Cumulative Effect of Head Injuries on Nonmotor Outcomes in Parkinson's Disease.

OBJECTIVE: Parkinson's disease (PD) is a neurodegenerative movement disorder that is a result of dopamine depletion in the basal ganglia. Individuals with a PD diagnosis experience motor symptoms (e.g., tremors) and nonmotor symptoms (e.g., cognitive decline). Previous studies suggest that progression of cognitive dysfunction in other neurologic populations can be predicted by cumulative head injuries. The study examined the association between lifelong number of head injuries and nonmotor outcomes (cognitive complaints, depression, and quality of life). METHODS: Participants consisted of 3,483 individuals with PD diagnoses who were enrolled in the Fox Insight study. Participants completed a self-report questionnaire to quantify the number of head injuries experienced throughout life. Participants also completed measures of nonmotor outcomes (cognitive complaints, depression, and quality of life) every 6 months over a 3-year period. RESULTS: Cognitive complaints were more common among those experiencing more head injuries. Further, more severe depression and greater difficulties in quality of life were reported among individuals experiencing a greater number of head injuries. Additional analyses revealed the effect between cognitive complaints and number of head injuries was driven by individuals who experienced five or more head injuries in their lifetime. CONCLUSIONS: Among individuals with PD, a patient report of past head injuries may have prognostic implications for important nonmotor outcomes. Report of multiple head injuries may be particularly concerning.

Apathy as a Within-Person Mediator of Depressive Symptoms and Cognition in Parkinson's Disease: Longitudinal Mediation Analyses.

OBJECTIVE: Greater depressive symptoms are associated with worse cognitive functions in Parkinson's disease (PD); however, it is unclear what underlying factors drive this association. Apathy commonly develops in PD and may be a pathway through which depressive symptoms negatively influence cognition. Prior research examining depressive symptoms, apathy, and cognition in PD is limited by being predominantly cross-sectional. This study examined the role of apathy as a within- and between-person mediator for the longitudinal relationships between depression severity and cognitive functioning in patients with early PD. METHODS: Participants included 487 individuals newly diagnosed with PD followed annually for up to 5 years by the Parkinson's Progression Marker Initiative. At each visit, participants completed depressive symptom measures, apathy ratings, and cognitive tests. Multi-level structural equation models examined both the within- and between-person effects of depressive symptoms on cognition through apathy, controlling for demographics and motor severity. RESULTS: At the within-person level, apathy mediated the association between depressive symptoms and select cognitive functions (global cognition, attention/working memory, visuospatial functions, and immediate verbal memory; indirect effects, bootstrap p's <0.05). Significant between-person direct effects were found for depressive symptoms predicting apathy (boostrap p <0.001) and lower scores on most cognitive tests (bootstrap p's <0.05). However, the indirect effects did not reach significance, suggesting between-person mediation did not occur. CONCLUSION: Findings suggest worsening of depressive symptoms over time in patients with PD may be a risk factor for increased apathy and subsequent decline in specific cognitive functions.

The joint effect of aging and HIV infection on microstructure of white matter bundles.

Recent evidence suggests the aging process is accelerated by HIV. Degradation of white matter (WM) has been independently associated with HIV and healthy aging. Thus, WM may be vulnerable to joint effects of HIV and aging. Diffusion-weighted imaging (DWI) was conducted with HIV-seropositive (n = 72) and HIV-seronegative (n = 34) adults. DWI data underwent tractography, which was parcellated into 18 WM tracts of interest (TOIs). Functional Analysis of Diffusion Tensor Tract Statistics (FADTTS) regression was conducted assessing the joint effect of advanced age and HIV on fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) along TOI fibers. In addition to main effects of age and HIV on WM microstructure, the interactive effect of age and HIV was significantly related to lower FA and higher MD, AD, and RD across all TOIs. The location of findings was consistent with the clinical presentation of HIV-associated neurocognitive disorders. While older age is related to poorer WM microstructure, its detrimental effect on WM is stronger among HIV+ relative to HIV- individuals. Loss of WM integrity in the context of advancing age may place HIV+ individuals at increased risk for brain and cognitive compromise.

Symptom Dimensions of Depression and Apathy and Their Relationship With Cognition in Parkinson's Disease.

OBJECTIVES: Both depression and apathy, alone and in combination, have been shown to negatively affect cognition in patients with Parkinson's disease (PD). However, the influence of specific symptom dimensions of depression and apathy on cognition is not well understood. The current study investigated the relationship between symptom dimensions of depression and apathy, based on factors identified in Kirsch-Darrow et al. (2011), and memory and executive function in PD. METHODS: A sample of 138 non-demented individuals with PD (mean age=64.51±7.43 years) underwent neuropsychological testing and completed the Beck Depression Inventory, 2nd Edition, and Apathy Scale. Separate hierarchical regression models examined the relationship between symptom dimensions of depression and apathy ("pure" depressive symptoms, "pure" apathy, loss of interest/pleasure [anhedonia], and somatic symptoms) and three cognitive domain composites: immediate verbal memory, delayed verbal memory, and executive function. RESULTS: After adjusting for general cognitive status and the influence of the other symptom dimensions, "pure" depressive symptoms were negatively associated with the delayed verbal memory composite (p<.034) and somatic symptoms were positively associated with the executive function composite (p<.026). No symptom dimensions were significantly related to the immediate verbal memory composite. CONCLUSIONS: Findings suggest that specific mood symptoms are associated with delayed verbal memory and executive function performance in non-demented patients with PD. Further research is needed to better understand possible mechanisms through which specific symptom dimensions of depression and apathy are associated with cognition in PD. (JINS, 2018, 24, 269-282).

The effects of HIV and aging on subcortical shape alterations: A 3D morphometric study.

Standard volumetric neuroimaging studies have demonstrated preferential atrophy of subcortical structures among individuals with HIV. However, to our knowledge, no study has investigated subcortical shape alterations secondary to HIV and whether advancing age impacts that relationship. This study employed 3D morphometry to examine the independent and interactive effects of HIV and age on shape differences in nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus in 81 participants ranging in age from 24 to 76 including 59 HIV+ individuals and 22 HIV-seronegative controls. T1-weighted MRI underwent a preprocessing pipeline followed by automated subcortical segmentation. Parametric statistical analyses were used to determine independent effects of HIV infection and age on volume and shape in each region of interest (ROI) and the interaction between age and HIV serostatus in predicting volume/shape in each ROI. Significant main effects for HIV were found in the shape of right caudate and nucleus accumbens, left pallidum, and hippocampus. Age was associated with differences in shape in left pallidum, right nucleus accumbens and putamen, and bilateral caudate, hippocampus, and thalamus. Of greatest interest, an age × HIV interaction effect was found in the shape of bilateral nucleus accumbens, amygdala, caudate, and thalamus as well as right pallidum and putamen such that increasing age in HIV participants was associated with greater shape alterations. Traditional volumemetric analyses revealed main effects for both HIV and age but no age × HIV interaction. These findings may suggest that age and HIV infection conferred additional deleterious effects on subcortical shape abnormalities beyond the independent effects of these factors. Hum Brain Mapp 38:1025-1037, 2017. © 2016 Wiley Periodicals, Inc.

Improvements in brain and behavior following eradication of hepatitis C.

Despite recent advances in treatment, hepatitis C remains a significant public health problem. The hepatitis C virus (HCV) is known to infiltrate the brain, yet findings from studies on associated neurocognitive and neuropathological changes are mixed. Furthermore, it remains unclear if HCV eradication improves HCV-associated neurological compromise. This study examined the longitudinal relationship between neurocognitive and neurophysiologic markers among healthy HCV- controls and HCV+ adults following successful HCV eradication. We hypothesized that neurocognitive outcomes following treatment would be related to both improved cognition and white matter integrity. Participants included 57 HCV+ participants who successfully cleared the virus at the end of treatment (sustained virologic responders [SVRs]) and 22 HCV- controls. Participants underwent neuropsychological testing and, for a nested subset of participants, neuroimaging (diffusion tensor imaging) at baseline and 12 weeks following completion of HCV therapy. Contrary to expectation, group-level longitudinal analyses did not reveal significant improvement in neurocognitive performance in the SVRs compared to the control group. However, a subgroup of SVRs demonstrated a significant improvement in cognition relative to controls, which was related to improved white matter integrity. Indeed, neuroimaging data revealed beneficial effects associated with clearing the virus, particularly in the posterior corona radiata and the superior longitudinal fasciculus. Findings suggest that a subgroup of HCV+ patients experienced improvements in cognitive functioning following eradication of HCV, which appears related to positive changes in white matter integrity. Future research should examine whether any additional improvements in neurocognition and white matter integrity among SVRs occur with longer follow-up periods.

Are Parkinson's Patients More Vulnerable to the Effects of Cardiovascular Risk: A Neuroimaging and Neuropsychological Study.

OBJECTIVES: This study examined whether individuals with Parkinson's disease (PD) are at increased vulnerability for vascular-related cognitive impairment relative to controls. The underlying assumption behind this hypothesis relates to brain reserve and that both PD and vascular risk factors impair similar fronto-executive cognitive systems. METHODS: The sample included 67 PD patients and 61 older controls (total N=128). Participants completed neuropsychological measures of executive functioning, processing speed, verbal delayed recall/memory, language, and auditory attention. Cardiovascular risk was assessed with the Framingham Cardiovascular Risk index. Participants underwent brain imaging (T1 and T2 FLAIR). Trained raters measured total and regional leukoaraiosis (periventricular, deep subcortical, and infracortical). RESULTS: Hierarchical regressions revealed that more severe cardiovascular risk was related to worse executive functioning, processing speed, and delayed verbal recall in both Parkinson patients and controls. More severe cardiovascular risk was related to worse language functioning in the PD group, but not controls. In contrast, leukoaraiosis related to both cardiovascular risk and executive functioning for controls, but not the PD group. CONCLUSIONS: Overall, results revealed that PD and cardiovascular risk factors are independent risk factors for cognitive impairment. Generally, the influence of cardiovascular risk factors on cognition is similar in PD patients and controls. (JINS, 2017, 23, 322-331).

Mood Differences Among Parkinson's Disease Patients With Mild Cognitive Impairment.

Studies with healthy elderly adults suggest that apathy, depression, and anxiety are more common among individuals with mild cognitive impairment (MCI). This study examined differences in mood/amotivational symptoms among patients with Parkinson's disease (PD) with and without MCI. Patients with PD (N=214) underwent neurocognitive evaluations including assessment of apathy (Apathy Scale), depression (Beck Depression Inventory-II), and trait anxiety (State-Trait Anxiety Inventory trait scale). Trait anxiety and depression were more severe in patients with PD with MCI. Delineation of MCI into amnestic and nonamnestic subtypes revealed greater depression, apathy, and anxiety among patients with PD with amnestic MCI relative to cognitively intact patients with PD. Patients with PD and MCI report greater mood symptoms compared to patients with PD who are cognitively intact.

Anxiety and Depression Are Better Correlates of Parkinson's Disease Quality of Life Than Apathy.

Due to controversy regarding the influence of apathy on quality of life (QoL), the authors examined the independent influence of apathy, depression, and trait anxiety in a nondemented sample of patients with Parkinson disease (PD). Participants (N=107) completed standard self-report measures of QoL and mood/motivation. Analyses investigated the contribution of these measures and empirically derived factor scores on QoL. QoL was predicted by trait anxiety, dysphoria, and decreased interest, with no independent contribution of apathy. Different patterns emerged with respect to domain-specific QoL, with trait anxiety being the strongest predictor across most domains. Anxiety was most widely related to QoL in PD, with minimal contribution of apathy. Future studies should examine different roles of PD mood/motivation symptoms on caregiver QoL.

Synergistic associations of depressive symptoms and aging on cognitive decline in early Parkinson's disease.

Objective: Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder. About 40%-50% of PD patients experience depression, making it one of the most common neuropsychiatric disturbances in PD. Cognitive deficits (e.g., difficulties with memory, attention) are an additional common complication in PD. Past studies among healthy aging individuals suggest that depression is a risk factor for cognitive decline, and the risk increases with older age. This study aims to examine the association between depressive symptoms on cognitive decline as a function of age among patients with PD. It is hypothesized that older PD patients with more severe depressive symptoms will be at greater risk of cognitive decline than their younger or less depressed counterparts. Methods: Four hundred and eighty-seven newly diagnosed patients with PD, were assessed for depression and cognition over a five-year period. Participants completed neuropsychological tests that assessed memory, learning, attention, visuospatial functioning, processing speed, and verbal fluency. Multilevel-modeling was used to examine the longitudinal association between cognition, age, and depressive symptoms. Results: Our results indicated a significant three-way interaction (age X occasion X depressive symptoms) predicting language and working memory/attention performance. More specifically, detrimental associations of depressive symptoms on cognitive decline in these domains were more pronounced among older adults. Conclusions: Our findings support that older PD patients with comorbid depressive symptoms experience greater cognitive decline compared to their younger counterparts. Findings suggest that older individuals with PD may be more vulnerable to neurotoxic effects of depression (e.g., neuroinflammation, HPA axis disruption), and better management of depression could potentially reduce cognitive decline and dementia risk.

Subjective cognitive complaints are important in PD-MCI criteria: Associations with CSF markers and cognitive decline.

INTRODUCTION: According to the Movement Disorder Society (MDS), subjective cognitive complaints (SCC) are a diagnostic criterion for PD-mild cognitive impairment (PD-MCI); however, studies often do not incorporate SCC when classifying PD-MCI. This inconsistent use may reflect mixed findings regarding the association between SCC and objective measures of cognitive impairment. Our study aimed to describe the extent that inclusion/exclusion of SCC affects the occurrence of PD-MCI, and if the inclusion of SCC is associated with faster cognitive decline and cerebrospinal fluid markers (CSF) of alpha-synuclein, amyloid beta, total tau, and phophorylated-tau. METHODS: Individuals with PD (N = 358) from the PPMI cohort whom completed measures of neuropsychological performance, subjective cognitive complaints, motor severity, and CSF markers were included. Participants were classified as cognitively normal (CN), PD-MCI with subjective cognitive complaints (PD-MCI + SCC) and PD-MCI without subjective cognitive complaints (PD-MCI -SCC). RESULTS: PD-MCI rates were consistently higher (16.5-19.1%) across the 5 years when SCC was not included in the diagnostic criteria as opposed to when SCC was included (4.4-11.0%). PD-MCI + SCC experienced greater cognitive decline and had significantly higher levels of tau/ab and p-tau/ab relative to both the CN and PD-MCI - SCC groups. CONCLUSIONS: Inconsistent implementation of an SCC requirement in PD-MCI classifications may have important implications in terms of the occurrence of PD-MCI and its prognostic value. Classifying PD-MCI only using neuropsychological cut-off criterion, without regard to SCC, may lead to higher rates of PD-MCI. Inclusions of SCC in PD-MCI criteria in newly diagnosed PD participants may strengthen the ability to detect individuals at risk for future cognitive decline, though it is possible that this decline is related to Alzheimer's disease changes rather than worse PD pathology.

Mental health disparities and the role of perceived discrimination among Latinx individuals living with Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder with motor and non-motor symptoms including depression and cognitive impairment. There is underrepresentation of Latinxs in PD research as most of the research consists of non-Latinx white participants. The current study investigates longitudinal differences in health disparities among Latinx and White non-Latinx individuals living with PD. As a second aim, we examined the associations between perceived discrimination in healthcare and outcomes from aim 1. METHODS: The present study consisted of 25,298 individuals with PD who enrolled in the Fox Insight (FI) online study. Participants were followed annually for up to 3 years. Participants completed measures of depressive symptoms, health-related quality of life (HRQOL), cognitive complaints, subjective motor symptom severity, self-reported income, and perceived discrimination in healthcare. Multilevel models examined the longitudinal differences in non-motor and motor outcomes among Latinx (n = 1161) and White non-Latinx individuals (n = 24,137). RESULTS: Latinx participants reported significantly more depressive symptoms and worse HRQOL than non-Latinx individuals. No significant differences were found in cognitive complaints, or motor severity between Latinx and non-Latinx participants. The main effect of perceived discrimination was associated with both depressive symptoms and HRQOL. CONCLUSIONS: The current study provides initial evidence of mental health discrepancies among Latinx individuals living with PD and White non-Latinx counterparts. The combination of underrepresentation in research and possible health disparities among Latinx communities may affect the quality of clinical trials/studies and patient care.

Selection of deep brain stimulation candidates in private neurology practices: referral may be simpler than a computerized triage system.

OBJECTIVE: The objective of this study is to compare a computerized deep brain stimulation (DBS) screening module (Comparing Private Practice vs. Academic Centers in Selection of DBS Candidates [COMPRESS], NeuroTrax Corp., Bellaire, TX, USA) with traditional triage by a movement disorders specialized neurologist as the gold standard. METHODS: The COMPRESS consists of a combination of the Florida Surgical Questionnaire for Parkinson disease (FLASQ-PD), a cognitive assessment battery provided by MindStreams® (NeuroTrax Corp.), and the Geriatric Depression Scale and the Zung Anxiety Self-Assessment Scale. COMPRESS resulted in the classification of patients into three categories: "optimal candidate,""probable candidate," and "not a good candidate." Similar categorical ratings made by a referring private practice neurologist and by a trained movement disorders specialist were compared with the ratings generated by COMPRESS. RESULTS: A total of 19 subjects with Parkinson's disease were enrolled from five private neurological practices. The clinical impressions of the private practice neurologist vs. those of the movement disorders specialist were in agreement approximately half the time (10/19 cases). The movement disorders specialist and COMPRESS agreed on 15/19 cases. A further comparison between outcomes from the entire COMPRESS module and the FLASQ-PD questionnaire by itself resulted in high agreement (18/19 cases in agreement). CONCLUSIONS: The COMPRESS agreed with an in-person evaluation by a movement disorders neurologist approximately 80% of the time. The computerized COMPRESS did not provide any screening advantage over the short FLASQ-PD paper questionnaire. Larger studies will be needed to assess the utility and cost effectiveness of this computerized triage method for DBS.

Physical inactivity links depressive symptoms and cognitive functioning among individuals with Parkinson's disease.

OBJECTIVE: Parkinson's disease (PD) is a neurodegenerative disorder caused by disruption of dopamine-producing cells. PD is associated with motor symptoms and nonmotor symptoms including depression and cognitive impairment. Past research suggests an association between depression and cognitive impairment in PD. Physical activity may have a therapeutic effect on both depression and cognitive impairment. The present study investigates if physical activity mediates the association between depressive symptoms and cognition in a longitudinal sample of individuals with PD. METHOD: Participants include individuals newly diagnosed with PD (N = 487) enrolled in the Parkinson's Progression Marker Initiative (PPMI). Participants completed an array of neuropsychological tests over the course of 5 years, as well as questionnaires of depression and physical activity. Between-person and within-person effects of depression and cognition mediated through physical activity were analyzed using structural equation modeling. RESULTS: A significant direct effect demonstrated depression was associated with worse global cognitive functioning. Furthermore, there was a significant indirect within-person effect, indicating that physical activity fully mediated the association between depression and cognition. Individuals who became more depressed over time became less physically active and subsequently experienced cognitive decline over the 5-year period. CONCLUSIONS: Findings have implications for prognostic detection and/or the role of physical activity interventions to buffer effects of depression on cognitive impairment among individuals diagnosed with PD. Physical interventions may potentially be implemented among depressed persons to preserve cognitive functioning. Worsened depression early during PD may be a risk factor for inactivity and cognitive diminishment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Intraindividual variability in neuropsychological performance predicts longitudinal cortical volume loss in early Parkinson's disease.

OBJECTIVE: Cognitive impairment is common among individuals with Parkinson's disease (PD). Intraindividual variability (IIV) is a measure of variability across multiple tasks of cognitive functioning. Due to the limited amount of research, particularly among individuals with PD, IIV has been an underutilized metric of cognitive functioning both in research and clinical practice. Previous research demonstrated that individuals with PD have greater variability in cognitive performance relative to controls, and that IIV is predictive of future cognitive impairments. The aim of this study is to investigate the association between baseline IIV and change in cortical and subcortical volumes among individuals with PD. METHOD: The present study used data from 80 newly diagnosed PD patients who were part of a longitudinal cohort study (Parkinson progression marker initiative [PPMI]). Participants completed neuropsychological measures and underwent T1 structural magnetic resonance imaging (MRI) at baseline and the first annual follow-up. Neuropsychological tests assessed attention, processing speed, visuospatial functioning, verbal fluency learning, and memory. T1 scans were processed using standard Freesurfer protocols for extraction of regional volumes. RESULTS: Greater IIV at baseline was predictive of change in cortical volume in posterior temporal/parietal regions over the 1-year period. Baseline IIV predicted cortical volume changes above and beyond the main effect of motor severity and the baseline statistical mean/global cognition score. CONCLUSION: Our results provide initial evidence that IIV is a marker of longitudinal cortical volume loss. Evidence is building that IIV is a sensitive marker of cognitive impairment and the underlying neurodegeneration among individuals with PD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Beyond PD-MCI: objectively defined subtle cognitive decline predicts future cognitive and functional changes.

OBJECTIVE: Cognitive impairment is prevalent among individuals with Parkinson's disease (PD). Effort has been made to identify individuals at risk for cognitive decline and dementia. Objectively-defined subtle cognitive decline (Obj-SCD) is a novel classification that may identify individuals at risk for cognitive decline prior to a diagnosis of mild cognitive impairment (MCI). We examined the utility of Obj-SCD criteria to predict future cognitive decline and difficulties with activities of daily living (ADLs) among individuals with PD. METHOD: The sample included 483 individuals newly diagnosed with PD. Participants were followed for a five-year span with yearly visits where they completed neuropsychological tests. Participants were categorized as cognitively normal (CN), the newly proposed Obj-SCD, PD-MCI or Parkinson's disease dementia (PDD). Analyses determined if utilization of Obj-SCD criteria predicted subsequent cognitive impairment and difficulties with ADLs. RESULTS: At baseline, 372 (77%) participants were classified as CN, 40 (8.3%) classified as Obj-SCD, and 71 (14.7%) classified as PD-MCI. Analyses revealed that relative to the CN group, participants classified as Obj-SCD at baseline, were more likely to develop PD-MCI or PDD within 5 years (odds ratio 2.413; 95% confidence interval 1.215-4.792). Furthermore, the Obj-SCD represented an intermediate level of impairment, relative to the CN and PD-MCI groups, on an independent measure of cognition (Montreal Cognitive Assessment) and ADL. CONCLUSIONS: Findings provide evidence that Obj-SCD criteria can identify individuals at risk for cognitive decline and impairments in ADL. Obj-SCD criteria may identify individuals at risk for cognitive impairment who are not detected by PD-MCI criteria.

A bidirectional relationship between anxiety, depression and gastrointestinal symptoms in Parkinson's disease.

INTRODUCTION: Anxiety, depression and gastrointestinal (GI) symptoms are common non-motor symptoms in Parkinson's disease (PD). Past studies provide evidence of a disrupted microbiome-gut-brain axis in PD, which is associated with certain motor and non-motor symptoms in PD. Additionally, there is evidence of a bidirectional association between mental health and gut health among individuals with GI disorders. The current study examined the bidirectional association between GI symptoms and anxiety/depression among individuals newly diagnosed with PD. METHODS: We conducted a secondary data analysis of the Parkinson's Progression Markers Initiative. This included 487 individuals newly diagnosed with PD and followed for up to 5 years. Participants completed questionnaires of anxiety, depression and GI symptoms (Scales for Outcomes in Parkinson's Disease Autonomic; SCOPA-AUT) at each annual visit. Multilevel models examined the bidirectional-lagged relationship between GI symptoms and anxiety/depression. RESULTS: Models provided evidence for a bidirectional relationship between GI symptoms and anxiety/depression. Specifically, more severe GI symptoms predicted more severe anxious/depressive symptoms within the same year and at the following year. There was also evidence of the inverse directionality, meaning that more severe anxiety/depression predicted more severe GI symptoms concurrently and in the following year. DISCUSSION: Findings provide preliminary evidence for a cyclical relationship among gut health and mental health in PD. Future studies are needed to examine if the microbiome-gut-brain axis plays a mechanistic role.

Gastrointestinal symptoms are predictive of trajectories of cognitive functioning in de novo Parkinson's disease.

INTRODUCTION: Non-motor symptoms such as cognitive and gastrointestinal (GI) symptoms are common in Parkinson's disease (PD). In PD, GI-symptoms often present prior to motor symptoms. It is hypothesized that GI-symptoms reflect disruptions of the microbiome-gut-brain axis, which leads to altered immune functioning, chronic neuroinflammation, and subsequent neurodegeneration. Initial evidence links gut-dysbiosis to PD pathology and motor symptom severity. The present study examines the longitudinal relationship between severity of GI-symptoms and cognitive impairment in newly diagnosed PD patients. METHODS: A secondary data analysis of the Parkinson's Progression Markers Initiative (PPMI) included 423 newly diagnosed PD patients who were followed for up to 5 years. Participants underwent neuropsychological tests of processing speed, attention, visuospatial functioning, verbal learning and verbal delayed recall. Participant were classified as cognitive intact, mild cognitive impairment or Parkinson's disease dementia. Frequency of GI-symptoms were assessed with the Scales for Outcomes in Parkinson's Disease Autonomic (SCOPA-AUT). Multi-level models (MLM) examined the longitudinal relationship between GI symptoms and cognitive impairment. RESULTS: All cognitive outcomes were predicted by the main effect of GI symptoms, or the GI-symptom X Occasion interaction term. Specifically, more severe GI-symptoms were predictive of a less favorable trajectory of performance on tests of letter fluency, visuospatial, learning and memory. Cognitive performance was uniquely associated with GI-symptoms and unrelated to non-GI autonomic symptoms. CONCLUSIONS: The presence of GI symptoms may serve as an early marker of cognitive impairment in PD. Future studies should examine specific mechanisms underlying the relationship between gut-dysbiosis and cognitive impairment.

Greater intraindividual variability in neuropsychological performance predicts cognitive impairment in de novo Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder that commonly results in cognitive impairments and dementia. Intraindividual variability of neuropsychological performance is a sensitive marker of cognitive decline in other neurologic populations. However, studies have not examined the longitudinal utility of intraindividual variability in predicting future cognitive impairments among individuals with PD. In the current study, we hypothesized that increased intraindividual variability would predict future cognitive decline independent of traditional neuropsychological markers of cognitive impairment. METHODS: The sample included 423 newly diagnosed PD patients and 175 healthy controls, who were followed up to 5 years (baseline, first, second, third, fourth, and fifth annual follow-up). Participants underwent tests of learning, memory, processing speed, attention, verbal fluency, and visuospatial functioning. Cognitive status (cognitive intact, mild cognitive impairment, and dementia) was classified based on previously established criteria. Multilevel models were computed to examine the longitudinal relationship between intraindividual variability, cognitive status, and general cognitive functioning. RESULTS: Analyses revealed that increased intraindividual variability was predictive of incident cognitive decline among individuals with PD. Specifically, greater dispersion in neuropsychological performance was associated with greater risk of transitioning from cognitively intact to mild cognitive impairment or transitioning from mild cognitive impairment to dementia. Additional analyses revealed a significant Intraindividual Variability × Group (PD or control) interaction, meaning that intraindividual variability was predictive of declines in cognitive functioning among PD participants only but not healthy controls. CONCLUSION: Intraindividual variability may be a harbinger for future cognitive decline among individuals with PD. (PsycINFO Database Record (c) 2020 APA, all rights reserved).