Drug Development.

A 10 mg/kg every 2 week (Q2W) dose of the humanized IgG1 monoclonal antibody lecanemab was approved after demonstrating significant clinical benefit in slowing cognitive decline in early Alzheimer's disease (AD) in two clinical studies (the phase 2 Study 201 and phase 3 Clarity AD). A less frequent every 4 weeks lecanemab 10 mg/kg maintenance dosing (Q4W) has been proposed after a sufficient initial Q2W treatment. To further understand long-term benefit of continued Q4W lecanemab treatment, a quantitative systems pharmacology (QSP) model was developed which mechanistically describes AD pathophysiology using multivariate data from clinical studies.

Drug Development.

Background: Lecanemab is an approved anti-amyloid monoclonal antibody that binds with highest affinity to soluble Aβ protofibrils, which are more toxic than monomers or insoluble fibrils/plaque. In clinical studies, biweekly lecanemab treatment demonstrated a slowing of decline in clinical (global, cognitive, functional, and quality of life) outcomes, and reduction in brain amyloid in early Alzheimer's disease (AD). Herein, we describe the impact of lecanemab treatment on tau PET.

Drug Development.

The most recent Alzheimer's clinical trials, including those which reported successful outcomes, use neuroimaging biomarkers of both amyloid and tau for screening participants and demonstrating a treatment effect on pathology. Some of these trials, notably Lecanemab, hint at a potential sex bias in treatment outcome, alluding to major implications for clinical practice when recommending treatment options. Sex differences in treatment response are not surprising given that women are at greater risk of progression to AD dementia, particularly if they carry APOEe4.

Drug Development.

Anti-amyloid therapies are ideal candidates for prevention trials. Secondary prevention in those at risk of ADAD (DIAN-TU) has shown reduction of brain amyloid deposition leads to significant downstream biological change; early secondary prevention using a monoclonal antibody in sporadic AD (AHEAD 3-45) is ongoing and will provide critical information on whether treating earlier leads to greater clinical benefit. However, this is not preventing disease but delaying onset in those with presymptomatic disease.

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.

Drug Development.

Alzheimer's disease (AD) is a common copathology in Lewy body dementia (LBD). The presence of AD is associated with a distinct clinical presentation, faster progression, and shorter survival in LBD. However, the relationship between-alpha synuclein and AD remains incompletely understood.

Dementia Care Research and Psychosocial Factors.

Background: The progressive nature of dementia and the complex needs means that people living with dementia require tailored approaches to address their changing care needs over time. These include physical multimorbidity, psychological, behavioural, and cognitive symptoms and possible risks arising from these and helping family caregivers. However, provision of these interventions is highly variable between and within countries, partly due to uncertainty about their efficacy and scarce resources.

Dementia Care Research and Psychosocial Factors.

Background: People living with dementia (PwD) experience progressive functional decline with increasing dependence on their caregivers. Advanced care planning (ACP) has the potential to promote quality of life, reduce iatrogenic harm, and minimize overutilization of healthcare resources, yet planning ahead in the context of dementia is challenging and requires consideration of numerous factors over an extended period of time. We examined caregivers' perceptions of current and end-stage medical care preferences in PwD and the impact of ACP-related discussions between caregivers and PwD.

Drug Development.

Cerebral beta-amyloid accumulation is the key initiator of Alzheimer's disease (AD) pathology. Most familial early-onset AD mutations in the APP, PSEN1/2 genes increase the ratio of Abeta42:Abeta40, which drives beta-amyloid accumulation in the brain. In 2001, the late Steve Wagner, Maria Kounnas, and I directed an agnostic high-throughput screen for compounds that would reverse the Abeta42:Abeta40, ratio, and discovered the first non-NSAID (second generation) gamma secretase modulators (GSM) at TorreyPines Therapeutics.

Drug Development.

Background: Irsenontrine (e2027) is a potent and selective PDE9 inhibitor that increases cellular cGMP which is important for glutamatergic synaptic function. Irsenontrine was investigated to improve cognition in Lewy Body Dementia (LBD; DLB and PDD), and recent phase 2 study data suggests that irsenontrine could be more effective in DLB patients without amyloid copathology. Here, we evaluated differential change from baseline levels in proteins associated with cGMP pathway in DLB participants without amyloid co-pathology (DLB A-) compared to DLB participants with amyloid co-pathology (DLB A+).

Dementia Care Research and Psychosocial Factors.

Background: Research on biomarkers for Alzheimer's pathology has progressed rapidly. We summarize the evidence and make recommendations about biomarkers for future clinical use.

Method: Our interdisciplinary, international, multicultural group of experts in the Lancet Commission on dementia adopted a triangulation framework, prioritizing systematic reviews and meta-analyses and agreed on the best evidence for recommendations.

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: Our authors from around the world met to summarise the available knowledge, decide which potentially modifiable risk factors for dementia have compelling evidence and create the most comprehensive analysis to date for potentially modifiable risk factors to inform policy, give individuals the opportunity to control their risks and generate research.

Method: We incorporated all risk factors for which we judged there was strong enough evidence. We used the largest recent worldwide meta-analyses for risk factor prevalence and relative risk and if not available the best data.

Dementia Care Research and Psychosocial Factors.

Background: Research has consistently shown decreased quality of life (QoL) in people with dementia, with predictors of QoL ranging from education to emotional status. This study, along with a one year follow-up study, investigated the impact of Awe Walks as an intervention targeting emotional status for the first time in dementia. Awe-a positive emotion elicited when in the presence of vast things not immediately understood-promotes social connection and fosters well-being by encouraging a "small self".

Dementia Care Research and Psychosocial Factors.

Background: Research on the relationship between self-efficacy and symptoms of depression and anxiety among individuals with mild cognitive impairment (MCI) has been limited. Furthermore, few studies have explored this relationship within the context of dyadic couples (patient/care partners) rather than focusing solely on individuals. The purpose of this study was to examine the associations between self-efficacy in patient/care partner couples dealing with mild cognitive impairment and their symptoms of depression and anxiety using a dyadic analysis approach.

Dementia Care Research and Psychosocial Factors.

Background: Given the widespread of tele-assessment and tele-rehabilitation in speech language pathology and clinical neuropsychology for monolingual English-speaking patients with acquired neurogenic language and cognitive disorders, there is an urgent need to implement a culturally and linguistically tailored telepractice for multilingual people living with dementia (MPLWD), for whom there is no consensus on a standard model. This study aims to investigate the delivery model of remote assessment and intervention for this population.

Method: A systematic scoping review was conducted in December 2023 following frameworks described by Arksey and O'Malley (2007).

Dementia Care Research and Psychosocial Factors.

Background: The 2020 Lancet Commission on dementia prevention, intervention and care estimated that up to 40% of dementia cases could be prevented by tackling 12 potentially modifiable risk factors, namely less education, hearing loss, hypertension, physical inactivity, diabetes, social isolation, excessive alcohol consumption, air pollution, smoking, obesity, traumatic brain injury, depression. As more evidence on risk factors emerges, the Lancet standing commission on dementia met to update evidence on established dementia risk factors and to consider the evidence for other risk factors.

Method: We used a lifecourse approach to understand how to reduce risk or prevent dementia, as many risks operate at different timepoints in the lifespan.

Dementia Care Research and Psychosocial Factors.

Background: Within the dementia space, many caregivers lack understanding of hospice care and may not be well prepared for transition to hospice. Nonetheless, few studies have explored hospice transition specifically from the perspective of caregivers for persons with dementia and how it impacts their mental health. In this study, we aimed to examine caregivers' mental health indicators and their correlation structure based on the timing of hospice transition.

Dementia Care Research and Psychosocial Factors.

Background: Caring for nursing home residents with dementia can be challenging. Staff who work in nursing homes tend to have high staff turnover. In order to help with staff retention, there needs to be an understanding of the job role.

Dementia Care Research and Psychosocial Factors.

Background: The COVID-19 pandemic had a major impact on healthcare, contributing to a mass exodus of the workforce. This poses a concern for Alzheimer's disease and related dementias (ADRD) care, which benefits from consistent care routine and staff that know the resident. Therefore, it is important to understand nursing home staff perspectives on maintaining high staff morale, which impacts recruitment, retention, and care quality.

Dementia Care Research and Psychosocial Factors.

Background: Caring for family caregivers of dementia patients has grown to an important topic. Social media platforms, like Twitter, provide great resources for studying the needs of caregivers. It would be beneficial to understand the caregivers' interested or concerned topics from their tweets.

Dementia Care Research and Psychosocial Factors.

Background: As the landscape of ADRD diagnoses evolves to include biomarker testing, there is a pressing need to understand the unique experiences, challenges, and support needs of families undergoing evaluations of cognitive decline, particularly in a manner that prioritizes cultural considerations from voices historically underrepresented in ADRD research. The current study aims to understand the AD biomarker disclosure journey of persons from underrepresented groups with the goal of informing culturally responsive approaches to the care of patients and their families navigating the complexities of ADRD diagnoses.

Method: Virtual focus groups are being conducted over a secure video conferencing platform, with a trained facilitator guiding the discussion.

Dementia Care Research and Psychosocial Factors.

Background: Research heavily suggests that brain-derived neurotrophic factor (BDNF), vital for neuronal growth and plasticity, and cholecystokinin (CCK), a satiety hormone that regulates BDNF levels, are altered in Alzheimer's Disease pathophysiology. Factors such as dysbiosis of gut microbiota and poor food habits may affect CCK and BDNF release and brain function. The objective is to evaluate the effects of dietary habits, gut microbiota, and exercise on BDNF and CCK release in Alzheimer's Disease patients.

Dementia Care Research and Psychosocial Factors.

Background: The recent breakthrough in monoclonal antibody treatment for Alzheimer's disease (AD) has ushered in a new phase in AD healthcare. However, associated amyloid-related imaging abnormalities (ARIA) present a significant risk to patients, necessitating careful monitoring. Detection by radiologists can be challenging and may suffer from inconsistency.

Dementia Care Research and Psychosocial Factors.

Background: Social health factors have been robustly associated with better cognitive health in older adults; however, less is known about how social network size affects the relationship between in-vivo biomarkers of Alzheimer's disease (AD) pathology and brain aging outcomes. We examined the independent and interactive relationships between plasma pTau181 and social network size on memory function and medial temporal lobe (MTL) volume in older adults.

Method: Participants were 58 community-dwelling older adults (mean age = 75.