Motor Symptomatology Research Articles

Interplay Between Inhibitory Control and Behavioural Flexibility: Impact of Dorsomedial Striatal Dopamine Denervation in Mice

In Parkinson’s disease, nigrostriatal dopamine (DA) degeneration is commonly associated with motor symptomatology. However, non-motor symptoms affecting cognitive function, such as behavioural flexibility and inhibitory control may also appear early in the disease. Here we addressed the role of DA innervation of the dorsomedial striatum (DMS) in mediating these functions in 6-hydroxydopamine (6-OHDA)-lesioned mice using instrumental conditioning in various tasks. Behavioural flexibility was studied in a simple reversal task (nose-poke discrimination) or in reversal of a two-step sequence of actions (central followed by lateral nose-poke). Our results show that mild DA lesions of the DMS induces behavioural flexibility deficits in the sequential reversal learning only. In the first sessions following reversal of contingency, lesioned mice enhanced perseverative sequence of actions to the initial rewarded side then produced premature responses directly to the correct side omitting the central response, thus disrupting the two-step sequence of actions. These deficits may be linked to increased impulsivity as 6-OHDA-lesioned mice were unable to inhibit a previously learned motor response in a cued response inhibition task assessing proactive inhibitory control. Our findings show that partial DA denervation restricted to DMS impairs behavioural flexibility and proactive response inhibition in mice. Such striatal DA lesion may thus represent a valuable animal model for exploring deficits in executive control documented in early stage of Parkinson’s disease.

Assessment of non motor symptoms in Parkinsonism syndromes

BACKGROUND: James Parkinson described Parkinson's disease in 1817. He described the motor and non motor findings in Parkinson's disease. Despite this emphasis on motor symptomatology, several studies have shown that the non-motor symptoms of Parkinson's disease, such as depression, psychosis, falls, and sleep disturbance, have greater significance when assessed by quality-of-life measures, institutionalization rates, or health economics.. OBJECTIVE:- To study the prevalence and duration of non motor symptoms in patients with parkinsonism syndromes.

Determinants of self-efficacy in patients with Parkinson's disease.

Self-efficacy is the individual's assessment of his or hers ability to complete a specific task successfully and has been closely related to self-management and quality of life in several diseases. To investigate self-efficacy in a population of Parkinson's disease (PD) patients in Mexico and study the factors that are associated with this measure. We carried out a cross-sectional observational study involving patients with PD in an outpatient neurology clinic in Mexico, using the following instruments: Spanish version of the Chronic Disease Self-Efficacy Scale (CDSES), Quality of Life Questionnaire PDQ-8, Movement Disorders Society-Unified Parkinson's disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment (MoCA), and Non-Motor Symptom Scale (NMSS). Clinical and demographic variables were also recorded. We included 73 patients with a mean age of 65 years and most patients were male. Patients with lower CDSES scores (<7.75) had worse scores in MDS-UPDRS, NMSS, and PDQ-8 scales. CDSES scores were significantly correlated with MDS-UPDRS Part I (r=-0.497, p=<0.001), Part II (r= -0.271, p=0.020), Part III (r=-0.304, p=<0.001), PDQ-8 (r=-0.472, p=<0.001), and NMSS (r=-0.504, p=<0.001). Furthermore, when assessing the simultaneous effect of covariates associated with CDSES score, only Mood/Apathy domain of NMSS was significant (beta= -0.446, t= -3.807, p= 0.012). PD patients with lower self-efficacy scores had worse motor and non-motor symptomatology and quality of life. Mood/Apathy disorders were negatively associated with self-efficacy and contributed significantly to this measure.

High perceived isolation and reduced social support affect headache impact levels in migraine after the Covid-19 outbreak: A cross sectional survey on chronic and episodic patients.

ABSTRACTBackgroundPsychosocial variables are key factors influencing psycho-physical equilibrium in migraine patients. Social isolation and vulnerability to stressors may prevent efficient psychological adjustment negatively affecting adaptation to life changes, as that imposed during Covid-19 lockdown. Here, we explored psychosocial dimensions and changes in clinical condition during Covid-19 lockdown in migraine patients, with regard to migraine type and headache impact.MethodsSixty-four migraine patients (32 episodic and 32 chronic) and 64 healthy control subjects were included in a case-control cross-sectional study. A two-step clustering procedure split patients into two clusters, based on the Headache Impact Test. Perceived global distress, loneliness, empathy, and coping levels were compared in groups, as well as changes in clinical condition.ResultsMigraine patients reported higher general loneliness and lower social support compared to healthy control subjects. Emotional loneliness was more marked in patients with higher headache impact. This subgroup of patients more frequently reported changes in the therapeutic and care paths as the perceived cause of the occurrence of motor or extra-motor symptomatology.ConclusionsMigraine patients, especially those more severely affected, proved more vulnerable than healthy control subjects to Covid-19 lockdown. Long-lasting interruption of social interactions may be detrimental in fragile patients that are in need of structured support interventions to maintain psycho-physical wellbeing.

PassFlow: a multimodal workflow for predicting deep brain stimulation outcomes.

Deep Brain Stimulation (DBS) is a proven therapy for Parkinson's Disease (PD), frequently resulting in an enhancement of motor function. Nonetheless, several undesirable side effects can occur after DBS, which can worsen the quality of life of the patient. Thus, the clinical team has to carefully select patients on whom to perform DBS. Over the past decade, there have been some attempts to relate pre-operative data and DBS clinical outcomes, with most focused on the motor symptomatology. In this paper, we propose a machine learning-based method able to predict a large number of DBS clinical outcomes for PD. We propose a multimodal pipeline, referred to as PassFlow, which predicts 84 clinical post-operative clinical scores. PassFlow is composed of an artificial neural network to compress clinical information, an image processing method from the state-of-the-art to extract morphological biomarkers our of T1 imaging, and an SVM to perform the regressions. We validated PassFlow on 196 PD patients who undergone a DBS. PassFlow showed correlation coefficients as high as 0.71 and were able to significantly predict 63 out of the 84 scores, outperforming a comparative linear method. The number of metrics that are predicted with this pre-operative information was also found to be correlated with the number of patients with this information available, indicating that the PassFlow method is still actively learning. We presented a novel, machine learning-based pipeline to predict a variety of post-operative clinical outcomes of DBS for PD patients. PassFlow took into account various bio-markers, arising from different data modalities, showing high correlation coefficients for some scores from pre-operative data only. It indicates that many clinical outcomes of DBS can be predicted agnostic to the specific simulation parameters, as PassFlow has been validated without such stimulation-related information.

Melatonin as a Chronobiotic and Cytoprotective Agent in Parkinson's Disease.

This article discusses the role that melatonin may have in the prevention and treatment of Parkinson’s disease (PD). In parkinsonian patients circulating melatonin levels are consistently disrupted and the potential therapeutic value of melatonin on sleep disorders in PD was examined in a limited number of clinical studies using 2–5 mg/day melatonin at bedtime. The low levels of melatonin MT1 and MT2 receptor density in substantia nigra and amygdala found in PD patients supported the hypothesis that the altered sleep/wake cycle seen in PD could be due to a disrupted melatonergic system. Motor symptomatology is seen in PD patients when about 75% of the dopaminergic cells in the substantia nigra pars compacta region degenerate. Nevertheless, symptoms like rapid eye movement (REM) sleep behavior disorder (RBD), hyposmia or depression may precede the onset of motor symptoms in PD for years and are index of worse prognosis. Indeed, RBD patients may evolve to an α-synucleinopathy within 10 years of RBD onset. Daily bedtime administration of 3–12 mg of melatonin has been demonstrated effective in RDB treatment and may halt neurodegeneration to PD. In studies on animal models of PD melatonin was effective to curtail symptomatology in doses that allometrically projected to humans were in the 40–100 mg/day range, rarely employed clinically. Therefore, double-blind, placebo-controlled clinical studies are urgently needed in this respect.

A Long-Term, Real-Life Parkinson Monitoring Database Combining Unscripted Objective and Subjective Recordings

Accurate real-life monitoring of motor and non-motor symptoms is a challenge in Parkinson’s disease (PD). The unobtrusive capturing of symptoms and their naturalistic fluctuations within or between days can improve evaluation and titration of therapy. First-generation commercial PD motion sensors are promising to augment clinical decision-making in general neurological consultation, but concerns remain regarding their short-term validity, and long-term real-life usability. In addition, tools monitoring real-life subjective experiences of motor and non-motor symptoms are lacking. The dataset presented in this paper constitutes a combination of objective kinematic data and subjective experiential data, recorded parallel to each other in a naturalistic, long-term real-life setting. The objective data consists of accelerometer and gyroscope data, and the subjective data consists of data from ecological momentary assessments. Twenty PD patients were monitored without daily life restrictions for fourteen consecutive days. The two types of data can be used to address hypotheses on naturalistic motor and/or non-motor symptomatology in PD.

Effects of Virtual Reality with Motor Imagery Techniques in Patients with Parkinson’s Disease: Study Protocol for a Randomized Controlled Trial

Background: Parkinson’s disease (PD) is one of the most common neurological disorders, of insidious onset, with major motor symptomatology including bradykinesia, rest tremor, rigidity, and postural disturbances. Virtual reality (VR) and motor imagery (MI) are among the more innovative techniques for the rehabilitation of patients with PD which promote motor learning both through explicit and implicit processes. This study is unique in that it will examine the combined effects of VR and MI on motor function, balance and activities of daily living (ADLs) in patients with PD. Objective: The aim of this work is to investigate the effects of VR with MI techniques in addition to routine physical therapy on motor function, balance, and ADLs in patients with PD. Methods: This is a two-armed parallel design, single-blinded (assessor blinded), single-centered, randomized controlled trial, and the study protocol is based on SPIRIT guidelines. Thirty-four patients with PD (Modified Hoehn and Yahr stages I–III) will be randomly allocated with a 1:1 ratio into Group A (control group) and Group B (treatment group). Group A will be given routine physical therapy in 40-min sessions and 20 min of walking and cycling with a short period of rest, every alternate day (3 days per week) for 12 weeks, while for Group B routine physical therapy protocols along with VR and MI will be used in 60-min sessions, every alternate day (3 days per week) for 12 weeks. The primary outcome measures are as follows: (i) the Unified PD Rating Scale (UPDRS; part III), (ii) the Berg Balance Scale (BBS), and the Activities-Specific Balance Confidence Scale (ABC). The secondary outcome measure is the UPDRS (part II). Assessments will be recorded at baseline, the sixth and twelfth weeks of therapy, and 1 month after the discontinuation of therapy. Clinical Study Registration: This randomized controlled prospective study was registered with the Iranian Registry of clinical trials (IRCT20200221046567N1) on April 1, 2020 (https://www.irct.ir/trial/46073).

Isolated compression of the ulnar motor branch due to carpal joint ganglia: clinical series, surgical technique and postoperative outcomes

The entrapment of the ulnar nerve in Guyon’s canal (GC) is a well-known wrist canalicular syndrome which is usually followed by a gradual combination of both sensitive and motor symptomatology. However, GC nerve compression could also cause a pure hand motor dysfunction. This condition, less frequent than the classic Guyon’s syndrome, can be difficult to diagnose. Authors report a case series of eight patients affected by isolated compression of the ulnar nerve motor branch, due to piso-triquetrum or triquetro-hamate joint ganglia. Surgical technique and postoperative outcomes are discussed in this paper. The isolated compression of the ulnar nerve motor branch is a very rare clinical condition which is often linked to several causes. The rarity of the pathology is probably due to lack of knowledge and therefore to the difficulty in formulating a correct diagnosis. Surgical treatment appears to be decisive in most cases, although late diagnosis often leads to incomplete functional recovery.

Effects of a High-Intensity Progressive-Cycle Program on Quality of Life and Motor Symptomatology in a Parkinson's Disease Population: A Pilot Randomized Controlled Trial.

The benefits of aerobic exercise in persons with Parkinson's disease (PD) have been widely studied. Recent studies support the use of high-intensity aerobic exercise to improve oxidative stress values and functional performance in PD patients. The aim of this study is ascertain whether high-intensity aerobic training with lower extremity cycle ergometers and balance training can improve motor symptoms and quality of life in a PD population of Hoehn and Yahr disability score 1-3. The intervention took place in rehabilitation centers in secondary care. A pilot randomized controlled trial was carried out with 14 outpatients participated in the 8-week study. They were composed of a control group (CG; n = 7) that followed a balance protocol and an experimental group (EG; n = 7) that performed high-intensity (70% heart rate reserve) aerobic workout using a lower extremity cycle ergometer and a balance protocol once a week. The primary outcome measures included the 8-Foot Up-and-Go test, 6-Minute Walk test, 2-Minute Step test, Parkinson's Disease Questionnaire (PDQ39), Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Tinetti test. Significant improvements in the PDQ39 (F1.23 = 3.102; sig = 0.036), the MDS-UPDRS III (F1.23 = 4.723; sig = 0.033), and MDS-UPDRS Total (F1.23 = 4.117; sig = 0.047) were observed in the EG as against the CG. After taking into account the number of subjects in each group, the results suggest that the PD population can withstand high-intensity aerobic workouts with a lower extremity cycle ergometer. This exercise is a beneficial therapy for them because it reduces motor symptoms of the disease and furthermore increases and improves patient's quality of life.

Cannabinoids and the Coronavirus.

Cannabinoids and the Coronavirus.

Prognostic factors of Rapid symptoms progression in patients with newly diagnosed parkinson’s disease

Tracking symptoms progression in the early stages of Parkinson's disease (PD) is a laborious endeavor as the disease can be expressed with vastly different phenotypes, forcing clinicians to follow a multi-parametric approach in patient evaluation, looking for not only motor symptomatology but also non-motor complications, including cognitive decline, sleep problems and mood disturbances. Being neurodegenerative in nature, PD is expected to inflict a continuous degradation in patients' condition over time. The rate of symptoms progression, however, is found to be even more chaotic than the vastly different phenotypes that can be expressed in the initial stages of PD. In this work, an analysis of baseline PD characteristics is performed using machine learning techniques, to identify prognostic factors for early rapid progression of PD symptoms. Using open data from the Parkinson's Progression Markers Initiative (PPMI) study, an extensive set of baseline patient evaluation outcomes is examined to isolate determinants of rapid progression within the first two and four years of PD. The rate of symptoms progression is estimated by tracking the change of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score over the corresponding follow-up period. Patients are ranked according to their progression rates and those who expressed the highest rates of MDS-UPDRS total score increase per year of follow-up period are assigned into the rapid progression class, using 5- and 10-quantiles partition. Classification performance against the rapid progression class was evaluated in a per quantile partition analysis scheme and in quantile-independent approach, respectively. The results shown a more accurate patient discrimination with quantile partitioning, however, a much more compact subset of baseline factors is extracted in the latter, making a more suitable for actual interventions in practice. Classification accuracy improved in all cases when using the longer 4-year follow-up period to estimate PD progression, suggesting that a prolonged patient evaluation can provide better outcomes in identifying rapid progression phenotype. Non-motor symptoms are found to be the main determinants of rapid symptoms progression in both follow-up periods, with autonomic dysfunction, mood impairment, anxiety, REM sleep behavior disorders, cognitive decline and memory impairment being alarming signs at baseline evaluation, along with rigidity symptoms, certain laboratory blood test results and genetic mutations.

Impact of Levodopa in Lung Functions in Patients with Parkinson Disease.

Background:Parkinson's disease (PD) is the second-most common neurodegenerative disorder known primarily by its motor symptomatology. These motor manifestations are also hypothesised to affect the respiratory muscular function of PD patients contributing to restrictive pattern of ventilatory dysfunction. Previous reports attempting to detect these abnormalities through spirometric assessments have been inconclusive. Attempts at reversal of the restrictive abnormalities by levodopa therapy too, have yielded conflicting results.Objectives:This study aims to classify spirometric abnormalities in asymptomatic PD patients after levopopa withdrawal and document changes after levodopa replacement.Methods:Thirty-six non-smoker PD patients without pre-existing respiratory abnormalities were enrolled. Their standard spirometric values- FEV1, FVC and FEV1/FVC, were noted before and after their morning levodopa dose.Results:Nineteen patients had abnormal PFT values at baseline - 14 restrictive and 5 obstructive defects. Fourteen patients showed improvement in their pulmonary performances after dopamine administration with 6 showing complete reversibility. Statistically significant improvement in the post-levodopa FVC values was seen in patients with restrictive disorder (P value=0.04) but not for obstructive disorders.Discussions:This pilot study characterised that 39% of PD patients had restrictive ventilatory defects prior to morning dopamine administration. Of these, 40% showed improvement after levodopa administration.Conclusion:Restrictive defects are common in PD patients which are evident on routine spirometric screening. These defects are reversible on levodopa administration.

Prior MDMA administration aggravates MPTP-induced Parkinsonism in macaque monkeys

The aim of this study was to investigate the causal role of an early serotonin injury on parkinsonian-like motor symptomatology. Monkeys were pretreated with 3,4-methylenedioxy-N-methamphetamine (MDMA, or “ecstasy”), known to lesion serotonergic fibers, before being administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We combined behavioural assessment, PET imaging, and immunohistochemistry. Strikingly, prior MDMA administration aggravated MPTP-induced Parkinsonism and associated dopaminergic injury. Monkeys with early MDMA lesions developed parkinsonian deficits more rapidly and more severely. Interestingly, not all symptoms were impacted. Bradykinesia, rigidity and freezing were not affected by early MDMA lesions, whereas spontaneous activities, tremor and abnormal posture were significantly aggravated. Finally, as expected, MDMA induced a decrease of the serotonergic transporter availability. More surprisingly, we found that MDMA evoked also a decreased availability of the dopaminergic transporter to a lesser extent. Altogether, these results show that MDMA administration in non-human primates not only damage serotonergic terminals, but also injure dopaminergic neurons and enhance MPTP neurotoxic action, a completely new result in primates.

Effects of a High-intensity Progressive-cycle Program on Quality of Life and Motor Symptomatology in Parkinson's Disease

Effects of a High-intensity Progressive-cycle Program on Quality of Life and Motor Symptomatology in Parkinson's Disease

Efficacy of safinamide on non-motor symptoms in a cohort of patients affected by idiopathic Parkinson's disease.

The primary endpoint of this work was to evaluate the effect of safinamide on non-motor symptoms (NMS) in patients affected by idiopathic Parkinson's disease (PD) complicated by motor fluctuations. We retrospectively collected data from 20 subjects affected by idiopathic PD in treatment with L-dopa alone or in combination with dopamine agonists, who began to be treated with safinamide due to the occurrence of motor fluctuations. Secondary endpoints included SCales for Outcomes in Parkinson's disease (SCOPA) Motor Scale, cognitive assessment, the Hoehn and Yahr stage, Clinical Impression of Severity Index for Parkinson's Disease, Hospital Anxiety And Depression Scale, Physical and Mental Fatigue, Parkinson's disease Sleep Scale, Parkinson's Disease Questionnaire-8 (PDQ-8) and EQ-5D. Each one of these scales/questionnaires was performed at baseline and T1. For efficacy analyses, continuous variables were treated with descriptive statistics, using mean and standard deviations. A non-parametric test (the Friedman test) was carried out to evaluate the statistical significance of the results observed. We found a statistically significant reduction of the total score of NMS, of 6 domains out of 9, and 13 items out of 30. A statistically significant reduction of SCOPA Motor Scale, PDQ-8, and CISI was also detected. In conclusion, our data showed a positive effect of safinamide on NMS and confirm its positive effect on motor symptomatology.

Striatal cholinergic interneurons regulate cognitive and affective dysfunction in partially dopamine-depleted mice.

Early non-motor symptoms such as mood disorders and cognitive deficits are increasingly recognised in Parkinson's disease (PD). They may precede the characteristic motor symptomatology caused by dopamine (DA) neuronal loss in the substantia nigra pars compacta (SNc). It is well known that striatal cholinergic interneurons (ChIs) are emerging as key regulators of PD motor symptom, however, their involvement in the cognitive and affective alterations occurring in the premotor phase of PD is poorly understood. We used optogenetic photoinhibition of striatal ChIs in mice with mild nigrostriatal 6-hydroxydopamine (6-OHDA) lesions and assessed their role in anxiety-like behaviour in the elevated plus maze, social memory recognition of a congener and visuospatial object recognition. In transgenic mice specifically expressing halorhodopsin (eNpHR) in cholinergic neurons, striatal ChIs photoinhibition reduced the anxiety-like behaviour and reversed social and spatial short-term memory impairment induced by moderate DA depletion (e.g., 50% loss of tyrosine hydroxylase TH-positive neurons in the SNc). Systemic injection of telenzepine (0.3mg/kg), a preferential M1 muscarinic cholinergic receptors antagonist, improved anxiety-like behaviour, social memory recognition but not spatial memory deficits. Our results suggest that dysfunction of the striatal cholinergic system may play a role in the short-term cognitive and emotional deficits of partially DA-depleted mice. Blocking cholinergic activity with M1 muscarinic receptor antagonists may represent a possible therapeutic target, although not exclusive, to modulate these early non-motor deficits.

Correlation of phenotype with genotype and protein structure in RYR1-related disorders

Variants in the skeletal muscle ryanodine receptor 1 gene (RYR1) result in a spectrum of RYR1-related disorders. Presentation during infancy is typical and ranges from delayed motor milestones and proximal muscle weakness to severe respiratory impairment and ophthalmoplegia. We aimed to elucidate correlations between genotype, protein structure and clinical phenotype in this rare disease population. Genetic and clinical data from 47 affected individuals were analyzed and variants mapped to the cryo-EM RyR1 structure. Comparisons of clinical severity, motor and respiratory function and symptomatology were made according to the mode of inheritance and affected RyR1 structural domain(s). Overall, 49 RYR1 variants were identified in 47 cases (dominant/de novo, n = 35; recessive, n = 12). Three variants were previously unreported. In recessive cases, facial weakness, neonatal hypotonia, ophthalmoplegia/paresis, ptosis, and scapular winging were more frequently observed than in dominant/de novo cases (all, p < 0.05). Both dominant/de novo and recessive cases exhibited core myopathy histopathology. Clinically severe cases were typically recessive or had variants localized to the RyR1 cytosolic shell domain. Motor deficits were most apparent in the MFM-32 standing and transfers dimension, [median (IQR) 85.4 (18.8)% of maximum score] and recessive cases exhibited significantly greater overall motor function impairment compared to dominant/de novo cases [79.7 (18.8)% vs. 87.5 (17.7)% of maximum score, p = 0.03]. Variant mapping revealed patterns of clinical severity across RyR1 domains, including a structural plane of interest within the RyR1 cytosolic shell, in which 84% of variants affected the bridging solenoid. We have corroborated genotype-phenotype correlations and identified RyR1 regions that may be especially sensitive to structural modification.

Effect of a specific inpatient multidisciplinary rehabilitation program on postural and gait stability in Huntington's disease – Pilot study

Postural and gait instability in Huntington's disease (HD) is an essential part of the motor symptomatology causing falls contributing to morbidity and mortality. Rehabilitation (Rhb) is considered beneficial in stability treatment. However, the number of studies is still limited. This is the first multidisciplinary inpatient study using a specific program aimed at postural and gait stability in HD. We aimed to evaluate the short-and long-term effects of an inpatient multidisciplinary rehabilitation program on postural and gait instability in HD. A sample of 16 HD subjects without severe cognitive deficit or depression were included, 13 subjects completed the full course. They underwent a 3-week specific inpatient rehabilitation focused on stability. The examination was at baseline, after the completion, 1 and 3 months after the rehabilitation. The testing included: gait stability examination (Dynamic Gait Index; DGI), posturography examination of postural stability Limits of Stability on a stable (PSS) and 20% unstable (PSU) platform and the motor function evaluation by Unified Huntington's Disease Rating Scale (UHDRS-TMS). There was a significant improvement in DGI immediately after the Rhb and a significant 3 months lasting improvement in PSS. There was no significant improvement in PSU and UHDRS-TMS. Specific Rhb methods improved postural and gait instability in early- and mid-stage HD patients. The improvement in PSS persisted 3 months. We found no improvement in PSU, which is probably a too difficult test for this degree of stability impairment. The improvement in DGI does not persist after 1 month. This study offers a verified specific Rhb protocol for stability training in HD.

Differences in cognitive performance in nondemented Parkinson’s disease: A latent profile analysis of cognitive subtypes

ABSTRACTIntroduction: Cognitive impairments are common in Parkinson’s disease (PD) patients without dementia. These deficits are quite heterogeneous, which makes it difficult to recognize and treat them. For this reason, many authors have attempted to classify patients into more homogeneous groups with diverse results. The present study was designed to analyze the cognitive heterogeneity in PD patients using a novel data-driven approach, latent profile analysis (LPA), to classify patients according to cognitive characteristics. This methodology, which has been used in previous studies focused on motor and psychiatric symptomatology, seems to be better than traditional cluster analysis for the establishment and comparison between different subgroups because it does not require prior decision making about some theoretical or methodological aspects.Method: LPA was applied to 71 PD patients evaluated with a broad neuropsychological battery including different memory and executive function tests. The clusters obtained from the analysis were described by making comparisons with a control group of 51 healthy subjects matched in age, sex, and educational level.Results: The LPA resulted in a four-cluster solution, which could be described as: (a) executive dysfunction (32.4%), (b) memory and executive dysfunction (28.2%), (c) memory dysfunction (23.9%), and (d) noncognitive dysfunction (15.5%). These four PD cluster differ in age and Mini-Mental State Examination (MMSE) score. However, there were no differences between clusters in disease duration, clinical impression of severity index, depression, and cognitive reserve.Conclusions: LPA is a very interesting method for the establishment of more homogeneous groups of PD patients based on their neuropsychological characteristics. Moreover, the distinction between different cognitive profiles will allow us to design interventions better adapted to each patient.