scholarly journals Semantic Recollection in Parkinson’s Disease: Functional Reconfiguration and MAPT Variants

2021 ◽  
Vol 13 ◽  
Author(s):  
Deborah L. Harrington ◽  
Qian Shen ◽  
Vida Sadeghi ◽  
Mingxiong Huang ◽  
Irene Litvan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Functional Connectivity ◽  
Semantic Network ◽  
Therapeutic Interventions ◽  
Group Differences ◽  
Cognitively Normal ◽  
Network Analyses ◽  
Functional Connections ◽  
Semantic Cognition

Decline in semantic cognition in early stages of Parkinson’s disease (PD) is a leading risk factor for future dementia, yet the underlying neural mechanisms are not understood. The present study addressed this gap by investigating the functional connectivity of regions involved in semantic recollection. We further examined whether microtubule-associated protein tau (MAPT) risk variants, which may accelerate cognitive decline, altered the strength of regional functional connections. Cognitively normal PD and healthy elder controls underwent fMRI while performing a fame-discrimination task, which activates the semantic network. Analyses focused on disturbances in fame-modulated functional connectivity in PD for regions that govern semantic recollection and interrelated processes. Group differences were found in multiple connectivity features, which were reduced into principal components that reflected the strength of fame-modulated regional couplings with other brain areas. Despite the absence of group differences in semantic cognition, two aberrant connectivity patterns were uncovered in PD. One pattern was related to a loss in frontal, parietal, and temporal connection topologies that governed semantic recollection in older controls. Another pattern was characterized by functional reconfiguration, wherein frontal, parietal, temporal and caudate couplings were strengthened with areas that were not recruited by controls. Correlations between principal component scores and cognitive measures suggested that reconfigured frontal coupling topologies in PD supported compensatory routes for accessing semantic content, whereas reconfigured parietal, temporal, and caudate connection topologies were detrimental or unrelated to cognition. Increased tau transcription diminished recruitment of compensatory frontal topologies but amplified recruitment of parietal topologies that were unfavorable for cognition. Collectively, the findings provide a new understanding of early vulnerabilities in the functional architecture of regional connectivity during semantic recollection in cognitively normal PD. The findings also have implications for tracking cognitive progression and selecting patients who stand to benefit from therapeutic interventions.

scholarly journals Alterations in striato-thalamo-pallidal intrinsic functional connectivity as a prodrome of Parkinson’s disease

2017 ◽  
Author(s):  
Eran Dayan ◽  
Nina Browner
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Functional Connectivity ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Motor Dysfunction ◽  
Prodromal Phase ◽  
Sleep Behavior ◽  
Functional Connections ◽  
Input And Output

AbstractAlthough the diagnosis of Parkinson’s disease (PD) remains anchored around the cardinal motor symptoms of bradykinesia, rest tremor, rigidity and postural instability, it is becoming increasingly clear that the clinical phase of the disease is preceded by a long period of neurodegeneration, which is not readily evident in terms of motor dysfunction. The neurobiological mechanisms that underpin this prodromal phase of PD remain poorly understood. Based on converging evidence of basal ganglia (BG) dysfunction in early PD, we set out to establish whether the prodromal phase of the disease is characterized by alterations in functional communication within the input and output structures of the BG. We analyzed resting-state functional MRI data collected from patients with REM sleep behavior disorder (RBD) and/or hyposmia, two of the strongest markers of prodromal PD, in comparison to age-matched controls. Relative to controls, subjects in the prodromal group showed reduced intra- and interhemispheric functional connectivity in a striato-thalamo-pallidal network. Functional connectivity alterations were restricted to the BG and did not extend to functional connections with the cortex. The data suggest that local interactions between input and output BG structures may be disrupted already in the prodromal phase of PD.

scholarly journals Severe hyposmia and aberrant functional connectivity in cognitively normal Parkinson’s disease

PLoS ONE ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. e0190072 ◽  
Author(s):  
Noritaka Yoneyama ◽  
Hirohisa Watanabe ◽  
Kazuya Kawabata ◽  
Epifanio Bagarinao ◽  
Kazuhiro Hara ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Functional Connectivity ◽  
Cognitively Normal

scholarly journals A model of repetitive mild brain injury without symptoms – risk for Parkinson’s disease with aging?

2018 ◽  
Author(s):  
Praveen Kulkarni ◽  
Thomas R Morrison ◽  
Xuezhu Cai ◽  
Sade Iriah ◽  
Mary S. Lang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Brain Injury ◽  
Functional Connectivity ◽  
Male Rats ◽  
Central Amygdala ◽  
Momentum Exchange ◽  
Functional Connections ◽  
Mild Brain Injury ◽  
And Function

AbstractObjectivesTo test the hypothesis that repetitive mild traumatic brain injury in early life may be a potential risk factor for Parkinson’s disease.MethodsA closed-head momentum exchange model was used to produce one or three mild concussions in young adult male rats as compare to non-injured, age and weight-matched controls. Six-seven weeks post-injury, rats were studied for deficits in cognitive and motor function Changes in brain anatomy and function were evaluated through analysis of resting state functional connectivity, diffusion weighted imaging with quantitative anisotropy and immunohistochemistry for neuroinflammation.ResultsHead injuries occurred without skull fracture or signs of intracranial bleeding or contusion. There were no significant differences in cognitive or motors behaviors between experimental groups. Rats concussed three times showed altered diffusivity in white matter tracts, basal ganglia, central amygdala, brainstem, and cerebellum. With a single concussion, the affected areas were limited to the caudate/putamen and central amygdala. Disruption of functional connectivity was most pronounced with three concussions as the midbrain dopamine system, hippocampus and brainstem/cerebellum showed hypoconnectivity. The suprachiasmatic nucleus was isolated from all functional connections. Interestingly, rats exposed to one concussion showedenhancedfunctional connectivity (or hyperconnectivity) across brain sites, particularly between the olfactory system and the cerebellum. Immunostaining for microglia activation showed inflammation in striatum and substantia nigra with three concussions but not with one.InterpretationNeuroradiological and immunohistochemical evidence of altered brain structure and function, particularly in striatal and midbrain dopaminergic areas, persists long after mild repetitive head injury. These changes may be long lasting and serve as early biomarkers of neurodegeneration and risk for Parkinson’s disease with aging.

scholarly journals Elevated caudate connectivity in cognitively normal Parkinson’s disease patients

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Natalie Wright ◽  
Abrar Alhindi ◽  
Colleen Millikin ◽  
Mandana Modirrousta ◽  
Sean Udow ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Functional Connectivity ◽  
Caudate Nucleus ◽  
Strong Positive Correlation ◽  
Healthy Controls ◽  
Cognitively Normal ◽  
The Right

Abstract Mild cognitive impairment (MCI) is common in Parkinson’s disease patients. However, its underlying mechanism is not well understood, which has hindered new treatment discoveries specific to MCI. The aim of this study was to investigate functional connectivity changes of the caudate nucleus in cognitively impaired Parkinson’s patients. We recruited 18 Parkinson’s disease patients—10 PDNC [normal cognition Parkinson’s disease; Montreal Cognitive Assessment (MoCA) ≥ 26], 8 PDLC (low cognition Parkinson’s disease; MoCA < 26) —and 10 age-matched healthy controls. All subjects were scanned with resting-state functional magnetic resonance imaging (MRI) and perfusion MRI. We analyzed these data for graph theory metrics and Alzheimer’s disease-like pattern score, respectively. A strong positive correlation was found between the functional connectivity of the right caudate nucleus and MoCA scores in Parkinson’s patient groups, but not in healthy control subjects. Interestingly, PDNC’s functional connectivity of the right caudate was significantly higher than both PDLC and healthy controls, while PDLC and healthy controls were not significantly different from each other. We found that Alzheimer’s disease-like metabolic/perfusion pattern score correlated with MoCA scores in healthy controls, but not in Parkinson’s disease. Increased caudate connectivity may be related to a compensatory mechanism found in cognitively normal patients with Parkinson’s disease. Our findings support and complement the dual syndrome hypothesis.

To rise and to fall: functional connectivity in cognitively normal and cognitively impaired patients with Parkinson's disease

2015 ◽  
Vol 36 (4) ◽  
pp. 1727-1735 ◽  
Author(s):  
Martin Gorges ◽  
Hans-Peter Müller ◽  
Dorothée Lulé ◽  
Elmar H. Pinkhardt ◽  
Albert C. Ludolph ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Functional Connectivity ◽  
Cognitively Impaired ◽  
Cognitively Normal

Constipation is Associated with Development of Cognitive Impairment in de novo Parkinson’s Disease: A Longitudinal Analysis of Two International Cohorts

2021 ◽  
pp. 1-11
Author(s):  
Valentina Leta ◽  
Daniele Urso ◽  
Lucia Batzu ◽  
Daniel Weintraub ◽  
Nataliya Titova ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
De Novo ◽  
Motor Dysfunction ◽  
Group Differences ◽  
Motor Symptoms ◽  
Kaplan Meier ◽  
Patients At Risk ◽  
Non Motor Symptoms

Background: Constipation is regarded as one of the prodromal features of Parkinson’s disease (PD) and there is emerging evidence linking gastrointestinal dysfunction and cognitive impairment (CI) in PD. Objective: We explored whether constipation is associated with development of CI in two independent cohorts of de novo PD patients (n = 196 from the Non-motor International Longitudinal Study [NILS] and n = 423 from the Parkinson’s Progression Markers Initiative [PPMI] study). Methods: Constipation was clinically defined using the Non-Motor Symptoms Scale (NMSS) item-21 [NILS] and Scales for Outcomes in PD-Autonomic (SCOPA-AUT) item-5 [PPMI]. We assessed baseline group differences (PD with or without constipation) in CI, global non-motor symptoms burden, motor dysfunction, and striatal dopaminergic denervation. Kaplan-Meier method estimated group differences in cumulative proportion of patients with incident CI over three years. In PPMI, we subsequently performed univariate and multivariate Cox survival analyses to evaluate whether constipation predicts incident mild cognitive impairment or dementia over a 6-year period, including constipation and other known predictors of CI as covariates. Results: Patients with constipation had greater motor and global non-motor burden in both cohorts at baseline (p <  0.05). Kaplan-Meier plots showed faster conversion to CI in patients with constipation in both cohorts (p <  0.05). In PPMI, 37 subjects developed dementia during a mean follow-up of 4.9 years, and constipation was an independent predictor of dementia onset (hazard ratio = 2.311; p = 0.02). Conclusion: Constipation in de novo PD patients is associated with development of cognitive decline and may serve as a clinical biomarker for identification of patients at risk for cognitive impairment.

Evaluation of Motor and Cognitive Performance in People with Parkinson’s Disease Using Instrumented Trail-Making Test

Gerontology ◽  
2021 ◽  
pp. 1-7
Author(s):  
Ram kinker Mishra ◽  
Catherine Park ◽  
He Zhou ◽  
Bijan Najafi ◽  
T. Adam Thrasher
Keyword(s):  
Older Adults ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Performance ◽  
Pairwise Comparison ◽  
Walking Test ◽  
Cognitively Normal ◽  
Early Results ◽  
Trail Making ◽  
Changes Over Time

<b><i>Introduction:</i></b> Parkinson’s disease (PD) progressively impairs motor and cognitive performance. The current tools to detect decline in motor and cognitive functioning are often impractical for busy clinics and home settings. To address the gap, we designed an instrumented trail-making task (iTMT) based on a wearable sensor (worn on the shin) with interactive game-based software installed on a tablet. The iTMT test includes reaching to 5 indexed circles, a combination of numbers (1–3) and letters (A&amp;B) randomly positioned inside target circles, in a sequential order, which virtually appears on a screen kept in front of the participants, by rotating one’s ankle joint while standing and holding a chair for safety. By measuring time to complete iTMT task (iTMT time), iTMT enables quantifying cognitive-motor performance. <b><i>Purpose:</i></b> This study’s objective is to examine the feasibility of iTMT to detect early cognitive-motor decline in PDs. <b><i>Method:</i></b> Three groups of volunteers, including 14 cognitively normal (CN) older adults, 14 PDs, and 11 mild cognitive impaireds (MCI), were recruited. Participants completed MoCA, 20 m walking test, and 3 trials of iTMT. <b><i>Results:</i></b> All participants enabled to complete iTMT with &#x3c;3 min, indicating high feasibility. The average iTMT time for CN-Older, PD, and MCI participants were 20.9 ± 0.9 s, 32.3 ± 2.4 s, and 40.9 ± 4.5 s, respectively. After adjusting for age and education level, pairwise comparison suggested large effect sizes for iTMT between CN-older versus PD (Cohen’s <i>d</i> = 1.7, <i>p</i> = 0.024) and CN-older versus MCI (<i>d</i> = 1.57, <i>p</i> &#x3c; 0.01). Significant correlations were observed when comparing iTMT time with the gait speed (<i>r</i> = −0.4, <i>p</i> = 0.011) and MoCA score (<i>r</i> = −0.56, <i>p</i> &#x3c; 0.01). <b><i>Conclusion:</i></b> This study demonstrated the feasibility and early results supporting the potential application of iTMT to determine cognitive-motor and distinguishing individuals with MCI and PD from CN-older adults. Future studies are warranted to test the ability of iTMT to track its subtle changes over time.

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