Early-to-mid stage idiopathic Parkinson's disease shows enhanced cytotoxicity and differentiation in CD8 T-cells in females.

Neuroinflammation in the brain contributes to the pathogenesis of Parkinson's disease (PD), but the potential dysregulation of peripheral immunity has not been systematically investigated for idiopathic PD (iPD). Here we showed an elevated peripheral cytotoxic immune milieu, with more terminally-differentiated effector memory (TEMRA) CD8 T, CD8+ NKT cells and circulating cytotoxic molecules in fresh blood of patients with early-to-mid iPD, especially females, after analyzing > 700 innate and adaptive immune features. This profile, also reflected by fewer CD8+FOXP3+ T cells, was confirmed in another subcohort. Co-expression between cytotoxic molecules was selectively enhanced in CD8 TEMRA and effector memory (TEM) cells. Single-cell RNA-sequencing analysis demonstrated the accelerated differentiation within CD8 compartments, enhanced cytotoxic pathways in CD8 TEMRA and TEM cells, while CD8 central memory (TCM) and naïve cells were already more-active and transcriptionally-reprogrammed. Our work provides a comprehensive map of dysregulated peripheral immunity in iPD, proposing candidates for early diagnosis and treatments.

Retrograde procedural memory is impaired in people with Parkinson's disease with freezing of gait.

Background: Freezing of gait (FOG), is associated with impairment of different cognitive functions. Previous studies hypothesized that FOG may be due to a loss of automaticity. Research question: To explore whether FOG is associated with impairment in cognitive functions, focusing on retrograde procedural memory, the memory responsible for the automatic, implicit stored procedures that have been acquired in earlier life stages. Methods: In this cross-sectional, case-control study, 288 people with typical Parkinson's disease (PD) from the Luxembourg Parkinson's Study were assigned to Freezers (FOG+) and non-Freezers (FOG-) based on the MDS-UPDRS 2.13 (self-reported FOG episodes) and 3.11 (FOG evaluated by clinicians during gait assessment). Both groups were matched on age, sex and disease duration. Global cognition (MoCA), retrograde procedural memory and visuo-constructive abilities (CUPRO), psychomotor speed and mental flexibility (TMT) were assessed. Furthermore, we repeated our analyses by additionally controlling for depression (BDI-I). Results: Besides lower global cognition (MoCA; p = 0.007) and mental flexibility (TMT-B and Delta-TMT; p < 0.001), FOG+ showed a lower performance in retrograde procedural memory (CUPRO-IS1; p < 0.001) compared to FOG-. After controlling additionally for depression, our main outcome variable CUPRO-IS1 remained significantly lower in FOG+ (p = 0.010). Conclusion: Our findings demonstrated that besides lower global cognition and mental flexibility scores, FOG+ showed lower performance in retrograde procedural memory compared to matched FOG-control patients, even when accounting for factors such as age, sex, disease duration or depression. Significance: In the context of limited treatment options, especially for non-invasive therapeutic approaches, these insights on procedural memory and FOG may lead to new hypotheses on FOG etiology and consequently the development of new treatment options.

Retrograde Procedural Memory in Parkinson's Disease: A Cross-Sectional, Case-Control Study.

BACKGROUND: The analysis of the procedural memory is particularly relevant in neurodegenerative disorders like Parkinson's disease, due to the central role of the basal ganglia in procedural memory. It has been shown that anterograde procedural memory, the ability to learn a new skill, is impaired in Parkinson's disease. However, retrograde procedural memory, the long-term retention and execution of skills learned in earlier life stages, has not yet been systematically investigated in Parkinson's disease. OBJECTIVE: This study aims to investigate retrograde procedural memory in people with Parkinson's disease. We hypothesized that retrograde procedural memory is impaired in people with Parkinson's disease compared to an age- and gender-matched control group. METHODS: First, we developed the CUPRO evaluation system, an extended evaluation system based on the Cube Copying Test, to distinguish the cube copying procedure, representing functioning of retrograde procedural memory, and the final result, representing the visuo-constructive abilities. Development of the evaluation system included tests of discriminant validity. RESULTS: Comparing people with typical Parkinson's disease (n = 201) with age- and gender-matched control subjects (n = 201), we identified cube copying performance to be significantly impaired in people with Parkinson's disease (p = 0.008). No significant correlation was observed between retrograde procedural memory and disease duration. CONCLUSION: We demonstrated lower cube copying performance in people with Parkinson's disease compared to control subjects, which suggests an impaired functioning of retrograde procedural memory in Parkinson's disease.

Unmet Needs of People With Parkinson's Disease and Their Caregivers During COVID-19-Related Confinement: An Explorative Secondary Data Analysis.

Self-perceived unmet needs in people with typical and atypical parkinsonism (PwP) and their caregivers, support network, personalized ways to address self-perceived unmet needs during confinement, as well as the prevalence of self-reported COVID-19 related symptoms, confirmed SARS-CoV-2 infection, and self-reported COVID-19 related hospitalization in Luxembourg and the Greater Region were assessed. From 18th March to 10th April 2020, 679 PwP were contacted by phone. Data was collected in the form of a semi-structured interview. The thematic synthesis identified 25 themes where PwP need to be supported in order to cope with consequences of the pandemic, and to adapt their daily and health-related activities. The present work highlights that in the context of personalized medicine, depending on the individual needs of support of the patient the identified self-perceived unmet needs were addressed in various ways ranging from one-directed information over interaction up to proactive counseling and monitoring. Family and health professionals, but also other support systems were taking care of the unmet needs of PwP (e.g., shopping, picking-up medication, etc.) during the pandemic. 7/606 PwP (1.15%) reported COVID-19 related symptoms, 4/606 (0.66%) underwent a rRT-PCR-based diagnostic test and 2/606 (0.33%) were confirmed as SARS-CoV-2 positive. None of these PwP reported being hospitalized due to COVID-19. Our results will allow health professionals to expand their services in a meaningful way i.e., personalize their support in the identified themes and thus improve the healthcare of PwP in times of crisis.