Cognitive Neurological Disorders Research Articles

Electrocardiographic approach strategies in patients with Parkinson disease treated with deep brain stimulation.

Deep brain stimulation (DBS) is an interdisciplinary and reversible therapy that uses high-frequency electrical stimulation to correct aberrant neural pathways in motor and cognitive neurological disorders. However, the high frequency of the waves used in DBS can interfere with electrical recording devices (e.g., electrocardiogram, electroencephalogram, cardiac monitor), creating artifacts that hinder their interpretation. The compatibility of DBS with these devices varies and depends on factors such as the underlying disease and the configuration of the neurostimulator. In emergencies where obtaining an electrocardiogram is crucial, the need for more consensus on reducing electrical artifacts in patients with DBS becomes a significant challenge. Various strategies have been proposed to attenuate the artifact generated by DBS, such as changing the DBS configuration from monopolar to bipolar, temporarily deactivating DBS during electrocardiographic recording, applying frequency filters both lower and higher than those used by DBS, and using non-standard leads. However, the inexperience of medical personnel, variability in DBS models, or the lack of a controller at the time of approach limit the application of these strategies. Current evidence on their reproducibility and efficacy is limited. Due to the growing elderly population and the rising utilization of DBS, it is imperative to create electrocardiographic methods that are easily accessible and reproducible for general physicians and emergency services.

180 Cognitive disorders in takotsubo syndrome: incidence, short, and long term outcome. Results from a prospective multi-centre registry

Abstract Aims Takotsubo syndrome (TTS) is an acute and reversible left ventricular dysfunction, whose pathophysiological mechanisms are not completely known. There are evidence suggesting a possible link between neurological disease and TTS. Aim of the study was to evaluate incidence and prognostic value of cognitive neurological disorders among TTS patients. Methods and results 379 consecutive patients were enrolled in a prospective multicentre registry. History, clinical features, echocardiographic parameters, in-hospital complications and long-term Follow-up events of all patients were recorded. Cognitive neurological disorders included Alzheimer disease, old age dementia and cognitive impairment for other causes. Prevalence of cognitive neurological disorders among TTS patients was 5.5% (num = 21). Among this subset of patients 48% (num = 10) had Alzheimer syndrome, 24% (num = 5) old age dementia and 28% (num = 6) cognitive impairment for other causes. Compared to the control group, these patients were older (81 ± 5 vs. 71 ± 12, P = 0.01) and predominantly men (24% vs. 9%, P = 0.01). No differences in term of cardiovascular risk factors and left ventricular ejection fraction at admission and discharge were found among the two groups. TTS patients with cognitive neurological disorders experienced higher rate of in-hospital complications (62% vs. 28%, P = 0.01), that were mainly driven by higher rate of pulmonary oedema (14% vs. 9%, P = 0.01), cardiogenic shock (29% vs. 8%, P = 0.01), death (24% vs. 4% P = 0.01), ischaemic stroke (10% vs. 4%, P = 0.01), and left ventricular thrombi (10% vs. 3%, P = 0.01). At long-term follow-up patients with cognitive neurological disorders when compared to those without, experienced higher rate of mayor cardiovascular events (48% vs. 16%, P = 0.01), cardiovascular re-hospitalization (14% vs. 10%, P = 0.01) and death (43% vs. 9%, P = 0.01). Conclusions TTS patients with cognitive neurological disorders had an increased risk of in and out of hospital mayor cardiac adverse events and mortality at short and long-term follow-up.

Cognitive disorders in takotsubo syndrome: incidence, short and long-term outcome. Results from a prospective multi-center registry

Abstract Background Takotsubo syndrome (TTS) is an acute and reversible left ventricular dysfunction, whose pathophysiological mechanisms are not completely known. There are evidence suggesting a possible link between neurological disease and TTS. Aim of the study was to evaluate incidence and prognostic value of cognitive neurological disorders among TTS patients. Methods 379 consecutive patients were enrolled in a prospective multicenter registry. History, clinical features, echocardiographic parameters, in-hospital complications and long-term follow up events of all patients were recorded. Cognitive neurological disorders included Alzheimer disease, old age dementia and cognitive impairment for other causes. Results Prevalence of cognitive neurological disorders among TTS patients was 5.5% (num=21). Among this subset of patients 48% (num=10) had Alzheimer syndrome, 24% (num=5) old age dementia and 28% (num=6) cognitive impairment for other causes. Compared to the control group, these patients were older (81±5 vs 71±12, p=0.01) and predominantly men (24% vs 9%, p=0.01). No differences in term of cardiovascular risk factors and left ventricular ejection fraction at admission and discharge were found among the two groups. TTS patients with cognitive neurological disorders experienced higher rate of in-hospital complications (62% vs 28% p=0.01), that were mainly driven by higher rate of pulmonary edema (14% vs 9% p=0.01), cardiogenic shock (29% vs 8%, p=0.01), death (24% vs 4% p=0.01), ischemic stroke (10% vs 4% p=0.01) and left ventricular thrombi (10% vs 3%, p=0.01). At long term follow up patients with cognitive neurological disorders when compared to those without, experienced higher rate of mayor cardiovascular events (48% vs 16%, p=0.01), cardiovascular re-hospitalization (14% vs 10%, p=0.01) and death (43% vs 9%, p=0.01). Conclusion TTS patients with cognitive neurological disorders had an increased risk of in and out of hospital mayor cardiac adverse events and mortality at short and long-term follow-up. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Ospedali Riuniti di Foggia-Università di Foggia

Inhibitor screening assay for neurexin-LRRTM adhesion protein interaction involved in synaptic maintenance and neurological disorders

Synaptic adhesion molecules, including presynaptic neurexins (NRXNs) and post-synaptic leucine-rich repeat transmembrane (LRRTM) proteins are important for development and maintenance of brain neuronal networks. NRXNs are probably the best characterized synaptic adhesion molecules, and one of the major presynaptic organizer proteins. The LRRTMs were found as ligands for NRXNs. Many of the synaptic adhesion proteins have been linked to neurological cognitive disorders, such as schizophrenia and autism spectrum disorders, making them targets of interest for both biological studies, and towards drug development. Therefore, we decided to develop a screening method to target the adhesion proteins, here the LRRTM-NRXN interaction, to find small molecule probes for further studies in cellular settings. To our knowledge, no potent small molecule compounds against the neuronal synaptic adhesion proteins are available. We utilized the AlphaScreen technology, and developed an assay targeting the NRXN-LRRTM2 interaction. We carried out screening of 2000 compounds and identified hits with moderate IC50-values. We also established an orthogonal in-cell Western blot assay to validate hits. This paves way for future development of specific high affinity compounds by further high throughput screening of larger compound libraries using the methods established here. The method could also be applied to screening other NRXN-ligand interactions.

Functional cognitive disorders: demographic and clinical features contribute to a positive diagnosis.

To examine features associated with functional cognitive disorders (FCDs) compared with neurological cognitive disorders (dementia, mild cognitive impairment, transient amnesias) in consecutive patients referred to a secondary care cognitive disorders clinic. Patients diagnosed with either neurological cognitive disorder or FCD were compared by demographic (age, gender, handedness, referral source) and clinical features (family history of dementia, clinical signs, Likert screening measure of subjective memory complaint, mini-Addenbrooke's Cognitive Examination). Patients diagnosed with FCD were younger than those with neurological cognitive disorders, and more likely to attend alone, have a family history of dementia and be categorized as positive for subjective memory complaint. These data suggest features which may be helpful in making a positive diagnosis of FCD and differentiating from neurological cognitive disorders.

How does angiotensin AT2 receptor activation help neuronal differentiation and improve neuronal pathological situations?

The angiotensin type 2 (AT2) receptor of angiotensin II has long been thought to be limited to few tissues, with the primary effect of counteracting the angiotensin type 1 (AT1) receptor. Functional studies in neuronal cells have demonstrated AT2 receptor capability to modulate neuronal excitability, neurite elongation, and neuronal migration, suggesting that it may be an important regulator of brain functions. The observation that the AT2 receptor was expressed in brain areas implicated in learning and memory led to the hypothesis that it may also be implicated in cognitive functions. However, linking signaling pathways to physiological effects has always proven challenging since information relative to its physiological functions has mainly emerged from indirect observations, either from the blockade of the AT1 receptor or through the use of transgenic animals. From a mechanistic standpoint, the main intracellular pathways linked to AT2 receptor stimulation include modulation of phosphorylation by activation of kinases and phosphatases or the production of nitric oxide and cGMP, some of which are associated with the Gi-coupling protein. The receptor can also interact with other receptors, either G protein-coupled such as bradykinin, or growth factor receptors such as nerve growth factor or platelet-derived growth factor receptors. More recently, new advances have also led to identification of various partner proteins, thus providing new insights into this receptor’s mechanism of action. This review summarizes the recent advances regarding the signaling pathways induced by the AT2 receptor in neuronal cells, and discussed the potential therapeutic relevance of central actions of this enigmatic receptor. In particular, we highlight the possibility that selective AT2 receptor activation by non-peptide and selective agonists could represent new pharmacological tools that may help to improve impaired cognitive performance in Alzheimer’s disease and other neurological cognitive disorders.

Angiotensin II, a neuropeptide at the frontier between endocrinology and neuroscience: is there a link between the angiotensin II type 2 receptor and Alzheimer’s disease?

Amyloid-β peptide deposition, abnormal hyperphosphorylation of tau, as well as inflammation and vascular damage, are associated with the development of Alzheimer’s disease (AD). Angiotensin II (Ang II) is a peripheral hormone, as well as a neuropeptide, which binds two major receptors, namely the Ang II type 1 receptor (AT1R) and the type 2 receptor (AT2R). Activation of the AT2R counteracts most of the AT1R-mediated actions, promoting vasodilation, decreasing the expression of pro-inflammatory cytokines, both in the brain and in the cardiovascular system. There is evidence that treatment with AT1R blockers (ARBs) attenuates learning and memory deficits. Studies suggest that the therapeutic effects of ARBs may reflect this unopposed activation of the AT2R in addition to the inhibition of the AT1R. Within the context of AD, modulation of AT2R signaling could improve cognitive performance not only through its action on blood flow/brain microcirculation but also through more specific effects on neurons. This review summarizes the current state of knowledge and potential therapeutic relevance of central actions of this enigmatic receptor. In particular, we highlight the possibility that selective AT2R activation by non-peptide and highly selective agonists, acting on neuronal plasticity, could represent new pharmacological tools that may help improve impaired cognitive performance in AD and other neurological cognitive disorders.