Cerebellar Volume and Disease Staging in Parkinson's Disease: An ENIGMA-PD Study.

BACKGROUND: Increasing evidence points to a pathophysiological role for the cerebellum in Parkinson's disease (PD). However, regional cerebellar changes associated with motor and non-motor functioning remain to be elucidated. OBJECTIVE: To quantify cross-sectional regional cerebellar lobule volumes using three dimensional T1-weighted anatomical brain magnetic resonance imaging from the global ENIGMA-PD working group. METHODS: Cerebellar parcellation was performed using a deep learning-based approach from 2487 people with PD and 1212 age and sex-matched controls across 22 sites. Linear mixed effects models compared total and regional cerebellar volume in people with PD at each Hoehn and Yahr (HY) disease stage, to an age- and sex- matched control group. Associations with motor symptom severity and Montreal Cognitive Assessment scores were investigated. RESULTS: Overall, people with PD had a regionally smaller posterior lobe (dmax = -0.15). HY stage-specific analyses revealed a larger anterior lobule V bilaterally (dmax = 0.28) in people with PD in HY stage 1 compared to controls. In contrast, smaller bilateral lobule VII volume in the posterior lobe was observed in HY stages 3, 4, and 5 (dmax = -0.76), which was incrementally lower with higher disease stage. Within PD, cognitively impaired individuals had lower total cerebellar volume compared to cognitively normal individuals (d = -0.17). CONCLUSIONS: We provide evidence of a dissociation between anterior "motor" lobe and posterior "non-motor" lobe cerebellar regions in PD. Whereas less severe stages of the disease are associated with larger motor lobe regions, more severe stages of the disease are marked by smaller non-motor regions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Narrative discourse production in Parkinson's disease: Decoupling the role of cognitive-linguistic and motor speech changes.

Introduction: the interplay between neuropsychological and communicative abilities in Parkinson's disease (PD) has been relatively overlooked, and it is not entirely understood which difficulties are consequent to impaired motor control, and which have a linguistic/cognitive basis. Here, we examined narrative discourse in PD using a multi-level analysis procedure considering sentence-level (productivity, lexical-grammatical processing) and discourse-level processes (narrative organization, informativeness), and partialling out patients' motor speech impairments. The interaction between cognitive (i.e. linguistic and executive) and communication abilities was also investigated. Methods: Twenty-nine PD subjects in the mild stage of the disease were compared to 29 matched healthy comparators (HC) on quantitative measures of narrative discourse derived from two picture description tasks. Multivariate (considering articulation rate and educational attainment as covariates) and univariate (with group membership as independent variable) analyses of variance were conducted on separate linguistic domains. The contribution of executive/linguistic abilities to PD's narrative performance was explored by multiple regression analyses on narrative measures significantly differentiating patients from HC. Results: significant reductions in patients were observed on measures of productivity (less well-formed words, shorter sentences) and informativeness (fewer conceptual units, less informative elements, lower number of details) and these alterations were explained by variations in linguistic abilities (action and object naming) rather than executive abilities. Articulation rate and educational attainment did not impact the observed reduced productivity and under-informativeness. Conclusion: referential narrative discourse is altered in PD, regardless of motor impairments in speech production. The observed reductions in productivity/informativeness aspects of narratives were related to naming abilities and in particular to verbs processing, consistently with the neurocognitive model of motor language coupling. Since narratives are amenable to recurrent and automated analysis for the identification of linguistic patterns potentially anticipating the development of PD and the onset of cognitive deterioration, discourse abilities should be quantitatively and repeatedly profiled in the disorder.

Neuropsychiatric, neuropsychological, and neuroimaging features in isolated REM sleep behavior disorder: The importance of MCI.

BACKGROUND: Mild cognitive impairment (MCI) is frequently diagnosed in patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD), although the extent of MCI-associated neuropathology has not yet been quantified. The present study compared the differences in neuropsychiatric, neuropsychological, and neuroimaging markers of neurodegeneration in MCI-iRBD and iRBD patients with normal cognition. METHODS: Sixty-one patients with iRBD were included in the study: 30 patients were included in the MCI subgroup (RBD-MCI) and 31 in the normal cognition subgroup (RBD-NC). Both groups underwent neuropsychiatric and neuropsychological assessments to evaluate psychopathological symptoms and neuropsychological functions. Brain [18F]FDG PET and 123I-FP-CIT-SPECT were performed to evaluate brain glucose metabolism and nigrostriatal dopaminergic function in convenient subgroups of patients, respectively. RESULTS: Neuropsychological measures generally confirmed overall cognitive decline in patients with iRBD-MCI. Immediate long-term verbal memory and visuospatial functions, as well as attentional-executive impairment were evident in the MCI group compared to the NC group. Neuroimaging results indicated reduced brain glucose uptake in the bilateral posterior cingulate cortex and more evident nigrostriatal deafferentation in the RBD-MCI group. There were no differences in psychopathological symptoms between the two groups. CONCLUSIONS: This study confirmed that iRBD patients with MCI had a more impaired cognitive status that those with NC. Moreover, the MCI subgroup presented reduced cerebral glucose consumption in brain areas critical for cognition, and a more severe deafferentation of the nigro-striatal regions, highlighting the importance of identifying iRBD patients with MCI for urgent neuroprotective trials.

Targeting NAAA counters dopamine neuron loss and symptom progression in mouse models of parkinsonism.

The lysosomal cysteine hydrolase N-acylethanolamine acid amidase (NAAA) deactivates palmitoylethanolamide (PEA), a lipid-derived PPAR-α agonist that is critically involved in the control of pain and inflammation. In this study, we asked whether NAAA-regulated PEA signaling might contribute to dopamine neuron degeneration and parkinsonism induced by the mitochondrial neurotoxins, 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In vitro experiments showed that 6-OHDA and MPTP enhanced NAAA expression and lowered PEA content in human SH-SY5Y cells. A similar effect was observed in mouse midbrain dopamine neurons following intra-striatal 6-OHDA injection. Importantly, deletion of the Naaa gene or pharmacological inhibition of NAAA activity substantially attenuated both dopamine neuron death and parkinsonian symptoms in mice treated with 6-OHDA or MPTP. Moreover, NAAA expression was elevated in postmortem brain cortex and premortem blood-derived exosomes from persons with Parkinson's disease compared to age-matched controls. The results identify NAAA-regulated PEA signaling as a molecular control point for dopaminergic neuron survival and a potential target for neuroprotective intervention.

Precision Medicine into Clinical Practice: A Web-Based Tool Enables Real-Time Pharmacogenetic Assessment of Tailored Treatments in Psychiatric Disorders.

The management of neuropsychiatric disorders involves different pharmacological treatments. In order to perform efficacious drug treatments, the metabolism of CYP genes can help to foresee potential drug-drug interactions. The NeuroPGx software is an open-source web-based tool for genotype/diplotype/phenotype interpretation for neuropharmacogenomic purposes. The software provides information about: (i) the genotypes of evaluated SNPs (single nucleotide polymorphisms); (ii) the main diplotypes in CYP genes and corresponding metabolization phenotypes; (iii) the list of neuropsychiatric drugs with recommended dosage adjustment (according to CPIC and DPWG guidelines); (iv) the list of possible (rare) diplotypes and corresponding metabolization phenotypes. The combined application of NeuroPGx software to the OpenArray technology results in an easy, quick, and highly automated device ready to be used in routine clinical practice.

Immune System and Neuroinflammation in Idiopathic Parkinson's Disease: Association Analysis of Genetic Variants and miRNAs Interactions.

The present study investigated the association of SNPs involved in the regulation of immune response, cellular degenerative and neuroinflammatory pathways with the susceptibility and progression of idiopathic Parkinson's Disease (PD). In particular, 342 PD patients were subjected to a genotyping analysis of a panel of 120 SNPs by Open Array Technology. As control group, 503 samples representative of the European general population were utilized. The genetic analysis identified 26 SNPs associated with PD susceptibility. Of them, 12 SNPs were described as significant expression Quantitative Loci (eQTL) variants in different brain regions associated with motor and non-motor PD phenomenology. Moreover, the study highlighted 11 novel susceptibility genes for PD, which may alter multiple signaling pathways critically involved in peripheral immune response, neuroinflammation, neurodegeneration and dopaminergic neurons wiring. The study of miRNA-target genes highlighted a possible role of miR-499a, miR-196a2, and miR-29a in the modulation of multiple neuroinflammatory and neurodegenerative mechanisms underlying PD physiopathology. The study described a network of interconnected genes (APOE, CLU, IL6, IL7R, IL12B, INPP5D, MAPK1, MEF2C, MIF, and TNFSF14), which may act as upstream regulators in the modulation of biological pathways relevant to PD. Intriguingly, IL6 stands out as a master gene regulator since it may indirectly regulate the network of interconnected genes. The study highlighted different genes and miRNAs interactions potentially involved in PD physiopathology, which are worth to be further explored to improve the knowledge of disease and the research of novel treatments strategies.

Cognitive and Neuropsychiatric Profiles in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson's Disease.

A bstract : Rapid eye movement (REM) sleep behavior disorder (RBD) is a risk factor for developing Parkinson's disease (PD) and may represent its prodromal state. We compared neuropsychological and neuropsychiatric phenotypes of idiopathic (i) RBD, PD and healthy comparators (HC) in order to identify iRBD specific characteristics. Thirty-eight patients with iRBD, 38 PD patients with RBD (PD + RBD), 38 PD patients without RBD (PD-RBD) and 38 HC underwent a comprehensive neurological, neuropsychological and neuropsychiatric evaluation. iRBD, PD + RBD and PD-RBD performed worse than HC in short-term verbal memory, praxia, language and executive functions. iRBD had higher levels of anxiety, depression, apathy and alexithymia than HC. iRBD had higher levels of apathy than PD + RBD. Both PD groups had higher levels of anxiety and depression than HC. Surprisingly, iRBD performed better than all groups in long-term verbal memory. Patients diagnosed with iRBD are characterized by poor global cognitive performance, but better long-term memory and higher levels of depression, anxiety, alexithymia and apathy. Alexithymia and apathy in patients diagnosed with iRBD may be the expression of precocious derangement of emotional regulation, subsequently observed also in PD. Cognitive and neuropsychiatric symptoms of iRBD are early clinical manifestations of widespread neurodegeneration.

Cerebellar GABA Levels and Cognitive Interference in Parkinson's disease and Healthy Comparators.

The neuroanatomical and molecular substrates for cognitive impairment in Parkinson Disease (PD) are far from clear. Evidence suggests a non-dopaminergic basis, and a crucial role for cerebellum in cognitive control in PD. We investigated whether a PD cognitive marker (response inhibition) was differently controlled by g-amino butyric acid (GABA) and/or by glutamate-glutamine (Glx) levels in the cerebellum of idiopathic PD patients, and healthy comparators (HC). Magnetic resonance spectroscopy of GABA/Glx (MEGA-PRESS acquisition sequence) was performed at 3 Tesla, and response inhibition assessed by the Stroop Word-Color Test (SWCT) and the Wisconsin Card Sorting Test (WCST). Linear correlations between cerebellar GABA/Glx levels, SWCT time/error interference effects and WCST perseverative errors were performed to test differences between correlation coefficients in PD and HC. Results showed that higher levels of mean cerebellar GABA were associated to SWCT increased time and error interference effects in PD, and the contrary in HC. Such effect dissociated by hemisphere, while correlation coefficients differences were significant in both right and left cerebellum. We conclude that MRS measured levels of cerebellar GABA are related in PD patients with decreased efficiency in filtering task-irrelevant information. This is crucial for developing pharmacological treatments for PD to potentially preserve cognitive functioning.

Foot Pressure Wearable Sensors for Freezing of Gait Detection in Parkinson's Disease.

Freezing of Gait (FoG) is a common symptom in Parkinson's Disease (PD) occurring with significant variability and severity and is associated with increased risk of falls. FoG detection in everyday life is not trivial, particularly in patients manifesting the symptom only in specific conditions. Various wearable devices have been proposed to detect PD symptoms, primarily based on inertial sensors. We here report the results of the validation of a novel system based on a pair of pressure insoles equipped with a 3D accelerometer to detect FoG episodes. Twenty PD patients attended a motor assessment protocol organized into eight multiple video recorded sessions, both in clinical and ecological settings and both in the ON and OFF state. We compared the FoG episodes detected using the processed data gathered from the insoles with those tagged by a clinician on video recordings. The algorithm correctly detected 90% of the episodes. The false positive rate was 6% and the false negative rate 4%. The algorithm reliably detects freezing of gait in clinical settings while performing ecological tasks. This result is promising for freezing of gait detection in everyday life via wearable instrumented insoles that can be integrated into a more complex system for comprehensive motor symptom monitoring in PD.

Management and Treatment of Patients With Major Depressive Disorder and Chronic Diseases: A Multidisciplinary Approach.

In patients with physical chronic diseases, the prevalence of major depressive disorder (MDD) is approximately 2- to 3-fold higher than in the general population, and it can reach up to 20-40%. The comorbidity of MDD with chronic medical diseases is associated with poorer quality of life, increased medical symptom burden, poor adherence to self-care regimens, increased risk of functional impairment, morbidity, and mortality, and also higher medical costs. Despite this evidence, in routine practice, psychological issues and concerns are frequently inadequately managed. This consensus document proposes that a proper diagnosis, a multidisciplinary approach, and a personalized treatment plan would allow patients with MDD and chronic comorbidities to be more compliant, to improve the outcomes, to reduce possible relapses in the long term, and to prevent or better manage complications and adverse events. This proposal might be useful for any health professionals who deal with patients with chronic diseases, as it can help to pay more attention to the emotional impact of these conditions, in particular in terms of depressive symptoms.

Feasibility and Utility of mHealth for the Remote Monitoring of Parkinson Disease: Ancillary Study of the PD_manager Randomized Controlled Trial.

BACKGROUND: Mobile health, predominantly wearable technology and mobile apps, have been considered in Parkinson disease to provide valuable ecological data between face-to-face visits and improve monitoring of motor symptoms remotely. OBJECTIVE: We explored the feasibility of using a technology-based mHealth platform comprising a smartphone in combination with a smartwatch and a pair of smart insoles, described in this study as the PD_manager system, to collect clinically meaningful data. We also explored outcomes and disease-related factors that are important determinants to establish feasibility. Finally, we further validated a tremor evaluation method with data collected while patients performed their daily activities. METHODS: PD_manager trial was an open-label parallel group randomized study.The mHealth platform consists of a wristband, a pair of sensor insoles, a smartphone (with dedicated mobile Android apps) and a knowledge platform serving as the cloud backend. Compliance was assessed with statistical analysis and the factors affecting it using appropriate regression analysis. The correlation of the scores of our previous algorithm for tremor evaluation and the respective Unified Parkinson's Disease Rating Scale estimations by clinicians were explored. RESULTS: Of the 75 study participants, 65 (87%) completed the protocol. They used the PD_manager system for a median 11.57 (SD 3.15) days. Regression analysis suggests that the main factor associated with high use was caregivers' burden. Motor Aspects of Experiences of Daily Living and patients' self-rated health status also influence the system's use. Our algorithm provided clinically meaningful data for the detection and evaluation of tremor. CONCLUSIONS: We found that PD patients, regardless of their demographics and disease characteristics, used the system for 11 to 14 days. The study further supports that mHealth can be an effective tool for the ecologically valid, passive, unobtrusive monitoring and evaluation of symptoms. Future studies will be required to demonstrate that an mHealth platform can improve disease management and care. TRIAL REGISTRATION: ISRCTN Registry ISRCTN17396879; http://www.isrctn.com/ISRCTN17396879. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-018-2767-4.

Drug Choices and Advancements for Managing Depression in Parkinson's Disease.

Depression is a frequent non-motor symptom of Parkinson's disease (PD), and may even precede the onset of motor symptoms of parkinsonism. Beyond its negative influence on mood, depression in PD is frequently associated with other neuropsychiatric symptoms and with late-stage complications such as dementia. Despite its profound impact on the quality of life and cognitive functioning in PD, depression in PD is often under-recognized and poorly treated. Pathophysiological studies demonstrated that depression in PD is associated with global dysfunction of interactions between discrete brain areas rather than focal structural or functional abnormalities, and that it is sustained by pathological changes of several neurotransmitter/receptor complexes. In general, all traditional antidepressants and some dopamine agonists have been found to be safe and well-tolerated to treat depressive symptoms in PD, despite initial warning on worsening of parkinsonism. Available data suggest that the time-course of response differs among antidepressants. Efficacy results from clinical trials with antidepressant in PD are, however, rather uncertain, although pooled analysis suggests a moderate benefit. Several issues may critically impact the results of clinical trials with antidepressants in PD, including the correct psychiatric diagnosis, the overlap of symptoms between depression and PD, and the selection of appropriate end-points and rating scales.

Alexithymia and anhedonia in early Richardson's syndrome and progressive supranuclear palsy with predominant parkinsonism.

INTRODUCTION: Phenotypic variants of progressive supranuclear palsy (PSP) are all characterized by the combination of motor symptoms of parkinsonism with a number of neuropsychiatric and cognitive disorders. Despite the strong effort in characterizing these features in PSP, alexithymia and anhedonia have not been investigated at present. Here, we aimed at investigating the qualitative and quantitative differences of alexithymia and anhedonia in the two more frequent variants of PSP, Richardson's syndrome (PSP-RS) and PSP with predominant parkinsonism (PSP-P) compared to Parkinson's disease (PD) patients recruited within 24 months after the onset of motor symptoms. METHODS: One hundred fifty-five PD, 11 PSP-P, and 14 PSP-RS patients underwent clinical, neuropsychiatric, and neuropsychological evaluations. Alexithymia was assessed using the Toronto Alexithymia Scale-20 item (TAS-20), and hedonic tone was measured by the Snaith-Hamilton Pleasure Scale (SHAPS). RESULTS: In PSP-P and PSP-RS patients, the frequency of alexithymia diagnosis was higher than in PD. On the TAS-20 scores, PSP-RS performed worse in the total score and in F2 sub-scale when compared to PD. Among patients with diagnosis of depression, PSP-RS showed higher scores in TAS-20 total and TAS-20 F2 than PD. No significant differences in TAS-20 scores were found in nondepressed patients. Finally, we did not find significant differences among PD, PSP-P, and PSP-RS groups in the SHAPS scores. CONCLUSIONS: Alexithymia is identifiable very early in PSP-P and PSP-RS patients. Alexithymic symptoms differentiate PSP-RS group from PD group but not between the two subtypes of PSP. Further, alexithymia in PSP seems to be predicted by the presence of depression. Altered emotional capability could be related to specific neurophysiological dysfunction occurring precociously in PSP; therefore, its identification could orient the diagnosis toward PSP cases.

Cortical thinning across Parkinson's disease stages and clinical correlates.

BACKGROUND: Imaging studies have revealed cortical thinning and subcortical atrophy occurring in Parkinson's disease (PD); however, the topographical distribution and clinical associations related to advancing stages of PD remains unclear. OBJECTIVE: We aimed to investigate the topographical distribution of cortical and subcortical morphometric changes, and their clinical associations, related to increasing disease severity. METHODS: In this cross-sectional imaging study, T1-weighted structural magnetic resonance imaging data for 80 non-demented PD patients and 30 age-matched healthy controls were analysed using FreeSurfer software suite to derive morphometric changes using whole-brain vertex-wise analysis, and surface-based (cortical) and volume-based (subcortical) parcellation maps. PD patients were divided into three groups of mild (n = 27), moderate (n = 27), and severe (n = 26) PD based disease duration and Hoehn and Yahr and Unified Parkinson's Disease Rating Scale Part-III motor severity scores. RESULTS: Whole-brain vertex-wise analysis revealed cortical thinning in the orbitofrontal cortex in early PD (P = .011), and in the superior frontal (P = .002), caudal middle frontal gyrus (P = .001) and inferior parietal cortex (P = .006) in moderate PD. Severe PD patients showed additional cortical thinning in temporal and occipital cortices (P < .005). Subcortical volume loss was detected in the thalamus (P = .012) and hippocampus (P = .032) in moderate PD, which extended to the caudate (P = .012), putamen (P = .042) and amygdala (P = .008) in severe PD. Increasing disease duration and motor severity scores, correlated with cortical thinning in frontal, temporal, parietal and occipital cortices, and subcortical volumetric loss in the thalamus, caudate, putamen, amygdala and hippocampus. Lower global cognitive status, measured with MMSE, correlated with cortical thinning in temporal, parietal, frontal and cingulate cortices, and with volumetric loss in the hippocampus (r = 0.31; P = .009); suggesting subclinical pathogenic changes occur prior to the onset of cognitive impairment. CONCLUSION: In conclusion, in more severe disease stages PD patients exhibit progressive cortical thinning and subcortical volume loss which could have relevance to the development of cognitive impairment.

Alpha-synuclein in salivary gland as biomarker for Parkinson's disease.

Estimates of the accuracy of clinical diagnosis of Parkinson's disease (PD) range between 46% and 90%, the accuracy of diagnosis dependent on prolonged clinical observation and clinical response to levodopa. For this reason, we need reliable diagnostic biomarkers. The cardinal hallmark of PD is alpha-synuclein aggregation in the brain. Demonstrating pathological alpha-synuclein in live patients would be useful for identifying and monitoring PD patients. By autopsy studies and in vivo studies, the presence of alpha-synuclein has been demonstrated even outside the central nervous system and the gastro-enteric tract appears to be the most promising candidate tissue for biopsy-taking and the esophagus and salivary glands appear to be the area with the highest concentration of alpha-synuclein. The purpose of our study is to conduct a review to determine the utility of salivary gland biopsy for the histological diagnosis of PD. A computerized medline study was carried out through the use of pubmed: using the MeSH terms: 'salivary gland biopsy for PD', 'PD and dysphagia', 'alpha-synuclein and salivary gland'. We found 9 articles about minor salivary glands and submandibular gland biopsy for diagnosis of PD. According to the results of this review, the submandibular gland biopsy is the test with the increased sensitivity and specificity compared to the biopsy of the minor salivary glands (sensitivity: 0.85 and 0.37 respectability and specificity: 0.96 and 0.94 respectively). New studies are necessary on a wider population to confirm these results.

Acceptability to patients, carers and clinicians of an mHealth platform for the management of Parkinson's disease (PD_Manager): study protocol for a pilot randomised controlled trial.

BACKGROUND: Parkinson's disease is a degenerative neurological condition causing multiple motor and non-motor symptoms that have a serious adverse effect on quality of life. Management is problematic due to the variable and fluctuating nature of symptoms, often hourly and daily. The PD_Manager mHealth platform aims to provide a continuous feed of data on symptoms to improve clinical understanding of the status of any individual patient and inform care planning. The objectives of this trial are to (1) assess patient (and family carer) perspectives of PD_Manager regarding comfort, acceptability and ease of use; (2) assess clinician views about the utility of the data generated by PD_Manager for clinical decision making and the acceptability of the system in clinical practice. METHODS/DESIGN: This trial is an unblinded, parallel, two-group, randomised controlled pilot study. A total of 200 persons with Parkinson's disease (Hoehn and Yahr stage 3, experiencing motor fluctuations at least 2 h per day), with primary family carers, in three countries (110 Rome, 50 Venice, Italy; 20 each in Ioannina, Greece and Surrey, England) will be recruited. Following informed consent, baseline information will be gathered, including the following: age, gender, education, attitudes to technology (patient and carer); time since Parkinson's diagnosis, symptom status and comorbidities (patient only). Randomisation will assign participants (1:1 in each country), to PD_Manager vs control, stratifying by age (1 ≤ 70 : 1 > 70) and gender (60% M: 40% F). The PD_Manager system captures continuous data on motor symptoms, sleep, activity, speech quality and emotional state using wearable devices (wristband, insoles) and a smartphone (with apps) for storing and transmitting the information. Control group participants will be asked to keep a symptom diary covering the same elements as PD_Manager records. After a minimum of two weeks, each participant will attend a consultation with a specialist doctor for review of the data gathered (by either means), and changes to management will be initiated as indicated. Patients, carers and clinicians will be asked for feedback on the acceptability and utility of the data collection methods. The PD_Manager intervention, compared to a symptom diary, will be evaluated in a cost-consequences framework. DISCUSSION: Information gathered will inform further development of the PD_Manager system and a larger effectiveness trial. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN17396879 . Registered on 15 March 2017.

Psychiatric profile of motor subtypes of de novo drug-naïve Parkinson's disease patients.

BACKGROUND: Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder. It is well established that different motor subtypes of PD evolve with different clinical courses and prognoses. The complete psychiatric profile underlying these different phenotypes since the very early stage of the disease is debated. AIMS OF THE STUDY: We aimed at investigating the psychiatric profile of the three motor subtypes of PD (akinetic-rigid, tremor-dominant, and mixed) in de novo drug-naïve patients with PD. METHODS: Sixty-eight patients with PD, divided into 39 akinetic-rigid (AR), seven mixed (MIX), and 22 tremor-dominant (TD) patients underwent a complete assessment of psychiatric, cognitive, and motor symptoms. RESULTS: No significant differences were found among groups. CONCLUSIONS: Our results suggest that a differentiation of the psychiatric symptoms associated with specific motor subtypes of PD is not detectable in de novo drug-naïve patients. Previous evidence that emerges later along the disease progression may be a consequence of the dopaminergic and nondopaminergic damage increase.

Anosognosia for cognitive and behavioral symptoms in Parkinson's disease with mild dementia and mild cognitive impairment: Frequency and neuropsychological/neuropsychiatric correlates.

INTRODUCTION: Anosognosia is a multidimensional phenomenon with detrimental effects on patients' illness course, therapy compliance and quality of life. We aimed at investigating anosognosia for cognitive and behavioral symptoms in Parkinson's Disease (PD) with dementia (PDD) and, for the first time, in PD with Mild Cognitive Impairment (MCI-PD). METHODS: Community dwelling subjects (47 mild PDD, 136 multidomain MCI-PD (mdMCI-PD), 5 single domain MCI-PD (sdMCI-PD), and 197 PD without cognitive impairment (noCI-PD) were enrolled in a cross-sectional design study. All the subjects were administered the Anosognosia Questionnaire for Dementia, the Mental Deterioration Battery and a number of neuropsychiatric inventories. RESULTS: A diagnosis of anosognosia was made in 36% of patients with mild PDD and 16% with mdMCI-PD, whether it was negligible in sdMCI-PD and noCI-PD. Higher severity of anosognosia for cognitive impairment was also found in PDD and in mdMCI-PD. SdMCI-PD had the lower severity of anosognosia for cognitive impairment. Higher anosognosia for cognitive impairment was associated to lower depression in noCI-PD (r = -0.227, p = 0.0013) and mdMCI-PD (r = -0.266, p = 0.0016), and to reduced hedonic tone in noCI-PD (r = -0.191, p = 0.0071). Greater anosognosia was associated to lower executive performances in PDD (r = 0.424, p = 0.0074). CONCLUSIONS: Anosognosia for non-motor symptoms is frequent in PD patients with mild dementia or mdMCI. Results confirm the role of neuropsychiatric characteristics in anosognosia also in PD, the high prevalence of anosognosia in neurodegenerative illnesses and suggest a common pathogenic path for anosognosia in different neurodegenerative and psychiatric disorders.

Neuropsychiatric and cognitive profile of early Richardson's syndrome, Progressive Supranuclear Palsy-parkinsonism and Parkinson's disease.

INTRODUCTION: The two main variants of Progressive Supranuclear Palsy (PSP), Richardson's syndrome (PSP-RS) and PSP-parkinsonism (PSP-P), share motor and non-motor features with Parkinson's disease (PD) particularly in the early stages. This makes the precocious diagnosis more challenging. We aimed at defining qualitative and quantitative differences of neuropsychiatric and neuropsychological profiles between PSP-P, PSP-RS and PD patients recruited within 24 months after the onset of symptoms, in order to clarify if the identification of peculiar cognitive and psychiatric symptoms is of help for early PSP diagnosis. METHODS: PD (n = 155), PSP-P (n = 11) and PSP-RS (n = 14) patients were identified. All patients were submitted to clinical, neurological, neuropsychiatric diagnostic evaluation and to a comprehensive neuropsychiatric and neuropsychological battery. Predictors of PSP-P and PSP-RS diagnosis were identified by multivariate logistic regressions including neuropsychiatric and neuropsychological features that differed significantly among groups. RESULTS: The three groups differed significantly at the Apathy Rating Scale score and at several neuropsychological domains. The multivariate logistic regressions indicated that the diagnosis of PSP-RS was predicted by phonological verbal fluency deficit whereas the presence of apathy significantly predicted the PSP-P diagnosis. CONCLUSION: Peculiar neuropsychiatric and neuropsychological symptoms are identifiable very precociously in PSP-P, PSP-RS and PD patients. Early phonological verbal fluency deficit identifies patients with PSP-RS whereas apathy supports the diagnosis of PSP-P.