a novel mechanism of action that improves motor symptoms associated with Lewy body dementia on top of standard of care while improving or not worsening non-motor symptoms associated with traditional dopaminergic therapy.

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Whether multiple nutritional deficiencies have a synergic effect on mobility loss remains unknown. This study aims to evaluate associations between multi-nutritional deficits and physical performance evolution among community-dwelling older adults.

The scientists here included 386 participants from the Multidomain Alzheimer Preventive Trial not receiving omega-3 polyunsaturated fatty acid supplementation and who had available data on nutritional deficits.

Baseline nutritional deficits were defined as plasma 25 hydroxyvitamin D <20 ng/ml, plasma homocysteine >14 mol/L, or erythrocyte omega-3 PUFA index 4.87%.

The Short Physical Performance Battery, gait speed, and chair rise time were used to assess physical performance at baseline and after 6, 12, 24, 36, 48, and 60 months.

Within-group comparisons showed that physical function worsened over time, particularly in participants with 2 nutritional deficits; however, no between-group differences were observed when individuals without deficit and those with either 1 or 2 deficits were compared.

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The subthalamic nucleus (STN) is considered a key structure in motor, behavioral, and emotional control.

Although identification of the functional topography of the STN has therapeutic implications in the treatment of the motor features of Parkinson's disease, the details of its functional and somatotopic organization in humans are not well understood.

The aim of this study was to characterize the functional organization of the STN and its correlation with the motor outcomes induced by subthalamotomy.

A diffusion-weighted imaging/functional magnetic resonance imaging-driven somatotopic parcellation of the STN was defined to delineate the representation of the upper and lower limb in the STN.

Functional magnetic resonance imaging-driven parcellation demonstrated dual segregation of motor cortico-subthalamic projections in humans.

Moreover, the relationship between lesion topography and functional anatomy of the STN explains specific improvement in bradykinesia, rigidity, and tremor induced by subthalamotomy.

Identifying the functional topography of the STN will facilitate better definition of the optimal location for functional neurosurgical approaches, that is, electrode placement and lesion location, and improve specific cardinal features in Parkinson disease.

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