Longitudinal cognitive changes in patients with early Parkinson's disease and neuropsychiatric symptoms

Meng, Detao; Jin, Zhaohui; Wang, Yixuan; Fang, Boyan

doi:10.1111/cns.14173

Cited by 8 publications

(4 citation statements)

References 55 publications

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“…Interestingly, a 14-year continuous follow-up study by Lin Sun et al highlighted that a higher proportion of older adults with anxiety symptoms progressed to cognitive impairment (39.2%) than those without anxiety symptoms (22.6%), implying that anxiety might increase the risk of developing cognitive impairment by damaging axons or synapses [ 47 ]. Studies have also shown that anxiety increases the risk of developing dementia in patients with mild cognitive impairment [ 48 ] and may serve as a predictor of cognitive decline in those with Parkinson’s disease [ 49 ]. All these studies suggest that anxiety induces and increases the progression of cognitive impairment.…”

Section: Discussionmentioning

confidence: 99%

Intermittent hypoxia exacerbates anxiety in high-fat diet-induced diabetic mice by inhibiting TREM2-regulated IFNAR1 signaling

Ni,

Niu,

Cao

et al. 2024

J Neuroinflammation

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Background Type 2 diabetes mellitus (T2DM) and obstructive sleep apnea (OSA) are mutual risk factors, with both conditions inducing cognitive impairment and anxiety. However, whether OSA exacerbates cognitive impairment and anxiety in patients with T2DM remains unclear. Moreover, TREM2 upregulation has been suggested to play a protective role in attenuating microglia activation and improving synaptic function in T2DM mice. The aim of this study was to explore the regulatory mechanisms of TREM2 and the cognitive and anxiety-like behavioral changes in mice with OSA combined with T2DM. Methods A T2DM with OSA model was developed by treating mice with a 60% kcal high-fat diet (HFD) combined with intermittent hypoxia (IH). Spatial learning memory capacity and anxiety in mice were investigated. Neuronal damage in the brain was determined by the quantity of synapses density, the number and morphology of brain microglia, and pro-inflammatory factors. For mechanism exploration, an in vitro model of T2DM combined with OSA was generated by co-treating microglia with high glucose (HG) and IH. Regulation of TREM2 on IFNAR1-STAT1 pathway was determined by RNA sequencing and qRT-PCR. Results Our results showed that HFD mice exhibited significant cognitive dysfunction and anxiety-like behavior, accompanied by significant synaptic loss. Furthermore, significant activation of brain microglia and enhanced microglial phagocytosis of synapses were observed. Moreover, IH was found to significantly aggravate anxiety in the HFD mice. The mechanism of HG treatment may potentially involve the promotion of TREM2 upregulation, which in turn attenuates the proinflammatory microglia by inhibiting the IFNAR1-STAT1 pathway. Conversely, a significant reduction in TREM2 in IH-co-treated HFD mice and HG-treated microglia resulted in the further activation of the IFNAR1-STAT1 pathway and consequently increased proinflammatory microglial activation. Conclusions HFD upregulated the IFNAR1-STAT1 pathway and induced proinflammatory microglia, leading to synaptic damage and causing anxiety and cognitive deficits. The upregulated TREM2 inT2DM mice brain exerted a negative regulation of the IFNAR1-STAT1 pathway. Mice with T2DM combined with OSA exacerbated anxiety via the downregulation of TREM2, causing heightened IFNAR1-STAT1 pathway activation and consequently increasing proinflammatory microglia. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Intermittent hypoxia exacerbates anxiety in high-fat diet-induced diabetic mice by inhibiting TREM2-regulated IFNAR1 signaling

Ni,

Niu,

Cao

et al. 2024

J Neuroinflammation

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“…MDD modulates the initiation and/or episodic symptom exacerbations of most 'autoimmune'/'immune-mediated' disorders, including multiple sclerosis [184], rheumatoid arthritis [183], Alzheimer's disease [185], Parkinson's disease [186] and SLE [187], indicating the role that MDD pathophysiology has in their course. MDD pathophysiology includes gut dysbiosis/permeability, pro-inflammatory cytokines, IDO induction and the conversion of tryptophan to kynurenine, leading to enhanced AhR activation, thereby dysregulating the tryptophan-melatonin pathway [188], and allowing the MDD pathophysiology to be intimately linked to the pathophysiological processes underpinning 'autoimmune' disorders.…”

Section: Autoimmunity and Psychiatric Disordersmentioning

confidence: 99%

Redefining Autoimmune Disorders’ Pathoetiology: Implications for Mood and Psychotic Disorders’ Association with Neurodegenerative and Classical Autoimmune Disorders

Anderson¹,

Almulla

Reíter

et al. 2023

Cells

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Although previously restricted to a limited number of medical conditions, there is a growing appreciation that ‘autoimmune’ (or immune-mediated) processes are important aspects of a wide array of diverse medical conditions, including cancers, neurodegenerative diseases and psychiatric disorders. All of these classes of medical conditions are associated with alterations in mitochondrial function across an array of diverse cell types. Accumulating data indicate the presence of the mitochondrial melatonergic pathway in possibly all body cells, with important consequences for pathways crucial in driving CD8+ T cell and B-cell ‘autoimmune’-linked processes. Melatonin suppression coupled with the upregulation of oxidative stress suppress PTEN-induced kinase 1 (PINK1)/parkin-driven mitophagy, raising the levels of the major histocompatibility complex (MHC)-1, which underpins the chemoattraction of CD8+ T cells and the activation of antibody-producing B-cells. Many factors and processes closely associated with autoimmunity, including gut microbiome/permeability, circadian rhythms, aging, the aryl hydrocarbon receptor, brain-derived neurotrophic factor (BDNF) and its receptor tyrosine receptor kinase B (TrkB) all interact with the mitochondrial melatonergic pathway. A number of future research directions and novel treatment implications are indicated for this wide collection of poorly conceptualized and treated medical presentations. It is proposed that the etiology of many ‘autoimmune’/‘immune-mediated’ disorders should be conceptualized as significantly determined by mitochondrial dysregulation, with alterations in the mitochondrial melatonergic pathway being an important aspect of these pathoetiologies.

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“…In PD, NPSs have been associated with a worse quality of life, increased motor disability, and increased probability of placement in nursing homes [13,14]. Longitudinal studies have shown that individual NPSs, including apathy, visual hallucinations, depression, and anxiety are associated with a higher risk of cognitive decline in PD and conversion from MCI to PDD [15][16][17]. Hence, appropriate behavioral markers represent promising candidates as predictors or early indicators of cognitive decline in PD, which could be used in combination with fluid, genetic, or neuroimaging biomarkers.…”

Section: Introductionmentioning

confidence: 99%

Mild Behavioral Impairment in Parkinson’s Disease: An Updated Review on the Clinical, Genetic, Neuroanatomical, and Pathophysiological Aspects

Angelopoulou,

Bougea,

Hatzimanolis

et al. 2024

Medicina

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Neuropsychiatric symptoms (NPS), including depression, anxiety, apathy, visual hallucinations, and impulse control disorders, are very common during the course of Parkinson’s disease (PD), occurring even at the prodromal and premotor stages. Mild behavioral impairment (MBI) represents a recently described neurobehavioral syndrome, characterized by the emergence of persistent and impactful NPS in later life, reflecting arisk of dementia. Accumulating evidence suggests that MBI is highly prevalent in non-demented patients with PD, also being associated with an advanced disease stage, more severe motor deficits, as well as global and multiple-domain cognitive impairment. Neuroimaging studies have revealed that MBI in patients with PD may be related todistinct patterns of brain atrophy, altered neuronal connectivity, and distribution of dopamine transporter (DAT) depletion, shedding more light on its pathophysiological background. Genetic studies in PD patients have also shown that specific single-nucleotide polymorphisms (SNPs) may be associated with MBI, paving the way for future research in this field. In this review, we summarize and critically discuss the emerging evidence on the frequency, associated clinical and genetic factors, as well as neuroanatomical and neurophysiological correlates of MBI in PD, aiming to elucidate the underlying pathophysiology and its potential role as an early “marker” of cognitive decline, particularly in this population. In addition, we aim to identify research gaps, and propose novel relative areas of interest that could aid in our better understanding of the relationship of this newly defined diagnostic entity with PD.

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Longitudinal cognitive changes in patients with early Parkinson's disease and neuropsychiatric symptoms

Cited by 8 publications

References 55 publications

Intermittent hypoxia exacerbates anxiety in high-fat diet-induced diabetic mice by inhibiting TREM2-regulated IFNAR1 signaling

Intermittent hypoxia exacerbates anxiety in high-fat diet-induced diabetic mice by inhibiting TREM2-regulated IFNAR1 signaling

Redefining Autoimmune Disorders’ Pathoetiology: Implications for Mood and Psychotic Disorders’ Association with Neurodegenerative and Classical Autoimmune Disorders

Mild Behavioral Impairment in Parkinson’s Disease: An Updated Review on the Clinical, Genetic, Neuroanatomical, and Pathophysiological Aspects

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