Research Showcase – Wearable Technology in Depression and Dementia
Ta-Wei Guu examines whether continuous data from wearable devices can reveal aspects of older adults’ depression and dementia that conventional clinical assessments miss. The session covers behavioural patterns, sleep disruption and treatment responses measured outside clinical settings, and considers how repeated observations can track changes in health over time. Guu also presents plans for a technology-enabled longitudinal cohort to study ageing populations over months and years, discussing how the resulting patterns could inform research and clinical practice. The session includes questions and discussion. Guu is an assistant professor and consultant psychiatrist at CMUBH in Taiwan, with an affiliation to King’s College London. Online via Dementia Researcher Communities livestream. Wednesday 21 October 2026, 12:00–12:45 BST (Europe/London; UTC+1). This free event requires a Dementia Researcher Communities account: open the event page, sign in or create an account, and RSVP to access the livestream. Organized by Dementia Researcher, delivered by University College London.
Using Fast Periodic Visual Stimulation to measure cognitive function in dementia
Fast periodic visual stimulation (FPVS) has emerged as a promising tool for assessing cognitive function in individuals with dementia. This technique leverages electroencephalography (EEG) to measure brain responses to rapidly presented visual stimuli, offering a non-invasive and objective method for evaluating a range of cognitive functions. Unlike traditional cognitive assessments, FPVS does not rely on behavioural responses, making it particularly suitable for individuals with cognitive impairment. In this talk I will highlight a series of studies that have demonstrated its ability to detect subtle deficits in recognition memory, visual processing and attention in dementia patients using EEG in the lab, at home and in clinic. The method is quick, cost-effective, and scalable, utilizing widely available EEG technology. FPVS holds significant potential as a functional biomarker for early diagnosis and monitoring of dementia, paving the way for timely interventions and improved patient outcomes.
From the guts to the brain through adaptive immunity in the prevention of Alzheimer’ disease
Dr. Pasinetti is the Saunders Family Chair and Professor of Neurology at Icahn School of medicine at Mount Sinai, New York. His studies allowed him to develop novel therapeutic approaches through investigation of preventable risk factors including mood disorders in the promotion of resilience against neurodegenerative disorder. In his presentation Dr. Pasinetti will discuss novel concepts about the gut-brain axis in mechanisms associated to peripheral adaptive immunity as therapeutic targets to mitigate the onset and the progression of Alzheimer’s disease and other form of dementia.
Diagnosing dementia using Fastball neurocognitive assessment
Fastball is a novel, fast, passive biomarker of cognitive function, that uses cheap, scalable electroencephalography (EEG) technology. It is sensitive to early dementia; language, education, effort and anxiety independent and can be used in any setting including patients’ homes. It can capture a range of cognitive functions including semantic memory, recognition memory, attention and visual function. We have shown that Fastball is sensitive to cognitive dysfunction in Alzheimer’s disease and Mild Cognitive Impairment, with data collected in patients’ homes using low-cost portable EEG. We are now preparing for significant scale-up and the validation of Fastball in primary and secondary care.
Taking the pulse of ageing: the role of cerebrovascular risk factors in ageing and dementia
Cerebrovascular support is critical for healthy cognitive ageing. Reduced cerebral blood flow in ageing is caused, among other things, by hypertension, arteriosclerosis (i.e. stiffening of the arteries) and plaque formation. Arterial stiffness is predictive of cognitive decline, is a critical risk factor for cerebrovascular accidents, and has been linked to heightened risks for Alzheimer’s Disease and other forms of dementia. The elasticity of cerebral arteries is influenced by lifestyle factors, including cardiorespiratory fitness. Monica will discuss data obtained in their laboratory with new noninvasive measures of cerebrovascular health (pulse-DOT, a diffuse optical tomographic method for studying cerebral arteriosclerosis), in conjunction with structural and functional brain measures and cognitive assessments. These findings support a model in which localised changes in arteriosclerosis lead to specific profiles of structural, functional, and cognitive declines, paving a way to individualised interventions.
Apathy and impulsivity in neurological disease – cause, effect and treatment
How do protein-RNA condensates form and contribute to disease?
In recent years, it has become clear that intrinsically disordered regions (IDRs) of RBPs, and the structure of RNAs, often contribute to the condensation of RNPs. To understand the transcriptomic features of such RNP condensates, we’ve used an improved individual nucleotide resolution CLIP protocol (iiCLIP), which produces highly sensitive and specific data, and thus enables quantitative comparisons of interactions across conditions (Lee et al., 2021). This showed how the IDR-dependent condensation properties of TDP-43 specify its RNA binding and regulatory repertoire (Hallegger et al., 2021). Moreover, we developed software for discovery and visualisation of RNA binding motifs that uncovered common binding patterns of RBPs on long multivalent RNA regions that are composed of dispersed motif clusters (Kuret et al, 2021). Finally, we used hybrid iCLIP (hiCLIP) to characterise the RNA structures mediating the assembly of Staufen RNPs across mammalian brain development, which demonstrated the roles of long-range RNA duplexes in the compaction of long 3’UTRs. I will present how the combined analysis of the characteristics of IDRs in RBPs, multivalent RNA regions and RNA structures is required to understand the formation and functions of RNP condensates, and how they change in diseases.
Mapping Individual Trajectories of Structural and Cognitive Decline in Mild Cognitive Impairment
The US has an aging population. For the first time in US history, the number of older adults is projected to outnumber that of children by 2034. This combined with the fact that the prevalence of Alzheimer's Disease increases exponentially with age makes for a worrying combination. Mild cognitive impairment (MCI) is an intermediate stage of cognitive decline between being cognitively normal and having full-blown Dementia, with every third person with MCI progressing to dementia of the Alzheimer's Type (DAT). While there is no known way to reverse symptoms once they begin, early prediction of disease can help stall its progression and help with early financial planning. While grey matter volume loss in the Hippocampus and Entorhinal Cortex (EC) are characteristic biomarkers of DAT, little is known about the rates of decrease of these volumes within individuals in MCI state across time. We used longitudinal growth curve models to map individual trajectories of volume loss in subjects with MCI. We then looked at whether these rates of volume decrease could predict progression to DAT right in the MCI stage. Finally, we evaluated whether these rates of Hippocampal and EC volume loss were correlated with individual rates of decline of episodic memory, visuospatial ability, and executive function.
Biopsychosocial pathways in dementia inequalities
In the United States, racial/ethnic inequalities in Alzheimer's disease and related dementias persist even after controlling for socioeconomic factors and physical health. These persistent and unexplained disparities suggest: (1) there are unrecognized dementia risk factors that are socially patterned and/or (2) known dementia risk factors exhibit differential impact across social groups. Pursuing these research directions with data from multiple longitudinal studies of brain and cognitive aging has revealed several challenges to the study of late-life health inequalities, highlighted evidence for both risk and resilience within marginalized communities, and inspired new data collection efforts to advance the field.
The Role of Cerebrovascular Pathology in Aging and Neurodegenerative Disease Populations
Late-life cognitive impairment and dementia are heterogeneous and multifactorial conditions driven by a combination of genetic, vascular, and lifestyle-related factors. More than 75% of patients with dementia have evidence of cerebrovascular pathology at autopsy. Cerebrovascular disease lesions can be detected on structural MRI and used as biomarkers to determine the extent of cerebrovascular pathology. These biomarkers are associated with cognitive difficulties and increase the risk of dementia for the same level of neurodegenerative pathology. Given that some of the risk factors for cerebrovascular disease are potentially modifiable, identifying the role of cerebrovascular pathology in aging and neurodegenerative disease populations opens a window for prevention of cognitive decline and dementia.
Using vision to understand dementia in Parkinson's disease
Mechanisms to medicines in neurodegeneration
Dysregulation of protein synthesis both globally and locally in neurons and astrocytes is a key feature of neurodegenerative diseases. Aberrant signalling through the Unfolded Protein Response (UPR) and related Integrated Stress Response (ISR) have become major targets for neuroprotection in these disorders. In addition, other homeostatic mechanisms and stress responses, including the cold shock response, appear to regulate local translation and RNA splicing to control synapse maintenance and regeneration and can also be targeted therapeutically for neuroprotection. We have defined the role of UPR/ISR and the cold-shock response in neurodegenerative disorders and have developed translational strategies targeting them for new treatments for dementia.
Roles of microglia in the pathogenesis of neurodegeneration
Microglia are implicated in a variety of functions in the central nervous system, ranging from shaping neural circuits during early brain development, to surveying the brain parenchyma, and providing trophic support to neurons across the entire lifespan. In neurodegeneration, microglia have been considered for long time mere bystanders, accompanying and worsening neuronal damage. However, recent evidence indicates that microglia can causally contribute to neurodegenerative diseases, and that their dysfunction can even be at the origin of the pathology. In fact, the broad range of physiological roles microglia play in the healthy brain suggest that faulty microglia can initiate neurodegeneration through several possible mechanisms. In particular, in this seminar, we will discuss how dysfunctional microglia can affect synaptic function leading to pathological synapse loss, thus putting microglia center stage in the pathogenesis of brain disorders.
Multimorbidity in the ageing human brain: lessons from neuropathological assessment
Age-associated dementias are neuropathologically characterized by the identification of hallmark intracellular and extracellular deposition of proteins, i.e., hyperphosphorylated-tau, amyloid-β, and α-synuclein, or cerebrovascular lesions. The neuropathological assessment and staging of these pathologies allows for a diagnosis of a distinct disease, e.g., amyloid-β plaques and hyperphosphorylated tau pathology in Alzheimer's disease. Neuropathological assessment in large scale cohorts, such as the UK’s Brains for Dementia Research (BDR) programme, has made it increasingly clear that the ageing brain is characterized by the presence of multiple age-associated pathologies rather than just the ‘pure’ hallmark lesion as commonly perceived. These additional pathologies can range from low/intermediate levels, that are assumed to have little if any clinical significance, to a full-blown mixed disease where there is the presence of two distinct diseases. In our recent paper (McAleese et al. 2021 Concomitant neurodegenerative pathologies contribute to the transition from mild cognitive impairment to dementia, https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12291, Alzheimer's & Dementia), using the BDR cohort, we investigated the frequency of multimorbidity and specifically investigated the impact of additional low-level pathology on cognition. In this study, of 670 donated post-mortem brains, we found that almost 70% of cases exhibited multimorbidity and only 22% were considered a pure diagnosis. Importantly, no case of Lewy Body dementia or vascular dementia was considered pure. A key finding is that the presence of low levels of additional pathology increased the likelihood of having mild dementia vs mild cognitive impairment by almost 20-fold, indicating low levels of additional pathology do impact the clinical progression of a distinct disease. Given the high prevalence and the potential clinical impact, cerebral multimorbidity should be at the forefront of consideration in dementia research.
AI-guided solutions for early detection of neurodegenerative disorders
Despite the importance of early diagnosis of dementia for prognosis and personalised interventions, we still lack robust tools for predicting individual progression to dementia. We propose a trajectory modelling approach that mines multimodal data from patients at early dementia stages to derive individualised prognostic scores of cognitive decline Our approach has potential to facilitate effective stratification of individuals based on prognostic disease trajectories, reducing patient misclassification with important implications for clinical practice.
Mathematical models of neurodegenerative diseases
Neurodegenerative diseases such as Alzheimer’s or Parkinson’s are devastating conditions with poorly understood mechanisms and no cure. Yet, a striking feature of these conditions is the characteristic pattern of invasion throughout the brain, leading to well-codified disease stages associated with various cognitive deficits and pathologies. How can we use mathematical modelling to gain insight into this process and, doing so, gain understanding about how the brain works? In this talk, I will show that by linking new mathematical theories to recent progress in imaging, we can unravel some of the universal features associated with dementia and, more generally, brain functions.
Challenges in Frontotemporal Dementia: clinical, genetic and pathological heterogeneity
Early constipation predicts faster dementia onset in Parkinson’s disease
Constipation is a common but not a universal feature in early PD, suggesting that gut involvement is heterogeneous and may be part of a distinct PD subtype with prognostic implications. We analysed data from the Parkinson’s Incidence Cohorts Collaboration, composed of incident community-based cohorts of PD patients assessed longitudinally over 8 years. Constipation was assessed with the MDS-UPDRS constipation item or a comparable categorical scale. Primary PD outcomes of interest were dementia, postural instability and death. PD patients were stratified according to constipation severity at diagnosis: none (n=313, 67.3%), minor (n=97, 20.9%) and major (n=55, 11.8%). Clinical progression to all 3 outcomes was more rapid in those with more severe constipation at baseline (Kaplan Meier survival analysis). Cox regression analysis, adjusting for relevant confounders, confirmed a significant relationship between constipation severity and progression to dementia, but not postural instability or death. Early constipation may predict an accelerated progression of neurodegenerative pathology. Conclusions: We show widespread cortical and subcortical grey matter micro-structure associations with schizophrenia PRS. Across all investigated phenotypes NDI, a measure of the density of myelinated axons and dendrites, showed the most robust associations with schizophrenia PRS. We interpret these results as indicative of reduced density of myelinated axons and dendritic arborization in large-scale cortico-subcortical networks mediating the genetic risk for schizophrenia.
Targeting the synapse in Alzheimer’s Disease
Alzheimer’s Disease is characterised by the accumulation of misfolded proteins, namely amyloid and tau, however it is synapse loss which leads to the cognitive impairments associated with the disease. Many studies have focussed on single time points to determine the effects of pathology on synapses however this does not inform on the plasticity of the synapses, that is how they behave in vivo as the pathology progresses. Here we used in vivo two-photon microscopy to assess the temporal dynamics of axonal boutons and dendritic spines in mouse models of tauopathy[1] (rTg4510) and amyloidopathy[2] (J20). This revealed that pre- and post-synaptic components are differentially affected in both AD models in response to pathology. In the Tg4510 model, differences in the stability and turnover of axonal boutons and dendritic spines immediately prior to neurite degeneration was revealed. Moreover, the dystrophic neurites could be partially rescued by transgene suppression. Understanding the imbalance in the response of pre- and post-synaptic components is crucial for drug discovery studies targeting the synapse in Alzheimer’s Disease. To investigate how sub-types of synapses are affected in human tissue, the Multi-‘omics Atlas Project, a UKDRI initiative to comprehensively map the pathology in human AD, will determine the synaptome changes using imaging and synaptic proteomics in human post mortem AD tissue. The use of multiple brain regions and multiple stages of disease will enable a pseudotemporal profile of pathology and the associated synapse alterations to be determined. These data will be compared to data from preclinical models to determine the functional implications of the human findings, to better inform preclinical drug discovery studies and to develop a therapeutic strategy to target synapses in Alzheimer’s Disease[3].
Phospholipid regulation in cognitive impairment and vascular dementia
An imbalance in lipid metabolism in neurodegeneration is still poorly understood. Phospholipids (PLs) have multifactorial participation in vascular dementia as Alzheimer, post-stroke dementia, CADASIL between others. Which include the hyperactivation of phospholipases, mitochondrial stress, peroxisomal dysfunction and irregular fatty acid composition triggering proinflammation in a very early stage of cognitive impairment. The reestablishment of physiological conditions of cholesterol, sphingolipids, phospholipids and others are an interesting therapeutic target to reduce the progression of AD. We propose the positive effect of BACE1 silencing produces a balance of phospholipid profile in desaturase enzymes-depending mode to reduce the inflammation response, and recover the cognitive function in an Alzheimer´s animal and brain stroke models. Pointing out there is a great need for new well-designed research focused in preventing phospholipids imbalance, and their consequent energy metabolism impairment, pro-inflammation and enzymatic over-processing, which would help to prevent unhealthy aging and AD progression.
Blood phosphorylated tau as biomarkers for Alzheimer’s disease
Alzheimer's disease (AD) is the most common cause of dementia, and its health and socioeconomic burdens are of major concern. Presently, a definite diagnosis of AD is established by examining brain tissue after death. These examinations focus on two major pathological hallmarks of AD in the brain: (i) amyloid plaques consisting of aggregated amyloid beta (Aβ) peptides and (ii) neurofibrillary tangles made of abnormally phosphorylated tau protein. In living individuals, AD diagnosis relies on two main approaches: (i) brain imaging of tau tangles and Aβ plaques using a technique called positron emission tomography (PET) and (ii) measuring biochemical changes in tau (including phosphorylated tau at threonine-181 [p-tau181]) and the Aβ42 peptide metabolized into CSF. Unlike Aβ42, CSF p-tau181 is highly specific for AD but its usability is restricted by the need of a lumbar puncture. Moreover, PET imaging is expensive and only available in specialised medical centres. Due to these shortcomings, a simple blood test that can detect disease-related changes in the brain is a high priority for AD research, clinical care and therapy testing. In this webinar, I will discuss the discovery of p-tau biomarkers in blood and the biochemistry of how these markers differ from those found in CSF. Furthermore, I will critically review the performance of blood p-tau biomarkers across the AD pathological process and how they associate with and predict Aβ and tau pathophysiological and neuropathological changes. Furthermore, I will evaluate the potential advantages, challenges and context of use of blood p-tau in clinical practice, therapeutic trials and population screening.
Development and Application of PET Imaging for Dementia Research
Molecular imaging using Positron Emission Tomography (PET) has become a major biomedical imaging technology. Its application towards characterisation of biochemical processes in disease could enable early detection and diagnosis, development of novel therapies and treatment evaluation. The technology is underpinned by the use of imaging probes radiolabelled with short-lived radioisotopes which can be specific and selective for biological targets in vivo e.g. markers for receptors, protein deposits, enzymes and metabolism. My talk will focus on the increasing development and application of PET imaging to clinical research in neurodegenerative diseases, for which it can be applied to delineate and understand the various pathological components of these disorders.
Population studies and ageing brains, in a time of COVID
This presentation will include a brief resume of research in older populations led from Cambridge that have informed current clinical understanding and policy regarding services and prevention for and of dementia. These population studies have more recently been ‘re-purposed’ with enthusiasm from participants into a trial platform, and this also has enabled ongoing follow-up by telephone during the COVID pandemic. Although there are no formal outputs from these latter developments general impressions will be shared.
Microglia function and dysfunction in Alzheimer’s disease
Emerging genetic studies of late-onset Alzheimer’s Disease implicate the brain’s resident macrophages in the pathogenesis of AD. More than half the risk genes associated with late-onset AD are selectively expressed in microglia and peripheral myeloid cells; yet we know little about the underlying biology or how myeloid cells contribute to AD pathogenesis. Using single-cell RNA sequencing and spatial transcriptomics we identified molecular signatures that can be used to localize and monitor distinct microglia functional states in the human and mouse brain. Our results show that microglia assume diverse functional states in development, aging and injury, including populations corresponding to known microglial functions including proliferation, migration, inflammation, and synaptic phagocytosis. We identified several innate immune pathways by which microglia recognize and prune synapses during development and in models of Alzheimer’s disease, including the classical complement cascade. Illuminating the mechanisms by which developing synaptic circuits are sculpted is providing important insight on understanding how to protect synapses in Alzheimer’s and other neurodegenerative diseases of synaptic dysfunction.
A decade of TMEM106B research
Epigenetics and Dementia: Lessons From the 20-Year Indianapolis-Ibadan Dementia Study
Dementia is of global interest because of the rapid increase in both the number of individuals affected and the population at risk. It is essential that the risk factors be carefully delineated for the formulation of preventive strategies. Epigenetics refers to external modifications that turn genes "on" or "off”, and cross-cultural studies of migrant populations provide information on the interplay of environmental factors on genetic predisposition. The Indianapolis-Ibadan Dementia Study compared the prevalence, incidence and risk factors of dementia in African Americans and Yoruba to tease out the role of epigenetics in dementia. The presentation will provide details on biomarkers of dementia, vascular risk factors and the association with apolipoprotein E in the Yoruba. The purpose will be to inspire early career researchers on possibilities and research strategies applicable in African populations
Semantic variant of primary progressive aphasia, clinical manifestation and underlying neuropathology
More than Bystanders in Dementia, Learning What Microglia Do
Genome-wide association studies implicate microglia in Alzheimer’s disease (AD) pathogenesis, but how microglia contribute to cognitive decline in AD is unclear. Emerging research suggests microglia, the resident macrophages of the central nervous system, to be active participants in brain wiring. One mechanism by which microglia help eliminate synapses is through the classical complement pathway (C1q, CR3/C3). Data from multiple laboratories collectively suggest that there may be an aberrant reactivation of the complement-dependent pruning pathway in multiple models of neurologic diseases including AD. These data altogether suggest that microglia participate in synaptic pathology. However, how and which synapses are targeted are unknown. Furthermore, whether microglia directly impair synaptic function is unknown. Primary goals of my laboratory are to understand how higher cognitive functions such as learning and memory involve microglial biology in the healthy adult brain and dissect immune mechanisms behind the region-specific vulnerability of synapse loss and neuronal dysfunction during disease. Mechanistic insight into local signals that regulate neuroglia interactions will be key to developing potential therapeutic avenues to target in disease.
Mechanisms of pathogenesis in the tauopathies
The distribution of pathological tau in the brain of patients with AD is highly predicable, and as disease worsens, it spreads transynaptically from initial regions of vulnerability. The reason why only some neurons are vulnerable to the accumulation and propagation of pathological forms of tau, and the mechanisms by which tauopathy spreads through the brain are not well understood. Using a combination of immunohistochemistry and computational analysis we have examined pathway differences between vulnerable and resistant neurons. How tau spreads across a synapse has been examined in vitro using different model systems. Our data show that dysregulation of tau homeostasis determines the cellular and regional vulnerability of specific neurons to tau pathology (H. Fu et al. 2019. Nat. Neuro. 22 (1):47-56) and that deficits in tau homeostasis can exacerbate tau accumulation and propagation. Aging appears to impact similar neuronal populations. Mechanisms and consequences of abnormal tau accumulation within neurons, its transfer between cells, pathology propagation and therapeutic opportunities will be discussed.