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Introduction Cognitive impairment is common in Parkinson's disease (PD) and PD patients with mild cognitive impairment (PD-MCI) are at increased risk of developing Parkinson's disease dementia (PDD). Reliable biomarkers are required for objective identification of cognitive decline in PD. In this pilot study, serum levels of well-known mediators of neuroinflammation were measured in PD patients with or without MCI to find out the involvement of neuroinflammation and microglial activation in PD-MCI. Methods 36 PD-MCI, 25 PD patients with normal cognition (PD-NC) and 19 healthy controls were recruited. Serum levels of NLR family pyrin domain containing 1 (NLRP1), NLRP3, caspase-1, NF-kB, IL-1b and IL-18 were measured by ELISA and a panel of neuropsychological tests was administered. Results PD-MCI patients showed significantly reduced levels of NF-kB, IL-1b and IL-18, whereas NLRP1, NLRP3 and caspase-1 levels were comparable among PD-NC and PD-MCI patients. IL-18 levels were positively correlated with Addenbrooke's Cognitive Examination-Revised and Symbol Digit Modalities Test scores. Conclusion Levels of several microglial activation mediators are reduced in PD-MCI patients inferring a protective role to certain inflammation factors against cognitive decline in PD.

PubMed ID: 32632889 Parkinson's disease (PD) with mild cognitive impairment (PD-MCI) is currently diagnosed based on an arbitrarily predefined standard deviation of neuropsychological test scores, and more objective biomarkers for PD-MCI diagnosis are needed. The purpose of this study was to define possible brain perfusion-based biomarkers of not only mild cognitive impairment, but also risky gene carriers in PD using arterial spin labeling magnetic resonance imaging (ASL-MRI). Fifteen healthy controls (HC), 26 cognitively normal PD (PD-CN), and 27 PD-MCI subjects participated in this study. ASL-MRI data were acquired by signal targeting with alternating radio-frequency labeling with Look-Locker sequence at 3 T. Single nucleotide polymorphism genotyping for rs9468 [microtubule-associated protein tau (MAPT) H1/H1 versus H1/H2 haplotype] was performed using a Stratagene Mx3005p real-time polymerase chain-reaction system (Agilent Technologies, USA). There were 15 subjects withMAPTH1/H1 and 11 subjects withMAPTH1/H2 within PD-MCI, and 33 subjects withMAPTH1/H1 and 19 subjects withMAPTH1/H2 within all PD. Voxel-wise differences of cerebral blood flow (CBF) values between HC, PD-CN and PD-MCI were assessed by one-way analysis of variance followed by pairwise post hoc comparisons. Further, the subgroup of PD patients carrying the riskyMAPTH1/H1 haplotype was compared with noncarriers (MAPTH1/H2 haplotype) in terms of CBF by a two-samplettest. A pattern that could be summarized as "posterior hypoperfusion" (PH) differentiated the PD-MCI group from the HC group with an accuracy of 92.6% (sensitivity = 93%, specificity = 93%). Additionally, the PD patients withMAPTH1/H1 haplotype had decreased perfusion than the ones with H1/H2 haplotype at the posterior areas of the visual network (VN), default mode network (DMN), and dorsal attention network (DAN). The PH-type pattern in ASL-MRI could be employed as a biomarker of both current cognitive impairment and future cognitive decline in PD. This study was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) 1001 Grant #115S219 and Istanbul University Scientific Research Projects Unit Project #1567/42362 Publisher's Version

Event-related potentials (ERPs) and oscillations (EROs) are reliable measures of cognition, but they require time-locked electroencephalographic (EEG) data to repetitive triggers that are not available in continuous sensory input streams. However, such real-life-like stimulation by videos or virtual-reality environments may serve as powerful means of creating specific cognitive or affective states and help to investigate dysfunctions in psychiatric and neurological disorders more efficiently. This study aims to develop a method to generate ERPs and EROs during watching videos. Repeated luminance changes were introduced on short video segments, while EEGs of 10 subjects were recorded. The ERP/EROs time-locked to these distortions were analyzed in time and time–frequency domains and tested for their cognitive significance through a long term memory test that included frames from the watched videos. For each subject, ERPs and EROs corresponding to video segments of recalled images with 25% shortest and 25% longest reaction times were compared. ERPs produced by transient luminance changes displayed statistically significant fluctuations both in time and time–frequency domains. Statistical analyses showed that a positivity around 450 ms, a negativity around 500 ms and delta and theta EROs correlated with memory performance. Few studies mixed video streams with simultaneous ERP/ERO experiments with discrete task-relevant or passively presented auditory or somatosensory stimuli, while the present study, by obtaining ERPs and EROs to task-irrelevant events in the same sensory modality as that of the continuous sensory input, produces minimal interference with the main focus of attention on the video stream.