Gastrointestinal symptoms are predictive of trajectories of cognitive functioning in de novo Parkinson's disease

Jones, Jacob D.; Rahmani, Elizabeth; Garcia, Erik J.; Jacobs, Jonathan P.

doi:10.1016/j.parkreldis.2020.01.009

Cited by 48 publications

(45 citation statements)

References 29 publications

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“…in PD. As such our findings are in line with previous data suggesting that early autonomic dysfunction has to be considered as a risk marker for a more severe form of disease since the earliest stages [13,[16][17][18][19]. Recent evidence suggests several risk and prodromal markers of PD (including constipation, male sex and age) are associate with diverse gut microbiome composition further supporting the pivotal role of the gut-brain axis in disease pathogenesis [20].…”

Section: Discussionsupporting

confidence: 91%

“…Accordingly, PC confers greater risk of developing PD in women and healthy subjects aged above 65 year-old [4]. On the other hand and similarly to other autonomic symptoms, once the motor symptoms have manifested, the presence of constipation since the early phase represents a risk factor for a more severe motor and cognitive burden of disease [16][17][18]. Notwithstanding, to date, evidence suggesting a relationship between the presence of constipation in prodromal phase and disease phenotype after onset of motor symptoms are lacking.…”

Section: Discussionmentioning

confidence: 99%

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The PRIAMO study: age- and sex-related relationship between prodromal constipation and disease phenotype in early Parkinson’s disease

Picillo¹,

Palladino²,

Erro³

et al. 2020

J Neurol

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Objectives To explore the impact of sex and age on relationship between prodromal constipation and disease phenotype in Parkinson’s disease at early stages. Methods A total of 385 Parkinson’s disease patients from the PRIAMO study were classified according to the presence of prodromal constipation and followed for 24 months. Multivariable mixed-effect models were applied. All analyses were performed separately for sex (64.1% men) and median age (different by sex: 67 years-old in men and 68 years-old in women). Results As for sex, prodromal constipation was associated with greater odds of attention/memory complaints and apathy symptoms in women only. As for age, prodromal constipation was associated with lower cognitive and higher apathy scores in older patients only. Conclusions Prodromal constipation anticipates lower cognitive performances and more severe apathy since the earliest stages in women and older patients. Sex- and age-related heterogeneity of prodromal markers of Parkinson’s disease may impact disease phenotype.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

The PRIAMO study: age- and sex-related relationship between prodromal constipation and disease phenotype in early Parkinson’s disease

Picillo¹,

Palladino²,

Erro³

et al. 2020

J Neurol

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“…18 Very recently, Jones et al reported that gastrointestinal symptoms were significantly related to cognitive decline in patients with de novo PD. 23 Moreover, other researchers previously showed that cognitive decline or dementia risk in patients with PD was highly associated with the PIGD type, but not the TD type. 24,25 Collectively, these results may suggest that PIGD and gastrointestinal dysfunction are potentially interconnected in association with the pathophysiologic progression of PD, inferring that the relationship between gastrointestinal symptoms and PIGD might be implicated in the gut-brain axis theory of PD.…”

Section: Discussionmentioning

confidence: 98%

Impact of motor subtype on non‐motor symptoms and fall‐related features in patients with early Parkinson's disease

Kwon¹,

Lee²,

Lee³

et al. 2021

Geriatrics Gerontology Int

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Clinical implications for motor phenotypes of Parkinson's disease (PD) remain to be further elucidated, particularly at the early stages of the disease. We aimed to compare the non-motor and fall-related features between tremor-dominant (TD) and postural instabilitygait difficulty (PIGD) subtypes in patients with early PD.Methods: PD was categorized into TD, intermediate and PIGD types, according to the literature. Not only motor symptoms, but also non-motor symptoms for global cognition, depression, anxiety, fatigue and dysautonomia, were measured in detail. In addition, fall-related features, including a previous history of falls, fear of fall measurement and gait freezing were assessed.Results: In patients with early PD (disease duration no more than 5 years), 35 patients with TD-type PD and 31 patients with PIGD-type PD were finally evaluated for the study. Compared with the TD group, the PIGD group showed higher fatigue, gastrointestinal dysfunction and fall-related parameter scores. Moreover, the PIGD scores were significantly correlated with all of those symptoms.Conclusions: Our findings suggest that PIGD is significantly linked to fatigue, gastrointestinal dysfunction and fall-related features during the early stages of PD.

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“…Earlier studies have reported the relationship between the brain and the GI system, the so-called gut-brain axis or brain-gut axis. It has been hypothesized that GI dysfunctions could reflect the disruptions of the microbiome-gut-brain axis, leading to serious GI inflammatory diseases (e.g., acute pancreatitis or inflammatory bowel disease), endothelial dysfunction, altered immune functioning and regulation of appetite control, neural inflammation, subsequent neurodegeneration, cognitive or psychoneurological disorders (e.g., depression, anxiety, autism, dementia), and disease progression of PD [8][9][10][11][12][13][14][15][16][17][18][19]. In addition to the use of peptides for the improvement of gastrointestinal or digestive dysfunctions [13,[20][21][22], and in order to improve GI function and the balance of microbiota, probiotics could be one of the powerful tools to be used for altering the PD-associated microbiota composition and mitigating the related inflammatory process [12,23].…”

Section: Introductionmentioning

confidence: 99%

Probiotics Alleviate the Progressive Deterioration of Motor Functions in a Mouse Model of Parkinson’s Disease

et al. 2020

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Parkinson’s disease (PD) is one of the common long-term degenerative disorders that primarily affect motor systems. Gastrointestinal (GI) symptoms are common in individuals with PD and often present before motor symptoms. It has been found that gut dysbiosis to PD pathology is related to the severity of motor and non-motor symptoms in PD. Probiotics have been reported to have the ability to improve the symptoms related to constipation in PD patients. However, the evidence from preclinical or clinical research to verify the beneficial effects of probiotics for the motor functions in PD is still limited. An experimental PD animal model could be helpful in exploring the potential therapeutic strategy using probiotics. In the current study, we examined whether daily and long-term administration of probiotics has neuroprotective effects on nigrostriatal dopamine neurons and whether it can further alleviate the motor dysfunctions in PD mice. Transgenic MitoPark PD mice were chosen for this study and the effects of daily probiotic treatment on gait, beam balance, motor coordination, and the degeneration levels of dopaminergic neurons were identified. From the results, compared with the sham treatment group, we found that the daily administration of probiotics significantly reduced the motor impairments in gait pattern, balance function, and motor coordination. Immunohistochemically, a tyrosine hydroxylase (TH)-positive cell in the substantia nigra was significantly preserved in the probiotic-treated PD mice. These results showed that long-term administration of probiotics has neuroprotective effects on dopamine neurons and further attenuates the deterioration of motor dysfunctions in MitoPark PD mice. Our data further highlighted the promising possibility of the potential use of probiotics, which could be the relevant approach for further application on human PD subjects.

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Gastrointestinal symptoms are predictive of trajectories of cognitive functioning in de novo Parkinson's disease

Cited by 48 publications

References 29 publications

The PRIAMO study: age- and sex-related relationship between prodromal constipation and disease phenotype in early Parkinson’s disease

The PRIAMO study: age- and sex-related relationship between prodromal constipation and disease phenotype in early Parkinson’s disease

Impact of motor subtype on non‐motor symptoms and fall‐related features in patients with early Parkinson's disease

Probiotics Alleviate the Progressive Deterioration of Motor Functions in a Mouse Model of Parkinson’s Disease

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