BACKGROUND:This study aimed at identifying neuropsychological sub-phenotypes in amyotrophic lateral sclerosis (ALS) within the mild cognitive impairment (MCI) and mild behavioral impairment (MBI) frameworks. METHODS:We used individual task-/item-level data from the cognitive and behavioral sections of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) from 901 non-demented ALS to derive neuropsychological sub-phenotypes pursuant to classical MCI and MBI frameworks and in accordance with an expanded version of Strong's criteria, which also addressed memory and visuo-spatial measures. RESULTS:The prevalence of MCI and MBI was 39% and 37%, respectively in this retrospective review. The following MCI sub-phenotypes were identified: dysexecutive MCI-single- and multiple-domain (dMCI-sd: 63%; dMCI-md: 24%, respectively); non-dysexecutive MCI-single- and multiple-domain (ndMCI-sd: 12%; ndMCI-md: 1%, respectively). MBI was classified as follows: apathetic MBI-single- and multiple-domain (aMBI-sd: 40%; aMBI-md: 20%, respectively); apathetic-disinihibited/perseverative MBI-multiple domain (ad/pMBI-md: 21%); disinihibited/perseverative MBI-multiple domain (d/pMBI-md: 7%); psychotic MBI-single- and multiple-domain (psyMBI-sd: 2%; psyMBI-md: 3%, respectively); unclassifiable MBI-multiple domain (uMBI-md: 1%). 143 (16%) of patients exhibited mild cognitive and behavioral impairment (MCBI). CONCLUSIONS:This study delivers a provisional, ECAS-based classification for the neuropsychological sub-phenotyping of non-demented ALS patients, which, with further validation, might be useful for both research and clinical purposes.

This study aimed to provide preliminary information on the clinical usability of a set of Italian telephone-based cognitive screening (TBCS) tests in patients with neurodegenerative MCI and dementia. Eighty-one patients with MCI (N = 32) and dementia (N = 49) due to Alzheimer’s disease, frontotemporal lobar degeneration and Lewy body disease and 100 healthy controls (HCs) were administered a battery of TBCS tests assessing global cognition (Telephone Interview for Cognitive Status), executive functioning (Telephone-based Frontal Assessment Battery), verbal fluency (Telephone-based Phonemic and Semantic Verbal Fluency), working memory (Telephone-based Backward Digit Span) and language (Telephone Language Screener). For each test, we assessed their (1) applicability, (2) construct validity against in-person first- and second-level cognitive measures, (3) ecological validity against the Amsterdam IADL Questionnaire-Short Version (A-IADL-Q-SV), (4) capability to discriminate MCI and dementia patients from HCs and (5) to discriminate MCI from dementia. TBCS tests could be completed by the majority of patients (75–96

This study aimed to compare different algorithms based on the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) to classify patients with amyotrophic lateral sclerosis (ALS) according to their neuropsychological phenotype to identify possible discrepancies among these systems. ECAS-Cognitive and -Carer Interview (ECAS-C/-CI) scores of N = 901 patients with ALS without a formal diagnosis of dementia were retrospectively retrieved. Patients were classified, pursuant to Strong et al.’s criteria, as cognitively and behaviourally normal (ALScbn), cognitively and/or behaviourally impaired (ALSci/bi/cbi), or Possible ALS-FTD, according the following ECAS-based algorithms: (1) Abrahams’, solely addressing ECAS-C total and ALS-Specific subtotals; (2) Poletti et al.’s, addressing single task-level ECAS-C scores; (3) “Subscale”, addressing ECAS-C subscales (i.e., Language, Executive, Fluency, Memory and Visuospatial). All algorithms relied on single-item-level ECAS-CI scores for behavioural classifications. Whilst agreement rates among these classifications were moderate to high (84–86

BackgroundThe yes-no reversal (YNR) phenomenon consists in a patient saying "yes" when meaning "no", or vice-versa.ObjectiveTo investigate the prevalence of the YNR phenomenon in mild cognitive impairment (MCI) and dementia across different neurodegenerative, chronic cerebrovascular, or mixed etiologies, and to explore its demographic and clinical correlates.MethodsInformants of N = 267 patients with MCI or dementia due to possible/probable Alzheimer's disease (AD; N = 164), frontotemporal lobar degeneration (N = 25), Lewy body disease (N = 18), mixed-i.e., AD and chronic cerebrovascular-etiologies (N = 37), Aβ-negative degenerative etiologies (N = 6), and chronic cerebrovascular disease (N = 17) were inquired on the occurrence of YNRs in everyday-life conversations. YNR+ and YNR- patients were compared on demographics (i.e., age, sex, education), disease duration (in months), disease severity (i.e., MCI versus dementia), etiology and total and subscale-/item-level Mini-Mental State Examination (MMSE) scores. A multiple logistic model was also run on the presence/absence of YNRs by addressing, as predictors, variables that yielded significance at an univariable level.ResultsThe YNR phenomenon was recorded in 23 patients (8.61%), all of them being demented (i.e., no MCI patient showed YNRs). YNR+ patients were younger and scored lower on Immediate recall and Language subscores of the MMSE. The prevalence of YNRs was higher in non-AD- (∼18%) versus AD-related (∼5%) etiologies. The effects of disease severity and etiology were confirmed by the multiple logistic model, while the others were not.ConclusionsThe YNR phenomenon is a clinical sign possibly associated with dementia due to non-AD etiologies.

Chronic activation of glial cells leads to the dysfunction and degeneration of motor and cortical neurons in amyotrophic lateral sclerosis and frontotemporal dementia with an unknown mechanism. To shed light on the molecular pathogenetic processes underlying the exordium and contribution of gliosis to disease onset and progression, we used cells, mice and patient-derived cells modelling TDP-43, SOD1 and C9ORF72-linked and sporadic ALS. Our data reveal a sequential disease progression, starting with enhanced glial reactivity and proliferation, and transitioning into inflammation with upregulation of pro-inflammatory genes. Using mouse genetics, we show that expression of mutant TDP-43 in astrocytes is necessary to cause gliosis and behavioural abnormalities. Mechanistically, we show that glial MYC gain-of-function drives neurodegeneration by promoting the release of astrocyte-derived extracellular vesicles that nonetheless fail to provide trophic support to surrounding neurons. Our research reveals a novel functional role for MYC in glia-to-neuron miscommunication in ALS.

We explored the comparability of the “Serial 7s” (S7) and Spelling Backwards (SB) tasks from MMSE in 313 patients with MCI ( N =54) and dementia ( N =259) due to Alzheimer’s disease (AD), frontotemporal lobar degeneration, Lewy body disease, non-AD degenerative (NADD), chronic cerebrovascular disease (CVD) or mixed (AD+CVD) etiologies. Although the two tasks were significantly associated with each other ( r =.54), a two one-sided test revealed that they were not statistically equivalent. Consistently, a linear mixed model testing the effect of task Type (S7 vs. SB) net of demographics, disease duration, disease severity and etiology revealed that the S7 condition was more difficult to be performed ( M =1.69) than the SB one ( M =3.03). Hence, in MCI and dementia due to chronic-degenerative etiologies, the S7 and the SB tasks from the MMSE are not comparable. Users should exert caution when qualitatively interpreting examinees’ attentional levels based on these tasks.

Background Clinically relevant anxiety can be detected in patients with amyotrophic lateral sclerosis (ALS), but its prevalence and determinants have not yet been fully assessed. Aims This study aimed at assessing the prevalence and clinical underpinnings of anxiety in ALS. Method Non-demented ALS patients (N = 433) and healthy controls (N = 313) were administered the State- and Trait-Anxiety Inventory – Form Y (STAI-Y1 for state-anxiety and STAI-Y2 for trait-anxiety) and the Beck Depression Inventory (BDI). Patients were further assessed for cognition (Edinburgh Cognitive and Behavioural ALS Screen), behaviour (Frontal Behavioural Inventory) and motor status (disease duration, ALS Functional Rating Scale-Revised and progression rate). The prevalence of clinically significant state- and trait-anxiety were estimated by applying age-stratified cut-offs to STAI-Y1/-Y2 t-scores. Linear and logistic regressions were run to test the determinants of STAI-Y1/-Y2 scores. Results STAI-Y1 and -Y2 scores above cut-off were detected in 18.2 and 13.9% of patients, respectively – with proportions being higher in cases versus controls (ps < 0.001). BDI, but neither cognitive/behavioural nor motor variables, was identified as a significant predictor of STAI-Y1/-Y2 scores (ps < 0.003). The cognitive–affective subscale of BDI was the sole predictor of scores above cut-off on both STAI-Y1 and STAI-Y2 (ps < 0.001). Conclusions Clinically significant levels of state- and trait-anxiety occur in ∼18 and ∼14% of non-demented ALS patients, respectively, mostly driven by cognitive and affective facets of depression, and are independent of motor and cognitive/behavioural features.

BackgroundIn clinical settings, the head turning sign (HTS) occurs when patients with cognitive complaints turn their head toward the accompanying person seeking assistance. Due to its nature, and unlike other non-canonical neurological signs of cognitive impairment, the HTS is likely to occur in ecological, daily-life scenarios too. However, this hypothesis has not been tested yet.ObjectiveTo assess the prevalence and clinical correlates of the "ecological HTS" (eHTS) in MCI and dementia due to chronic-degenerative etiologies.MethodsThis retrospective cohort included 112 patients with MCI/dementia due to Alzheimer's disease (AD; N = 71), frontotemporal lobar degeneration (N = 6), Lewy body disease (N = 6), chronic cerebrovascular diseases (CVD; N = 11), mixed (i.e., AD + CVD; N = 15) unspecified non-AD neurodegenerative etiologies (N = 3). We recorded the number of HTSs displayed by patients during the MMSE and inquired accompanying persons whether the HTS occurred in daily life too.ResultsThe overall prevalence of the eHTS in the cohort was 50%; its distribution was independent of demographics, disease severity (i.e., MCI versus dementia), and etiology. Within multiple logistic models, the presence of the eHTS + proved to be predicted both by lower scores on the Spatial Orientation subtest of the MMSE and by a higher number of HTSs during the execution of the MMSE. Moreover, a trend towards longer disease duration and the occurrence of the eHTS was found.ConclusionsIn MCI and dementia, the HTS is an ecologically valid non-canonical sign, frequently occurs in daily life too, associated with longer disease duration and spatial disorientation.

A variety of common and rare genetic factors have been implicated in the development of amyotrophic lateral sclerosis (ALS), and the evidence is that a genetic component is present in most affected individuals. However, our current understanding of ALS genetics causally explains only a small proportion of sporadic ALS, which accounts for over 90

Theory of mind (ToM), the ability to infer others' beliefs (cognitive ToM) and emotions (affective ToM), is compromised in behavioural variant frontotemporal dementia (bvFTD). However, its diagnostic and prognostic value in other frontotemporal dementia (FTD) variants remains underexplored due to limited understanding of the underlying neural mechanisms. This study investigated whether ToM deficits are shared across the frontotemporal dementia spectrum and explored the functional connectivity alterations underlying these disturbances using resting-state functional magnetic resonance imaging. Sixty-seven FTD patients [14 non-fluent variant primary progressive aphasia (nfvPPA), 17 semantic variant primary progressive aphasia (svPPA), 23 bvFTD, 13 right temporal variant frontotemporal dementia (rtvFTD); 34 women; mean age 66.5 ± 7.7 years] and two control groups (48 age-matched healthy controls; 50 young healthy controls) underwent clinical, neuropsychological and brain magnetic resonance imaging assessments. ToM was evaluated in patients using the Story-Based Empathy Task (SET), which includes the Story-Based Empathy Task affective subtest (SET-EA) and the Story-Based Empathy Task cognitive subtest (SET-IA). Resting-state functional connectivity networks were obtained in young healthy controls using seed-based analysis centred on the left medial prefrontal cortex for affective ToM and the right supramarginal gyrus for cognitive ToM. In addition, four large-scale functional networks were reconstructed to reflect disease-specific vulnerability. Functional brain connectivity within all networks was quantified using graph analysis and connectomics, and between-group comparisons were performed on both global and seed-based regional metrics. All patient groups showed similar impairments in affective and cognitive ToM performance. Network analyses revealed two dissociable but interconnected ToM systems. Global metrics of network topology indicated increased path length and reduced nodal strength in both ToM networks, particularly in bvFTD and nfvPPA patients (P < 0.05). Direct seed-based connectivity analyses confirmed widespread functional connectivity reductions from key nodes (e.g. left inferior frontal gyrus, anterior cingulate cortex) in these groups. In contrast, svPPA and rtvFTD cases exhibited relatively preserved functional connectivity within ToM circuits. Correlation analyses revealed associations between cognitive ToM network metrics and global ToM performance, and between functional connectivity in the salience network and behavioural dysfunction. Affective and cognitive ToM abilities are comparably impaired across FTD variants, suggesting that socio-cognitive impairments may represent a core and early feature across the FTD spectrum. Such deficits are mirrored by patterns of functional disconnection within dedicated large-scale networks, with bvFTD and nfvPPA showing the most pronounced disruptions. This study underscores the diagnostic relevance of socio-cognitive markers and highlights their potential as clinical and biomarker targets in future therapeutic interventions.

Amyotrophic lateral sclerosis (ALS) is a heritable disorder where rare variants with low-to-moderate penetrance are thought to dominate genetic risk. To identify such rare variants, we harmonized and analyzed exome data from 22 cohorts, totaling 17,919 individuals with ALS and 200,703 controls across discovery and replication phases. Rare variant analyses identified several new risk genes, with replication confirming association of YKT6 and supporting HTR3C, GBGT1 and KNTC1. We also provide strong, independent validation for genes with limited previous evidence: ARPP21, DNAJC7 and CFAP410. Notably, in ARPP21, we identified a new high-effect variant (p.P747L) and confirmed that p.P563L is an ALS-associated variant leading to an aggressive disease course. Beyond new discoveries, our analyses largely recapitulated the known genetic architecture of ALS, identifying risk variants in over 20% of cases and supporting a cumulative oligogenic risk model. These findings highlight new translational targets and show that rare variant analyses capture substantially more genetic risk than common variant genome-wide association studies.

BackgroundDefining motor phenotypes in amyotrophic lateral sclerosis (ALS) is important for individualized care and optimal therapeutic trial design. The "ALS-OPM" classification is based on the onset region (O), the propagation of motor symptoms (P), and the degree of clinical upper (UMN) and/or lower (LMN) motor neuron dysfunction (M).MethodsAn international ALS expert focus group was held in September 2025, followed by a consensus process through which revisions of the OPM classification were finalized.ResultsOnset (O1-4) identifies first motor symptoms as relating to the head (O1), distal/proximal arm (O2d/p), respiratory/axial trunk (O3r/a), or distal/proximal leg (O4d/p). Onset symptoms are defined by weakness or slowed, poorly coordinated voluntary movements in the muscles of the head, arm, trunk, or leg, including dysarthria, dysphagia, dysphonia, dyspnea, and axial instability. Propagation (P1(n)) or absence of propagation (P0(n)) of motor symptoms from the onset region to another body region are designated, where n denotes the number of months from onset to propagation or assessment. The degree of UMN dysfunction (slowed, poorly coordinated voluntary movements, hyperreflexia and/or spastic muscle tone, emotional lability) and/or LMN dysfunction (weakness with associated muscle atrophy) is classified as follows: balanced UMN and LMN dysfunction (M0); dominant (M1d) or pure UMN dysfunction (M1p); dominant (M2d) or pure LMN dysfunction (M2p); and dissociated UMN/LMN dysfunction (M3), in which the arms and legs predominantly show LMN and UMN involvement, respectively.ConclusionThe revised ALS-OPM classification aims to make it routine, practical and feasible to capture phenotype in clinical practice and therapeutic trials.

Polyneuropathies are common and often require specialist expertise for accurate diagnosis. This study evaluated the diagnostic performance of ChatGPT-4o on real-world polyneuropathy cases, comparing it to peripheral neuropathy specialists and non-specialist neurologists. One hundred cases were selected from two tertiary centers in Milan, Italy. Standardized summaries included clinical, laboratory, and electrophysiological data. ChatGPT-4o was prompted to provide a leading diagnosis, two differentials, and a confirmatory test. Neurologists reviewed the same cases and generated comparable outputs, then could revise their responses after viewing ChatGPT-4o's suggestions. ChatGPT-4o achieved 65.5% leading diagnosis accuracy, comparable to non-specialists (63.0%) but lower than specialists (74.0%, p = 0.002). For differential diagnoses, it outperformed non-specialists (82.0% vs. 77.5%, p = 0.043) and recommended more appropriate tests (68.0% vs. 53.0%, p < 0.001). After reviewing ChatGPT-4o outputs, non-specialists revised their assessments in 21.8% of cases, improving accuracy. ChatGPT-4o shows potential as a diagnostic aid, particularly in non-specialist or resource-limited settings.

Serum neurofilament light and heavy chains (sNfL and sNfH) have been assessed as neuronal markers for amyotrophic lateral sclerosis (ALS) and dementias. Whereas sNfL has robust literature, systematic studies on sNfH are lacking. Here, we aimed to assess the diagnostic value of sNfH in comparison to sNfL in a broad range of neurodegenerative disorders. We measured with immunoassays sNfH and sNfL in patients recruited in the multicenter German Frontotemporal Lobar Degeneration (FTLD) Consortium (n = 340) and in a single-center German cohort (n = 290). We assessed the diagnostic accuracy of serum biomarkers for ALS and dementia subtypes and their relationship with cognitive impairment. sNfH and sNfL were significantly increased in ALS (n = 90) vs. controls (n = 109) and ALS mimics (n = 56, p < 0.001), with sNfL showing higher discriminative accuracy (AUC = 0.94–0.95) than sNfH (AUC = 0.87–0.88). sNfH/sNfL ratio did not improve the diagnostic performance. Both markers were elevated in patients with dementia (n = 289) vs. controls (p < 0.001). sNfL was higher in behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA) and Creutzfeldt-Jakob disease (CJD) than in Alzheimer’s disease (AD), whereas sNfH was similar in AD, PPA and bvFTD. sNfL, but not sNfH, was correlated with cognitive impairment at baseline and cognitive decline at follow-up in AD and bvFTD. sNfH and sNfL are elevated in motoneuron and dementia disorders. sNfH showed good discriminative accuracy for ALS, which was slightly lower than that of sNfL. sNfL, but not sNfH, showed prognostic value for assessing cognitive decline in dementia.

ObjectiveThe recent examination of a woman who presented a migraine attack with visual aura and unilateral mydriasis, followed, a few days later, by an episode of Takotsubo Syndrome, prompted us to review the existing literature correlating migraine and TS as well as the most recent studies regarding the association between Takotsubo Syndrome and neurological dysfunction. Our aim is to define the role of dysautonomia and the contribution of the Autonomic Nervous System in the pathogenesis of both diseases, also, to define the functional role of the hypothalamus in the both the determination of headache attacks and the onset of clinical manifestations in other organs and tissues.BackgroundMigraine with aura and Takotsubo Syndrome (TS) share emotional, psychological and physical triggering factors which are implicated in the pathogenetic process. The autonomic nervous system plays a crucial, though antipodal, role in both pathologies. Indeed, migraine clinical manifestations imply the activation of the parasympathetic system whereas a massive catecholamine release following sympathetic nervous system activation is pivotal in triggering the Takotsubo Syndrome.MethodsReview of anatomy, physiology and neural regulation in both physiological and stress responses. Examination of the functional connections of the hypothalamus.Results and discussionThe coexistence of psycho-emotional stressors, endocrine/hormonal factors and a possible genetic predisposition might explain the pathophysiological overlap between these two distinct clinical manifestations. The hypothalamus is functionally connected with all the pain-related brain regions and pathways and can be responsible for the clinical manifestations in both the nervous system and the cardiovascular apparatus. Migraine is the most frequent chronic, early onset condition associated with TS.

Unawareness of chorea is well-known in Huntington’s disease (HD). This study investigated unawareness for the whole gamut of motor impairments in daily life, which has not been explored previously. Data from 71 consecutive patients with stage I or II HD were assessed retrospectively. The motor section of UHDRS; the total functional capacity; a short battery of cognitive tests; the SANS and SAPS scales for negative and positive psychiatric symptoms; the Hamilton scales for depression (HAM-D) and anxiety (HAM-A); and a semi-structured questionnaire to assign motor anosognosia on a scale from 0 (fully aware) to 3 (severely unaware), were administered. Twenty-seven (38

OBJECTIVE:This study aimed at reviewing currently available evidence on cognitive and behavioral involvement in spinal and bulbar muscular atrophy (SBMA). METHODS:This review was performed in accordance with the 2020 PRISMA guidelines. We included case reports/series and group studies reporting data on the neuropsychological features of SBMA patients. RESULTS:Out of 123 unique records identified, 11 studies were included (N = 5 case reports/series; N = 6 group studies), comprising 151 SBMA patients. Among case reports and series, 6 out of 10 patients were reported to exhibit some degree of neuropsychological involvement, with two being diagnosed with a dementia condition resembling the characteristics of behavioral variant-frontotemporal dementia. Three of the 6 case-control studies found no cognitive differences between SBMA patients and healthy controls. Cognitive deficits reported in group studies mostly involved the executive, attentional, memory and visuo-spatial/-constructive domains. CONCLUSIONS:The available evidence on cognitive and behavioral involvement in SBMA is scarce and conflicting. However, it is conceivable that at least some patients may exhibit dysexecutive-type changes, possibly reflecting a frontal system involvement.

This study validated the Italian version of the In-Person Telephone Interview for Cognitive Status (IP-TICS). 468 healthy Italian individuals (176 males; age: 57.5 ± 15.4, education: 13.2 ± 3.7) completed the TICS, IP-TICS, MMSE and MoCA. Correlational analyses explored the construct validity of the IP-TICS against the TICS, MMSE and MoCA. Hierarchical Confirmatory Factor Analyses tested the configural, metric and scalar invariance between the TICS and IP-TICS. Statistical equivalence was assessed via a two one-sided test (TOST) procedure. Equating norms were derived via log-linear smoothing equipercentile equating (LSEE) analyses, with TOST procedures assessing equivalence between empirical and LSEE-derived scores. The IP-TICS converged with the TICS, MMSE and MoCA, showing configural and metric invariance and equivalence with the TICS. Empirical and LSEE-derived scores were statistically equivalent. Findings support the convergence, equivalence and invariance between the TICS and the IP-TICS. The IP-TICS converges with established in-person screeners.

Background: Progressive Supranuclear Palsy (PSP) is a rare, heterogeneous neurodegenerative disease for which no treatment is currently available. In the context of clinical trials, the representativeness of the included patients is crucial for the generalizability of the results. Herein, we present results from a multicenter perspective study to identify the most restrictive criteria for patient selection and to assess the representativeness of eligible patients. Methods: we enrolled 221 PSP patients diagnosed according to the MDS clinical criteria. All patients were screened with a set of inclusion and exclusion criteria based on previous and ongoing clinical trials in PSP and underwent motor and cognitive evaluation with the Montreal Cognitive Assessment battery and the PSP rating scale, respectively. Then, clinical features of eligible and non-eligible patients were compared at baseline and after 15,93 +/- 8,77 months follow up. Results: Eligible (28 patients, 12,6 %) patients were younger, showed shorter disease duration and lower severity but similar distribution of PSP phenotype and disease progression rates compared to non-eligible patients. The most restrictive non-modifiable criteria were independent gait, disease duration and cognitive status. Willingness to undergo lumbar puncture and treatment stability for previous 60 days represented potentially modifiable criteria. Conclusion: Overall, PSP eligible for clinical trials are representative of the general PSP population. While motor and cognitive impairment represent the most important non-modifiable barriers to enter a clinical trial, other criteria as willingness to undergo lumbar puncture and treatment stability are potentially modifiable. Specific strategies are discussed to increase the number of eligible patients working on potentially modifiable criteria.

Adaptive deep brain stimulation (aDBS) is a closed-loop system that adjusts stimulation based on patient biomarkers. This study evaluated the cognitive safety of aDBS in Parkinson’s disease (PD). Sixteen PD patients with bilateral subthalamic DBS underwent cognitive assessments (attention, language, memory) 6 days post-surgery during an 8 h protocol. Testing occurred at five time points: T1 (aDBS, medication “off”), T2/T4 (aDBS, medication “on”), and T3/T5 (aDBS “on”, medication “off”). Four patients followed the same protocol with continuousDBS (cDBS). Results showed no cognitive fluctuations in aDBS patients (p ≥ 0.110). However, cDBS patients exhibited significant reaction time (RT) variations (p = 0.019), with RTs lower at T1 than T3 (p = 0.011) and T5 (p = 0.021), and at T4 compared to T2 (p = 0.002). These findings suggest that 8 h aDBS may not adversely affect cognitive performance, providing preliminary evidence of its cognitive safety and stability in PD.