Immunosenescence in Neurological Diseases—Is There Enough Evidence?

Bsteh, Gabriel; Zrzavy, Tobias; Hoeftberger, Romana; Berger, Thomas

doi:10.3390/biomedicines10112864

Cited by 5 publications

(5 citation statements)

References 81 publications

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“…Additionally, there is a general decline in immune function and an increased predisposition to a proinflammatory state ( 28 ). The available evidence indicates that this phenomenon may be expedited in pwMS, leading to a higher proportion of memory CD4 T cells and impaired regulation via immune-checkpoint mechanisms ( 29 , 30 ).…”

Section: Discussionmentioning

confidence: 99%

Immunophenotyping in routine clinical practice for predicting treatment response and adverse events in patients with MS

Zrzavy,

Rieder,

Wuketich

et al. 2024

Front. Neurol.

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BackgroundRecent studies proposed cellular immunoprofiling as a surrogate for predicting treatment response and/or stratifying the occurrence of adverse events (AEs) in persons with multiple sclerosis (pwMS). However, applicability in real-world circumstances is not sufficiently addressed.ObjectiveWe aimed to explore whether standard routine clinical leukocyte phenotyping before treatment initiation could help stratify patients according to treatment response or AEs in a real-world MS cohort.MethodsIn this retrospective study, 150 pwMS were included, who had been newly initiated on a disease-modifying drug (DMD) and had been assessed for standard immunophenotyping before DMD initiation (baseline) and at least once during the following year. Multivariate models were used to assess an association of immune subsets and the association between immune cell profiles regarding treatment response and AEs.ResultsWe found that the composition of T cell subsets was associated with relapse activity, as an increased proportion of CD8+ lymphocytes at baseline indicated a higher likelihood of subsequent relapse (about 9% per 1% increase in CD8+ proportion of all CD3+ cells). This was particularly driven by patients receiving anti-CD20 therapy, where also EDSS worsening was associated with a higher number of CD8+ cells at baseline (3% increase per 10 cells). In the overall cohort, an increase in the proportion of NK cells was associated with a higher risk of EDSS worsening (5% per 1% increase). Occurrence of AEs was associated with a higher percentage of T cells and a lower number of percentual NKT cells at baseline.ConclusionImmune cell profiles are associated with treatment response and the occurrence of AEs in pwMS. Hence, immunophenotyping may serve as a valuable biomarker to enable individually tailored treatment strategies in pwMS.

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Section: Discussionmentioning

confidence: 99%

Immunophenotyping in routine clinical practice for predicting treatment response and adverse events in patients with MS

Zrzavy,

Rieder,

Wuketich

et al. 2024

Front. Neurol.

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“…The natural aging of the immune system, known as "immunosenescence", could be responsible for the shift in MS from an inflammatory to a neurodegenerative nature (60). As we age, the innate and adaptive immune systems undergo numerous changes, including decreased pool of naïve T cells, decreased diversity in T-cell and B-cell receptors, age-related changes in B cell development and function, and accumulation of memory T cells (61,62).…”

Section: Underlying Pathophysiologymentioning

confidence: 99%

Managing multiple sclerosis in individuals aged 55 and above: a comprehensive review

Fernández,

Sörensen,

Comi

et al. 2024

Front. Immunol.

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Multiple Sclerosis (MS) management in individuals aged 55 and above presents unique challenges due to the complex interaction between aging, comorbidities, immunosenescence, and MS pathophysiology. This comprehensive review explores the evolving landscape of MS in older adults, including the increased incidence and prevalence of MS in this age group, the shift in disease phenotypes from relapsing-remitting to progressive forms, and the presence of multimorbidity and polypharmacy. We aim to provide an updated review of the available evidence of disease-modifying treatments (DMTs) in older patients, including the efficacy and safety of existing therapies, emerging treatments such as Bruton tyrosine kinase (BTKs) inhibitors and those targeting remyelination and neuroprotection, and the critical decisions surrounding the initiation, de-escalation, and discontinuation of DMTs. Non-pharmacologic approaches, including physical therapy, neuromodulation therapies, cognitive rehabilitation, and psychotherapy, are also examined for their role in holistic care. The importance of MS Care Units and advance care planning are explored as a cornerstone in providing patient-centric care, ensuring alignment with patient preferences in the disease trajectory. Finally, the review emphasizes the need for personalized management and continuous monitoring of MS patients, alongside advocating for inclusive study designs in clinical research to improve the management of this growing patient demographic.

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“…Normal aging decreases the brain's viability and increases its vulnerability to damage, 128,129 but neuronal loss is not a salient feature. [130][131][132] Instead, careful stereological studies have concluded that age-related changes in the central nervous system (CNS) in the cognitively intact, aging brain include alterations to neuron extensions (e.g., retraction of dendritic arbors and synapses); 133,134 deterioration of non-neuronal cells (e.g., oligodendrocytes, astrocytes, microglia); [135][136][137][138] and biochemical and molecular changes (e.g., reduced efficacy of neurotransmitters). [139][140][141][142] These effects of aging in the healthy brain differ from those seen with pathological aging due to neurological conditions such as Alzheimer's disease.…”

Section: Postmortem Neuropathologymentioning

confidence: 99%

Alcohol Use Disorder and Dementia: A Review

Zahr

2024

ARCR

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PURPOSE By 2040, 21.6% of Americans will be over age 65, and the population of those older than age 85 is estimated to reach 14.4 million. Although not causative, older age is a risk factor for dementia: every 5 years beyond age 65, the risk doubles; approximately one-third of those older than age 85 are diagnosed with dementia. As current alcohol consumption among older adults is significantly higher compared to previous generations, a pressing question is whether drinking alcohol increases the risk for Alzheimer’s disease or other forms of dementia. SEARCH METHODS Databases explored included PubMed, Web of Science, and ScienceDirect. To accomplish this narrative review on the effects of alcohol consumption on dementia risk, the literature covered included clinical diagnoses, epidemiology, neuropsychology, postmortem pathology, neuroimaging and other biomarkers, and translational studies. Searches conducted between January 12 and August 1, 2023, included the following terms and combinations: “aging,” “alcoholism,” “alcohol use disorder (AUD),” “brain,” “CNS,” “dementia,” “Wernicke,” “Korsakoff,” “Alzheimer,” “vascular,” “frontotemporal,” “Lewy body,” “clinical,” “diagnosis,” “epidemiology,” “pathology,” “autopsy,” “postmortem,” “histology,” “cognitive,” “motor,” “neuropsychological,” “magnetic resonance,” “imaging,” “PET,” “ligand,” “degeneration,” “atrophy,” “translational,” “rodent,” “rat,” “mouse,” “model,” “amyloid,” “neurofibrillary tangles,” “α-synuclein,” or “presenilin.” When relevant, “species” (i.e., “humans” or “other animals”) was selected as an additional filter. Review articles were avoided when possible. SEARCH RESULTS The two terms “alcoholism” and “aging” retrieved about 1,350 papers; adding phrases—for example, “postmortem” or “magnetic resonance”—limited the number to fewer than 100 papers. Using the traditional term, “alcoholism” with “dementia” resulted in 876 citations, but using the currently accepted term “alcohol use disorder (AUD)” with “dementia” produced only 87 papers. Similarly, whereas the terms “Alzheimer’s” and “alcoholism” yielded 318 results, “Alzheimer’s” and “alcohol use disorder (AUD)” returned only 40 citations. As pertinent postmortem pathology papers were published in the 1950s and recent animal models of Alzheimer’s disease were created in the early 2000s, articles referenced span the years 1957 to 2024. In total, more than 5,000 articles were considered; about 400 are herein referenced. DISCUSSION AND CONCLUSIONS Chronic alcohol misuse accelerates brain aging and contributes to cognitive impairments, including those in the mnemonic domain. The consensus among studies from multiple disciplines, however, is that alcohol misuse can increase the risk for dementia, but not necessarily Alzheimer’s disease. Key issues to consider include the reversibility of brain damage following abstinence from chronic alcohol misuse compared to the degenerative and progressive course of ...

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Immunosenescence in Neurological Diseases—Is There Enough Evidence?

Cited by 5 publications

References 81 publications

Immunophenotyping in routine clinical practice for predicting treatment response and adverse events in patients with MS

Immunophenotyping in routine clinical practice for predicting treatment response and adverse events in patients with MS

Managing multiple sclerosis in individuals aged 55 and above: a comprehensive review

Alcohol Use Disorder and Dementia: A Review

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