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

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.

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

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.727057 ◽

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.

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Functional connectivity of the tremor network in essential tremor plus and tremor dominant Parkinson's disease

Parkinsonism & Related Disorders ◽

10.1016/j.parkreldis.2020.06.413 ◽

2020 ◽

Vol 79 ◽

pp. e114

Author(s):

S. Prasad ◽

J. Saini ◽

R.D. Bharath ◽

P.K. Pal

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Functional Connectivity ◽

Essential Tremor

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Altered intrinsic brain functional connectivity in drug-naïve Parkinson’s disease patients with LRRK2 mutations

Neuroscience Letters ◽

10.1016/j.neulet.2018.03.038 ◽

2018 ◽

Vol 675 ◽

pp. 145-151 ◽

Cited By ~ 5

Author(s):

Yanbing Hou ◽

Chunyan Luo ◽

Jing Yang ◽

Ruwei Ou ◽

Wei Song ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Functional Connectivity ◽

Drug Naïve ◽

Brain Functional Connectivity

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

Gerontology ◽

10.1159/000515940 ◽

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

Introduction: 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&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. Purpose: This study’s objective is to examine the feasibility of iTMT to detect early cognitive-motor decline in PDs. Method: 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. Results: All participants enabled to complete iTMT with <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 d = 1.7, p = 0.024) and CN-older versus MCI (d = 1.57, p < 0.01). Significant correlations were observed when comparing iTMT time with the gait speed (r = −0.4, p = 0.011) and MoCA score (r = −0.56, p < 0.01). Conclusion: 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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