Deep brain stimulation (DBS) is an important treatment for Parkinson’s disease, tremor and dystonia in appropriately selected patients. The Canada Health Act emphasizes equity and “reasonable access to medically necessary hospital and physician services.” How to define “reasonable access” has not been well studied. We aimed to assess access to DBS implantation surgery and to determine the time required from initial assessment through to surgery and which step(s) delay the implantation.

DBS implants from 2016 to 2023 at the University of Alberta were analyzed. The neurologists’ decision to proceed with DBS marks the start of the workup. The time required to see a neurosurgeon, psychiatrist, neuropsychologist and healthcare allies and to receive DBS surgery was assessed. The impact of COVID-19 was studied.

The total time from starting the workup to DBS surgery was 387.76 ± 125.19 days prior to COVID-19, and marked delay occurred during and post-COVID-19 (840.15 ± 165.41 days and 839.78 ± 300.66 days, respectively). Most workups were done within 6 months pre-COVID-19, although a big range existed due to variable factors. The longest delay to surgery was from consent to DBS implantation, owing to a lack of operative time. There has not been a recovery post-pandemic.

Time to DBS implantation surgery from initial decision is lengthy and more than doubled over the course of the COVID-19 pandemic. The biggest delay was in the time from consent to implantation surgery, which has not improved despite the pandemic having ended.

Cervical dystonia (CD) is a movement disorder characterized by involuntary muscle contractions causing sustained twisting movements and abnormal postures of the neck and head. Assumed affected neuronal regions are the cortico-striatal-thalamo-cortical circuits, which are also involved in cognitive functioning. Indeed, impairments in different cognitive domains have been found in CD patients. However, to date studies have only investigated a limited range of cognitive functions within the same sample. In particular, social cognition (SC) is often missing from study designs. Hence, we aimed to evaluate a broad range of cognitive functions including SC in CD patients.

In the present study 20 idiopathic CD patients and 40 age-, gender-, and IQ-matched healthy controls (HCs) were assessed with tests for non-SC (verbal memory, psychomotor speed, and executive functions) as well as for SC (emotion recognition, Theory of Mind (ToM), and empathy).

CD patients scored on average significantly lower than HC on tests for non-SC, but did not show impairments on any of the tests for SC.

The current study showed impairments in non-SC in CD, but intact social cognitive functions. These results underline the importance of recognizing non-motor symptoms in idiopathic CD patients, but emphasize a focus on identifying strengths and weaknesses in cognitive functioning as these influence daily life activities.

To explore the usefulness of the Lowenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L) [Crocco et al, 2013], a novel memory-based cognitive stress test capitalizing on semantic interference, in Huntington’s Disease (HD).

12 healthy adults (HA) and 14 individuals with manifest HD were administered the LASSI-L as part of an annual research visit with the UCSD Huntington’s Disease Clinical Research Center (HDCRC.) Participants in each group were well matched with regard to age and education. Individuals with manifest HD had an average MoCA score of 26, total functional capacity score of 10, and total motor score of 21 suggesting that they were in the early stages of HD. The LASSI-L examines different types of semantic interference that occur in the learning/encoding process. There are free and cued recall trials for two lists of semantically related words with certain trials specific to different aspects of semantic interference including proactive, retroactive, and failure to recover from proactive interference. T-tests for all recall trials and number of intrusions for each trial were conducted between HA and those with HD to examine whether HD renders one more prone to semantic interference in both encoding and retrieval memory processes.

Individuals with HD recalled fewer words on average than HA across all recall trials except for the initial free recall of the first word list. HD individuals recalled significantly fewer (∼1.5) words during the initial (t=-2.8, p=.005, Cohen’s d=2.7) and secondary (t=-2.9, p=.003, Cohen’s d=2.6) cued recall trials from the words on the first list. Individuals with HD also recalled significantly fewer words on initial free recall (t=-2.9, p=.003, Cohen’s d=2.6) and cued recall trials of the second list, with the initial cued recall (t=-2.8, p=.005, Cohen’s d=3.1) sensitive to proactive semantic interference and the second cued recall (t=-3.3, p=.001, Cohen’s d=2.6) sensitive to failure to recover from proactive semantic interference. In addition, individuals with HD also recalled significantly fewer (∼2.2) words on delayed cued recall of the first list, a measure of retroactive semantic interference, than HA (t=-4.8, p<.001, Cohen’s d=2.4). Lastly, individuals with HD recalled fewer (∼4.1) words than HA on delayed free recall of both word lists (t=-3.5, p<.001, Cohen’s d=5.9). The groups did not differ significantly with regard to number of total intrusions per trial.

Overall, our study supports the usefulness of the LASSI-L for neuropsychological assessment of HD in clinical and research settings. In comparison to a demographically similar group of HA, individuals with manifest HD showed significant differences in frontally mediated retrieval processes as well as semantic interference processes that affect efficient encoding of novel information.

Non-motor symptoms, such as mild cognitive impairment and dementia, are an overwhelming cause of disability in Parkinson’s disease (PD). While subthalamic nucleus deep brain stimulation (STN DBS) is safe and effective for motor symptoms, declines in verbal fluency after bilateral DBS surgery have been widely replicated. However, little is known about cognitive outcomes following unilateral surgeries.

We enrolled 31 PD patients who underwent unilateral STN-DBS in a randomized, cross-over, double-blind study (SUNDIAL Trial). Targets were chosen based on treatment of the most symptomatic side (n = 17 left hemisphere and 14 right hemisphere). All participants completed a neuropsychological battery (FAS/CFL, AVLT, DKEFS Color-Word Test) at baseline, then 2, 4, and 6 months post-surgery. Outcomes include raw scores for verbal fluency, immediate and delayed recall, and DKEFS Color-Word Inhibition trial (Trial 3) completion time. At 2, 4, and 6 months, the neurostimulation type (directional versus ring mode) was randomized for each participant. We compared baseline scores for all cognitive outcome measures using Welch’s two-sample t-tests and used linear mixed effects models to examine longitudinal effects of hemisphere and stimulation on cognition. This test battery was converted to a teleneuropsychology administration because of COVID-19 mid-study, and this was included as a covariate in all statistical models, along with years of education, baseline cognitive scores, and levodopa equivalent medication dose at each time point.

At baseline, patients who underwent left hemisphere implants scored lower on verbal fluency than right implants (t(20.66) = -2.49, p = 0.02). There were not significant differences between hemispheres in immediate recall (p = 0.57), delayed recall (p = 0.22), or response inhibition (p = 0.51). Post-operatively, left STN DBS patients experienced significant declines in verbal fluency over the study period (p = 0.02), while patients with right-sided stimulation demonstrated improvements (p < .001). There was no main effect of stimulation parameters (directional versus ring) on verbal fluency, memory, or inhibition, but there was a three-way interaction between time, stimulation parameters, and hemisphere on inhibition, such that left STN DBS patients receiving ring stimulation completed the inhibition trial faster (p = 0.035). After surgery, right STN DBS patients displayed faster inhibition times than patients with left implants (p = 0.015).

Declines in verbal fluency after bilateral stimulation are the most commonly reported cognitive sequalae of DBS for movement disorders. Here we found group level declines in verbal fluency after unilateral left STN implants, but not right STN DBS up to 6 months after surgery. Patients with right hemisphere implants displayed improvements in verbal fluency. Compared to bilateral DBS, unilateral DBS surgery, particularly in the right hemisphere, is likely a modifiable risk factor for verbal fluency declines in patients with Parkinson’s disease.

Subjective cognitive complaints are common in individuals with Parkinson’s disease and Essential Tremor. One scale often used to capture the type and severity of subjective cognitive concerns is the Cognitive Change Index-20 (CCI-20). Created by Saykin et al (2006), the CCI-20 is a questionnaire that assesses perception of cognitive changes in memory, executive function, and language domains. Despite its multidomain structure, previous research has not empirically examined whether the CCI-20's underlying factor structure aligns with the cognitive domains proposed during its original development. Thus, the goal of the current study was to investigate the factor structure of the CCI-20 in individuals with movement disorders (Parkinson’s disease, Essential Tremor) who are known to experience varying degrees of cognitive sequelae as part of their disease progression.

Participants included a convenience sample of 216 non-demented individuals with Parkinson disease (n=149) or Essential Tremor (n=67) who were seen at the University of Florida Fixel Institute Movement Disorders Center. All received the CCI-20 as part of a neuropsychological evaluation. The CCI-20 consists of 20 items, rated on a 5-point Likert scale, that ask questions about change in memory (12 items), executive function (5 items), and language (3 items) over the past 5 years. An exploratory factor analysis was conducted on CCI-20 scores using Promax rotation with factor extraction based on scree plot visual inspection and Kaiser’s rule (eigenvalues >1.0). Cronbach’s alpha was used to assess internal consistency reliability. Finally, Spearman correlations determined associations between factors and mood measures of depression (Beck Depression Inventory-II, BDI-II), apathy (Apathy Scale, AS), and anxiety (State-Trait Anxiety Inventory, STAI).

Because the Parkinson’s disease and Essential Tremor groups did not statistically differ in their CCI-20 total scores, they were combined into a single group for analyses. This resulted in 216 participants who were well-educated (m=15.01±2.92), in their mid-60's (m=67.72±9.33), predominantly male (63%), and non-Hispanic White (93.6%). The factor analysis resulted in 3 factors: factor 1 included 8 memory items (items 1-4, 6, 10-12; loadings from .524 to .920); factor 2 included all executive and language (items 13-20; loadings from .605 to .824), and factor 3 included four remaining memory items (items 5, 7-9; loadings from .628 to .810). Reliability of the 20 CCI items was good (a = .94), and reliability within each factor ranged from adequate (Factor 3, a = .78) to good (Factors 1 and 2, a = .90). All factors showed significant weak to moderate associations with BDI-II, AS, and STAI (state and trait) scores.

The CCI-20 revealed three distinct dimensions of subjective cognitive complaints that did not correspond to the memory, executive function, and language domains. Rather, the CCI-20 was decomposed into two different dimensions of memory complaints and one dimension of non-memory complaints. Mood symptoms played a significant role in driving all dimensions of subjective cognitive complaints. Future studies should confirm this triadic structure in a healthy older adult sample and explore the relationship between factors and objective cognitive performance beyond the contribution of mood. T32-AG061892; T32-NS082168

Essential tremor (ET) is the most common movement disorder, characterized by bilateral action tremors of the upper extremities. Surgical interventions can be considered for severe cases that are refractory to medication. Magnetic resonance-guided focused ultrasound (MRgFUS) of the ventral intermediate nucleus of the thalamus (Vim) is a recently approved, minimally invasive treatment for unilateral tremor. While patients are generally pleased with unilateral treatment, many patients are bothered by tremor on the untreated side. Historically, bilateral thalamotomy has been associated with a higher rate of adverse events, including cognitive impairment. MRgFUS Vim thalamotomy for bilateral tremor is currently being investigated. The goal of the present study was to evaluate the effect of bilateral MRgFUS Vim thalamotomy on cognition.

Twelve patients with medication-refractory essential tremor (mean age = 68.77 +/- 11.78 years, mean education = 14.34 +/- 2.71 years, 8 male) were included in the present study. Three of the 12 patients met criteria for mild cognitive impairment (MCI). All patients successfully underwent unilateral MRgFUS thalamotomy at least 48 weeks before the second thalamotomy. A battery of neuropsychological tests was administered to patients before (considered baseline in the present study) and three months following the second thalamotomy. Baseline evaluations occurred on average 144.64 +/- 91.53 weeks (range: 55.00 - 346.58) after the first thalamotomy. The neuropsychological battery assessed domains of processing speed (Oral Symbol Digit Modalities Test, D-KEFS Color-Word Naming and Reading), attention (WAIS-IV Digit Span Forward), executive function (D-KEFS Color-Word Inhibition and Inhibition/Switching), working memory (WAIS-IV Digit Span Backward and Sequencing), verbal fluency (D-KEFS Letter Fluency and Animal Fluency), confrontation naming (Boston Naming Test), verbal memory (Hopkins Verbal Learning Test-Revised), and visuospatial perception (Judgment of Line Orientation). Alternate versions of tests were used when possible. Cognitive changes were analyzed at the group and individual level. Group level changes were assessed with paired sample t-tests (corrected for multiple comparisons). At the individual level, postoperative declines > 1.5 SD from baseline were considered clinically significant.

Participants’ baseline intellectual functioning ranged from low average to superior (as measured by the WTAR). The mean baseline score on the Montreal Cognitive Assessment was 24.58 (range: 17 - 30). At the group level, there were no significant changes in cognitive scores from baseline to follow-up (all p values > 0.635). At the individual level, one patient with MCI declined > 1.5 SD on the verbal memory composite. No other patients showed declines > 1.5 SD.

Our preliminary findings suggest that bilateral MRgFUS Vim thalamotomy is relatively safe from a cognitive perspective. However, a single patient with MCI exhibited clinically significant postoperative decline in verbal memory. Future studies with larger sample sizes are needed to investigate the factors that increase the risk of postoperative cognitive decline, including pre-existing cognitive impairment, older age, and lesion size.

Spinocerebellar ataxia type one (SCA1) is an autosomal dominant neurodegenerative disease caused by an expanded CAG repeat that encodes glutamine (polyQ) in the affected ATXN1 gene. SCA1 pathology is commonly characterized by the degeneration of the cerebellar Purkinje cells (PC) and brainstem. Symptoms include motor dysfunction, cognitive impairments, bulbar dysfunction, and premature death. Atxn1175Q/2Q knock-in mice were previously developed to model SCA1 by inserting 175 expanded CAG repeats into one allele of the Atxn1 gene, producing mice expressing ATXN1 throughout the brain and displaying SCA1 symptoms. Previous research has indicated the role of localization of the ATXN1 protein to the nucleus in pathology. Therefore, the Atxn1175QK772T/2Q mouse model was created by disrupting the NLS in the expanded Atxn1175Q/2Q mice by replacing lysine with threonine at position 772 in the nuclear localization sequence (NLS). Since this amino acid change previously blocked PC disease in another mouse model, the Atxn1175QK772T/2Q mice were created to examine how the NLS mutation affects neuronal cells. RNA sequencing analysis was previously performed and found differentially expressed genes (DEG) with Atxn1175Q/2Q downregulated compared to Atxn1175QK772T/2Q and Atxn12Q/2Q in the cerebellum, medulla, cortex, hippocampus, and striatum. The aim was to analyze these brain regions to validate the RNAseq differential gene expression at a protein level.

Therefore, western blots were performed on the following mouse models (n=12): wild type mice (Atxn12Q/2Q), mice with the nuclear localization sequence mutation (Atxn12QK772T/2Q), and mice with 175 expanded CAG repeats (Atxn1175/2Q). Based off the RNAseq data, the cerebellum was tested with ion channel genes (Cav3.1, Kcnma1, and Trpc3) and the striatum was tested with a gene found in medium-spiny neurons (DARPP-32).

In the cerebellum, Atxn1175/2Q was significantly downregulated compared to Atxn1175QK772T/2Q in Cav3.1, Trpc3, and Kcnma1. Atxn1175Q/2Q was significantly downregulated compared to Atxn12Q/2Q in Trpc3 and Kcnma1. Atxn1175QK772T/2Q was significantly downregulated compared to Atxn12Q/2Q in Trpc3. In the striatum, there was significantly reduced DARPP-32 expression found between Atxn12Q/2Q and Atxn1175QK772T/2Q, Atxn12Q/2Q and Atxn1175Q/2Q, and Atxn1175Q/2Q and Atxn1175QK772T/2Q.

Therefore, the significantly reduced gene expression at the protein level in the cerebellum and striatum validate RNAseq differentially expressed genes. Additionally, the downregulation of both the Atxn1175Q/2Q and Atxn1175QK772TQ/2Q compared to Atxn12Q/2Q in the striatum supports the lack of learning of those mouse models on the rotarod, suggesting that the nuclear localization mutation does not rescue learning. Interestingly, the downregulation of Atxn1175Q/2Q compared to Atxn1175QK772TQ/2Q likely supports the age-related motor decline rescue in the rotarod seen in Atxn1175QK772T/2Q and not Atxn1175Q/2Q.

Timing, or the decision of when to act, is essential to mammalian behaviors from escaping predators to driving a car. It requires cognitive functions such as working memory for time-based rules and attention to the passing of time. Thus, it can be used as a proxy for higher order executive functions that are difficult to measure but are impaired in many neurological disorders. Therefore, insights from studies of interval timing, tasks which require estimating time intervals of several seconds, have great value for our understanding of human disease. Crucial to timing is the basal ganglia, which integrates cortical activity with midbrain dopamine signals and sends out signals to the spinal cord that regulate movement, motivation, and other behaviors. We have previously found that within the basal ganglia, medium spiny neurons of the striatum exhibit ramping activity in time-related tasks. In other words, they gradually increase or decrease firing frequency across a timed interval, and this is thought to encode time. Yet it is still unknown how the encoding of time is translated into time-based motor responses. To answer this question, we turned to the external globus pallidus (GPe) because it is a regulatory hub within the basal ganglia and is thus well positioned to regulate timing behavior. We sought to examine how the GPe functions in response to time-based demands.

We recorded from neuronal ensembles using 16 channel electrode arrays implanted in the GPe of five mice while they performed an interval timing task called the switch interval timing task. Spike sorting was then used to identify signal from individual neurons.

Data were compiled from 43 neurons over several trials. Principal component analysis of neural firing activity was then conducted and revealed a downward ramping pattern in GPe neurons during interval timing trials. Data were then separated based on trials in which mice made correct decisions and those in which mice made a mistake. We found that when mice make correct timing decisions, there is downward ramping activity in the GPe, yet when mice make timing mistakes, this ramping pattern is lost.

Our findings suggest that the GPe processes timing signals through ramping activity, before projecting to the output nuclei of the basal ganglia. This is a novel finding and contributes to a growing understanding of the temporal code of the basal ganglia. The full extent of this code is still unknown, but this insight contributes to a better understanding of how the globus pallidus represents cognition. If we can better explain the neural correlates of timing, we can use this knowledge to inform therapeutic interventions for basal ganglia dysfunction, which could have profound implications for diseases like Parkinson’s disease, which affects millions around the world.

While Parkinson’s disease (PD) is traditionally known as a movement disorder, cognitive decline is one of the most debilitating and common non-motor symptoms. Cognitive profiles of individuals with PD are notably heterogeneous (Goldman et al., 2018). While this variability may arise from the disease itself, other factors might play a role. Greater anticholinergic medication use has been linked to worse cognition in those with PD (Fox et al., 2011, Shah et al., 2013). However, past studies on this topic had small sample sizes, limited ranges of disease duration, and only used cognitive screeners. Thus, this study aimed to examine this question within a large, clinical sample, using a more comprehensive neuropsychological battery. We hypothesized that higher anticholinergic medication usage would relate to worse cognitive performance, particularly memory.

Participants included 491 nondemented individuals with PD (m=64.7, SD=9.04 years old; education m=15.01, SD=2.79; 71.9% male; 94.3% non-Hispanics white) who underwent a comprehensive neuropsychological assessment at the UF Fixel Institute’s movement disorders program. Medications at the time of the neuropsychological evaluation were identified from chart review and scored based on anticholinergic properties using the Magellan Anticholinergic Risk Scale (Rudolph J.L., et al, 2008); each medication was scored from 0 (no load) to 3 (high load). The neuropsychological battery included measures across 5 cognitive domains: (1) executive function (Trails B, Stroop Interference, Letter Fluency), (2) verbal delayed memory (WMS-III Logical Memory and Hopkin’s Verbal Learning Test-Revised delayed recalls), (3) language (Boston Naming Test-II, Animal Fluency), (4) visuospatial skills (Judgment of Line Orientation, Face Recognition Test), and (5) attention/working memory (WAIS-III Digit Span Forward and Backward). The published normative scores for each task were converted into z-scores and averaged into a domain composite. Due to non-normality of Magellan scores, Spearman correlations examined the relationship between each cognitive domain composite score and Magellan scores.

As predicted, higher Magellan scores were significantly associated with worse memory (r=-0.11, p=0.016), with a small effect size. There were no significant relationships between Magellan scores and the remaining cognitive domains (EF, language, visuospatial, attention).

We found that greater anticholinergic burden was associated with worse performance on memory, but not other neuropsychological domains, in a large cohort of nondemented individuals with PD who underwent comprehensive assessment. This finding corresponds to previous literature in smaller PD cohorts. Though the effect size was low, this finding highlights the importance of monitoring anticholinergic burden in PD patients in order to minimize detrimental effects of medications on memory function. Future work should examine whether greater anticholinergic burden predicts future progression of memory decline.

Acknowledgement: Supported in part by the NIH, T32-NS082168

The Cognitive Change Index (CCI-20) is a validated questionnaire that assesses subjective cognitive complaints (SCCs) across memory, language, and executive domains. We aimed to: (a) examine the internal consistency and construct validity of the CCI-20 in patients with movement disorders and (b) learn how the CCI-20 corresponds to objective neuropsychological and mood performance in individuals with Parkinson’s disease (PD) or essential tremor (ET) seeking deep brain stimulation (DBS).

216 participants (N = 149 PD; N = 67 ET) underwent neuropsychological evaluation and received the CCI-20. The proposed domains of the CCI-20 were examined via confirmatory (CFA) and exploratory (EFA) factor analyses. Hierarchical regressions were used to assess the relationship among subjective cognitive complaints, neuropsychological performance and mood symptoms.

PD and ET groups were similar across neuropsychological, mood, and CCI-20 scores and were combined into one group who was well educated (m = 15.01 ± 2.92), in their mid-60’s (m = 67.72 ± 9.33), predominantly male (63%), and non-Hispanic White (93.6%). Previously proposed 3-domain CCI-20 model failed to achieve adequate fit. Subsequent EFA revealed two CCI-20 factors: memory and non-memory (p < 0.001; CFI = 0.924). Regressions indicated apathy and depressive symptoms were associated with greater memory and total cognitive complaints, while poor executive function and anxiety were associated with more non-memory complaints.

Two distinct dimensions were identified in the CCI-20: memory and non-memory complaints. Non-memory complaints were indicative of worse executive function, consistent with PD and ET cognitive profiles. Mood significantly contributed to all CCI-20 dimensions. Future studies should explore the utility of SCCs in predicting cognitive decline in these populations.

To describe the development and initial experience of a clinical research program in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) in Canada: The Rossy PSP Centre, to share the data acquisition tools adopted, and to report preliminary results.

Extensive demographic and longitudinal clinical information is collected every 6 months using standardized forms. Biofluids are collected for biobanking and genetic analysis, and many patients are enrolled in neuroimaging research protocols. Brain donation is an important component of the program, and standardized processing protocols have been established, including very short death to autopsy times in patients undergoing medical assistance in dying.

Between Oct 2019 and Dec 2021, 132 patients were screened, 91 fulfilling criteria for PSP and 19 for CBS; age 71 years; 41% female; duration 5 years, age-of-onset 66 years. The most common symptoms at onset were postural instability and falls (45%), cognitive-behavioral changes (22%), and Parkinsonism (9%). The predominant clinical phenotype was Richardson syndrome (82%). Levodopa and amantadine resulted in partial and short-lasting benefit.

The Rossy PSP Centre has been established to advance clinical and basic research in PSP and related tauopathies. The extent of the clinical data collected permits deep phenotyping of patients and allows for future clinical and basic research. Preliminary results showed expected distribution of phenotypes, demographics, and response to symptomatic treatments in our cohort. Longitudinal data will provide insight into the early diagnosis and management of PSP. Future steps include enrollment of patients in earlier stages, development of biomarkers, and fast-tracking well-characterized patients into clinical trials.

Parkinson’s disease patients with subjective cognitive decline (PD-SCD) and mild cognitive impairment (PD-MCI) have an increased risk of dementia (PDD). Thus, the identification of early cognitive changes that can be useful predictors of PDD is a highly relevant challenge. Posterior cortically based functions, including linguistic processes, have been associated with PDD. However, investigations that have focused on linguistic functions in PD-MCI are scarce and none of them include PD-SCD patients. Our aim was to study language performance in PD-SCD and PD-MCI. Moreover, language subcomponents were considered as predictors of PDD.

Forty-six PD patients and twenty controls were evaluated with a neuropsychological protocol. Patients were classified as PD-SCD and PD-MCI. Language production and comprehension was assessed. Follow-up assessment was conducted to a mean of 7.5 years after the baseline.

PD-MCI patients showed a poor performance in naming (actions and nouns), action generation, anaphora resolution and sentence comprehension (with and without center-embedded relative clause). PD-SCD showed a poor performance in action naming and action generation. Deficit in action naming was an independent risk factor for PDD during the follow-up. Moreover, the combination of deficit in action words and sentence comprehension without a center-embedded relative clause was associated with a greater risk.

The results are of relevance because they suggest that a specific pattern of linguistic dysfunctions, that can be present even in the early stages of the disease, can predict future dementia, reinforcing the importance of advancing in the knowledge of linguistic dysfunctions in predementia stages of PD.