Drug Development.

Background: Genetic variants in GRN, the gene encoding progranulin, are causal for or are associated with the risk of multiple neurodegenerative diseases. Modulating progranulin has been considered as a therapeutic strategy for neurodegenerative diseases including Frontotemporal Dementia (FTD) and Alzheimer's Disease (AD). Here, we integrated genetics with proteomic data to determine the causal human evidence for the therapeutic benefit of modulating progranulin in AD.

Drug Development.

Background: The presence of multiple comorbid pathologic features in late-onset dementia has been well documented across cohort studies that incorporate autopsy evaluation. It is likely that such mixed pathology potentially confounds the results of interventional trials that are designed to target a solitary pathophysiologic mechanism in Alzheimer's disease and related dementias (ADRD).

Method: The UK ADRC autopsy database was screened for participants who had previously engaged in therapeutic interventional trials for Alzheimer's disease, vascular cognitive impairment, dementia, and/or ADRD prevention trials from 2005 to the present.

Drug Development.

Background: There is an urgent need for new therapeutic and diagnostic targets for Alzheimer's disease (AD). Dementia afflicts roughly 55 million individuals worldwide, and the prevalence is increasing with longer lifespans and the absence of preventive therapies. Given the demonstrated heterogeneity of Alzheimer's disease in biological and genetic components, it is critical to identify new therapeutic approaches.

Drug Development.

Background: Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue licensed for the treatment of type 2 diabetes mellitus (T2DM). Preclinical evidence in transgenic models of Alzheimer's disease suggests that liraglutide exerts neuroprotective effects by reducing amyloid oligomers, normalising synaptic plasticity and cerebral glucose uptake, and increasing the proliferation of neuronal progenitor cells.

Method: This is a multi-centre, randomised, double-blind, placebo-controlled, phase IIb trial of liraglutide in participants with mild to moderate Alzheimer's dementia, conducted at several centres in the UK.

Drug Development.

Background: While a number of recent anti-amyloid antibodies demonstrated a robust reduction of amyloid biomarkers in clinical trials, the impact on functional improvement is much more variable. We hypothesize that this larger variability is driven by comedications, common genotype variants and underlying tau pathology.

Method: In a previously calibrated computational neuroscience model of ADAS-Cog, we implemented the effect of soluble amyloid monomers and oligomers on glutamate and nicotinic AChR neurotransmission and the effect of intracellular tau oligomers on voltage-gated Na and K+ channels and synaptic density.

Drug Development.

Introduction: The United States is undergoing a demographic shift with increasing proportions of older adults. Currently, one in three older adults pass away with a form of Alzheimer's disease or related dementias (ADRD). This figure is higher in underrepresented and underserved groups including older adults in rural Appalachian communities.

Photocurrent Generation by Plant Light-Harvesting Complexes is Enhanced by Lipid-Linked Chromophores in a Self-Assembled Lipid Membrane.

The light-harvesting pigment-protein complex II (LHCII) from plants can be used as a component for biohybrid photovoltaic devices, acting as a photosensitizer to increase the photocurrent generated when devices are illuminated with sunlight. LHCII is effective at photon absorption in the red and blue regions of the visible spectrum, however, it has low absorption in the green region (550-650 nm). Previous studies have shown that synthetic chromophores can be used to fill this spectral gap and transfer additional energy to LHCII, but it was uncertain whether this would translate into an improved performance for photovoltaics.

Drug Development.

Background: It is essential that both drug and lifestyle-based interventions aimed at delaying the functional decline in conditions like Alzheimer's disease and related dementias (ADRDs) capture change in functioning that incorporates the person's voice. Such brain health priorities can vary across populations and it is unclear to what degree findings from the ePSOM program in the UK might apply to the US.

Methods: We conducted an online nationwide study to understand what matters to people aged 50 and older about their brain health in the US.

Drug Development.

Background: Neuroinflammation is a critical factor of Alzheimer's Disease (AD). Dysregulation of complement leads to excessive inflammation, direct damage to self-cells and propagation of injury. This is likely of particular relevance in the brain where inflammation is poorly tolerated and brain cells are vulnerable to direct damage by complement.

Drug Development.

Background: In the brain as in other organs, complement contributes to immune defence and housekeeping to maintain homeostasis. Sources of complement may include local production by brain cells and influx from the periphery, the latter severely restricted by the blood brain barrier (BBB) in healthy brain. Dysregulation of complement leads to excessive inflammation, direct damage to self-cells and propagation of injury.

Drug Development.

Background: Lecanemab is a humanized IgG1 monoclonal antibody that binds with high affinity to Aβ soluble protofibrils. In two clinical study evaluations of lecanemab, Clarity AD (NCT03887455) and lecanemab phase 2 study (Study 201, NCT01767311), the drug showed statistically significant reduction in disease progression during 18 months of treatment relative to placebo. Anti-amyloid immunotherapy can result in higher rates of "pseudo-atrophy" (ie, whole brain volume loss or ventricular enlargement) relative to disease progression observed in placebo-treated subjects.

Drug Development.

Background: Evidence suggests glucagon-like peptide 1 receptor agonists (GLP-1RAs) may have therapeutic potential in Alzheimer's disease (AD). Cumulative evidence has indicated a potential reduction in cognitive decline in people with AD, while real-world evidence has shown decreased dementia risk in patients with type 2 diabetes. Non-clinical data reveal that GLP-1RAs impact neuroinflammation and other biological processes believed to be involved in AD pathophysiology, including effects on central and peripheral immune cells.

Dementia Care Research and Psychosocial Factors.

Background: Close to 23% of unplanned hospital admissions for people living with dementia (PLWD) are due to potentially preventable causes such as severe urinary tract infections (UTIs), falls, and respiratory problems. These affect the well-being of PLWD, cause stress to carers and increase pressure on healthcare services.

Method: We use routinely collected in-home sensory data to monitor nocturnal activity and sleep data.

Dementia Care Research and Psychosocial Factors.

Background: Currently ∼50% of people with dementia experience behavioural symptoms linked to unmanaged distress. Effective and safe management of these symptoms is critical to maintain the quality of life and overall care of people with dementia. Technological solutions have the potential to help with research into these symptoms.

Dementia Care Research and Psychosocial Factors.

Background: Understand individuals' self-perception of aging is crucial for promoting a positive aging experience, better health with good quality of life, addressing activities participation, and can help by advocating policies and interventions that support the diverse needs of an aging population. This study aims to examine the validity and reliability of the Chinese version of BAPQ (C-BAPQ) for the healthy older people by assessing the content validity, test-retest reliability, and correlational analyses with mental health by Depression, Anxiety, and Stress Scale (DASS-21), quality of life by the Short Form 36 Health Survey (SF-36) and activity participation by the Model of Human Occupation Screening Tool (MOHOST). Moreover, to study the factor structure of the Chinese version of BAPQ (C-BAPQ) by using exploratory factor analysis.

Dementia Care Research and Psychosocial Factors.

Background: Long-term care (LTC) home residents may be isolated or lonely. Social connection is important for their physical, mental and cognitive health, quality of life and care. However, measuring social connection in LTC residents is challenging and there are no existing measures with adequately established psychometric properties.

Dementia Care Research and Psychosocial Factors.

Background: Data from high-income countries (HICs) suggest a decline in age-specific incidence rates of dementia. However, this has happened primarily in HICs, with low- and middle- income countries (LMICs) facing two main challenges: a higher burden of risk factors and, in general, a faster ageing population. Most people with dementia live in LMICs, and this is set to increase, thus requiring urgent and robust action to prevent, treat and support people with dementia and their families.

Dementia Care Research and Psychosocial Factors.

Background: Responses to individualized music in people living with dementia can be indicated by both verbal and non-verbal cues. Evidence suggests that elevated pupil dilation responses to familiar vs. unfamiliar music are preserved in people living with typical Alzheimer's disease (tAD), and to an extent in people with its atypical 'visual' variant (Posterior Cortical Atrophy; PCA) (Brotherhood et al.

Dementia Care Research and Psychosocial Factors.

Background: Marital status and living status are components of social isolation (SI), a modifiable factor thought to impact cognitive resilience, which has the potential to impact cognition throughout the course of Alzheimer's and related dementia (ADRD) diagnosis. Electronic health records (EHRs) offer access to large scale clinical data, capable of longitudinal analyses.

Method: Cognitive function measurement - Montreal Cognitive Assessment (MoCA) - data, demographic (including marital and living status as SI proxies) data and ADRD diagnosis data from patients aged 50+ years from Oxford Health NHS Foundation Trust (UK) were extracted using natural language processing algorithms from EHRs dated 1995 to 2022.

Dementia Care Research and Psychosocial Factors.

Background: Changes in sleep patterns are common in Alzheimer's disease and impact the quality of life of both people living with Alzheimer's (PLWA) and their caregivers. Longitudinal recordings and assessment of night-to-night variations in sleep and physiology can improve our understanding of how sleep influences clinical outcomes and caregiver wellbeing.

Method: We collected sleep diary and contactless sleep technology data (Withings sleep analyser, WSA) in community dwelling PLWA (N = 16, Age = 72.

Dementia Care Research and Psychosocial Factors.

Background: Approximately 944,000 people are living with dementia in the UK (∼0.8% of the population). The World Health Organisation consider dementia a public health priority.

Dementia Care Research and Psychosocial Factors.

Background: Environmental factors account for a considerable percentage of dementia cases. Studies in animal models have shown that environmental enrichment (EE; i.e.

Dementia Care Research and Psychosocial Factors.

Background: Dementia rarely travels alone. People with dementia (PwD) often have multiple other physical diagnoses (multimorbidity) and experience poor quality, fragmented care. Over two thirds of carers of PwD are spouses, over half of which are 85 years old or above.

Dementia Care Research and Psychosocial Factors.

Background: Personality traits, especially neuroticism, can influence susceptibility to dementia. Although social contact can mitigate stress and risk of dementia, the extent to which social contact can mitigate excess risk associated with neuroticism remains unclear. The objective of study was to investigate changes in neuroticism-associated excess risk of dementia arising from different levels of social contact.

Dementia Care Research and Psychosocial Factors.

Background: Ethnic diversity communities are frequently underrepresented in dementia research. Reasons include lack of identification with dementia research studies, promotional material for dementia prevention and accessibility. The result of this underrepresentation means that new developments for dementia treatments will be not be trialled on these communities.