Speakers
Maw Pin Tan
University of Malaya, Malaysia
Title: Tools for Assessment of Cognitive Function in Older Malaysians
Malaysia is considered an upper middle income developing country. Due to rapid economic development, our population is now ageing rapidly with the number of individuals aged 60 years and over increasing from 9% today to 15% by 2030. With dementia being an age related condition affecting the oldest old, there is a desperate need now for our nation to develop effective strategies for the prevention and management of dementia. Our country comprises three main ethnic groups with English, Bahasa Malaysia, Mandarin Chinese and Tamil being the most commonly used languages. Few dementia assessment tools exist in all four languages. We had conducted a systematic review of dementia assessment tools validated in Asian Nations. In this systematic review, only the MoCA and the MMSE had been validated in Malaysia. Subsequently we had successfully validated two further tools: the Picture Memory Impairment Scale (PMIS) and the Identification of Dementia in Africa (IDEA) tool. Future research should identify appropriate screening strategies, diagnostic tests as to develop more culturally appropriate neuropsychological tests for Malaysia.
Suzana Shahar
Universiti Kebangsaan Malaysia, Malaysia
Title: Tools for Assessment of Cognitive Function in Older Malaysians
Aging is a major risk factor for neurodegenerative diseases including Alzheimer’s disease. Dating back to prehistoric times, the evolutions of human ageing and longevity have changes dramatically over the past 400 years, and this phenomenon is expected to change in the immediate future, with human ageing is a complex process influenced by multiple interacting factors including genetics, biology, and behaviour, physical, social and psychological aspects of the human environment and lifestyle, of which nutrition is one of the most important aspect to determine longevity. Evidence indicates that oxidative stress is involved in the pathogenesis of neurodegenerative diseases, with specific nutrients including folate, antioxidants vitamins and omega 3 fatty acid can block neuronal death in vitro and may have therapeutic properties in animal models of neurodegenerative diseases. Several large scale prospective studies have indicated the neuroprotective effect of such nutrients, however, results from clinical trials on human are rather limited and sometimes contradicting. Epidemiological study of dietary pattern has also revealed the contributions of specific food including fish, fruits and vegetables, nuts and herbs such as curry and also beverages including green tea are also neuroprotective. However, this might be confounded with the environmental factors and cultural factors that those individuals consuming healthy foods might also engage to healthy lifestyle. In conclusion, one should not be obsessed on a specific nutrient or brain food but rather consider the whole spectrum of neuroprotective lifestyles in reducing the risk of neurodegenerative diseases.
Hirohisa Watanabe
Brain & Mind Research Center, Nagoya University, Japan
Title: Neural network imaging and clinical features in patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration spectrum
ALS has traditionally been considered a progressive neurodegenerative disorder in which the motor system is selectively targeted. Age at onset influences on wide-ranged clinical features of sporadic ALS (JNS 2009, J Neurol. 2016). More recently, edaravone showed efficacy in a small subset of people with ALS (Lancet Neurol 2017). In contrast, FTLD is a pathological entity of sporadic and familial neurodegenerative disease, clinically characterized by bvFTD and language disorders. However, some ALS patients also present with the characteristic clinical findings of FTD and mild cognitive impairment and/or behavioral features (JNS. 2011, ALSFTLD 2016). Besides, some FTLD patients can show upper and lower motor symptoms (JAMA Neurol 2014). More recently, TDP-43, a major component of ubiquitinated inclusions, is a critically important pathogenic protein found in both sporadic ALS and FTLD. Since almost all sporadic ALS cases and more than half of sporadic FTLD cases have cytoplasmic inclusions consisting of the cleaved form of hyper-phosphorylated TDP-43, several investigators proposed a concept of TDP-43 proteinopathy, which implicates FTLD-TDP and ALS as a continuous disease spectrum (JAMA Neurol 2014, BMJ Open 2014). Although the pathophysiology and continuity of ALS/FTD spectrum remains to determine, modern anatomical and functional neuroimaging techniques have showed structural and functional disruptions of neural cortico-subcortical-networks and provided a critical perception into a better understanding of pathophysiology and prognosis (ALSFTLD 2009, 2011, JNNP 2017). We also have confirmed that the caudate and its anatomical networks can be highly involved in ALS/FTD spectrum using neuroradiological and pathological studies (ALSFTLD 2016, JNEN 2016, 2017). Interestingly, caudate nucleus can be one of the most vulnerable subcortical structures and be associated with cognitive decline. Currently, we identified the decision-making abnormality and dynamic network changes which may have a potential for earlier cognitive decline in ALS/FTD spectrum.
Satoshi Maesawa
Brain & Mind Research Center, Nagoya University, Japan
Title: Network analysis using resting state fMRI & EEG-fMRI for detection of epileptogenesis
Focal epilepsy is recently considered disorder of brain network rather than regional brain disease. Functional connectivity changes in and around the epileptic zone (EZ) in patients with focal epilepsy are still unknown. Although many researches in focal epilepsy have demonstrated increased pattern of connectivity surrounding the EZ (Morgan VL,2015, Negishi M, 2011), some have included contradictory observations (Doucet G, 2013). We hypothesized increased regional connectivity in EZ as well as some propagation areas, which could be identified by “hub analysis”, a novel method to analyze functional connectivity using resting-state fMRI (rsfMRI), with comparison to large normal cohort datasets. 18 patients with medically uncontrollable focal epilepsy were enrolled, whose EZ was identified with presurgical routine checkup, and resection surgery was performed afterwards. Hub analysis was performed as follows: The voxel-based degree, defined as the number of voxels with time courses that are strongly correlated with that of the given voxel (r>0.75), was computed. Compared to datasets of normal healthy cohorts (n=83), the cluster of voxels with degree z-score greater than 3 was defined as “hub”. In 16/18 cases (88.9%), obvious hubs were seen in and around EZ. EZ-hub was included in resection area postoperatively in 11/18 cases, demonstrating a trend to correlate to good surgical outcome. Mirror hubs were also observed in the contralateral side in 15/18 cases and were stronger than EZ-hubs. Interestingly, laterality indices (LI; EZ hub – mirror hub / EZ hub + mirror hub) were significantly high in good outcome group (P<0.01). Accordingly, hubs may represent regions with pathologically strong connections related to epilepsy, and these results supported the hypothesis for increased regional connectivity in EZ as well as some propagation areas. In addition, as another topic, recent trends of EEG-fMRI will be discussed in the presentation, including introduction of our recent work (sub-second analysis for focus detection)
Li Junhua
National University of Singapore, Singapore
Title: Brian Connectivity Alterations in Elderly Population
Elderly population was dramatically increased in modern society, which requires neuroimaging studies to understand brain alterations caused by aging so as to provide better healthcare for them. In this presentation, I will introduce the experimental protocol, graph theoretical analysis, and according results obtained from the analysis of neuroimaging data (e.g., fMRI). The findings of the brain inter-regional connectivity as well as the topology will be detained in the presentation.
Andrei Dragomir
University of Houston, Visiting Scholar@ National University of Singapore, Singapore
Title: Multilevel Multimodal Biomarkers of Alzheimer’s Disease
A major rise in prevalence and impact of Alzheimer’s Disease (AD) is projected in the coming decades, resulting from increasing life expectancy, thus leading to substantially increased healthcare costs. While brain disruptions at the time of diagnosis are irreversible, it is widely accepted that AD pathology develops decades before clinical symptoms onset. If incipient processes can be detected early in the disease progression, prospective intervention for preventing or slowing the disease can be designed. Currently, due to the absence of a mechanistic understanding of disease progression and major failures in clinical trials, no new drug is expected to be available until 2025. Furthermore, there is no noninvasive biomarker available to detect and monitor early stages of disease progression. For identifying accurate noninvasive biomarkers, comprehensive genotype-phenotype evidence needs to be considered, in order to capture the wide range of dysfunctions characterizing AD pathology. In this talk we’ll report on an integrative multilevel, multimodal framework we are developing for studying progression in prodromal stage of AD, in order to identify genomic and neuroimaging, as well as cross-level biomarkers. We investigate from a systems perspective, pathways and subnetworks reflecting characteristic pathology changes in patients with amnestic mild cognitive impairment (aMCI), the prodromal stage of AD. The –omics level analysis integrates in an innovative manner molecular data from patients’ blood samples. At the same time, patients’ brain level anomalies and functional disruptions are investigated through MRI neuroimaging, using complex networks analysis methods. Consequently, our research integrates genotype-phenotype evidence in a comprehensively noninvasive approach. Our overall approach is rooted in network medicine, having as central goal the development of a network-based multimodal and multilevel framework which enables noninvasive diagnosis, provides support for monitoring therapies, and helps understand heretofore unexamined deep level relations between genetic and neuroimaging phenotype.
Gloria Fan-Pei Yang
National Tsinghua University, Taiwan
Title: Neural Mechanisms of Cognitive Control in the healthy elderly
As people age, the ability of cognitive control declines with the thinning of cortices and reduced connectivity of cerebral regions. It remains unclear how this decline is manifested in brain activation. A large number of previous studies have proposed the right-hemisphere compensation theory based on the right-lateralized activations in linguistic and visual attention tasks. The present study uses the Stroop task to investigate the dual control function in the healthy elders in comparison to young people. Twenty-eight healthy elders and 23 young people participated in the study. Stimuli were presented in two separate blocks, each containing 12 trials of four experimental conditions. In one block, participants were asked judge the value of two juxtaposed digits, and press the right button if the digit on the right has a bigger value, and vice versa. In the other block, participants were asked to judge the size of two juxtaposed digits, and press the right button if the digit on the right is bigger in size, and vice versa. Each pair of stimuli was presented on the screen for 2000 ms followed by an inter-stimuli interval of 4000ms, 6000ms, or 8000ms. Participants were told to respond as fast and accurately as possible. Data were acquired by a 3T magnetic resonance (MR) scanner (Magnetom Prisma, Siemens, Germany). Functional series were acquired using an echo planar imaging (EPI) sequence (repetition time (TR) = 2500 ms; echo time (TE) = 30; matrix size = 64*64*64, voxel size 3*3*3 mm, no inter-scan interval). A T1-weighted anatomical data set was obtained from each participant (spatial resolution .93*.93* .93 mm). Data analysis was performed using SPM5 (Wellcome Department of Cognitive Neurology, London, UK). An independent-sampled t-test was conducted to compare activation difference(s) between groups. The results revealed that the elderly showed hyper-activations in the the left medial frontal gyrus, the left precuneus, the right superior frontal gyrus and the right anterior cingulate. This provides evidence against previous claim that the elderly always show the right-lateralized activation pattern. Instead, the integrated reasoning network in the left is more active in the elderly than in the young. The error-monitoring and executive function network is more active in the right in the elderly than in the young. The findings do not support the right-hemisphere compensation theory as the lateralization pattern varies with different cognitive networks. We may need alternative models for the change of cognitive networks in the elderly.
Toshiharu Nakai
National Center for Geriatrics & Gerontology, Japan
Title: Neuroinformatics for Aging
Depending on the extension of lifespan, societies have been rapidly getting aged especially in Asian countries. Nowadays, the idea of `active ageing' (successful ageing) the view that longer life must be accompanied by continuing opportunities for health is driving many community-based programs to support physical exercises for older adults. In such programs, the effects of physical exercises (PE) on cognitive function have been the concern. In this study, we aimed to investigate the short-term effects of verbal training on resting state networks in older adults. Verbal training has the characteristics of both cognitive and physical training and it may be useful for social programs for older adults. If we could predict the outcome of cognitive training 1 or 2 months after starting the intervention, the program will be better optimized for each participant.
Annabel Chen Shen-Hsing
Nanyang Technological University, Singapore
Title: Optimizing Learning in the Aging Brain: A Neuroinformatics Challenge
Functional neuroimaging has helped advanced the field of research in cognitive aging. It has extended knowledge in neuropsychology of aging to exploring underlying mechanisms in neuroimaging models. Early concepts of neural compensation and dedifferentiation in age-related cognition have been characterized in various studies of task-fMRI, resting-state networks and diffusion MRI. We are beginning to understand these various phenomenon seen in large scale neuro-networks. These neuroimaging aging models have provided testable hypotheses that can evaluate contributions of individual differences such as cognitive reserve and physical activity levels. However, the capacity to learn in the aging brain is less investigated and not as well understood. The field of aging neuroscience is progressing into developing non-invasiveneuromodulations to optimize cognition in aging. It has opened up avenues for us to examine individual differences in cognitive changes and possibly individual responses to neuromodulations. Currently, with the advancement of data sharing, collaborations across countries thus enabling larger datasets, we are poised to harnessneuroinformatics to help push the frontiers of modeling in aging neuroscience. The multidisciplinary research of neuroinformatics would allow the fusion of multi-modal neuroimaging and behavioral data to develop predictive models with explanatory power. The neuroinformatics challenge for aging neuroscience is to develop such models with empirical data to help us understand the individual’s capacity to benefit from neuromodulations for cognitive wellness in aging.
Epifanio Bagarinao
Brain & Mind Research Center, Nagoya University, Japan
Title: Application of Real Time Functional MRI for Motor Imagery Task Training
Real-time functional magnetic resonance imaging (rtfMRI) enables the real-time measurement and analysis of ongoing brain activity using the BOLD signal. One of its applications is neurofeedback (NF) training, a self-modulation method to control mental training more efficiently by providing feedback signals directly derived from measured brain activity. This is particularly useful for motor imagery (MI) tasks training, which has been recently developed as a rehabilitation tool after cerebrovascular disorder. With rtfMRI, direct comparison between ongoing brain states and that associated with the MI task can be performed, which could be very useful in assessing task performance during MI training. RtfMRI could also play an important role in improving the efficacy of brain-machine interface (BMI) systems. This can be done by directly translating ongoing brain states into BMI commands. Specifically, the mental representation of body movements can be matched with the target outputs to better manipulate machines or devices. In this study, we designed a BMI model based on rtfMRI using MI tasks to manipulate the arm movement of a small humanoid robot which provides a visual representation of the MI and also acts as NF signal. We compared brain activations with and without NF to investigate the efficacy of using NF during MI tasks training. The performance of the BMI model to discriminate brain states associated with the MI tasks and the model’s ability to convert these states to commands for the output device was also examined.
Subapriya Suppiah
Universiti Putra Malaysa, Malaysia
Title: Quantifying glucose hypermetabolism seen on 18F-FDG Positron Emission Tomography Computed Tomography Imaging in Alzheimers' Disease
Alzheimer’s disease is a clinicopathological diagnosis, which can be aided by diagnostic imaging in certain selected cases. Clinically, the patients present with a progressive decline in cognitive function and the hallmark of AD is the histological detection of beta amyloid plaques (Aβ) by brain biopsy or at autopsy. Diagnostic imaging can play a role in the management of AD by providing structural and functional information to exclude possible secondary causes and offer additional information to differentiate the subtypes, especially if there is atypical presentation. The utility of functional imaging in clinical practice, such as Tc99m-HMPAO SPECT and 18F-FDG PET/CT as well as Amyloid imaging PET/CT, is gaining momentum as a non-invasive biomarker to provide better diagnostic accuracy. Although Amyloid PET/CT imaging has not been widely used in Asian countries, it is useful to know about this type of advances in imaging that have been utilized in Europe and the United Kingdom to aid in improved specificity for detecting Aβ plaques and may play a role in treatment monitoring. Emphasis will be given on clinical indications, limitations and image interpretation techniques.
Tang Tong Boon
Universiti Teknologi PETRONAS, Malaysia
Title: Visualizing Hyperactivation in Neurodegeneration based on Prefrontal Oxygenation: A Comparative Study of Mild Alzheimer’s Disease, Mild Cognitive Impairment and Healthy Control
Cognitive performance is relatively preserved during early cognitive impairment, owing to compensatory mechanism. We explored functional near-infrared spectroscopy (fNIRS) with a semantic verbal fluency task (SVFT) to investigate the potential compensation exhibited by the prefrontal cortex (PFC) in Mild Cognitive Impairment (MCI) and mild Alzheimer’s disease (AD). In addition, a group of healthy controls (HC) was included. A total of 61 volunteers (31 HC, 12 patients with MCI, and 18 patients with mild AD) took part in this study. Although not statistically significant, MCI showed greater mean activation of both the right and left PFC, followed by HC and mild AD. Analysis showed that in the left PFC, time taken for HC to achieve their activation level was shorter than MCI and mild AD (p = 0.0047 and p = 0.0498, respectively); in the right PFC, mild AD took longer time to achieve their activation level than HC and MCI (p = 0.0469 and p = 0.0335 respectively); in the right PFC, HC and MCI showed steeper slope as compared to mild AD (p = 0.0432 and p = 0. 0107, respectively). These results were however not significant when corrected by Bonferroni-Holm method. Our results also found a moderate positive correlation (R = 0.5886) between the oxygenation level in the left PFC and clinical measure (Mini-Mental State Examination score) uniquely in MCI subjects, but not HC and mild AD. The hyperactivation in MCI coupled with a better SVFT performance might suggest the presence of neural compensation, although it is not known to what degree hyperactivation, as a potential indicator for compensatory mechanism, manifests. On the other hand, the hypoactivation plus a poorer SVFT performance in mild AD might indicate the inability to compensate due to the degree of structural impairment. In consistent with scaffolding theory of aging and cognition, the task-elicited hyperactivation in MCI might indeed reflect the presence of compensatory mechanisms and and the hypoactivation in mild AD might be due to the inability to compensate. Future studies will look into the fNIRS parameters individually instead of making multiple comparisons, and the validity of them as prognostic biomarkers of neurodegeneration.
Hanna Lu
Chinese University of Hong Kong, China
Title: ‘Two-level’ measurements of information processing speed (IPS) as cognitive markers in the differential diagnosis of DSM-5 neurocognitive disorders (NCD)
Information processing speed (IPS) is an updated diagnostic factor for neurocognitive disorders (NCD) in DSM-5. This study investigated the characteristics of processing speed and their diagnostic values in NCD patients. A flanker test was conducted in 31 adults with NCD due to vascular disease (NCD-vascular), 36 patients with NCD due to Alzheimer’s disease (NCD-AD), and 137 healthy controls. The processing speed was evaluated using two measurements: mean reaction time (RT) and intra-individual variability of RT. Mean RT represents the global IPS. Intra-individual variability of RT is the short-term fluctuation of RT and consists of two indices, which are intra-individual coefficient of variation of reaction time (ICV-RT) and intra-individual standard deviations (iSD). We observed elevated ICV-RT and iSD in NCD-AD and NCD-vascular patients. Additionally, there was a slowed RT in NCD-AD patients. The intra-individual variability of RT had a moderate power to differentiate NCD subgroups. The mean RT was able to discriminate the NCD-AD from NCD-vascular patients. Our findings highlight the clinical utility of the combined ‘two-level’ measurements of processing speed to distinguish between individuals with different cognitive status. Furthermore, the ‘two-level’ features of processing speed embedded in the psychometric property may also reflect the diverse aetiology underlying certain ‘disease-specific’ neurocognitive disorders.