Relationship between circulating CD4+ T lymphocytes and cognitive impairment in patients with Parkinson’s disease

Magistrelli, Luca; Storelli, Elisa; Rasini, Emanuela; Contaldi, Elena; Comi, Cristoforo; Cosentino, Marco; Marino, Franca

doi:10.1016/j.bbi.2020.07.005

Cited by 50 publications

(31 citation statements)

References 37 publications

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“…Additionally, lowered number of CD4+ T lymphocyte seemed to be an independent risk factor of cognitive impairment in ALS patients. Alterations of the peripheral immune system have been reported to be related to cognitive impairment in other neurodegenerative disease [26][27][28][29]. Reduction of B and T lymphocytes was detected in patients with dementia of different patterns including AD, vascular dementia, and FTD [26].…”

Section: Discussionmentioning

confidence: 99%

“…In PD patients with cognitive impairment, Hu et al detected significant lower numbers of CD4+, CD8+, and total T lymphocyte, and decreased CD4+/CD8+ T ratio [28]. Magistrelli et al found that PD patients with cognitive impairment had increased activated regulatory Tlymphocyte (Treg) and Th1 lymphocytes [29]. The imbalance between CD4+ T lymphocyte subpopulations may lead to a proinflammatory state with an overproduction of proinflammatory cytokines that could impair the blood-brain barrier, reach the central nervous system (CNS), and further aggravate neurodegeneration [32].…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, changed peripheral immunity was found to be related to cognitive impairment of patients with various neurodegenerative diseases, such as Alzheimer's disease (AD) [26,27] and Parkinson's disease (PD) [28,29]. Nevertheless, there has been no study exploring the relationship between the peripheral blood lymphocyte subsets and the cognitive status in ALS patients.…”

Section: Introductionmentioning

confidence: 99%

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Decreased blood CD4+ T lymphocyte helps predict cognitive impairment in patients with amyotrophic lateral sclerosis

et al. 2021

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Background ALS patients have changed peripheral immunity. It is unknown whether peripheral immunity is related to cognitive dysfunction in ALS patients. Objective To explore the relationship between the peripheral blood lymphocyte subsets and the cognitive status in ALS patients. Methods Among 81 ALS patients, we compared the demographic, clinical, and peripheral levels of total T lymphocyte, CD4+ T lymphocyte, CD8+ T lymphocyte, B lymphocyte, and NK cell between those with cognitive impairment (ALS-ci) and those without (ALS-nci). The cognitive status was evaluated via the Chinese version of the Edinburgh cognitive and behavioral screen (ECAS). Significant predictors of cognitive impairment in univariate logistic regression analysis were further examined using multivariate logistic regression analysis. Results 39.5% of all ALS patients had cognitive impairment. The ALS-ci group had shorter education time, older age at both symptom onset and testing, longer disease duration, and lower levels of peripheral total, CD4+, and CD8+ T lymphocyte and B lymphocyte than the ALS-nci group. Frequency of behavioral impairment did not differ between the two groups. While parameters with significant differences identified by group comparison were also significant predictors of cognitive impairment in univariate logistic regression analysis except the level of B lymphocyte, only older age at testing, education time less than 9 years, and lower level of CD4+ T lymphocyte remained significant in multivariate logistic regression analysis. The predictive model combining these three parameters had an area under the receiver operating characteristic curve value of 0.842 with a sensitivity of 90.6% and a specificity of 67.3%. Conclusion In Chinese ALS patients, blood CD4+ T lymphocyte might help evaluate cognitive impairment along with age and education level.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Decreased blood CD4+ T lymphocyte helps predict cognitive impairment in patients with amyotrophic lateral sclerosis

et al. 2021

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“…Elevations of peripheral inflammatory factors were found in the PD-RBD group compared with the PD-NRBD group ( 142 ). Cognitive damage in PD patients was associated with a higher level of circulating lymphocytes and—in drug-naive ones at least—with dysregulation of the T regulatory cells ( 143 ). In addition, an altered brain glucose metabolism was observed in PD patients with RBD and MCI ( 138 , 144 – 147 ).…”

Section: Discussionmentioning

confidence: 99%

Association Between REM Sleep Behavior Disorder and Cognitive Dysfunctions in Parkinson's Disease: A Systematic Review and Meta-Analysis of Observational Studies

Mao

Huang

et al. 2020

Front. Neurol.

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Background: Rapid eye movement sleep behavior disorder (RBD) is thought to be a prodromal symptom of Parkinson's disease (PD). RBD is also thought to be involved in cognitive decline and dementia in PD. In PD, although the relationship between RBD and cognitive dysfunctions was confirmed by considerable studies, whether RBD was associated with distinct types of cognitive defects is worth of study. Objectives: This systematic review summarizes the evidence relating to cognitive dysfunction in PD patients with RBD (PD-RBD) and those without and explores their specificity to cognitive domains. Methods: A meta-analysis using a random-effects model was performed for 16 different cognitive domains, including global cognitive function, memory (long-term verbal recall, long-term verbal recognition, long-term visual recall, short-term spatial recall, and short-term verbal recall), executive function (general, fluid reasoning, generativity, shifting, inhibition, and updating), language, processing speed/complex attention/working memory, visuospatial/constructional ability, and psychomotor ability. The cognitive difference between the groups of patients was measured as a standardized mean difference (SMD, Cohen's d). PD-RBD patients were classified into Confirmed-RBD (definite diagnosis with polysomnography, PSG) and Probable-RBD (without PSG re-confirmation). In some domains, RBD patients could not be analyzed separately due to the exiguity of primary studies; this analysis refers to such RBD patients as "Mixed-RBD." Results: Thirty-nine studies with 6,695 PD subjects were finally included. Confirmed-RBD patients showed worse performance than those without in global cognitive function, long-term verbal recall, long-term verbal recognition, generativity, inhibition, shifting, language, and visuospatial/constructional ability; Probable-RBD, in global cognitive function and shifting; and Mixed-RBD, in long-term visual recall, Mao et al. RBD and Cognition in PD? short-term spatial recall, general executive function, and processing speed/complex attention/working memory. Conclusion: This meta-analysis strongly suggests a relationship between RBD, Confirmed-RBD in particular, and cognitive dysfunctions in PD patients. Early and routine screening by sensitive and targeted cognitive tasks is necessary for all PD-RBD patients because it may offer the therapeutic time window before they evolve to irreversible dementia.

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“…A study identified a significant decrease in the number of CD4+ lymphocytes in PD patients, but did not find any significant difference in the percentage of CD4+ cells between PD patients and healthy controls (Kustrimovic et al, 2016). Previous studies found an ongoing loss of CD4+ T cells as the disease progresses in PD patients (Stevens et al, 2012), and PD patients with cognitive impairment had a higher number of circulating lymphocytes than patients with normal cognitive function (Magistrelli et al, 2020), and the heterogeneity of the PD patients may account for the discrepancies. In the present study, we found an increase in the percentage of CD4+ T lymphocyte in PD patients.…”

Section: Discussionmentioning

confidence: 96%

Evidence for Peripheral Immune Activation in Parkinson’s Disease

Chen

Wang

et al. 2021

Front. Aging Neurosci.

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BackgroundAccumulating evidence has revealed that peripheral immunity is involved in Parkinson’s disease (PD). However, the results regarding the percentage of T-cell subsets are inconsistent, and the changes of immunoglobins levels have been seldom studied in PD patients.MethodsSerum levels of the percentage of T-cell subsets and immunoglobulins were measured in 761 PD patients and 761 age- and gender-matched healthy controls. The correlations between the variables of peripheral immune activation (PIA) and the clinical characteristics of PD were analyzed using correlation analysis.ResultsThe pooled results showed that PD patients had higher proportional levels of CD3+ T and CD4+ T lymphocytes than healthy controls. CD8+ T cell percentages were similar in PD patients and controls, and the CD4/CD8 ratio was significantly higher in the PD population. No significant differences in IgG, IgA, or IgM levels between these two groups were found. CD4+ T cell percentage was inversely correlated with the H&Y stage, and IgG level was positively correlated with disease duration and UPDRS part III. Subgroup analyses showed that these associations existed in female patients, but not in male patients.ConclusionThe enhanced immune activation in the peripheral system is indicated in PD, and dynamic alterations in CD4+ T cell percentage and IgG level suggest an active role for peripheral immunity in the disease progression, especially in female PD patients.

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Relationship between circulating CD4+ T lymphocytes and cognitive impairment in patients with Parkinson’s disease

Cited by 50 publications

References 37 publications

Decreased blood CD4+ T lymphocyte helps predict cognitive impairment in patients with amyotrophic lateral sclerosis

Decreased blood CD4+ T lymphocyte helps predict cognitive impairment in patients with amyotrophic lateral sclerosis

Association Between REM Sleep Behavior Disorder and Cognitive Dysfunctions in Parkinson's Disease: A Systematic Review and Meta-Analysis of Observational Studies

Evidence for Peripheral Immune Activation in Parkinson’s Disease

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