Non-demented Parkinson's Disease Research Articles

Cardiac sympathetic denervation and anxiety in Parkinson disease

BackgroundAnxiety in Parkinson disease (PD) negatively impacts quality of life. While research predominantly focuses on central nervous system changes, some evidence suggests a connection between peripheral autonomic dysfunctions and PD-related anxiety. The role of the peripheral autonomic nervous system in this context may be overlooked. ObjectivesThis study explores the link between anxiety symptoms and cardiac sympathetic denervation in PD using 11C-meta-hydroxyephedrine ([11C]HED) PET cardiac imaging. MethodsWe studied 34 non-demented PD subjects, assessing anxiety levels through the Spielberg Anxiety State-Trait test trait section (STAI-T). Patients underwent comprehensive assessments along with [11C]HED cardiac and [11C]DTBZ brain PET. To identify subdimensions of STAI-T, we employed principal components analysis (PCA). We examined associations between the anxiety subdimensions and two measures of cardiac sympathetic denervation from [11C]HED PET. We utilized correlation and linear regression models for these analyses. ResultsPCA revealed two STAI-T results components: anxiety-depressive and pure anxiety subcomponents. Only pure anxiety significantly correlated with measures of cardiac sympathetic denervation (rhos −0.40, p = 0.018; 0.35, p = 0.043). Regression models confirmed a significant association, with cardiac sympathetic denervation explaining ∼20 % of pure anxiety variance, independent of sex, dopaminergic impairment, and anxiolytic treatments. DiscussionThis study provides preliminary evidence of peripheral autonomic nervous system abnormalities contributing to PD-related anxiety, suggesting dysregulation in peripheral autonomic functions influencing anxiety perception.

The relationship between objective and subjective executive function in Parkinson’s disease

ABSTRACT Introduction Difficulties in executive functioning (EF) are common in PD; however, the relationship between subjective and objective EF is unclear. Understanding this relationship could help guide clinical EF assessment. This study examined the relationship between subjective self-reported EF (SEF) and objective EF (OEF) and predictors of SEF-OEF discrepancies in PD. Method One-hundred and sixteen non-demented PD participants completed measures of OEF (i.e. problem-solving, cognitive flexibility, inhibition, and working memory) and SEF (Frontal Systems Behavior Scale-Self Executive Dysfunction Subscale). Pearson bivariate correlations and linear regressions were performed to examine the relationship between SEF and OEF and the non-motor symptoms (e.g. mood, fatigue), demographic, and PD characteristic (e.g. MCI status) predictors of discrepancies between OEF and SEF (|OEF minus SEF scores|). Correlates of under-, over-, and accurate-reporting were also explored. Results Greater SEF complaints and worse OEF were significantly associated (β =.200, p = .009) and 64% of participants accurately identified their level of OEF abilities. Fewer years of education and greater symptoms of depression, anxiety, and fatigue significantly correlated with greater discrepancies between OEF and SEF. Fatigue was the best predictor of EF discrepancy in the overall sample (β = .281, p = .022). Exploratory analyses revealed apathy and fatigue associated with greater under-reporting, while anxiety associated with greater over-reporting. Conclusions SEF and OEF are significantly related in PD. Approximately 64% of non-demented persons with PD accurately reported their EF skill level, while 28% under-reported and 8% over-reported. SEF-OEF discrepancies were predicted by fatigue in the overall sample. Preliminary evidence suggests reduced apathy and fatigue symptoms relate to more under-reporting, while anxiety relates to greater over-reporting. Given the prevalence of these non-motor symptoms in PD, it is important to carefully consider them when assessing EF in PD.

A multi-site study on sex differences in cortical thickness in non-demented Parkinson’s disease

Clinical, cognitive, and atrophy characteristics depending on sex have been previously reported in Parkinson’s disease (PD). However, though sex differences in cortical gray matter measures in early drug naïve patients have been described, little is known about differences in cortical thickness (CTh) as the disease advances. Our multi-site sample comprised 211 non-demented PD patients (64.45% males; mean age 65.58 ± 8.44 years old; mean disease duration 6.42 ± 5.11 years) and 86 healthy controls (50% males; mean age 65.49 ± 9.33 years old) with available T1-weighted 3 T MRI data from four international research centers. Sex differences in regional mean CTh estimations were analyzed using generalized linear models. The relation of CTh in regions showing sex differences with age, disease duration, and age of onset was examined through multiple linear regression. PD males showed thinner cortex than PD females in six frontal (bilateral caudal middle frontal, bilateral superior frontal, left precentral and right pars orbitalis), three parietal (bilateral inferior parietal and left supramarginal), and one limbic region (right posterior cingulate). In PD males, lower CTh values in nine out of ten regions were associated with longer disease duration and older age, whereas in PD females, lower CTh was associated with older age but with longer disease duration only in one region. Overall, male patients show a more widespread pattern of reduced CTh compared with female patients. Disease duration seems more relevant to explain reduced CTh in male patients, suggesting worse prognostic over time. Further studies should explore sex-specific cortical atrophy trajectories using large longitudinal multi-site data.

Diagnostic value of vietnamese smell identification test in Parkinson's disease

IntroductionThe Vietnamese Smell Identification Test (VSIT) has been validated in determining olfactory dysfunction in the Vietnamese population; however, its value in diagnosing Parkinson's disease (PD) has not been established. MethodsThis case-control study was conducted at University Medical Center HCMC, Ho Chi Minh City, Vietnam. The study sample included non-demented PD patients and healthy controls (HC) who were gender- and age-matched. All participants were evaluated for odor identification ability using the VSIT and the Brief Smell Identification Test (BSIT). ResultsA total of 218 HCs and 218 PD patients participated in the study. The median VSIT and BSIT scores were significantly different between PD and HC groups (VSIT, 5 (3) vs. 9 (2), P < 0.0001; BSIT, 6 (3) vs 8 (2), P < 0.0001). Using the cut-off of <8 for correct answers out of 12 odorants, the VSIT had higher sensitivity (84.4%) and specificity (86.2%) than those of the BSIT (sensitivity of 81.7% and specificity of 69.3%) for the diagnosis of PD. The area under the curve (AUC) value was greater for the VSIT than for the BSIT (0.909 vs 0.818). The smell identification scores were not significantly correlated with disease duration, disease severity, or LEDD (all p > 0.05). ConclusionThe VSIT can be a valuable ancillary tool for supporting the diagnosis of PD in Vietnam. Olfactory dysfunction in PD was unrelated to the disease duration and severity. The VSIT can be applied to improve the accuracy of clinical PD diagnosis.

Psychometrics and diagnostics of the Italian version of the Alternate Verbal Fluency Battery (AVFB) in non-demented Parkinson's disease patients.

Verbal fluency (VF) tasks are known as suitable for detecting cognitive impairment (CI) in Parkinson's disease (PD). This study thus aimed to evaluate the psychometrics and diagnostics of the Alternate Verbal Fluency Battery (AVFB) by Costa et al. (2014) in an Italian cohort of non-demented PD patients, as well as to derive disease-specific cut-offs for it. N = 192 non-demented PD patients were screened with the Montreal Cognitive Assessment (MoCA) and underwent the AVFB-which includes phonemic, semantic and alternate VF tests (PVF; SVF; AVF), as well as a Composite Shifting Index (CSI) reflecting the "cost" of shifting from a single- to a double-cued VF task. Construct validity and diagnostics were assessed for each AVFB measure against the MoCA. Internal reliability and factorial validity were also tested. The MoCA proved to be strongly associated with PVF, SVF and AVF scores, whilst moderately with the CSI. The AVFB was internally consistent and underpinned by a single component; however, an improvement in both internal reliability and fit to its factorial structure was observed when dropping the CSI. Demographically adjusted scores on PVF, SVF and AVF tests were diagnostically sound in detecting MoCA-defined cognitive impairment, whilst this was not true for the CSI. Disease-specific cut-offs for PVF, SVF and AVF tests were derived. In conclusion, PVF, SVF and AVF tests are reliable, valid and diagnostically sound instruments to detect cognitive impairment in non-demented PD patients and are therefore recommended for use in clinical practice and research.

Electrophysiological signatures of anxiety in Parkinson’s disease

Anxiety is a common non-motor symptom in Parkinson’s disease (PD) occurring in up to 31% of the patients and affecting their quality of life. Despite the high prevalence, anxiety symptoms in PD are often underdiagnosed and, therefore, undertreated. To date, functional and structural neuroimaging studies have contributed to our understanding of the motor and cognitive symptomatology of PD. Yet, the underlying pathophysiology of anxiety symptoms in PD remains largely unknown and studies on their neural correlates are missing. Here, we used resting-state electroencephalography (RS-EEG) of 68 non-demented PD patients with or without clinically-defined anxiety and 25 healthy controls (HC) to assess spectral and functional connectivity fingerprints characterizing the PD-related anxiety. When comparing the brain activity of the PD anxious group (PD-A, N = 18) to both PD non-anxious (PD-NA, N = 50) and HC groups (N = 25) at baseline, our results showed increased fronto-parietal delta power and decreased frontal beta power depicting the PD-A group. Results also revealed hyper-connectivity networks predominating in delta, theta and gamma bands against prominent hypo-connectivity networks in alpha and beta bands as network signatures of anxiety in PD where the frontal, temporal, limbic and insular lobes exhibited the majority of significant connections. Moreover, the revealed EEG-based electrophysiological signatures were strongly associated with the clinical scores of anxiety and followed their progression trend over the course of the disease. We believe that the identification of the electrophysiological correlates of anxiety in PD using EEG is conducive toward more accurate prognosis and can ultimately support personalized psychiatric follow-up and the development of new therapeutic strategies.

Cognitive Reserve in Parkinson's Disease without Dementia: β-Amyloid and Metabolic Assessment.

Cognitive reserve (CR) is the mismatch between preserved cognition and neuropathological damage. Amyloidopathy in Parkinson's disease (PD) could be associated with faster progression to dementia, but the putative protective effect of CR is unknown. To evaluate the effect of CR on β-amyloid burden and brain metabolism in non-demented PD subjects. Participants with PD (n = 53) underwent a clinical evaluation, [18 F]-fluorodeoxyglucose and [18 F]-flutemetamol positron emission tomography magnetic resonances, and were classified according to CR. The metabolic pattern of 16 controls was compared to PD subjects. The PD subjects showed hypometabolism mainly in the bilateral posterior cortex. Superior-CR subjects (n = 22) exhibited better cognitive performance, increased amyloid burden, and higher metabolism in several right hemisphere areas compared to low-medium-CR subjects (n = 31). Higher CR in non-demented PD is associated with better cognitive performance, which might reduce vulnerability to the effect of β-amyloid. Whether superior CR leads to protection against metabolic deterioration, and predominantly right hemisphere involvement, deserves further exploration.

17 Grit Predicts Lower Cognitive Fatigue in Persons with Parkinson’s Disease Independent of Cognitive Status

Objective:Fatigue, which can be classified into physical and cognitive subtypes (Schiehser et al., 2012), is a common non-motor symptom in persons with Parkinson’s disease (PD) that has no clear treatment. Cognitive changes, also common in PD (Litvan et al., 2012), may impact how patients perceive fatigue (Kukla et al., 2021). Grit is a personality trait defined as perseverance and passion towards a long-term goal, and is associated with multiple positive outcomes such as lower fatigue levels in healthy individuals (Martinez-Moreno et al., 2021). However, scarce research has examined the relationship between grit and fatigue in persons with PD. Therefore, we aimed to investigate the relationship between fatigue (cognitive and physical) and grit, as well as the impact of cognitive status (i.e., cognitive normal vs. mild cognitive impairment [MCI]) on this relationship in non-demented individuals with PD.Participants and Methods:Participants were 70 non-demented individuals with PD who were diagnosed as either cognitively normal (n=20) or MCI (n=50) based on Level II of the Movement Disorder Society PD-MCI criteria. Participants completed the Modified Fatigue Impact Scale (MFIS), which consists of two subscales (cognitive and physical fatigue) that are combined for a total overall fatigue score. Participants also completed the Grit Scale, which consists of items such as ambition, perseverance, and consistency. ANOVAs were conducted to determine differences in grit between PD-cognitively normal vs PD-MCI groups. Correlations and multiple hierarchical regressions controlling for significant demographics (i.e., age, education, sex), mood (i.e., depression, anxiety) and disease variables (i.e., disease duration, Levodopa equivalent dosage) with backwards elimination were conducted to evaluate the relationship between grit and fatigue (MFIS total score and MFIS cognitive and physical fatigue subscales).Results:There was no significant difference in grit total scores between PD patients who were cognitively normal or MCI (p = .336). Higher grit total scores predicted lower MFIS total (ß = -.290, p = .005) and lower cognitive fatigue (ß = -.336, p &lt; .001) scores in the total sample, above and beyond relevant covariates as well as cognitive status. Grit scores were not significantly associated with physical fatigue (ß = -.206, p = .066). Furthermore, cognitive status was not a significant predictor of fatigue scores in any of the models (all p’s &gt; .28).Conclusions:Findings indicate that higher levels of grit are associated with lower levels of fatigue, specifically cognitive fatigue, in individuals with PD. These results held true for those who were cognitively normal or with MCI, suggesting that grit may impact fatigue in non-demented PD patients regardless of cognitive status. These findings underscore the importance of considering grit when assessing or treating fatigue, particularly cognitive fatigue, in persons with PD.

Cognitive Self-Efficacy in Parkinson's Disease.

Cognitive self-efficacy (CSE), one's belief in their ability to control their cognitive performance, is important for participation in daily activities and rehabilitation. This study aims to understand how Parkinson's disease (PD) affects CSE. The Cognitive Self-Efficacy Questionnaire (CSEQ) was administered to 47 non-demented PD and 52 healthy comparison (HC) participants. Groups were compared on their self-reported ability to recognize (Part 1) and manage (Part 2) cognitive symptoms and to perform cognitively complex functional activities (Part 4). Relationships between CSEQ scores and individual characteristics were assessed within PD. It is found that the PD group had lower CSEQ scores than the HC group for all Parts. Within PD, Part 2 scores were lower than Parts 1 and 4; worse depressive symptoms and higher medication dosage correlated with lower CSE. People with PD may have low CSE, which can contribute to participation restrictions and reduced engagement in treatment. Occupational therapists should consider CSE with clients with PD.

Brain hypometabolism in non-demented microtubule-associated protein tau H1 carriers with Parkinson's disease.

The microtubule-associated protein tau (MAPT) H1 homozygosity (H1/H1 haplotype) is a genetic risk factor for neurodegenerative diseases, such as Parkinson's disease (PD). MAPT H1 homozygosity has been associated with conversion to PD; however, results are conflicting since some studies did not find a strong influence. Cortical hypometabolism is associated with cognitive impairment in PD. In this study, we aimed to evaluate the metabolic pattern in nondemented PD patients MAPT H1/H1 carriers in comparison with MAPT H1/H2 haplotype. In addition, we evaluated domain-specific cognitive differences according to MAPT haplotype. We compared a group of 26 H1/H1 and 20 H1/H2 carriers with late-onset PD. Participants underwent a comprehensive neuropsychological cognitive evaluation and a [18F]-Fluorodeoxyglucose PET-MR scan. MAPT H1/H1 carriers showed worse performance in the digit span forward test of attention compared to MAPT H1/H2 carriers. In the [18F]-Fluorodeoxyglucose PET comparisons, MAPT H1/H1 displayed hypometabolism in the frontal cortex, parahippocampal, and cingulate gyrus, as well as in the caudate and globus pallidus. PD patients MAPT H1/H1 carriers without dementia exhibit relative hypometabolism in several cortical areas as well as in the basal ganglia, and worse performance in attention than MAPT H1/H2 carriers. Longitudinal studies should assess if lower scores in attention and dysfunction in these areas are predictors of dementia in MAPT H1/H1 homozygotes.

Anxiety in Parkinson's Disease Is Associated with Changes in Brain Structural Connectivity.

Anxiety in Parkinson's disease (PD) has been associated with grey matter changes and functional changes in anxiety-related neuronal circuits. So far, no study has analyzed white matter (WM) changes in patients with PD and anxiety. The aim of this study was to identify WM changes by comparing PD patients with and without anxiety, using diffusion-tensor imaging (DTI). 108 non-demented PD patients with (n = 31) and without (n = 77) anxiety as defined by their score on the Parkinson Anxiety Scale participated. DTI was used to determine the fractional anisotropy (FA) and mean diffusivity (MD) in specific tracts within anxiety-related neuronal circuits. Mean FA and MD were compared between groups and correlated with the severity of anxiety adjusted by sex, center, Hoehn & Yahr stage, levodopa equivalent daily dosage, and Hamilton depression rating scale. Compared to patients without anxiety, PD patients with anxiety showed lower FA within the striato-orbitofrontal, striato-cingulate, cingulate-limbic, and caudate-thalamic tracts; higher FA within the striato-limbic and accumbens-thalamic tracts; higher MD within the striato-thalamic tract and lower MD within the striato-limbic tract. Anxiety in PD is associated with microstructural alterations in anxiety-related neuronal circuits within the WM. This result reinforces the view that PD-related anxiety is linked to structural alteration within the anxiety-related brain circuits.

Atypical brain FDG-PET patterns increase the risk of long-term cognitive and motor progression in Parkinson's disease

IntroductionBrain hypometabolism patterns have been previously associated with cognitive decline in Parkinson's disease (PD). Our aim is to evaluate the impact of single-subject fluorodeoxyglucose (FDG)-PET brain hypometabolism on long-term cognitive and motor outcomes in PD. MethodsForty-nine non-demented PD patients with baseline brain FDG-PET data underwent an extensive clinical follow-up for 8 years. The ability of FDG-PET to predict long-term cognitive and motor progression was evaluated using Cox regression and mixed ANCOVA models. ResultsParticipants were classified according to FDG-PET pattern in PD with typical (n = 26) and atypical cortical metabolism (n = 23). Patients with atypical brain hypometabolic patterns showed higher incidence of dementia (60% vs 3%; HR = 18.3), hallucinations (56% vs 7%, HR = 7.3) and faster motor decline compared to typical pattern group. ConclusionThis study argues for specific patterns of FDG-PET cortical hypometabolism in PD as a prognostic marker for long term cognitive and motor outcomes at single-subject level.

Diffusion and structural MRI as potential biomarkers in people with Parkinson's disease and cognitive impairment.

To explore the neuroimage change in Parkinson's disease (PD) patients with cognitive impairments, this study investigated the correlation between plasma biomarkers and morphological brain changes in patients with normal cognition and mild cognitive impairment. The objective was to identify the potential target deposition regions of the plasma biomarkers and to search for the relevant early neuroimaging biomarkers on the basis of different cognitive domains. Structural brain MRI and diffusion weighted images were analyzed from 49 eligible PD participants (male/female: 27/22; mean age: 73.4 ± 8.5years) from a retrospective analysis. Plasma levels of α-synuclein, amyloid beta peptide, and total tau were collected. A comprehensive neuropsychological assessment of the general and specific cognitive domains was performed. Difference between PD patients with normal cognition and impairment was examined. Regression analysis was performed to evaluate the correlation between image-derived index and plasma biomarkers or neuropsychological assessments. Significant correlation was found between plasma Aβ-42 level and fractional anisotropy of the middle occipital, angular, and middle temporal gyri of the left brain, as well as plasma T-tau level and the surface area of the isthmus or the average thickness of the posterior part of right cingulate gyrus. Visuospatial and executive function is positively correlated with axial diffusivity in bilateral cingulate gyri. In nondemented PD patients, the target regions for plasma deposition might be located in the cingulate, middle occipital, angular, and middle temporal gyri. Changes from multiple brain regions can be correlated to the performance of different cognitive domains. Cognitive impairment in Parkinson's disease is primarily linked to biomarkers associated with Alzheimer's disease rather than those related to Parkinson's disease and resembles the frontal variant of Alzheimer's disease, which may guide management strategies for cognitive impairment in Parkinson's disease. • Fractional anisotropy, surface area, and thickness in the cingulate, middle occipital, angular, and middle temporal gyri can be significantly correlated with plasma Aβ-42 and T-tau level. • Axial diffusivity in the cingulate gyri was correlated with visuospatial and executive function. • The pattern of cognitive impairment in Parkinson's disease can be similar to the frontal variant than typical Alzheimer's disease.

Associations of Alzheimer's-related plasma biomarkers with cognitive decline in Parkinson's disease.

Parkinson's disease (PD) is associated with cognitive decline through multiple mechanisms, including Alzheimer's disease (AD) pathology and cortical Lewy body involvement. However, its underlying mechanisms remain unclear. Recently, AD-related plasma biomarkers have emerged as potential tools for predicting abnormal pathological protein accumulation. We aimed to investigate the association between AD-related plasma biomarkers and cognitive decline in PD patients. Plasma biomarkers were measured in 70 PD patients (49 with nondemented Parkinson's disease (PDND) and 21 with Parkinson's disease dementia (PDD)) and 38 healthy controls (HCs) using a single-molecule array. The study evaluated (1) the correlation between plasma biomarkers and clinical parameters, (2) receiver operating characteristic curves and areas under the curve to evaluate the discrimination capacity of plasma biomarkers among groups, and (3) a generalized linear model to analyze associations with Addenbrooke's Cognitive Examination-Revised and Montreal Cognitive Assessment-Japanese version scores. Plasma glial fibrillary acidic protein significantly correlated with cognitive function tests, including all subdomains, with a notable increase in the PDD group compared with the HC and PDND groups, while plasma neurofilament light chain captured both cognitive decline and disease severity in the PDND and PDD groups. Plasma beta-amyloid 42/40 and pholphorylated-tau181 indicated AD pathology in the PDD group, but plasma beta-amyloid 42/40 was increased in the PDND group compared with HCs and decreased in the PDD group compared with the PDND group. AD-related plasma biomarkers may predict cognitive decline in PD and uncover underlying mechanisms suggesting astrocytic pathologies related to cognitive decline in PD.

Validity and diagnostics of the Italian version of the Montreal Cognitive Assessment (MoCA) in non-demented Parkinson’s disease patients

BackgroundThis study aimed at: (1) assessing, in an Italian cohort of non-demented Parkinson’s disease (PD) patients, the construct validity of the Montreal Cognitive Assessment (MoCA) against both first- and second-level cognitive measures; (2) delivering an exhaustive and updated evaluation of its diagnostic properties.MethodsA retrospective cohort of N = 237 non-demented PD patients having been administered the MoCA was addressed, of whom N = 169 further underwent the Mini-Mental State Examination (MMSE) and N = 68 the Parkinson’s Disease Cognitive Rating Scale (PD-CRS). A subsample (N = 60) also underwent a second-level cognitive battery encompassing measures of attention/executive functioning, language, memory, praxis and visuo-spatial abilities. Construct validity was assessed against both the PD-CRS and the second-level cognitive battery. Diagnostics were tested via receiver-operating characteristics analyses against a below-cut-off MMSE score.ResultsThe MoCA was associated with both PD-CRS scores (p < .001) and the vast majority of second-level cognitive measures (ps < .003). Both raw and adjusted MoCA scores proved to be highly accurate to the aim of identifying patients with MMSE-confirmed cognitive dysfunctions. A MoCA score adjusted for age and education according to the most recent normative dataset and < 19.015 is herewith suggested as indexing cognitive impairment in this population (AUC = .92; sensitivity = .92; specificity = .80).DiscussionThe Italian MoCA is a valid and diagnostically sound screener for global cognitive inefficiency in non-demented PD patients. Further studies are nevertheless needed that confirm its diagnostic values against a measure other than the MMSE.

Identifying key multi-modal predictors of incipient dementia in Parkinson's disease: a machine learning analysis and Tree SHAP interpretation.

Persons with Parkinson's disease (PD) differentially progress to cognitive impairment and dementia. With a 3-year longitudinal sample of initially non-demented PD patients measured on multiple dementia risk factors, we demonstrate that machine learning classifier algorithms can be combined with explainable artificial intelligence methods to identify and interpret leading predictors that discriminate those who later converted to dementia from those who did not. Participants were 48 well-characterized PD patients (Mbaseline age = 71.6; SD = 4.8; 44% female). We tested 38 multi-modal predictors from 10 domains (e.g., motor, cognitive) in a computationally competitive context to identify those that best discriminated two unobserved baseline groups, PD No Dementia (PDND), and PD Incipient Dementia (PDID). We used Random Forest (RF) classifier models for the discrimination goal and Tree SHapley Additive exPlanation (Tree SHAP) values for deep interpretation. An excellent RF model discriminated baseline PDID from PDND (AUC = 0.84; normalized Matthews Correlation Coefficient = 0.76). Tree SHAP showed that ten leading predictors of PDID accounted for 62.5% of the model, as well as their relative importance, direction, and magnitude (risk threshold). These predictors represented the motor (e.g., poorer gait), cognitive (e.g., slower Trail A), molecular (up-regulated metabolite panel), demographic (age), imaging (ventricular volume), and lifestyle (activities of daily living) domains. Our data-driven protocol integrated RF classifier models and Tree SHAP applications to selectively identify and interpret early dementia risk factors in a well-characterized sample of initially non-demented persons with PD. Results indicate that leading dementia predictors derive from multiple complementary risk domains.

Morphological characteristics differentiate dementia with Lewy bodies from Parkinson disease with and without dementia.

Dementia with Lewy bodies (DLB) and Parkinson disease (PD) with and without dementia are entities of a spectrum of Lewy body diseases. About 26.3% of all PD patients develop dementia increasing up to 83%. Parkinson disease-dementia (PDD) and DLB share many clinical and morphological features that separate them from non-demented PD (PDND). Clinically distinguished by the temporal sequence of motor and cognitive symptoms, the pathology of PDD and DLB includes variable combinations of Lewy body (LB) and Alzheimer (AD) lesions, both being more severe in DLB, but much less frequent and less severe in PDND. The objective of this study was to investigate the morphological differences between these three groups. 290 patients with pathologically confirmed PD were reviewed. 190 of them had clinical dementia; 110 met the neuropathological criteria of PDD and 80 of DLB. The major demographic and clinical data were obtained from medical records. Neuropathology included semiquantitative assessment of LB and AD pathologies including cerebral amyloid angiopathy (CAA). PDD patients were significantly older than PDND and DLB ones (83.9 vs 77.9years, p < 0.05); the age of DLB patients was between them (80.0years), while the disease duration was shortest in DLB. Brain weight was lowest in DLB, which showed higher Braak LB scores (mean 5.2 vs 4.2) and highest Braak tau stages (mean 5.2 vs 4.4 and 2.3, respectively). Thal Aβ phases were also highest in DLB (mean 4.1 vs 3.0 and 1.8, respectively). Major findings were frequency and degree of CAA, being highest in DLB (95% vs 50% and 24%, with scores 2.9 vs 0.7 and 0.3, respectively), whereas other small vessel lesions showed no significant differences. Striatal Aβ deposits also differentiated DLB from the other groups. This and other studies of larger cohorts of PD patients indicate that the association of CAA and cortical tau-but less-LB pathologies are associated with more severe cognitive decline and worse prognosis that distinguish DLB from PDD and PDND. The particular impact of both CAA and tau pathology supports the concept of a pathogenic continuum ranging from PDND to DLB + AD within the spectrum of age-related synucleinopathies.

Correction to Leonhardt et al. (2019).

A sample of 124 nondemented PD patients and 154 elderly controls was assessed with the Sniffin' Sticks Odor Identification Test (OIT) and the Subjective Olfactory Capability (SOC) domain of the Assessment of Self-Reported Olfactory Functioning and Olfaction-Related Quality of Life, additional to measures of depressive symptoms, verbal memory and executive functioning. Olfactory awareness groups were formed by means of the cut-offs of the OIT and the SOC. Significant correlations between the OIT and the SOC were moderate in participants with PD and small in controls. Of all PD patients, 52% overrated their sense of smell while 27% correctly identified themselves as being hyposmic, as opposed to corresponding 6% and 1% of healthy elderly. Overrating and aware of being hyposmic participants with PD showed worse executive functions than PD patients who were objectively and subjectively normosmic. The findings imply that, although people with PD are aware of hyposmia to some extent, the majority is affected by overestimation of the ability to smell, making self-reported functioning an unreliable source of information. Moreover, reduced odor identification and impaired executive functioning might underlie the same pathological changes within the brain and could serve as a marker for cognitive impairment in PD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Electrophysiological Signatures of Anxiety in Parkinson’s Disease (S51.008)

<h3>Objective:</h3> To assess the pattern of disturbances in the functional brain networks of Parkinson’s disease patients with anxiety (PD-A) compared to those without anxiety (PD-NA) and healthy controls (HC). <h3>Background:</h3> Anxiety is a common non motor symptom in PD occurring in up to 60% of the patients and affecting their quality of life. Despite their high prevalence, anxiety symptoms are often undiagnosed and untreated in PD. To date, functional and structural neuroimaging studies have contributed to our understanding of the motor and cognitive symptomatology of PD. Yet, the underlying pathophysiology of the anxiety symptoms in PD remains largely unknown and studies on their neural correlates are missing. <h3>Design/Methods:</h3> The present study comprised 68 non-demented PD patients and 25 healthy controls. PD patients were divided into two subgroups based on their Beck Anxiety Inventory (BAI) scale (cut-off=13): PD patients with anxiety (N=18) and without anxiety (N=50). Using their resting state high density electroencephalography (EEG) recordings at baseline, we assessed the frequency-dependent functional connectivity patterns that characterize the PD-A patients compared to both PD-NA patients and HC and we validated their relevance after 3 years. <h3>Results:</h3> We revealed different frequency-dependent pattern of connectivity that can characterize the PD-A group compared to PD-NA and HC: patterns with high functional connectivity were observed in delta, theta and gamma bands involving mainly fronto-temporal connections, whereas fronto-parietal patterns with low functional connectivity were pertinent in alpha and beta bands. Their corresponding network signature metric were strongly correlated with the anxiety scale of all the participants at baseline and after 3 years showing a predictive power of the revealed networks. <h3>Conclusions:</h3> Our findings suggest that PD-related anxiety can be characterized by a signature of different frequency-dependent pattern of disturbances in the functional brain networks. Resting state EEG could be a very promising biomarker for early detection of anxiety in PD. <b>Disclosure:</b> Mrs. Yassine has nothing to disclose. Mrs. Almarouk has nothing to disclose. Ute Gschwandtner has nothing to disclose. Dr. Auffret has received personal compensation for serving as an employee of France Développement Electronique. The institution of Dr. Auffret has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Britannia. Dr. Auffret has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Britannia. Dr. Auffret has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Britannia. Dr. Auffret has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Aguettant. The institution of Dr. Auffret has received research support from Association France Parkinson. The institution of Dr. Auffret has received research support from Homeperf. The institution of Dr. Auffret has received research support from LVL. The institution of Dr. Auffret has received research support from University of Rennes 1. The institution of Dr. Auffret has received research support from Aguettant. The institution of Dr. Auffret has received research support from Linde. The institution of Dr. Auffret has received research support from Plateforme Nationale pour la recherche sur la fin de vie. Dr. Auffret has received publishing royalties from a publication relating to health care. Mr. HASSAN has nothing to disclose. The institution of Dr. Fuhr has received research support from Roche. Mr. Verin has nothing to disclose.

The assessment of executive functions to test the integrity of the nigrostriatal network: A pilot study.

Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by motor and non-motor symptoms. The latter mainly include affective, sleep, and cognitive deficits. Non-demented PD patients often demonstrate impairments in several executive domains following neuropsychological evaluation. The current pilot study aims at assessing the discriminatory power of the Frontal Assessment Battery-15 (FAB15) in differentiating (i) non-demented PD patients and healthy controls and (ii) PD patients with more and less pronounced motor symptoms. Thirty-nine non-demented early-stage PD patients in the "on" dopamine state (26 females, mean age = 64.51 years, SD = 6.47, mean disease duration = 5.49 years, SD = 2.28) and 39 healthy participants (24 females, mean age = 62.60 years, SD = 5.51) were included in the study. All participants completed the FAB15. Motor symptoms of PD patients were quantified via the Unified Parkinson's Disease Rating Scale-Part III (UPDRS-Part III) and Hoehn and Yahr staging scale (H&Y). The FAB15 score, adjusted according to normative data for sex, age, and education, proved to be sufficiently able to discriminate PD patients from healthy controls (AUC = 0.69 [95% CI 0.60-0.75], SE = 0.06, p = 0.04, optimal cutoff = 11.29). Conversely, the battery lacked sufficient discriminative capability to differentiate PD patients based on the severity of motor symptoms. The FAB15 may be a valid tool for distinguishing PD patients from healthy controls. However, it might be less sensitive in identifying clinical phenotypes characterized by visuospatial impairments resulting from posteroparietal and/or temporal dysfunctions. In line with previous evidence, the battery demonstrated to be not expendable in the clinical practice for monitoring the severity of PD-related motor symptoms.