非痴呆型血管性认知功能障碍的研究进展

随着血管性痴呆(vascular dementia,VD)的发病率逐年升高,我们对血管性痴呆的研究也不断深入。目前国内外学者主张根据疾病的发展阶段对VD进行划分,从而针对不同阶段病情的发展进行有效的治疗,以免延误最佳治疗时机。非痴呆型血管性认知功能障碍(vascular cognitive impairment no dementia,VCIND)是血管性痴呆的早期阶段,多发生在血管性认知损害之前或早期。在认知损害发生之前,血管性因素及脑血管疾病是唯一可去除的病因,并且能够成为延缓甚至逆转痴呆进展的干预靶点。因此,早期诊断并及时治疗血管性因素及脑血管疾病对于降低血管性痴呆的发病率,预防血管性认知障碍(vascular cognitive impairment,VCI)具有重要意义。本文对近年来VCIND的流行病学、神经心理学、影像学、预防和治疗的进展作一综述。     

Neurochemical approaches of cerebrospinal fluid diagnostics in neurodegenerative diseases

Alzheimer's disease (AD), Parkinson's disease dementia (PDD)/Lewy-body disease (DLB), and frontotemporal dementia (FTD) are the major causes of memory impairment and dementia. As new therapeutic agents are visible for the different diseases, there is an ultimate need for an early and an early differential diagnosis. Since cerebrospinal fluid (CSF) is in direct contact with the central nervous system (CNS), potentially promising biomarkers might be seen there first. In principle, two research approaches can be considered for the laboratory diagnosis of dementias: (i) the direct detection of disease specific protein like Abeta-peptide-oligomers in AD or alpha-synuclein-aggregates in DLB and (ii) the detection of surrogate markers that show an altered pattern of expression in early stages of the disease or are used in the differential diagnosis of other dementias and thus enable an exclusion diagnosis. Especially Abeta-peptides and tau-protein measurements seem to employ a combination of these approaches. Until now it was shown that a combined determination of just these few markers (tau-proteins and Abeta-peptides) is already sufficient to achieve a high degree of diagnostic certainty in the diagnosis of AD. However although these markers seem to correlate with neuropathological changes and memory disturbances, these markers are not specific for a single form of dementia and further research is necessary to improve especially the early differential diagnosis of dementias.     

Can mild cognitive impairment and Alzheimer’s disease be diagnosed by monitoring a miRNA triad in the blood?

Objectively diagnosing age‐related cognitive impairment (ACI), mild cognitive impairment (MCI), and early‐stage Alzheimer''s disease (AD) is a difficult task, as most cognitive impairment is clinically established via questionnaires, history, and physical examinations. A recent study has suggested that monitoring a miRNA triad, miR‐181a‐5p, miR‐146a‐5p, and miR‐148a‐3p can identify ACI and its progression to MCI and AD (Islam et al., EMBO Mol Med. 13: e14997, 2021). This commentary deliberates findings from this article, such as elevated levels of the miRNA triad in the brain impairing neural plasticity and cognitive function, the efficiency of measuring the miRNA triad in the circulating blood diagnosing MCI and AD, and the promise for improving cognitive function in MCI and AD by inhibiting this miRNA triad. Additional studies required prior to employing this miRNA triad in clinical practice are also discussed.     

Tonsillolithiasis and orofacial pain

Tonsilloliths are rare calcified structures that usually result from chronic inflammation of the tonsils. Concretions show differences in size, shape and colour. They are usually asymptomatic but can be associated with halitosis, foreign body sensation, dysphagia and odynophagia, otalgia, and neck pain. A patient was referred because panoramic radiography performed by a general dentist revealed radiopaque shadows over the ascending rami of the mandible, located bilaterally: a solitary structure on the higher portion of the right side and two small structures on the left side. Paroxysmal attacks of orofacial pain and symptoms such as dysphagia and swallowing pain on the left side distributed within the tonsillar fossa and pharynx and the angle of the lower jaw were present. The computed tomography images revealed bilateral tonsilloliths. Clinically, there was no sign of inflammation, and the patient's past history revealed an approximately 2-year history of dysphagia, swallowing pain and left-sided neck pain. At the request of the patient, no surgical intervention was carried out. Glossopharyngeal neuralgia is a rare entity, and the aim of this report was to indicate the importance of tonsilloliths as a cause of orofacial pain.     

c-Fos induction in the brainstem following electrical stimulation of the trigeminal ganglion of chronically mandibular nerve-transected rats

Abstract

Neuronal excitability in the trigeminal sensory nuclei (TSN) changes after nerve transection. We examined the effects of chronic transection of the trigeminal nerve on the c-Fos-immunoreactivity in the TSN induced 2?h after 10?min of electrical stimulation of the trigeminal ganglion (TG) at C-fiber activating condition (1.0?mA, 5?ms, 5?Hz) in urethane-anesthetized rats. In the non-transected control rats, stimulation of the TG induced c-Fos-immunoreactive cells (c-Fos-IR cells) mostly in superficial layers (VcI/II) of the nucleus caudalis (Vc) in its full extent along the dorsomedial–ventrolateral axis, but modestly in the rostral TSN above the obex, the principal, oral, and interpolar nuclei. Three days, 1, 2, or 3 weeks after transection of the inferior alveolar (IAN), infraorbital, or masseteric nerves, the stimulation of the TG induced c-Fos-IR cells in the central terminal fields of the transected nerve in the rostral TSN and magnocellular zone of the Vc. However, the number of c-Fos-IR cells in the VcI/II decreased inside the central terminal fields of the transected nerve and increased outside the fields. These results indicate that transection of the trigeminal nerve increases the excitability of TSN neurons that receive inputs from injured mechanoreceptors and uninjured nociceptors, but decreases it from injured nociceptors. The altered c-Fos responses may imply mechanisms of neuropathic pain seen after nerve injury.     

Effect of homocysteine and nitric oxide levels on specific Computed Axial Tomography measurements in Alzheimer disease

The present study was undertaken to examine the effect of Homocysteine (Hcy) and nitric oxide (NO) levels on specific Computed Axial Tomography (CAT) measurements, as global brain atrophy and brain vascular lesion in Alzheimer Disease (AD) and in Vascular Dementia (VD) patients. We have analysed serum Hcy and NO levels in AD patients and compared the findings with those in VD patients and control subjects. Moreover we have studied the correlation of Hcy and NO levels with cognitive impairment and brain atrophy determined by Computed Axial Tomography. Hcy serum levels significantly increased in all demented patients compared to control group, independently from the dementia type. On the contrary, no differences were observed in NO serum levels between groups. Moreover, we found significant correlation between Hcy and brain atrophy in both demented groups; whereas NO levels correlated only in AD, but not in VD patients. The pathogenic effect of Hcy either in AD and VD patients appears to confirm a definitive vascular component in AD. As regards NO, our results highlight the role of NO as a beneficial molecule in AD and support the use of NO mimetics as an antineurodegenerative therapy for AD patients.     

Cognitive disorder in brain concussion

This paper presented original study results concerning the prevalence and clinical characteristics of cognitive impairment associated with brain concussion. The cognitive functions of 80 consecutive patients （mean age = 37.40±1l.74years; 50 men and 30 women） admitted to the hospital with brain concussions were evaluated. Their cognitive scores were compared with 40 age- and education-matched healthy volunteers without history of cranial trauma. Cognitive impairment without dementia was found in 93% of the patients. Cognitive impairment in brain concussion was also characterized by prominent cognitive slowness （bradyphrenia）, concentration decrease, free recall insufficiency, and visual-spatial dysfunction. Age and severity of anxiety significantly influence the cognitive performance of patients.     

Japanese Rice Wine can reduce psychophysical stress-induced depression-like behaviors and Fos expression in the trigeminal subnucleus caudalis evoked by masseter muscle injury in the rats

We determined if Japanese Rice Wine (Sake) had inhibitory effects on stress-induced enhancement of masseter muscle (MM) nociception in the rats. Male rats were subjected to the repeated forced swim stress (FS) or sham conditionings from Day ?3 to ?1. Daily administration of Sake or saline was conducted after each stress conditioning. At Day 0 the number of Fos positive cells, a marker for neural activity, was quantified at the trigeminal subnucleus caudalis (Vc) region by MM injury with formalin. FS increased MM-evoked Fos expression in the Vc region, which was inhibited by Sake compared to saline administration. Sake did not alter the number of Fos positive cells under sham conditions, indicating that inhibitory roles of Sake on neural activity in the Vc region were seen under FS conditions. These findings indicated that Sake had inhibitory roles on stress-induced MM nociception at the Vc region in our experimental conditions.