Neurodegenerative Diseases最新文献

Objective: This retrospective study analyzed the clinical characteristics and prognosis of the elderly amyotrophic lateral sclerosis (ALS) population in a large sample.

Methods: The study included 1,005 patients with sporadic ALS admitted to Chinese PLA General Hospital between March 2011 and March 2021. We stratified the ALS patients into young and old groups using 2 cutoffs for the age at disease onset (≥65 or ≥70 years old) and compared their demographic, clinical, and survival data.

Results: The mean onset age of all patients was 52.79 ± 10.55 years, with 123 (12.24%) having a disease onset ≥65 years and 44 (4.38%) having an onset ≥70 years. There were 624 (62.1%) male patients. More bulbar-onset cases were in the late-onset group (p = 0.001). The sex distribution, time from onset to diagnosis, and the time of symptom spread from spinal or bulbar localization to a generalized localization did not differ between groups. Late-onset patients progressed more rapidly and had a significantly shorter survival.

Conclusions: Chinese ALS patients have an earlier age at onset and a relatively smaller proportion of old onset than European and Japanese patients. Elderly patients are more likely to have bulbar onset, which is related to rapid progression and a shorter survival.

Background: Many factors affect sexuality in the elderly such as dementia which is a common cause of inappropriate sexual behaviors. These behavioral disturbances are distressing, disruptive, and impair the care of the patient.

Summary: The onset of dementia does not erase sexuality. Sexual expression can be an important aspect of well-being for older adults with dementia. This study gives a general overview about the relationship between sexuality and cognitive impairment. It starts with a general discussion of sexual aspects in the elderly. This is followed by research studies in this field including effects of dementia on sexual life, sexuality issues related to cognitive decline, inappropriate sexual behaviors in dementia patients, and sexuality in healthcare institutions. We discuss also ethical aspects in relation with sexuality and dementia. Finally, we show different approaches to treat inappropriate sexual behaviors.

Key messages: The discussion of sexuality in dementia raises many medical and ethical concerns. Inappropriate sexual behaviors are estimated to occur in about 7%-25% of demented patients. The question is how to address such a delicate subject and discuss it in an easy way without making the patient feel humiliated or mistreated. This narrative review reveals sexual problems and difficult questions encountered in daily practice with patients suffering from cognitive impairment.

Objective: We aimed to investigate costly punishment in patients with Huntington's disease (HD).

Background: HD is an autosomal dominant neurodegenerative disease with motor, cognitive, and psychiatric symptoms. As neuropsychiatric abnormalities often precede motor symptoms, we wanted to assess whether costly punishment is part of the neuropsychological profile of patients with HD.

Methods: A total of 40 non-demented subjects were prospectively enrolled in this study with a between-subject design comparing manifest HD patients (n = 18) to healthy controls (HC; n = 22). All participants performed 8 rounds of a costly punishment task, in which money was shared unevenly in 5 rounds or in a fair manner in the remaining 3 rounds. Participants then had to decide whether they wanted to punish the trustee. Furthermore, all participants underwent neuropsychological background tasks.

Results: HD patients performed worse in the neuropsychological background tests compared to HC (all p values <0.05). Moreover, HD patients punished more often in fair (Wald χ2 = 5.03, p = 0.025) but not in unfair rounds (Wald χ2 = 1.63, p = 0.202).

Conclusions: Our results demonstrate increased costly punishment during fair conditions in HD patients. Whether this behaviour is due to a lack of recognition of social norms, an impairment in top-down inhibition, or an effect of antidopaminergic medication remains unclear.

Objectives: In the present study, inflammatory factors, including interleukin (IL) and tumor necrosis factor-α (TNF-α) in the peripheral blood of patients with sporadic amyotrophic lateral sclerosis (sALS), were evaluated, and the issue of whether these variables were associated with the progression and severity of the disease examined.

Methods: Data on inflammatory factors, including IL-1, IL-2, IL-6, IL-8, IL-10, and TNF-α, were retrospectively collected from 248 sALS patients admitted to the Chinese PLA General Hospital between March 2018 and March 2021. The relationships between the variables and clinical features, including gender, age at onset, site of onset, time from onset to hospital admission, ALS functional rating scale score, and diagnostic category were analyzed.

Results: IL-1, IL-2, IL-6, IL-8, IL-10, and TNF-α levels were elevated in 43.75%, 7.04%, 16.42%, 25.35%, 1.41%, and 50.72% of ALS patients, respectively, compared with the normal value range. IL-2 and IL-6 levels were inversely associated with the ALS functional rating scale score (r = -0.280, p = 0.004 and r = -0.198, p = 0.048).

Conclusion: Elevated levels of inflammatory cytokines support the hypothesis of an inflammatory response in ALS, and IL-2 and IL-6 may be used as an inflammation-related biomarker for disease severity.

Background: Excessive daytime sleepiness (EDS) in Parkinson's disease (PD) may occur because of dysfunction on the brain areas in controlling wakefulness; however, the pathophysiology of EDS in PD has not been completely clarified. The Pb component of a middle-latency auditory evoked response (MLR) is generated from the cholinergic ascending reticular activating system (ARAS) projecting to the auditory cortex via the thalamus. We examined the association between EDS and the Pb component in patients with PD.

Methods: Participants were 38 patients with nondemented PD and 18 age-matched controls. EDS was evaluated using the Japanese version of the Epworth Sleepiness Scale (JESS). PD patients were classified into the high sleepiness (HS) group and the low sleepiness (LS) group by the score of JESS. MLRs were recorded from the scalp with each earlobe as a reference under presentation of 1-Hz and 65- to 90-dB click sounds.

Results: There was no difference in age, duration, and motor function between the HS PD and the LS PD groups. Peak latencies of Pb were not different between PD group and controls; however, Pb amplitudes were significantly increased in the HS PD group compared with the LS PD group and controls.

Conclusion: One of the mechanisms of EDS in PD was suggested to be dysregulation of cholinergic neurons from the ARAS projecting to cortical cholinergic neurons.

Background: Coronavirus disease 2019 (COVID-19), the far-reaching pandemic, has infected approximately 185 million of the world's population to date. After infection, certain groups, including older adults, men, and people of color, are more likely to have adverse medical outcomes. COVID-19 can affect multiple organ systems, even among asymptomatic/mild severity individuals, with progressively worse damage for those with higher severity infections.

Summary: The COVID-19 virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily attaches to cells through the angiotensin-converting enzyme 2 (ACE2) receptor, a universal receptor present in most major organ systems. As SARS-CoV-2 binds to the ACE2 receptor, its bioavailability becomes limited, thus disrupting homeostatic organ function and inducing an injury cascade. Organ damage can then arise from multiple sources including direct cellular infection, overactive detrimental systemic immune response, and ischemia/hypoxia through thromboembolisms or disruption of perfusion. In the brain, SARS-CoV-2 has neuroinvasive and neurotropic characteristics with acute and chronic neurovirulent potential. In the cardiovascular system, COVID-19 can induce myocardial and systemic vascular damage along with thrombosis. Other organ systems such as the lungs, kidney, and liver are all at risk for infection damage. Key Messages: Our hypothesis is that each injury consequence has the independent potential to contribute to long-term cognitive deficits with the possibility of progressing to or worsening pre-existing dementia. Already, reports from recovered COVID-19 patients indicate that cognitive alterations and long-term symptoms are prevalent. This critical review highlights the injury pathways possible through SARS-CoV-2 infection that have the potential to increase and contribute to cognitive impairment and dementia.

Background: Accumulating evidence suggests an implication of neuroinflammation in Alzheimer's disease (AD) pathogenesis. Homoharringtonine (HHT) is an antitumor reagent with anti-inflammatory activity. This study investigates whether and how HHT plays a role in disease progression in a mouse AD model.

Methods: HHT was injected into APP/PS1 mice every other day for 6 months. The effects of HHT on cognitive function were assessed by behavioral assays. β-Amyloid accumulation was assessed by ELISA analysis of Aβ40 and Aβ42. Neuronal loss and synaptic function were determined by levels of NeuN, synaptophysin, and PSD95. Neuroinflammation was assessed by glial markers and pro-inflammatory cytokines. Signal transducer and activator of transcription 3 (STAT3) signaling was evaluated by phosphorylated STAT3 and SOCS3 expression.

Results: We found that HHT at 2 mg/kg significantly alleviated cognitive deficits in APP/PS1 mice. HHT reduced soluble and insoluble Aβ40 and Aβ42 accumulation and attenuated the impairments of synaptic function in the AD mouse hippocampus. Finally, HHT inhibited neuroinflammation, suppressed STAT3 activation, and increased SOCS3 expression in the APP/PS1 mouse hippocampus.

Conclusion: Our results indicate that HHT inhibits disease progression in APP/PS1 mice by suppressing neuroinflammation through modulating the STAT3 signaling. Our findings suggest that HHT may potentially be used for preventing or slowing down AD pathogenesis and warrants further investigation.

Objectives: Our study aimed to identify the prevalence and severity of gastrointestinal (GI) symptoms and dysphagia in patients with amyotrophic lateral sclerosis (ALS) and to assess whether a correlation exists between these symptoms and the severity of ALS progression.

Methods: The presence and severity of GI symptoms and dysphagia were identified by means of the Gastrointestinal Symptom Rating Scale (GSRS) and the Functional Outcome Swallowing Scale (FOSS). The Revised ALS Functional Rating Scale (ALSFRS-R) was utilized to determine the severity of ALS. Analysis of data was performed with Spearman correlations in semi-qualitative variables of clinical scales. ALSFRS-R scores were divided into 2 categories: those with mild to moderate ALS (≥40-30 points) and patients with moderate to advanced ALS (29-≤20 points).

Results: We studied 43 patients with definite ALS. The most frequent GI symptoms were constipation (60.5%), rectal tenesmus (57.5%), hard stools (55.0%), and borborygmus (42.5%). The moderate to advanced ALS stage was correlated with constipation (r = 0.334; p = 0.028), acid regurgitation (r = 0.384; p = 0.013), eructation (r = 0.334; p = 0.032), rectal tenesmus (r = 0.498; p = 0.001), and functional dysphagia (r = 0.656; p = <0.001).

Conclusions: Early detection of these GI symptoms can guide timely therapeutic decisions to avoid weight loss, a predictor for worse prognosis. This study highlights the relevance of the detection of these symptoms in ALS patients who score ≤29 points in the ALSFRS-R scale to establish an appropriate treatment, prevent systemic complications, provide more comfort, and improve quality of life.

Background: Many evidences suggest a pathological link between neurodegenerative diseases and cancer. In fact, several epidemiologic studies indicate a decreased incidence of most cancer types in Parkinson's disease (PD) patients and some PD genes are involved in cancer networks.

Objective: The aim of this study is to assess the influence of several factors in the risk of cancer in a cohort of 753 PD patients and to study how these variables interact with each other.

Methods: We analyzed the effect of gender, tobacco, alcohol, type of PD (genetic or idiopathic PD), and two genetic variants, previously associated with cancer, rs5848-GRN and rs1042522-TP53.

Results: A higher age at PD onset was observed in patients who develop cancer before PD (p < 0.001). Alcohol consumption was a risk factor to develop cancer in PD patients (p = 0.011), while smoking was not a cancer risk factor in our cohort (p = 0.098). Among the genetic factors, the genotype TT GRN-rs5848 was statistically more frequent in PD patients without cancer (p = 0.05).

Conclusions: Our study identified several factors, genetic and nongenetic, which contribute to the risk for cancer in PD.