Integrity of the nucleus basalis of meynert and self-reported cognitive dysfunction during wearing-off periods in parkinson's disease.

BACKGROUND: Cognition in Parkinson's Disease can be impacted by the wearing-off phenomenon which results from changes in dopaminergic tone throughout the day. Given the well-established role of the cholinergic basal forebrain in cognition, we hypothesized that the Nucleus Basalis of Meynert may support cognitive processes during wearing-off periods. Specifically, we evaluated whether worsening of cognitive symptoms during wearing-off is more likely to occur with structural degeneration of the Nucleus Basalis of Meynert. METHODS: Cognitive wearing-off was evaluated via the Movement Disorders Society Non-Motor Fluctuation Assessment Questionnaire in 33 Parkinson's Disease participants undergoing evaluation for deep brain stimulation. Pre-operative diffusion MRIs were used to measure brain diffusion metrics of the Nucleus Basalis of Meynert and control regions (caudate and putamen). RESULTS: The number of cognitive symptoms which worsened during OFF periods positively correlated with mean diffusivity (ρ = 0.561, p = 0.0007) and generalized fractional anisotropy (ρ=-0.447, p = 0.009) within the Nucleus Basalis of Meynert but not in the caudate or putamen. Meanwhile, stable cognitive symptoms, and ON-state cognitive performance as measured by the DRS-2 did not correlate with Nucleus Basalis of Meynert metrics. Correlations were corrected for age, sex, scanner type, disease duration, education and LEDD. CONCLUSIONS: Our study suggests that reduced structural integrity of the Nucleus Basalis of Meynert is associated with worsening of participant-reported cognitive deficits during OFF periods, but not overall cognitive functioning in the ON-state. These findings support the hypothesis that structural integrity of the cholinergic Nucleus Basalis of Meynert may provide resilience to cognitive worsening during dopamine-related wearing-off.

Narcissism Is Not Associated With Success in U.S. Army Soldier Training.

INTRODUCTION: Narcissism has been studied for its role in leadership using various versions of the Narcissistic Personality Inventory (NPI). Narcissism is described as having a "dark and negative" side as well as a "positive or bright" side. The bright side of narcissism, in particular, has been studied for its role in leadership. In studies among military personnel in Finland and Hungary, the NPI has been associated with positive leadership traits. We assessed if measures of narcissistic personality were predictive of entrance to and graduation from the Army Ranger Course among United States (U.S.) Army personnel. MATERIALS AND METHODS: We included the NPI as one of the measures in the Ranger Resilience and Improved Performance on Phospholipid-bound Omega-3's (RRIPP-3) study. RRIPP-3 was a double-blind, placebo-controlled dietary supplement intervention trial at Fort Benning, GA, that enrolled 555 officers when they entered the U.S. Army Infantry Basic Officer Leadership Course (IBOLC) with the intention to complete the U.S. Ranger School. RRIPP-3 volunteer participants consumed eight dietary supplements daily containing 2.3 g of omega-3 (krill oil) or macadamia nut oil (control) over a 20-week period. Blood spot samples were collected to monitor intake compliance. Cognitive functioning, resilience, and mood were assessed at approximately 14 and 16 weeks. Dietary intake was also assessed. The 40-item, forced-choice NPI was included to assess if three factors of narcissism: Leadership/Authority, Grandiose/Exhibitionism, and Entitlement/Exploitativeness measures of narcissistic personality were associated with entrance to and graduation from the Army Ranger Course. RESULTS: Of the 555 soldiers enrolled in RRIPP-3, there were no statistically significant differences in the total NPI scores comparing U.S. Army IBOLC officers who enrolled (n = 225) versus did not enroll (n = 330, p = .649) or graduated (n = 95; versus did not graduate [n = 460, p = .451]) from the Ranger Course. None of the three-factor NPI subscales differed statistically comparing either enrollment in (p = .442, .510, and .589, respectively) or graduation from the Ranger Course (p = .814, .508, and .813, respectively). CONCLUSIONS: Although narcissism has been positively associated with military trainee success in other countries, we did not find an association between narcissism and trainee success among U.S. Army trainees, and accordingly the level of narcissism did not predict trainee success or failure.

Bridging the Gap: Association between Objective and Subjective Outcomes of Communication Performance in People with Parkinson's Disease Evaluated for Deep Brain Stimulation.

Background: Decrements in verbal fluency following deep brain stimulation (DBS) in people with Parkinson's disease (PwP) are common. As such, verbal fluency tasks are used in assessing DBS candidacy and target selection. However, the correspondence between testing performance and the patient's perception of communication abilities is not well-established. Methods: The Communication Participation Item Bank (CPIB) was administered to 85 PwP during pre-DBS neuropsychological evaluations. Central tendencies for CPIB responses and correlations between CPIB total scores, clinical and demographic factors, and language-based tasks were examined. Results: Most PwP indicated some degree of communication interference on the CPIB. Worse scores on semantic fluency and greater motor impairment were associated with more communication interference. Conclusions: Our findings suggest an incomplete correspondence between commonly used language-based tests and patient-reported outcomes of communication abilities. The need for a functional communication instrument that reflects the different aspects of communication abilities in functional contexts is emphasized.

The Rapid Access Memory Program for Addressing Concerns of Incipient Dementia in Academic Primary Care Settings.

BACKGROUND: Expedient diagnosis of incipient dementia is often hindered by time constraints in primary care visits, shortage of dementia specialists, and extended waitlists for comprehensive neuropsychological evaluations. METHODS: We developed the Rapid Access Memory Program (RAMP) to improve access of neuropsychological services for older adults presenting to our institutional primary care clinics with concerns of cognitive decline. RAMP provides abbreviated neurocognitive assessment, same-day patient feedback, expedited reporting to referring providers, and is financially self-supported. Here, we describe development of RAMP and clinical outcomes from the first 3 years. RESULTS: Of 160 patients seen, dementia was diagnosed in 30% and Mild Cognitive Impairment in 50%; Alzheimer's disease was the most common suspected etiology. New psychiatric diagnosis was made in about one-third (n = 54). Most frequent recommendations involved medication adjustments (initiating cholinesterase inhibitors, deprescribing anticholinergics), safety (driving, decision-making), and specialist referrals. Additionally, 27 (17%) subsequently enrolled in local research. CONCLUSIONS: Results support feasibility and utility of RAMP for connecting older adults in primary care with neuropsychological services.

Stigma and Social Avoidance in Adults with Essential Tremor.

Background: People with essential tremor (ET) can be subject to stigma, and some adopt avoidance behaviors. Characteristics associated with ET stigma and the relationship between perceived stigma and social dysfunction have not been studied. Objectives: To discern predictors of perceived stigma and social dysfunction in ET, and to identify potentially treatable psychological factors associated with social dysfunction. Methods: We surveyed ET patients (n = 158) on recalled stigma incidents and social dysfunction related to tremor, as well as clinical and demographic characteristics including tremor severity, and psychological constructs including anxiety, depression, mindfulness, resilience, and narcissism. Results: Worse tremor severity (Standardized beta [SB] 1.4, P < 0.001) especially among younger participants (interaction of age and tremor severity SB -0.9, P < 0.001) and presence of vocal tremor (SB 0.7, P = 0.002) predict perceived stigma. 53/157 (33.8%) participants met criteria for social dysfunction, employing maladaptive avoidance strategies. Scores for perceived stigma (Odds Ratio [OR] 1.2, P = 0.002), depression (OR 1.5, P = 0.004) and stigma psychological distress (OR 1.2, P = 0.001) as well as sex (OR 4.3 for females, P = 0.045) predicted social dysfunction. Conclusions: Depression and stigma psychological distress contribute to social dysfunction related to ET stigma. Treating these psychological factors may mitigate social avoidance behaviors prevalent among susceptible individuals: those who most perceive ET stigma, i.e. relatively younger patients with worse tremor or with vocal tremor, and in particular females who are more prone to social dysfunction than males with the same degree of perceived stigma.

Multi-session transcutaneous auricular vagus nerve stimulation for Parkinson's disease: evaluating feasibility, safety, and preliminary efficacy.

Background: In pre-clinical animal models of Parkinson's disease (PD), vagus nerve stimulation (VNS) can rescue motor deficits and protect susceptible neuronal populations. Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a non-invasive alternative to traditional invasive cervical VNS. This is the first report summarizing the safety, feasibility, and preliminary efficacy of repeated sessions of taVNS in participants with PD. Objectives: To evaluate the feasibility, safety, and possible efficacy of taVNS for motor and non-motor symptoms in mild to moderate PD. Methods: This is a double-blind, sham controlled RCT (NCT04157621) of taVNS in 30 subjects with mild to moderate PD without cognitive impairment. Participants received 10, 1-h taVNS sessions (25 Hz, 200% of sensory threshold, 500 µs pulse width, 60 s on and 30 s off) over a 2-week period. Primary outcome measures were feasibility and safety of the intervention; secondary outcomes included the MDS-UPDRS, cognitive function and self-reported symptom improvement. Results: taVNS treatment was feasible, however, daily in-office visits were reported as being burdensome for participants. While five participants in the taVNS group and three in the sham group self-reported one or more minor adverse events, no major adverse events occurred. There were no group differences on blood pressure and heart rate throughout the intervention. There were no group differences in MDS-UPDRS scores or self-reported measures. Although global cognitive scores remained stable across groups, there was a reduction in verbal fluency within the taVNS group. Conclusions: taVNS was safe, and well-tolerated in PD participants. Future studies of taVNS for PD should explore at-home stimulation devices and optimize stimulation parameters to reduce variability and maximize engagement of neural targets.

Poor effort on cognitive testing in voluntary research predicts failure in US Army Ranger School: Implications for clinical trial design.

INTRODUCTION: Failure to provide effortful performance on cognitive testing is not uncommon for participants in clinical trials and can significantly impact sensitivity to treatment effect. Whether poor effort on cognitive testing might relate to other behaviors of interest is unknown. In the current investigation, we examined whether effort on baseline cognitive testing in a randomized controlled trial to enhance resiliency in US Army Officers predicted subsequent success in Ranger school. METHODS: Baseline data on six cognitive tests were obtained from 237 US Army Officers entering a military training program prior to attempting Ranger School. Participation was voluntary and the Army was not informed of test scores. "Poor effort" was defined by chance-level accuracy or extreme outlier scores. Logistic regression examined likelihood of Ranger success according to the number of tests with poor effort. RESULTS: Overall, 170 (72%) participants provided good effort on all tests. For these participants, 47% were successful in Ranger, versus 32% with poor effort on one test and 14% with poor effort on two tests. Logistic regression analysis found poor effort on baseline testing predicted reduced likelihood of Ranger success, ß =-.486, p = .005. DISCUSSION: A substantial number of participants exhibited poor effort on testing, and poor effort was predictive of failure in Ranger school. Findings highlight the importance of assessing effort in clinical trials involving cognitive outcomes and suggest application of cognitive effort testing in trials where other motivated behavior is targeted. REGISTRATION: Clinical Trials.gov NCT02908932.

Are Standardized Tests Sensitive to Early Cognitive Change in Parkinson's Disease?

Introduction: Cognitive deficits within the first years of Parkinson's disease (PD) diagnosis are commonly reported, and progression to dementia greatly impacts independence. Identifying measures sensitive to early changes is critical for trials of symptomatic therapies and neuroprotection. Methods: A sample of 253 newly diagnosed PD patients and 134 Health Controls (HC) completed a brief cognitive battery annually over a 5-year period through the Parkinson's Progression Markers Initiative (PPMI). The battery included standardized measures of memory, visuospatial functions, processing speed, working memory, and verbal fluency. Inclusion criterion for HCs was performance above a cutoff for possible Mild Cognitive Impairment (pMCI) on cognitive screening (MoCA ⩾ 27) The PD sample was therefore divided to match HCs on baseline cognitive testing (PD-normal n = 169; PD-pMCI n = 84). The multivariate approach to repeated measures examined rates of change between groups on cognitive measures. Results: An interaction indicating slightly greater decline over time in PD-normal relative to HCs was observed on a measure of working memory: letter-number sequencing. Differential rates of change were not observed on any other measures. Motor symptoms on the dominant right upper extremity accounted for performance differences on a test with writing demands (Symbol-Digit Modality Test). PD-pMCI performed worse than PD-normal on all cognitive measures at baseline, but did not decline faster. Discussion: Working memory appears to decline slightly faster in early PD compared to HCs, while other domains remain similar. Within PD, faster decline was not associated with lower baseline cognition. These findings have implications for clinical trial outcome selection and study design.

Utility of the 20-Item Noise Pareidolia Task (NPT-20) for Assessing Visuoperceptual Disturbances Associated with Complex Visual Hallucinations in Parkinson's Disease.

Background: Complex visual hallucinations (VH) are a common complication of Parkinson's disease (PD). Recent studies have demonstrated relevance of face pareidolia to VH in PD and Lewy body dementia (LBD). Objective: This study examined utility of the 20-item Noise Pareidolia Task (NPT-20) in assessing visuoperceptual disturbances associated with VH in PD. Methods: Retrospective chart review included 46 consecutive PD patients who completed NPT-20 during clinical neuropsychological evaluation. Results: About half the sample (43%) reported VH. PD with VH made significantly more false-positive pareidolia errors on the NPT-20 (p < 0.0001). A cut-off of 2 errors yielded 40% sensitivity, 100% specificity to VH; cut-off of 1 yielded 75% sensitivity, 81% specificity. NPT-20 was not associated with any other clinical or demographic factor. Across groups, NPT-20 evinced moderate correlations with visuospatial functioning and visual memory. Conclusions: Current findings support utility of the NPT-20 for evaluating visuoperceptual disturbances associated with VH in PD.

Development of ETStig, a measure for stigma in essential tremor.

INTRODUCTION: People with essential tremor commonly experience psychological difficulties that are not addressed. The effect of stigma, i.e., negative judgement by others because of a perceived difference in this case shaky movement, is a heretofore unstudied element. This project was undertaken to develop and field test a new measure for stigma associated with essential tremor. METHODS: Under guidance from a patient panel and an expert panel of neurologists and psychologists, the essential tremor stigma construct was delineated, and survey items were written to quantify three dimensions of interest: cumulative experience of stigma; related psychological distress; and resulting behavioral dysfunction. After pilot testing and revision, the essential tremor stigma measure underwent field testing by 198 essential tremor patients at two academic neurology clinics. RESULTS: The experience, distress and dysfunction scales were shown to have good internal consistency and test-retest reliability. Retained items demonstrated acceptable correlations and response properties. The validity of the distress scale was supported by concurrence with an existing stigma scale for neurologic disease, while a patient's openness to psychologic referral was predicted by higher scores on the dysfunction scale. CONCLUSION: This new measure is introduced to study the phenomenon of stigma associated with essential tremor. It may prove useful in assessing potential treatments for the psychological distress and maladaptive behavior that result from this stigma.

Executive function and dopamine response in Parkinson's disease freezing of gait.

BACKGROUND: This investigation examined whether aspects of attention and executive functioning differed between Parkinson's Disease (PD) patients with freezing of gait (FOG) based on responsiveness to dopamine. We also explored association of cognition with FOG severity and gait metrics. METHODS: Fifty-four individuals with PD completed the study protocol: 17 without freezing (PDC), 23 with dopa-responsive FOG (RFOG), and 14 with dopa-unresponsive (URFOG). Standardized neuropsychological tests assessed attention (focused and sustained), psychomotor speed, and set-switching (time and errors). FOG severity was measured using the new FOG Questionnaire (nFOG-Q). Metrics from timed up and go (TUG) tasks were obtained while "on" and "off" dopamine, with and without dual cognitive tasks. RESULTS: After controlling for clinical and demographic factors, analysis of covariance revealed a significant between-group difference for set-switching errors; planned contrasts revealed increased set-switching errors in URFOG relative to RFOG and PD control groups. Groups were not different in other cognitive domains. FOG severity was modestly associated with set-switching errors in RFOG but not URFOG. TUG performances while "on" were associated with set-switching errors in PD controls, and with focused attention in RFOG. CONCLUSION: PD patients with dopa-unresponsive FOG are more prone to set-switching errors than those who respond to treatment. Furthermore, executive function appears relevant to FOG severity only in patients who show dopamine response. Together, these findings suggest disruption of a common dopamine-mediated pathway for FOG and ability to monitor rules while alternating cognitive processes. Consideration of dopa-response could be useful in characterizing cohorts and treating FOG in PD.

Virtual Reality Functional Capacity Assessment Tool (VRFCAT-SL) in Parkinson's Disease.

BACKGROUND: Cognitive impairment is common in Parkinson's disease (PD) and highly associated with loss of independence, caregiver burden, and assisted living placement. The need for cognitive functional capacity tools validated for use in PD clinical and research applications has thus been emphasized in the literature. The Virtual Reality Functional Capacity Assessment Tool (VRFCAT-SL) is a tablet-based instrument that assesses proficiency for performing real world tasks in a highly realistic environment. OBJECTIVE: The present study explored application of the VRFCAT-SL in clinical assessments of patients with PD. Specifically, we examined associations between VRFCAT-SL performance and measures of cognition, motor severity, and self-reported cognitive functioning. METHODS: The VRFCAT-SL was completed by a sample of 29 PD patients seen in clinic for a comprehensive neuropsychological evaluation. Fifteen patients met Movement Disorders Society Task Force criteria for mild cognitive impairment (PD-MCI); no patients were diagnosed with dementia. Non-parametric correlations between VRFCAT-SL performance and standardized neuropsychological tests and clinical measures were examined. RESULTS: VRFCAT-SL performance was moderately associated with global rank on neuropsychological testing and discriminated PD-MCI. Follow-up analyses found completion time was associated with visual memory, sustained attention, and set-switching, while errors were associated with psychomotor inhibition. No clinical or motor measures were associated with VRFCAT-SL performance. Self-report was not associated with VRFCAT-SL or neuropsychological test performance. CONCLUSION: The VRFCAT-SL appears to provide a useful measure of cognitive functional capacity that is not confounded by PD motor symptoms. Future studies will examine utility in PD dementia.

Impact of Fatty Acid Supplementation on Cognitive Performance among United States (US) Military Officers: The Ranger Resilience and Improved Performance on Phospholipid-Bound Omega-3's (RRIPP-3) Study.

Studies have assessed omega-3 fatty acids and cognitive decline among older adults and cognitive development among children, although less is known about cognitive or neurological effects among young adults. We examined whether omega-3 supplementation from krill oil could improve cognition and resilience among young military officers compared to a control. This double-blind, placebo-controlled trial enrolled 555 officers (mean age 23.4 ± 2.8, 98.6% male) entering the United States (US) Army Infantry Basic Officer Leaders Course (IBOLC) with the intention to complete the US Ranger Course. Volunteer participants consumed eight dietary supplements daily of krill oil containing 2.3 g omega-3 or control (macadamia nut oil) over an approximate 20-week period. Cognitive functioning, resilience, and mood were assessed during a well-rested period at approximately 14 weeks and after a battlefield simulation at 16 weeks. Blood spot samples were collected to monitor compliance and dietary intake was assessed. All hypotheses were tested using both 'Intention to Treat' (ITT) and 'As Per Protocol' (APP) approaches. Of the 555 randomized individuals, 245 (44.1%) completed the study. No statistically significant group-by-time interactions indicating treatment effect were found on any outcomes. Poor compliance was indicated by lower than expected omega-3 elevations in the treatment group, and may have contributed to a failure to detect a response.

"Feasibility and utility of a simple computerized test for measuring saccade latency in progressive supranuclear palsy- a proof-of-concept study".

BACKGROUND: Reliable detection of slowed vertical saccades may help discriminate progressive supranuclear palsy (PSP) from the subset of Parkinson's disease patients who lack tremor (akinetic-rigid or PD-postural instability and gait disorder PIGD subtype), and from age-related oculomotor changes. We investigated the feasibility of a camera-less computerized behavioral saccade latency paradigm previously validated in PD to discriminate probable PSP-Richardson syndrome (PSP-RS) from PD-PIGD and age-matched controls. METHODS: In this proof-of-concept case-control study, reflexive saccade latencies were measured in 5 subjects with probable PSP-RS, 5 subjects with PD-PIGD subtype, and 5 age-matched controls using the behavioral paradigm. The battery was repeated approximately one month later. All subjects were examined off levodopa by a movement disorders neurologist and by an ophthalmologist, who also performed a dilated eye exam. RESULTS: Vertical prosaccade latencies were longer in the PSP group (median = 903 ms) relative to PD (median = 268 ms) and control groups (median = 235 ms), with no overlap between groups (100% accuracy). PSP subjects also had larger vertical-horizontal discrepancies than comparison groups. Test-retest reliability for the behavioral saccade measures was good (interclass correlation coefficient = 0.948; 95% confidence interval [0.856, 0.982]), and the measures strongly correlated with clinical ratings. CONCLUSIONS: Computerized behavioral measurement of reflexive saccade latency is feasible in PSP, and potentially discriminates probable PSP-RS from the PD-PIGD subtype. Findings from this proof-of-concept study support utility of the approach for obtaining objective saccade metrics in clinical evaluations and for tracking change in future, larger trials of moderately advanced PSP. Future studies should also examine the behavioral paradigm in earlier presentations of PSP and other subtypes of PSP.