Day 1 :
- Ageing and Dementia | Novel Therapeutic Targets and Mechanisms for Treatment | Alzheimer’s Disease | Recent Studies & Case Reports | Psychiatry Mental health disorders | Dementia
University of Campania Luigi Vanvitelli, Italy
Vittorio Gentile is a recognized expert in the transglutaminase research area and has a strong background in the molecular biology and biochemical aspects of the transglutaminase (TG) enzymes expression, activity and function. His work has been focused to the tissue TG (TG2) characterization in normal and pathological cellular events (cell growth and differentiation, adhesion, apoptosis, neurodegeneration) by biochemical and molecular biology studies. Currently Dr. Gentile works as associate professor at the University of Campania “Luigi Vanvitelli”.
Background: Tissue type 2 Transglutaminase (TG2, E.C. 2.3.2,13) is reported to be involved in phagocytosis of apoptotic cells in mouse microglial BV2 cells and peripheral macrophages.
In this study, by using Lipopolysaccharide (LPS)- or Amyloid-1-42 (A1-42) peptide-stimulated mouse microglial cells BV2 or human THP-1 cells, we examined the effects of different neuronutraceutical compounds, such as Curcumin (Cu) and NPalmitoylethanolamine (PEA), known for their anti-inflammatory activity, on TG2 and several inflammatory or neuroprotective biomarkers expressions.
Methods: Mouse BV2 or human THP-1 cells were treated with LPS or Aβ1-42 in presence of Curcumin or PEA, in order to evaluate the expression of TG2 and other inflammatory or neuroprotective markers by RealTime PCR and Western Blot analyses.
Results: Curcumin and PEA were capable to reduce TG2 expression in mouse BV2 or human THP-1 cells during co-treatment with LPS or A1-42
Conclusions: The results show a role for TG2 as an important marker of neuroinflammation and suggest a possible use of Curcumin and PEA, in order to reduce LPS- or A1-42-induced T2 overexpression in mouse BV2 or human THP-1 cells.
Parveen Bazard is a Research Scientist at the Global Center for Hearing and Speech Research, Medical Engineering Dept., University of South Florida, Tampa, FL, USA. He works in the field of otolaryngology and audiology research with special focuses on drug discovery for hearing loss and alternative optical based cochlear implants. He did his Masters at the Indian Institute of Science, Bangalore, India and doctoral and postdoctoral studies at the University of South Florida, Tampa, FL, USA. During his PhD studies, he developed next generation neural stimulation methods – nanoparticles enabled optical neural stimulation for auditory and sensory prosthetic devices. After his PhD, he is carrying out research on drug development, pre-clinical projects for prevention and treatment of hearing loss. He publishes regularly in various peerreviewed journals that include ACS Nano (Impact Factor – 15); and has awarded 3 patents (1 pending approval) so far
According to the 2020 Lancet commission on dementia, hearing loss is the top modifiable risk factor against dementia, and risk of dementia worsens with every 10 dB of hearing loss. The commission also found an increased dementia risk for those not using hearing aids and, it recommends hearing aids to reduce the risk of cognitive decline and dementia. So, hearing loss treatment/management could be a way of significantly lowering the risk of dementia among our aged population. Hearing loss is an invisible disability and is among the top three medical chronic conditions among our aged population.
Apart from contributing to cognitive decline, hearing loss leads to social isolation, dependence on others and anxiety. Current treatments like hearing aids and cochlear implants often help improve the daily life of people with hearing loss. There is still no drug available to prevent/treat it. Recently, we have established that aldosterone – a natural occurring mineralocorticoid hormone has potential to treat certain aspects of age-related hearing loss in aging mice. Animals were treated with subcutaneous time-release pellets for four months.
A therapeutic effect was mediated via induced protein enhancement of Na-K-Cl and Na-K-ATPase – two key ion transporters that decline in the aging inner ear. Our clinical study revealed that higher serum aldosterone levels are associated with better hearing in elderly. Though not FDA-approved yet, it is likely that aldosterone will play a significant role in drug development for hearing loss. In sum, efforts to address the concerns of hearing loss – both in terms of drug development and alternative technologies for cochlear implants (i.e., new stimulation techniques), could significantly help to prevent dementia and other age linked cognitive deficits.
Waitemata District Health Board, New Zealand
Raghavakurup Radhakrishnan has completed his MBBS, DPM,DNB (Psychiatry); and he is a MRCPsych Consultant Psychiatrist in Old age Waitemata District Health Board, New Zealand. He has also published few articles in his area of interest which is Psychiatry
Cerebral Amyloid Angiopathy (CAA) is diagnosed in various settings including stroke units, memory clinics and geriatric psychiatry. CAA is also observed in community dwelling populations. Clinical presentations including neuropsychiatric presentations were described in the last two decades. Various neuropsychological manifestations have been described which include impairment in perceptual speed, episodic memory, semantic memory, attention and executive function and global cognitive impairment. Neuropsychological manifestations included a new manifestation of high impulsivity, in addition to organic personality change, and depression. This study focuses on neuropsychological impairments and psychiatric manifestations observed in CAA patients and discusses the possibility of a neuropsychological profile for CAA.
Cerebral Amyloid Angiopathy (CAA) is a neurovascular disease characterised by b-amyloid fibrils deposited in the walls of cerebral blood vessels. 1. A contemporary systematic overview collectively studied the results of four population groups based on pathological studies concerning the link between the presence of CAA (of any severity) and dementia, and found that 55-59% of patients living with dementia also suffered from CAA, while a CAA prevalence of only 28–38% was determined in patients without dementia. 2. CAA micro bleeds are believed to occur in greater than 30% of adults over the age of 70, and are potentially even more prevalent given the amount of symptomatic individuals with micro bleeds. 3. CAA is diagnosed in various settings including stroke units, memory clinics and geriatric psychiatry. CAA is observed in community dwelling populations as well. 4. Risk factors in the development of CAA include age. 5. A genetic facto, apolipoprotein E alleles. 6. Clinical presentations including neuropsychiatric presentations have been described in the last two decades. These include symptomatic intracerebral haemorrhage, cognitive impairment and dementia, rapidly progressive cognitive and neurological decline and transient neurological symptoms.
Various neuropsychological manifestations have been described which include impairment in perceptual speed, episodic memory, semantic memory, attention and executive function and global cognitive impairment. Cognitive disorders in CAA patients were frequent, in numerous domains. Patients exhibited significant deficits in language, processing speed and executive and memory functions compared to the control group, but were not different on attention and praxis domains. Studies showed that naming was the most impaired process, as in the deep group, followed by executive and processing speed. This pattern of frontal cognitive dysfunction was already highlighted in the CAA population.
In clinical settings Modified Boston criteria allow for probable or possible CAA diagnosis or exclusion of diagnosis of CAA. The Modified Boston criteria were proposed in 2010 in order to incorporate corticalsuperficial siderosis into the radiological diagnosis of probable CAA. They comprise of combined clinical, imaging and pathological parameters, and are based upon the original Boston criteria. The Modified Boston criteria for diagnosis of 'probable CAA' was pathologically validated in 2010, and compared to the Boston criteria had an increase in sensitivity (95%, 95% confidence interval (CI) 76% to 99%) with only a modest decrease in specificity (81%, 95% CI 62% to 93%).
Intracerebral haemorrhage from CAA is most common in the frontal lobes. CAA pathology might cause cortical atrophy, an effect that might at least partly be mediated by vascular dysfunction. CAA is mainly a neurological illness, but may present with psychiatric symptoms. Currently there are no studies that address the psychiatric manifestations of CAA in a systematic way. We report a case series describing four cases with neuropsychiatric manifestations presented to a geriatric psychiatric unit.
Case 1: A 77 year old male with a background of paroxysmal atrial fibrillation had presented with headache, drowsiness and left visual inattention. His Computerised Tomographic (CT) head scan showed a right temporal lobe acute intra parenchymal haemorrhage with 4mm of midline shift. A Magnetic Resonance Image (MRI) brain scan two months later showed a right temporal lobe residual haematoma with a background evidence of amyloid angiopathy on susceptibility weighted imaging (SWI) with confluent hyper intensity in the periventricular white matter of both occipital lobes on T2/FLAIR. On follow up he developed temporal lobe focal seizures. There was also evidence of cognitive decline [Addenbrooke’s Cognitive Examination (ACE III) - 71/100]. He was referred to a psychiatrist for depression, anhedonia and poor sleep with little response to Citalopram. There were no frank delusions or hallucinations and past psychiatric history was unremarkable. As there was only partial control of seizures on Leviteracetam and the potential for this agent to contribute to low mood this was cross-titrated with carbamazepine and eventually stopped. Additionally, Citalopram was switched to Mirtazapine. Following this depression markedly improved and seizures abated.
Shoumitro Deb is a Visiting Professor of Neuropsychiatry at Imperial College London, UK. Previously he was a substantive Professor of Neuropsychiatry at the University of Birmingham for many years. His research interests involve Intellectual Disabilities, Down syndrome and dementia, Epilepsy, psychopharmacology, and traumatic brain injury. He has over 235 publications (citation index: 6646, h-index: 42) and presented at over 240 national and international conferences. He ran a number of MSc courses in the UK universities. He developed Dementia Screening Questionnaire for individuals with intellectual disabilities (DSQIID) (www.ld-medication.bham.ac.uk) which has been translated into over 24 languages for worldwide use.
People with Down Syndrome (DS) are at a higher risk of developing Alzheimer’s Dementia at an early age compared with people without intellectual (learning) disabilities (ID). However, there are difficulties in making an early and accurate diagnosis of dementia in individuals with ID and the screening instruments such as the Mini Mental Status Examination that are used in the general population often show floor effects when used for individuals with DS because of their pre-existing cognitive impairment. Both informant-rated and direct neuropsychological tests have been used for the case detection of dementia for individuals with DS.
There are many similarities and some differences in the clinical manifestation of dementia in individuals with ID and the non-ID general population. Impaired recent memory and confusion in the context of relatively intact distant memory is likely to be an early symptom in individuals with ID who have a mild ID, whereas loss of skills and behaviour changes are likely to be an early feature for those with more severe ID. Many symptoms, including features of ‘frontal lobe dysfunction’ that tend to appear late in the dementing process in the general population, may appear early in individuals with ID and DS.
Ideally, individuals with ID should be screened for signs of dementia from before the age of 30/35. A multidisciplinary approach should be taken for diagnosing dementia in individuals with ID using a combination of informant-rated scales and neuropsychological tests in a longitudinal fashion over time. Important differential diagnoses include hypothyroidism, depression, and sensory impairment. Assessment should include physical, psychological, and social aspects including appropriate examinations and investigations. The evidence-base for the pharmacological management of dementia in ID and DS is poor, which does not allow to draw any definitive conclusion about their efficacy in this population. Therefore, non-pharmacological interventions should be considered.
Chang Gung University, Taiwan
Sunil Kumar received his PhD in Pharmacy from Punjab Technical University Jalandhar India. He has worked as a scientist at Arch pharmalabs ltd, Navi Mumbai, India. He also has worked as Assistant Professor from 2008 to 2011 at ISF College of Pharmacy, Moga, India. He has been awarded postdoctoral fellowship by National Science Council (NSC), Taiwan and performed his research work at Taipei medical University from 2013 to 2016, at National Taiwan University (NTU), 2017-2018 and Chang Gung University, taiwan 2018-2020. His research work is mainly based on medicinal and natural product chemistry specialized in anti-inflammatory and anti-cancer drug design. Dr. Kumar has cleared the prestigious GATE exam organized by IIT (Indian Institute of Technology). He has published more than 23 papers in reputed journals and has been serving as an editorial board member of a few journals
Neurotransmitters help to communicate and send/receive information all over the human body. From heart rate, blood pressure to fall asleep, these chemical messengers play a vital role. Chemically these are oxytocin, serotonin, GABA (γ-aminobutyric acid), glutamate dopamine, acetylcholine, noradrenaline, epinephrine and 5-hydroxytryptamine. Aging is an inevitable part of human development, which affects lifestyle in later stages.
Studies on neurobehavioral changes have observed that the concentration of the neurotransmitters in the elderly is altered significantly before the appearance of age related disorders such as Alzheimer Disease (AD) and Parkinson’s Disease (PD). For instance, choline acetyltransferase and 5-hydroxytryptamine were fewer in brains of dementia patients. Serotonin (5-HT) neurotransmitter loss in the elderly population causes behavioral changes. Imbalances in cholinergic and serotonergic function may be responsible for cognitive impairment in AD.
Identification of neurotransmitters is important for identifying and fighting the aging process and related conditions. This kind of study will be helpful to establish a connection between aging and neurotransmitters. Ultimately, aging related problems can be curtailed by modifying these neurotransmitters.
Thailand Institute of Scientific and Technological Research, Thailand
Pennapa Chonpathompikunlert is postdoctoral researcher from University of Tsuluba, Japan for 3 years and following Assistant Professor from Prince of Songkhla University, Thailand for 5 years and now move to Expert Centre of Innovative Health Food, Thailand Institute of Scientific and Technological Research as a research officer. Her research projects focusing on the role of encapsulation technology for drug or food ingredient delivery to treat various pathological conditions that related to a free radical pathway. Specifically, she is interested in behavioral testing in an animal model of neurodegenerative diseases such as AD, PD, stress condition and also interesting in brain tumor, stroke condition, an inflammatory disease such as OA, RA and pain condition. And nowadays, she moves to setup comet assay follow OECDGLP in present institute. She has published more than 30 papers in reputed journals.
Astaxanthin is a carotenoid with powerful antioxidant and anti-inflammatory activity. However, the effects of astaxanthin and encapsulated astaxanthin from white shrimp shell (Litopenaeus Vannamei) on Alzheimer’s Disease (AD) has not been elucidated) AD was induced by i.c.v. administration of Amyloidbeta (1-42) peptides in rats. This study aimed to investigate the effect of astaxanthin extract and encapsulated astaxanthin on cognition function.
Astaxanthin significantly reversed the cognitive and memory impairment, assessed by the Morris water maze test, Novel Object Recognition test and Novel Object Location test. Astaxanthin is able to act against oxidative injuries, through various mechanisms, by inhibiting superoxide anion, reduction of malondialdehyde (MDA) and protein oxidation product levels, increasing the levels or stimulating the activity of glutathione peroxidase enzymes in the cortex and hippocampus.
Astaxanthin 10 mg/kg encapsulated using cryogenic incorporated freeze-drying showed the similar effect with astaxanthin commercial 10 mg/kg and better effect with astaxanthin extract 10 mg/kg and vitamin E 100 mg/kg. Our study concludes preventive of astaxanthin, acting on cognitive functions and neurodegeneration caused by Aβ (1-42) peptides infused Wistar rats.
Gaurav Gupta is an acclaimed Senior IEEE Member and currently serving as an Assistant Professor at Yogananda School of Artificial Intelligence Computers and Data Science, Faculty of Engineering & Technology, Shoolini University, Solan (HP) India. He is certified Oracle Database administrator as well AWS Cloud certified Educator. He holds 15 years of teaching experience, and his academic contributions includes 25 international scientific papers, 15 reviews, 5 book reviews, 7 book chapters, 15 edited and authored books published by IEEE, Elsevier, Springer Nature, Taylor & Francis, and Wiley as well as conference papers, popular science articles. He also published 12+ books with national and international publishing house. He has also organized 4 special sessions, 2 workshops, 2 FDP’s. His area of interest is Machine Learning, IoT and Cloud Computing. He is an active member of the Institute of Electrical and Electronics Engineers (IEEE) Senior Member, IEEE Computer Society, IEEE Young Professional, International Association of Engineers (IAENG)
The rising number of elderly persons with cognitive impairment who roam raises safety issues. Alzheimer's disease is common form of dementia and characterized by a progressive loss of cognitive processes, such as short-term memory and spatial cognition. Aside from memory problems, a person with this disease has trouble with visual processing and even recognizing and identifying loved ones. Moreover, Alzheimer's disease puts a patient's entire family under stress. It could even be fatal, because people who have the condition may stroll right into danger without realizing it.
The fact that the patient must be observed 24 hours a day, seven days a week makes it difficult for the caregivers to give up their vocation in order to care for the patient. Recent technological advancements have made it feasible to connect everything on the planet to each other via the internet, this is what the wearable devices, sensors, wireless network, internet-of-thing nowadays, has enabled communication among the devices and gathering and storage of vast amount of data that is deemed very essential and relevant information.
And in this age of technological advancement using detecting gadgets and new innovations on wearable technologies aims to provide a more useful strategy to screening and tracking patients. Wearables hold a lot of promise for enhancing the quality of life of Alzheimer's patients while also reducing the burden on healthcare and lowering operational costs. We discuss the various tracking systems and devices available today, as well as their benefits and drawbacks.
Institute for Advanced Biomedical Technologies, Italy
Pierpaolo Croce has a back-ground in Engineering and Electrophysiological Data Analysis with specific emphasis on Electroencephalography (EEG), Functional Magnetic Resonance (fMRI) and Functional Near-Infrared Spectroscopy (fNIRS) data analysis. In particular, his work is focused on evaluation of global connectivity metrics extracted from multimodal Electrophysiological measurements (EEG, fMRI, fNIRS) to be used as prognostic indices in neurological diseases such as Alzheimer disease or Stroke. Moreover, his activity is also focused on the evaluation of modifications of such indices obtained by trans-cranial magnetic stimulation (TMS). This aspect is strictly related to the use of connectivity indices as tools for the evaluation of the disease recovery.
Alzheimer’s Disease (AD) is associated with modifications in cerebral blood perfusion and autoregulation. Hence, Neurovascular Coupling (NC) alteration could become a biomarker of the disease. NC might be assessed in clinical settings through multimodal electroencephalography (EEG) and Functional Near-Infrared Spectroscopy (fNIRS).
Multimodal EEG-fNIRS was recorded at rest in an ambulatory setting to assess NC and to evaluate the sensitivity and specificity of the methodology to AD. Global NC was evaluated with a general linear model (GLM) framework by regressing whole-head EEG power envelopes in three frequency bands (theta, alpha and beta) with average fNIRS oxy-and deoxy-hemoglobin concentration changes in the frontal and prefrontal cortices.
NC was lower in AD compared to healthy controls (HC) with significant differences in the linkage of theta and alpha bands with oxy-and deoxy-hemoglobin, respectively (p= 0.028 and p= 0.020). Importantly, standalone EEG and fNIRS metrics did not highlight differences between AD and HC. Furthermore, a multivariate datadriven analysis of NC between the three frequency bands and the two hemoglobin species delivered a crossvalidated classification performance of AD and HC with an Area Under the Curve, AUC= 0.905 (p= 2.17× 10− 5). The findings demonstrate that EEG-fNIRS may indeed represent a powerful ecological tool for clinical evaluation of NC and early identification of AD