Drug Development.

Background: Mivelsiran (ALN-APP) is an investigational, intrathecally administered RNA interference therapeutic designed to lower levels of amyloid-β (Aβ) peptide, a key driver of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) pathogenesis, by reducing upstream production of amyloid precursor protein (APP). We report additional safety, pharmacodynamic, and biomarker data from the double-blind, placebo-controlled, single ascending dose part of the ongoing mivelsiran Phase 1 study (NCT05231785).

Method: Patients with early-onset AD (symptom onset <65 years of age, Clinical Dementia Rating global score 0.

Drug Development.

Background: Recent growth in the functionality and use of technology has prompted an increased interest in the potential for remote or decentralised clinical trials in dementia. There are many potential benefits associated with decentralised medication trials, but the field is currently lacking specific recommendations for their delivery in the dementia field.

Method: A modified Delphi method engaged a panel with substantial expertise in dementia trial design and delivery and backgrounds that included neurology, psychiatry, pharmacology and psychology, to develop recommendations for the conduct of decentralised medication trials in dementia prevention.

Drug Development.

Numerous drugs (including disease-modifying therapies, cognitive enhancers and neuropsychiatric treatments) are being developed for Alzheimer's and related dementias (ADRD). Emerging neuroimaging modalities, and genetic and other biomarkers potentially enhance diagnostic and prognostic accuracy. These advances need to be assessed in real-world studies (RWS).

Drug Development.

Background: The LatAm-FINGERS trial marks a pioneering initiative as the first non-pharmacological clinical trial encompassing participants from 12 Latin American countries, including Argentina, Brazil, Bolivia, Chile, Colombia, Costa Rica, Ecuador, Dominican Republic, Mexico, Peru, Puerto Rico, and Uruguay. This initiative represents a significant advancement in promoting inclusivity and diversity in clinical trial recruitment, particularly in underserved populations.

Method: The LatAm-FINGERS trial is a multicenter randomized clinical trial evaluating a lifestyle intervention tailored for the Latin American population.

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: Progranulin (PGRN), a glycoprotein secreted by microglia and neurons, regulates lysosomal function, neuroinflammation, and has neurotrophic effects. Variants in the granulin gene (GRN) that cause a reduction of PGRN in plasma and cerebrospinal fluid (CSF) are associated with an increased risk of Alzheimer's disease (AD). The sortilin receptor (SORT1) on neurons and microglia regulates PGRN degradation.

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.

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.

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: 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: 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: The Promoting Independence Through quality Care at Home (PITCH) project aimed to improve outcomes for people with dementia and their carers via a co-designed training intervention for home care workers (HCWs). The results of the primary efficacy analysis of the successful stepped-wedge cluster RCT (n = 172 HCWs in 18 clusters in 7 Australian service providers) were presented at AAIC 2023.

Method: This presentation goes beyond efficacy and discusses the implementation science (process evaluation and behavioural change) and health economic analysis of the intervention.

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: Understanding how caregivers perceive their own aging process is essential for addressing their well-being and the quality of care they provide. This study aimed at exploring the relationship between caregivers' self-perception of ageing in relation to their strain experienced in caregiving, and their perceived physical and mental health symptoms. Moreover, to examine if the strain experience and perceived health condition were key predictors to their self-perception of ageing.

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: Dysphagia is an important feature of neurodegenerative diseases and potentially life-threatening in primary progressive aphasia (PPA), but remains poorly characterised in these syndromes. We hypothesised that dysphagia would be more prevalent in nonfluent/agrammatic variant (nfv)PPA than other PPA syndromes, predicted by accompanying motor features and associated with atrophy affecting regions implicated in swallowing control.

Methods: In a retrospective case-control study at our tertiary referral centre, we recruited 56 patients with PPA (21 nfvPPA, 22 semantic variant (sv)PPA, 13 logopenic variant (lv)PPA).

Dementia Care Research and Psychosocial Factors.

Background: How people affected by non-memory-led and inherited dementias (NMLDs) interact with online health resources is poorly understood. We conducted the world's largest survey exploring 'digital access in non-memory-led dementias' to learn directly from people with NMLD, their care partners and NMLD Healthcare Professionals (HCPs) about the NMLD experience interacting with web-based health resources.

Method: Four surveys [for individuals diagnosed with NMLD, care partners, care partner proxy for person with NMLD, HCP proxy] were co-developed with people with NMLD experience.

Dementia Care Research and Psychosocial Factors.

Background: Literature often focuses on loneliness as a risk factor for dementia. However, loneliness among those living with dementia (PLWD) is yet to be further explored.

Method: Secondary analysis of the English Longitudinal Study of Ageing.

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: Familial frontotemporal dementia is an autosomal dominant heritable form of frontotemporal dementia, a form of dementia characterised by changes in personality, behaviour and communication which typically onsets in mid-life. Children of an affected parent are at 50% risk of inheriting the responsible genetic mutation and developing frontotemporal dementia themselves. Individuals living at-risk have high psychological morbidity, for example they report struggling with guilt and anxiety about risk to themselves and their children, decisions about whether to get tested, uncertainty about onset of symptoms, and see their risk as a barrier in life.

Dementia Care Research and Psychosocial Factors.

Background: Family carers of people living with dementia provide care over many months or years with little to no formal support. Carers' experiences of compassion for themselves and others including receiving compassion can influence their caregiving experience and the quality of care they provide. However, little is known about healthcare professionals (HCPs) understanding of how compassion is experienced by family carers and how best HCPs can support family carers to cultivate and maintain compassion for themselves and others.

Dementia Care Research and Psychosocial Factors.

Background: People with dementia have complex palliative care needs including psycho-social, physical and spiritual; however, they are often unmet. It is important to empower people with dementia, family caregivers and professionals to work together to better assess and monitor ongoing needs. This study aimed to co-design and test the feasibility of an integrated model of palliative dementia care to support holistic assessment and decision making for care in the community and care homes (assisted living facilities).

Dementia Care Research and Psychosocial Factors.

Background: The risk of developing loneliness in informal carers of people with dementia is high. Individual and cultural factors might play a differentiated role in the explanation of loneliness. The aim of this study was to describe loneliness levels in a group of family carers in Chile and its associated factors.