Olfactory Testing in Frontotemporal Dementia: A Literature Review

Frontotemporal dementia (FTD) is a heterogeneous disorder featuring language impairment, personality changes, and executive defects, often due to the frontotemporal lobar degeneration (FTLD). Both FTD and FTLD are often associated with olfactory impairment, early biomarker for neurodegeneration, which can be evaluated with different techniques, among which low-cost olfactory tests are widely used. Therefore, we conducted a review of the literature focusing on papers published between January 1, 2007, and June 12, 2017, investigating the usefulness of olfactory testing in FTD/FTLD. A general decrease in the olfactory identification ability was seen in most of the articles and, taken together with a preserved odor discrimination, reveals a higher order impairment, possibly linked to cognitive decrease or language impairments, and not to a specific deficit of the olfactory system. This evidence could represent a useful add-on to the current literature, increasing the diagnostic value of olfactory assessment, particularly in cases where differential diagnosis is difficult

Intercepting dementia: awareness and innovation as key tools

Dementia is a common feature of several age-related brain diseases, leading to a progressive cognitive decline. Due to a growing aging rate, dementia-related disorders currently affect around 50 million people worldwide and by 2050 this number is expected to reach 150 million. Additionally to patients, these neurodegenerative pathologies have a strong impact on family members, caretakers, and other health professionals, therefore representing a public health burden that in 2020 accounted for over 1 trillion USD and is projected to nearly double in the next decade. To overcome this devastating condition, many organizations and collaborative networks sustain that only a complete understanding of dementia in its different characteristics can drive the scientific community towards the development of effective therapeutic approaches aiming at preventing its onset and halting its progression.In this work, we discuss two topics that represent fundamental resources in fighting dementia: (i) the importance of raising awareness about this condition to avoid stigma and gauging investment; and (ii) the introduction of novel screening measures to prevent and potentially revert cognitive decline. Finally, we discern how knowledge-based advocacy will help the rollout of clinical trials and the development of novel and timely pharmacological interventions

An Integrated Approach for the Monitoring of Brain and Autonomic Response of Children with Autism Spectrum Disorders during Treatment by Wearable Technologies

Autism Spectrum Disorders (ASD) are associated with physiological abnormalities, which are likely to contribute to the core symptoms of the condition. Wearable technologies can provide data in a semi-naturalistic setting, overcoming the limitations given by the constrained situations in which physiological signals are usually acquired. In this study an integrated system based on wearable technologies for the acquisition and analysis of neurophysiological and autonomic parameters during treatment is proposed and an application on five children with ASD is presented. Signals were acquired during a therapeutic session based on an imitation protocol in ASD children. Data were analyzed with the aim of extracting quantitative EEG (QEEG) features from EEG signals as well as heart rate and heart rate variability (HRV) from ECG. The system allowed evidencing changes in neurophysiological and autonomic response from the state of disengagement to the state of engagement of the children, evidencing a cognitive involvement in the children in the tasks proposed. The high grade of acceptability of the monitoring platform is promising for further development and implementation of the tool. In particular if the results of this feasibility study would be confirmed in a larger sample of subjects, the system proposed could be adopted in more naturalistic paradigms that allow real world stimuli to be incorporated into EEG/psychophysiological studies for the monitoring of the effect of the treatment and for the implementation of more individualized therapeutic programs

Wearable Sensors to Characterize the Autonomic Nervous System Correlates of Food-Like Odors Perception: A Pilot Study

Background: The sense of smell has been recently recognized as one of the most important sensory features in the human being, representing a reliable biomarker for a number of clinical conditions. The relationship between olfactory function and the person’s attitude towards food has frequently been investigated, often using questionnaires. The administration of minimally invasive methods for characterizing autonomic nervous system (ANS) functionality could help in objectivizing such measurements. Methods: The present study assessed ANS activation through the analysis of the electrocardiogram (ECG) and galvanic skin response (GSR) signals, in response to olfactory stimuli using non-invasive wearable devices. The ANS activation was also studied with respect to the odor familiarity, as well as with other olfactory and food dimensions (e.g., odor identification, odor pleasantness, food neophobia). Results: We demonstrated a significant activation of the ANS, in particular of its sympathetic branch, during the olfactory stimulation, with the ECG signal seen as more sensitive to detect ANS response to moderate olfactory stimuli rather than the GSR. Conclusions: When applied to a greater number of subjects, or to specific groups of patients, this methodology could represent a promising, reliable addition to diagnostic methods currently used in clinical settings

Natural and artificial sense of smell in biomedical and environmental applications

The sense of smell is one of the five human senses, whose importance has increased in last decades for scientific and clinical community. Indeed, olfaction was seen as an early biomarker for neurodegeneration and neuroregeneration, as well as for cognitive status, being the olfactory neurons the only neural cells whose regeneration was ascertained in human body. Thus, the employment of olfactory testing in research and clinical practice is nowadays always more frequent, especially in the most burdensome neurodegenerative conditions, such as Parkinson’s (PD) and Alzheimer’s (AD) Disease, where the link between cognitive decrease, disease progression and smell loss is more evident. A possible interesting add-on to current research knowledge about the link between olfaction and neurodegeneration could be represented by the olfactory assessment in elderly subjects with Mild Cognitive Impairment (MCI), a prodromal dementia possibly resulting in AD or PD within some years. Actually, the link between the two conditions is not clear, with several evidence towards an olfactory decrease even in MCI subjects, even though the studies published lack of methodological completeness. Concerning neuroregeneration, it is largely known that this phenomenon occurs in various parts of the human body, among which the olfactory bulb, and it is widely accepted that a number of external agents could inhibit adult neurogenesis, including X-rays exposure. It is also known that high-doses of ionizing radiation (IR) exposure are associated, for example, with DNA damage, resulting in a number of conditions, including cancer and cognitive detriment. On the other hand, the effects of low-doses of IR are currently poorly known, being widely influenced by the subjective individual’s response. Among the workers exposed to low-doses of IR, a quite important model is represented by the cohort of invasive cardiologists operating in the cardiac catheterization laboratory, resulting as the most massively exposed among the cohorts of clinicians, thus possibly representing an unique model for the investigation of cognitive effects of low-doses IR exposure. Nevertheless, olfaction is also influenced by a number of subjective factors, among which, for example, age, gender, smoking, comorbilities, but also by genetics, whose influence was already documented in recent literature studies. The Brain-Derived Neurotrophic Factor (BDNF) represents therefore a possible factor influencing smell ability, being largely associated with neural trafficking, neuron growth and cognitive functioning and, in some instance, with subjective attitude towards neurodegeneration. The association between olfaction and a BDNF polymorphism, Val66Met, was evaluated in elderly subjects, and seen to be associated with their brain aging. However, elderly subjects could display a number of comorbilities that could have accounted for spurious response to olfactory testing, thus this assessment performed in a cohort of young adults could provide a number of useful clean information, less affected by external biases. One of the possible useful employments of smell assessment is the evaluation of functional anosmia, possibly caused by associated conditions. One of such conditions is represented by Kallmann’s Syndrome (KS), the association of hypogonadotrophic hypogonadism (HH) and anosmia, this latter condition resulting from failed olfactory bulb development. Thus, the evaluation of olfactory function could be of extreme interest in clinical practice, especially in the case of differential diagnosis with respect to other similar conditions not associated with functional anosmia. A number of literature studies investigated the association between smell and neurodevelopmental disorders, including autism. Nevertheless, the olfactory evaluation in healthy subjects, not affected by the condition but displaying the so-called “autistic features”, like all human beings, associated with the attitude of the brain towards a more empathic or more systemizing behavior, has never been considered to date, and could represent an useful insight into a more precise knowledge of sensory processing in autistic and typical subjects. The processing of odorous stimuli is, to date, still largely investigated, and one of the most important research topics for scientific community is currently the evaluation of autonomic response to olfactory stimuli. Thus, the evaluation of physiological data, dealing with heart rate, vagal tone, or baroreflex could be interesting to enlighten knowledge in this field. All the models above stated have been succesfully implemented in this PhD thesis in order to add a noteworthy scientific contribution to the current research trends in this field. Furthermore, beyond the measurement of olfactory function in human models, we decided to explore the technological side of the sense of smell, represented by systems based on electronic nose. The E-Nose is a technological system, inspired to the functioning of human nose, employed for the detection and characterization of odorant compounds in several areas of interest, including food industry, environmental monitoring and diagnostics. It is used in complement or alternative to traditional laboratory analysis, such as Gas Chromatography-Mass Spectrometry (GC-MS), when such techniques result particularly obtrusive or of difficult application. In this thesis, systems based on E-Nose technology are applied to diagnostics, in particular for the support to traditional diagnosis methods for the discrimination of two pulmonary pathologies, namely Primary (PCD) and Secondary Ciliary Dyskinesia (SCD), both characterized by a lower ciliary clearance of mucus and by an abnormal production of Volatile Organic Compounds (VOCs) in exhaled breath, and to environmental monitoring, with such a similar tool implemented and integrated within an Autonomous Underwater Vehicle (AUV) and into a moored buoy for the detection of hydrocarbons on the sea surface of a marine protected area. Both the systems proposed demonstrated their operability in the fields of interest and could possibly form the future basis for integrated tools for both diagnostics and marine monitoring, respectively

Electronic Nose and Tongue for Assessing Human Microbiota

The technological developments of recent times have allowed the use of innovative approaches to support the diagnosis of various diseases. Many of such clinical conditions are often associated with metabolic unbalance, in turn producing an alteration of the gut microbiota even during asymptomatic stages. As such, studies regarding the microbiota composition in biological fluids obtained by humans are continuously growing, and the methodologies for their investigation are rapidly changing, making it less invasive and more affordable. To this extent, Electronic Nose and Electronic Tongue tools are gaining importance in the relevant field, making them a useful alternative—or support—to traditional analytical methods. In light of this, the present manuscript seeks to investigate the development and use of such tools in the gut microbiota assessment according to the current literature. Significant gaps are still present, particularly concerning the Electronic Tongue systems, however the current evidence highlights the strong potential such tools own to enter the daily clinical practice, with significant advancement concerning the patients’ acceptability and cost saving for healthcare providers

Metodologie biomediche innovative di analisi olfattometrica per la valutazione del danno neurodegenerativo

In un contesto clinico, l’importanza del senso dell’olfatto è notevolmente incrementata negli ultimi anni, anche in settori come le neuroscienze, in particolare per la valutazione del danno neurodegenerativo; si stima infatti che il 90% dei soggetti che presentano patologie quali l’Alzheimer o il Parkinson anche in fase preclinica abbiano comunque disturbi olfattivi. In questo studio, sono state utilizzate due tipologie di test olfattivi: il test di identificazione dell’odore ed il test di soglia olfattiva. Per il primo di questi, si è scelto di utilizzare il test, sviluppato dalla University of Pennsylvania, denominato UPSIT (University of Pennsylvania Smell Identification Test); mentre per il test di soglia è stato scelto il test STT (Smell Threshold Test), prodotto dalla Sensonics. In particolare, nello studio in questione, tali test sono stati effettuati su cardiologi interventisti e personale esposto in Sala di Emodinamica per andare a valutare la variazione della funzione olfattiva in relazione al danno neurodegenerativo legato a radiazioni ionizzanti. E’ infatti noto come, a causa dei numerosi interventi svolti da tali soggetti in ambito clinico, essi siano largamente esposti a radiazioni ionizzanti, soprattutto nello svolgimento di interventi di cateterismo, utilizzanti mezzo di contrasto e raggi X. Poiché in letteratura sono presenti diversi studi di questo genere analizzanti soprattutto militari, possiamo affermare come il presente lavoro sia il primo al mondo riguardante cardiologi, tecnici emodinamisti o, più in generale, personale medico-sanitario

Rich at risk: socio-economic drivers of COVID-19 pandemic spread

COVID-19, the novel coronavirus affecting the most part of worldwide countries since early 2020, is fast increasing its prevalence around the world, representing a significant emergency for the population and the health systems at large. While proper treatments are being developed, in-depth studies concerning its way of diffusion are necessary, in order to understand how the virus is actually spreading, through the investigation on some socio-economic indicators for the various countries in the world, retrieved through open-access data publicly available. The correlation analysis displayed significant relationships between COVID-19 incidence with several of such indicators, including the Gross Domestic Product per capita and the number of flights per capita, whereas mortality is mainly related to the main age of the population. All such data displayed an interesting mean to understand the way the virus has diffused worldwide, possibly representing the basis for future preventive measures to effectively challenge a new COVID-19 pandemic wave, but also other, similar pandemics

Electronic Nose and Tongue for Assessing Human Microbiota

The technological developments of recent times have allowed the use of innovative approaches to support the diagnosis of various diseases. Many of such clinical conditions are often associated with metabolic unbalance, in turn producing an alteration of the gut microbiota even during asymptomatic stages. As such, studies regarding the microbiota composition in biological fluids obtained by humans are continuously growing, and the methodologies for their investigation are rapidly changing, making it less invasive and more affordable. To this extent, Electronic Nose and Electronic Tongue tools are gaining importance in the relevant field, making them a useful alternative—or support—to traditional analytical methods. In light of this, the present manuscript seeks to investigate the development and use of such tools in the gut microbiota assessment according to the current literature. Significant gaps are still present, particularly concerning the Electronic Tongue systems, however the current evidence highlights the strong potential such tools own to enter the daily clinical practice, with significant advancement concerning the patients’ acceptability and cost saving for healthcare providers

IL33/ST2 Axis in Diabetic Kidney Disease: A Literature Review

Interleukin-33 (IL-33) is a cytokine belonging to the IL-1 family, playing a role in inflammatory, infectious and autoimmune diseases and expressed in the cellular nucleus in several tissues. High levels of IL-33 are expressed in epithelial barrier tissues and endothelial barriers. ST2 is a receptor for IL-33, expressed selectively on a subset of Th2 cells, mediating some of their functions. The IL-33/ST2 axis plays an important role in several acute and chronic inflammatory diseases, including asthma and rheumatoid arthritis. Different disorders are related to the activity of IL-33, ST2, or their axis, including cardiovascular disease or renal disturbances. Therefore, in the present work, a literature review was conducted, covering the period from 1 January 2000 to 30 November 2018, in PubMed, ScienceDirect, and Google Scholar database, to assess the involvement of the IL-33/ST2 axis in diabetic kidney disease. 6 articles directly dealing with the argument were identified, highlighting a clear link between IL-33/ST2 axis and diabetic kidney disease or related nephropathy. Overall, the involvement of ST2 seems to be more predictive than IL-33, especially in investigating the deterioration of kidney function; however, both compounds are pivotal in the field of renal diseases. Future studies are required to confirm the scientific evidences on larger and more heterogeneous cohorts