Background: Frontal lobe circuit dysfunction, including the mesolimbic network, plays an important role in learning reward behaviors and is involved in the development of impulsive compulsive disorders (ICDs) in Parkinson's disease (PD). ICDs in PD are characterized by disinhibited, reward-driven behaviors performed with poor impulse control, often linked to dopaminergic treatment. The purpose of the present study was to assess the presence of these behaviors in relation to frontal dysfunction and overall cognitive status in a cohort of patients with sporadic PD. Methods: The study consisted of 55 patients (n = 55), 36 males (65.5%), diagnosed with Parkinson's disease, assessed at the First Neurological Clinic of Eginition University Hospital in Athens. The participants had a mean age of 62.6 (±13.54) years, with an average of 11.94 (±3.00) years of education and a mean disease duration of 7.17 (±5.90) years. The evaluation tools used to assess the participants were the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP), Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB), and Geriatric Depression Scale (GDS). Results: The mean score on the QUIP was 0.64 (±1.05), with a threshold of 1. Of the total number of patients (n = 55), 18 (32.72%) showed behaviors related to ICDs. The most commonly reported impulsive compulsive behavior was an excessive preoccupation with hobbies (n = 7, 38.9%), followed by a tendency toward gambling (n = 6, 33.3%). The mean score on the MoCA scale was 24.69/30 (±4.25), while the mean score on the FAB scale was 14.70/18 (±2.45). Pearson's correlation analysis revealed a moderate positive correlation between total MoCA score and FAB (r = 0.588, p < 0.000) and a weak to moderate negative correlation between MoCA score and QUIP (r = -0.291, p = 0.038). Additionally, there was a statistically significant negative correlation between QUIP scores and performance on the MoCA attention subtests (Forward Digit Span, Backward Digit Span, and Vigilance tasks), (r = -0.389, p = 0.009). Conclusions: Lower global cognitive function, as measured by the MoCA, was strongly associated with reduced frontal lobe function, as measured by the FAB, in Parkinson's patients. Additionally, lower scores on the MoCA, particularly in the attention subtests, showed a weak to moderate correlation with increased impulsive compulsive behaviors, as measured by the QUIP.

The phenotype of p.A53T-α-synuclein (SNCA) mutation carriers with Parkinson’s disease (A53T-PD) appears more severe compared to idiopathic PD (iPD), however, information is limited. Here we conducted a comprehensive longitudinal study to investigate the progression of motor and nonmotor features of Α53Τ-PD compared to iPD. Detailed longitudinal 3-year data, concerning both motor and non-motor features, of 16 p.A53T-PD and 48 iPD, matched for age (51–53 years) and disease duration (approximately 4 years) at baseline, were downloaded from the Parkinson's Progression Markers Initiative (PPMI) database and compared between the two groups. Additionally, a cognitive composite score was generated by five cognitive tests, focused more on executive/visuospatial function. At baseline, global cognitive function, as assessed by the Montreal Cognitive Assessment (MOCA), was not significantly different between the two groups, in contrast to tests evaluating executive/visuospatial function, including the composite score, which were worse in A53T-PD. There was a significant decline over time in all neuropsychological tests in A53T-PD, while iPD remained stable. A similar pattern was revealed for motor status and function, as well as autonomic function, which were similar between the two groups at baseline, but deteriorated significantly only in A53T-PD over time. A53T-PD patients present an accelerated decline in both motor and non-motor parameters, with an impairment in executive-visuospatial function occurring early in the disease process. Such data may set the stage for targeted disease-modifying therapies in this particular subtype, while generated data may be widely applicable to iPD, which is largely a sporadic synucleinopathy.

Introduction: Human immunodeficiency virus (HIV)-associated neurocognitive impairment (NCI) remains a concern despite combination antiretroviral therapy (cART), with cognitive problems often persisting even after viral suppression. The mechanisms underlying neurocognitive deterioration in people living with HIV (PLWH) and the role of plasma biomarkers remain unclear. This study aims to evaluate neurocognitive trajectories and biomarker changes in a real-world cohort of newly diagnosed PLWH initiating cART in Greece. Methods: This prospective, single-center study assessed neuropsychological performance and plasma biomarkers in treatment-naïve PLWH at baseline and 18 months after cART initiation. HIV-associated neurocognitive disorder (HAND) was classified using the Frascati criteria, and plasma biomarkers of inflammation and monocyte activation were measured. Correlations between biomarkers and cognitive performance were analyzed. Results: A total of 39 treatment-naïve PLWH were enrolled in this study. At baseline, 45.7% of participants met criteria for HAND, predominantly, asymptomatic neurocognitive impairment (ANI). Over 18 months, neurocognitive function improved, particularly in speed of information processing, executive function, and visuospatial ability, while verbal fluency, fine motor dexterity, and attention/working memory remained unchanged. Biomarkers of inflammation and monocyte activation decreased following cART, except for neopterin, which increased (10.6 vs. 13 ng/mL, p = 0.002), and plasma NFL (7.5 vs. 7.2 pg/mL, p = 0.54), which remained stable. A negative correlation between monocyte activation markers and cognitive performance was observed only at follow-up, suggesting that systemic inflammation may mask these associations in untreated PLWH. Conclusions: Early cART initiation supports neurocognitive recovery and reduces immune activation in PLWH. The observed correlation between cognitive performance and monocyte activation markers after viral suppression highlights the potential utility of plasma biomarkers in predicting cognitive impairment.

INTRODUCTION:Previous research has shown that inflammatory immune biomarkers including peripheral white blood cell subpopulations differ between Parkinson's disease (PD) patients and healthy controls (HC), with PD exhibiting higher neutrophil to lymphocyte ratio (NLR). The aim of the present report was to assess the peripheral immune profile in patients or asymptomatic carriers harboring the p.A53T alpha-synuclein (SNCA) mutation. METHODS:Data regarding 31 p.A53T SNCA PD patients, 9 asymptomatic mutation carriers and 194 HCs were obtained from the database of the Parkinson's Progression Markers Initiative (PPMI). Focus was placed on peripheral immune blood cells subpopulations and clinical/imaging parameters at baseline. RESULTS:NLR, Absolute Neutrophil cell count and Neutrophils to total Leukocytes ratio were increased in the p.A53T SNCA PD group as compared to HCs [2.77 vs 2.18 (p < 0.001), 4.32 × 10^3 cells/μL vs 3.67 × 10^3 cells/μL (p = 0.001), 65.67 % vs 59.55 % (p < 0.001)]. Differences in NLR were mainly driven by the male patient subgroup. Lymphocytes to total Leukocytes and Monocytes to total Leukocytes ratio were lower in the p.A53T SNCA cohort as compared to HC [(p = 0.001) and (p = 0.002)]. Finally, we observed a positive correlation between the absolute Lymphocyte count and the mean putamen DATSCAN signal. Asymptomatic carriers did not differ statistically from either group. DISCUSSION:Our current study provides evidence of a specific pattern of peripheral immune response in the p.A53T SNCA PD group which aligns well with literature data in idiopathic and GBA-PD. Whether this peripheral immune activation represents a contributing cause or an effect of the neurodegenerative process will require further study.

Background: Virtual Reality (VR) is transforming neuropsychological assessment by providing immersive environments that closely replicate real-world conditions. This study presents the Trail Making Test in VR (TMT-VR), a novel adaptation of the traditional TMT, aimed at evaluating cognitive functions in adults with Attention Deficit Hyperactivity Disorder (ADHD). We examined the ecological validity, convergent validity, usability, and user experience of the TMT-VR compared to the traditional version. Methods: Fifty-three adults (18–40 years old), including 25 with ADHD and 28 neurotypical controls, completed both the traditional and VR versions of the TMT. The participants also provided feedback on the VR experience via standardized questionnaires. Results: The statistical analyses demonstrated a significant positive correlation between TMT-VR scores and both the traditional TMT and ADHD symptomatology as measured by the Adult Self-Report Scale, confirming the TMT-VR’s ecological and convergent validity. High usability and positive user experience ratings indicated strong acceptability of the VR platform. Notably, the ADHD group exhibited greater performance differences in the VR environment, suggesting that VR may more effectively capture real-world cognitive challenges. Conclusions: These findings suggest that TMT-VR is a valid, engaging, and ecologically valid tool for cognitive assessment in ADHD and other clinical populations, offering enhanced insights over traditional methods.

Background and Objectives: The phenotype of p.A53T-SNCA Parkinson's Disease (PD) mutation carriers appears more severe than that of iPD patients, however comprehensive comparative prospective studies are lacking. Here we conducted a longitudinal study to investigate, using multiple parameters, the progression of motor and nonmotor features of p.A53T-PD compared to iPD. Methods: Longitudinal 3-year data, concerning both motor and non-motor features, of 16 p.A53T-PD and 48 iPD, matched for age and disease duration at baseline, were downloaded from the Parkinson's Progression Markers Initiative (PPMI) database and compared between the two groups. Additionally, a cognitive composite score was generated by 5 cognitive tests, focused on executive/visuospatial function to better study cognitive change. Results: Neuropsychological assessments of global cognitive (MOCA), and especially executive/visuospatial function, reflected in the composite score, revealed significant cognitive decline in A53T-PD compared to iPD, but also across time for the group of A53T-PD. Autonomic dysfunction and items of MDS-UPDRS I, reflecting global cognitive function and psychotic features, were more prominent in A53T-PD. Motor assessments showed worse performance in A53T-PD, even though LEDD was significantly higher in A53T-PD. Discussion: The current longitudinal study indicates that A53T-PD represents a rapidly progressing subtype of PD, with accelerated decline in both motor and non-motor parameters, especially in cognitive function. Such data may set the stage for the application of targeted disease-modifying therapies in this particular subtype, in which the etiological link to alpha-synuclein is established, while generated data may be relevant to iPD, which is largely a sporadic synucleinopathy.

Background: Apolipoprotein E (APOE) genotype may be associated with the development of cognitive decline in idiopathic Parkinson's disease i(PD), however its effect in genetic PD is understudied. Objectives: In the current work we aimed to assess the impact of APOE genotype on cognition in iPD as well as in genetic PD with mutations in the Alpha-synuclein (SNCA) and Glycocerebrosidase (GBA1) genes. Methods: Two independent PD cohorts were analyzed: The first cohort (Athens) included 50 iPD patients, 35 patients with the p.A53T SNCA mutation and 59 patients with GBA1 mutations (13 mild /46 severe). The second cohort (Tuebingen) included 292 patients with GBA1 mutations (170 risk/ 52 mild/ 70 severe). All patients underwent cognitive testing and were genotyped for APOE. Results: In the iPD subgroup, carriers of at least one APOE exhibited lower Montreal Cognitive Assessment test (MoCA) score as compared to non-carriers (p=0.044). Notably, in the p.A53T SNCA subgroup, APOE carriers also had lower MoCA scores compared to non-carriers (p=0.039). There were no APOE-related differences in the two GBA1 subgroups (Athens, p=0.729; Tuebingen p=0.585). Conclusions: We confirm the impact of APOE on cognitive decline in iPD and for the first time report a similar effect in p.A53T SNCA mutation carriers, who represent the prototypical genetic synucleinopathy. Contrary, the lack of such an effect in two independent cohorts of GBA1 mutation carriers, who are thought to also manifest a predominant alpha-synuclein-driven cognitive decline, suggests differences in factors associated with cognitive dysfunction between different genetic forms of synucleinopathies.

The objective of the present work was to compare the levels of executive, emotional, and initiation apathy in individuals with mild cognitive impairment (MCI), mild Alzheimer’s disease dementia (ADD), and cognitively intact healthy controls (HCs). Fifty-two patients with mild ADD, 40 individuals with MCI, and 37 cognitively intact individuals were included in the current study. The participants were consecutive visitors to the Outpatient Memory Clinic of “Nestor” Alzheimer’s Center. The symptoms of apathy were measured with the dimensional apathy scale. Analyses showed that ADD patients had significantly higher degrees of executive, emotional, initiation, and overall apathy compared with both the MCI group and the HCs. Additionally, a significant difference was observed in the dimension of executive apathy between individuals with MCI and the HCs. In conclusion, the dimension of executive apathy was the most sensitive measure regarding the differentiation of individuals with mild ADD or MCI and HCs. Hence, detailed evaluation of executive apathy in older individuals referred to a memory clinic may provide useful information contributing to their diagnostic categorization and to the differentiation between neurocognitive disorders and healthy cognitive ageing.

The present study aims to explore the differences in the manifestation of cognitive decline and psychiatric symptoms across the different ages of MCI onset: early onset (EOMCI: <65 years old), middle onset (MOMCI: 65–75 years old), and late onset (LOMCI: >75 years old). It was hypothesized that individuals with EOMCI will preserve their cognitive functions to a greater extent as compared to individuals with LOMCI, even after adjusting the cognitive performance for age and education through the use of published Greek norms. The level of cognitive decline concerning MOMCI was evaluated for extracting more precise conclusions regarding the impact of the age of onset on the patterns of MCI symptomatology. The analyses of data were conducted in a Greek population of individuals with MCI, who were consecutive visitors of the Outpatient Memory Clinic of Nestor Alzheimer’s Centre in Athens, Greece. The sample consisted of 297 participants who fulfilled the following inclusion criteria: MCI diagnosis based on Petersen’s criteria, Greek mother language, and absence of a psychiatric history or chronic and incurable organic disease. The overall results support the presence of a cognitive advantage of the EOMCI group compared to the LOMCI group. In the MOMCI group, cognitive performance displayed a tendency to remain intermediate compared to the other two groups. Nonetheless, significant differences were observed when this group was compared with the LOMCI group. The current findings indicate that the age of onset should be taken under consideration in the neuropsychological assessment of individuals with MCI. The specific parameters could have implications in terms of prognosis as well as the design and implementation of tailored interventions.

Introduction: Previous epidemiological evidence has established the co-occurrence of malignant melanoma (MM) and Parkinson's disease (PD). Shared molecular mechanisms have been proposed to be implicated in this relationship. The aim of the present study was to assess the prevalence of MM in patients with sporadic and genetic types of PD, as well as in asymptomatic carriers of PD-related genes. Methods: Data regarding past medical history and concomitant disease of 1416 patients with PD (including 20 participants with prodromal disease who phenoconverted to PD), 275 healthy controls (HCs) and 670 asymptomatic carriers of PD-related genes were obtained from the database of the Parkinson's Progression Markers Initiative (PPMI). Focus was placed on information about a medical record of MM. We also retrieved data regarding the genetic status of selected PPMI participants with a positive MM history. Results: In total, 46 patients with PD reported a positive MM history. Concerning the genetic forms of PD, nine of these PD patients (2.47%) carried a Leucine Rich Repeat Kinase 2 (LRRK2) gene mutation (mainly the G2019S), while eight (4.49%) harbored a Glucocerebrosidase (GBA) gene mutation (mainly the N370S). No alpha-synuclein (SNCA) gene mutation was identified in patients with an MM history. The remaining 29 PD patients (3.5%) were genetically undetermined. In total, 18 asymptomatic carriers of PD-related genes had a positive medical history for MM: among them, 10 carried an LRRK2 gene mutation (2.69%) and 10 a GBA gene mutation (3.51%) (2 were dual carriers). MM history was identified for seven HCs (2.5%). Conclusions: We replicated the previously reported association between genetically undetermined PD (GU-PD) and MM. A correlation of LRRK2 mutations with the development of MM could not be verified in either symptomatic PD patients or asymptomatic carriers, implicating distinct pathogenetic mechanisms as compared to GU-PD. Importantly, despite the limited literature evidence on Gaucher disease, this study highlights for the first time the relatively high prevalence of MM among asymptomatic and symptomatic PD GBA mutation carriers, with potential clinical implications.

Background: the apolipoprotein e4 allele (APOE4) constitutes an established genetic risk factor for Alzheimer’s Disease Dementia (ADD). We aimed to explore the frequency of the APOE isoforms in the Greek population of Southern Greece. Methods: peripheral blood from 175 Greek AD patients, 113 with mild cognitive impairment (MCI), and 75 healthy individuals. DNA isolation was performed with a High Pure PCR Template Kit (Roche), followed by amplification with a real-time qPCR kit (TIB MolBiol) in Roche’s Light Cycler PCR platform. Results: APOE4 allele frequency was 20.57% in the ADD group, 17.69% in the MCI group, and 6.67% in the control group. APOE3/3 homozygosity was the most common genotype, while the frequency of APOE4/4 homozygosity was higher in the AD group (8.60%). APOE4 carrier status was associated with higher odds for ADD and MCI (OR: 4.49, 95% CI: [1.90–10.61] and OR: 3.82, 95% CI: [1.59–9.17], respectively). Conclusion: this study examines the APOE isoforms and is the first to report a higher APOE frequency in MCI compared with healthy controls in southern Greece. Importantly, we report the occurrence of the APOE4 allele, related to ADD, as amongst the lowest globally reported, even within the nation, thus enhancing the theory of ethnicity and latitude contribution.

Neuropsychology is a fast-growing specialty in Greece. This study surveyed the status of neuropsychologists in Greece investigating several aspects of the profession. An online-based questionnaire collected data from December 2019 to February 2020. A total of 133 participants specialized in neuropsychology were included in the final sample: 81% of the participants were women with a mean age of 35 years. In the total sample, 25.8% of the participants reported working in the hospital system, 18.5% in the university or college, and 17.7% in a private practice job. Greek professionals cited to engage actively in assessment (87.9%), in research (65.1%), in rehabilitation (47.7%), and teaching (30.2%). Professionals primarily declared to assess individuals with dementia (80.3%), depression (47.7%), and stroke (44.0%), and they reported neurologists, psychiatrists and psychologists as their leading sources of referrals. The top five perceived barriers to the field include the lack of recognized specialty (75.9%), the lack of clinical training opportunities (63.9%), the lack of strong professional associations (57.9%), the lack of access to neuropsychological instruments (57.9%) and the lack of willingness to collaborate between professionals (48.9%). The average monthly income of professionals represents a ratio of 0.76 in comparison to that of other scientists in the country and is the lowest reported among other countries. Despite the significant development of the profession, it is essential to create more clinical training opportunities, apply practices systematically to diverse populations, redefine the specialty of neuropsychology in the national health system of the country, and advocate for the profession.

BACKGROUND:The role of blood uric acid as a biomarker in symptomatic motor PD has been increasingly established in the literature. OBJECTIVE:Our present study assessed the role of serum uric acid as a putative biomarker in a prodromal PD cohort [REM Sleep Behavior disorder (RBD) and Hyposmia] followed longitudinally. METHODS:Longitudinal 5-year serum uric acid measurement data of 39 RBD patients and 26 Hyposmia patients with an abnormal DATSCAN imaging were downloaded from the Parkinson's Progression Markers Initiative database. These cohorts were compared with 423 de novo PD patients and 196 healthy controls enrolled in the same study. RESULTS:After adjusting for age, sex, body mass index, and concomitant disorders (hypertension/gout), baseline and longitudinal serum uric acid levels were higher in the RBD subgroup as compared to the established PD cohort (p = 0.004 and p = 0.001). (Baseline RBD 6.07±1.6 vs. Baseline PD 5.35±1.3 mg/dL and Year-5 RBD 5.7±1.3 vs. Year-5 PD 5.26±1.33). This was also true for longitudinal measurements in the Hyposmic subgroup (p = 0.008) (Baseline Hyposmic 5.7±1.6 vs. PD 5.35±1.3 mg/dL and Year-5 Hyposmic 5.58±1.6 vs. PD 5.26±1.33). CONCLUSION:Our results indicate that serum uric acid levels are higher in prodromal PD subjects with ongoing dopaminergic degeneration compared to those with manifest PD. These data indicate that the well-established decrease in the levels of serum uric acid occurs with the transition from prodromal to clinical PD. Whether the higher levels of serum uric acid observed in prodromal PD may provide protection against conversion to full-blown clinical PD will require further study.

Right temporal variant of frontotemporal dementia (rtv-FTD) represents an uncommon and recently described frontotemporal dementia (FTD) entity presenting with symptoms in many ways comparable to those of the frontal or behavioral variant of FTD (bv-FTD). The aims of this study were to explore the timing of cognitive and behavioral symptoms of rtv-FTD, and to compare the distinct cognitive deficits including prosopagnosia and behavioral symptoms of rtv-FTD patients with those observed in bv-FTD patients. We reviewed the records of 105 patients clinically diagnosed with FTD. A total of 7 patients (5 men/2 women) with FTD and marked right temporal atrophy in magnetic resonance imaging (MRI) were detected. Clinical features were compared with those observed in a group of 22 age-matched patients (16 men/6 women) with FTD and predominant frontal lobe atrophy. The main presenting symptoms of rtv-FTD were prosopagnosia, apathy, and episodic memory impairment. In contrast, social awkwardness and compulsive behaviors were dominant in later stages of the disease together with disinhibition and loss of insight with a marked personality change. Although the cognitive and behavioral profiles of patients with right temporal or frontal lobes atrophy present substantial similarities, each subtype has a number of distinct characteristics. It appears that prosopagnosia, obsessive behaviors, and psychotic symptoms are more prominent in rtv-FTD patients.

Objective of this study was to investigate whether specific motor and cognitive tests performed in clinic can predict behind-the-wheel driving behavior (DB) in Parkinson's disease (PD).

Background: The driving behavior of patients with mild Alzheimer’s disease dementia (ADD) and patients with mild cognitive impairment (MCI) is frequently characterized by errors. A genetic factor affecting cognition is apolipoprotein E4 (APOE4), with carriers of APOE4 showing greater episodic memory impairment than non-carriers. However, differences in the driving performance of the two groups have not been investigated. Objective: To compare driving performance in APOE4 carriers and matched non-carriers. Methods: Fourteen APOE4 carriers and 14 non-carriers with amnestic MCI or mild ADD underwent detailed medical and neuropsychological assessment and participated in a driving simulation experiment, involving driving in moderate and high traffic volume in a rural environment. Driving measures were speed, lateral position, headway distance and their SDs, and reaction time. APOE was genotyped through plasma samples. Results: Mixed two-way ANOVAs examining traffic volume and APOE4 status showed a significant effect of traffic volume on all driving variables, but a significant effect of APOE4 on speed variability only. APOE4 carriers were less variable in their speed than non-carriers; this remained significant after a Bonferroni correction. To further examine variability in the driving performance, coefficients of variation (COV) were computed. Larger headway distance COV and smaller lateral position COV were observed in high compared to moderate traffic. APOE4 carriers had smaller speed COV compared to non-carriers. Conclusion: The lower speed variability of APOE4 carriers in the absence of neuropsychological test differences indicates reduced speed adaptations, possibly as a compensatory strategy. Simulated driving may be a sensitive method for detecting performance differences in the absence of cognitive differences.

Intraindividual variability is a fundamental behavioural characteristic of aging but has been examined to a very limited extent in driving. This study investigated intraindividual variability in driving simulator measures in healthy drivers of different ages using the coefficient of variation (COV) as a variability measure. Participants were healthy volunteers who were regular drivers, who were divided into a "young" group, a "middle-aged" group, and an "old" group. They drove in two environments (rural, 72 drivers; urban, 60 drivers), under conditions of moderate and high traffic load, without and with distraction (conversation). Significant differences in COV were observed in the rural condition for headway distance and lateral position as a function of traffic load, with high traffic (without and with distraction) resulting in increased COV of headway and decreased COV of lateral position. Significant differences in COV were observed in the urban condition for headway distance only, with high traffic (without and with distraction) resulting in increased COV of headway. No age effects were found for any of the driving conditions. The results indicate that traffic load affected headway distance and lateral position in opposite directions in all three age groups: high traffic resulted in increased variability of headway in both rural and urban conditions but in decreased variability of lateral position in the rural conditions compared to moderate traffic irrespective of distraction. The study indicates that driving conditions affect the intraindividual variability of driving measures in selective ways, which may be linked to the extent of automatization of the driving variables and to adaptive changes to traffic condition challenges. (c) 2021 Elsevier Ltd. All rights reserved.

Background: Previous studies have highlighted serum uric acid as a putative idiopathic Parkinson’s disease (iPD) biomarker. Only one study, so far, showed higher levels of serum uric acid in leucine-rich repeat kinase 2 (LRRK + 2) carriers compared to those who developed PD, however a longitudinal comparison between LRRK2 + PD and healthy controls (HC) has not been performed. Objective: The aim of this study was to determine whether there are longitudinal differences in serum uric acid between iPD, LRRK2 + PD and HC and their association with motor and non-motor features. Methods: Longitudinal data of uric acid of 282 de novo iPD, 144 LRRK2 + PD patients, and 195 age-matched HC were obtained from the Parkinson’s Progression Markers Initiative (PPMI) database. We also used longitudinal Montreal Cognitive Assessment (MoCA), Movement Disorder Society–Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS-III), Geriatric Depression Scale (GDS) scores, and DaTSCAN striatal binding ratios (SBRs). Results: Longitudinal uric acid measurements were significantly lower in LRRK2 + PD patients compared to HC up to 5 years follow-up. There was no significant impact or correlation of adjusted or unadjusted uric acid levels with MoCA, MDS-UPDRS III, or GDS scores, the presence of RBD or DAT-SCAN SBRs. Conclusion: LRRK2 + PD group had significantly lower uric acid concentrations compared to HC after adjusting for age, sex and baseline BMI up to 5 years follow-up. There were no significant associations between uric acid levels and indices of disease severity. These findings identify serum uric acid as a marker linked to LRRK2 + PD.