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: Dysregulated GABA/somatostatin (SST) signaling has been implicated in psychiatric and neurodegenerative disorders. The inhibition of excitatory neurons by SST+ interneurons, particularly through α5-containing GABAA receptors (α5-GABAAR), plays a crucial role in mitigating cognitive functions. Previous research demonstrated that an α5-positive allosteric modulator (α5-PAM) mitigates working memory deficits and reverses neuronal atrophy in aged mice.

Drug Development.

Background: Microbiota of the distal part of the intestine produces Urolithin A (Uro A) as a derivative of ellagitannins hydrolysis. Recently, the mitophagy, anti-inflammatory, and antioxidant properties of Uro A have focused more attention on its probable beneficial effects on neurodegenerative states. The purpose of this research was to study the impact of Uro A on the histopathology of the cerebellum in a rat model of streptozotocin-induced Alzheimer's disease.

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.

The Alzheimer's Disease Neuroimaging Initiative (ADNI) has made many important contributions to the development of Alzheimer's Disease (AD) disease modifying treatments and diagnostic biomarkers. Since its funding in 2004 by the National Institutes of Aging, the goal of ADNI has been the validation of biomarkers for AD treatment trials. ADNI has enrolled over 2,400 participants in the USA and Canada for longitudinal clinical, cognitive, and biomarker studies.

Drug Development.

Background: A large body of evidence now indicates that the most pathogenic species of Aß in Alzheimer's disease (AD) consist of soluble toxic oligomers (AßO) as opposed to insoluble fibrils and monomers. Using our computational platform, we identified 4 different AßO-restricted conformational B cell epitopes (300, 301, 303, 305) that were tested as vaccines for their ability to induce an antibody response that selectively targets toxic AßO, without inducing potentially detrimental B or T cell responses against plaque or normal Aß. A novel ex vivo approach was then used to select an optimal vaccine configuration amongst the 15 possible combinations of the 4 epitopes to provide maximal binding to a toxic oligomer-enriched low molecular weight (LMW) fraction of soluble AD brain extracts.

Drug Development.

Background: Agitation is a common and disabling symptom of Alzheimer's dementia (AD). Pharmacological treatments are recommended if agitation is not responsive to psychosocial intervention. Citalopram was effective in treating agitation in AD but was associated with cognitive and cardiac risks linked to its R- but not S-enantiomer.

Drug Development.

Background: Randomized placebo-controlled trials (RCTs) are the gold standard to evaluate efficacy of new drug treatments for Alzheimer's disease. For example, the United States FDA approved the brain amyloid-targeting drug lecanemab following CLARITY AD, Biogen and Eisai's Phase 3 RCT. However, recruiting enough participants for a high-powered and demographically representative trial is difficult and expensive.

Drug Development.

Background: Alzheimer's disease (AD) is a neurodegenerative disorder primarily associated with aging, but manifests as a complex interplay of multiple factors. Decline in sex-hormones, particularly 17-beta estradiol, is linked to the aging process. The risk for onset of AD significantly increases with aging and loss of estradiol.

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.

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: 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.

Quadrupole-Central-Transition Na, K, Rb NMR Studies of Alkali Metal Ions under Different Molecular Tumbling Conditions: A Simple Model to Treat Chemical Exchange Involving Quadrupolar Nuclei.

We report a new NMR method for treating two-site chemical exchange involving half-integer quadrupolar nuclei in a solution. The new method was experimentally verified with extensive Na ( = 3/2), K ( = 3/2), and Rb ( = 3/2) NMR results from alkali metal ions (Na, K, and Rb) in a solution over a wide range of molecular tumbling conditions. In the fast-motion limit, all allowed single-quantum NMR transitions for a particular quadrupolar nucleus are degenerate giving rise to one Lorentzian signal.

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 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: In the last decade, virtual reality has become a popular tool for rehabilitation. It is quite useful in spatial rehabilitation for Alzheimer's disease (AD) as it allows safe navigation in a virtual environment which looks realistic. However, a drawback of virtual reality is cybersickness.

Dementia Care Research and Psychosocial Factors.

Background: Limited knowledge exists about the cultural approaches to managing the psychological and behavioral outcomes (PBO) of Alzheimer's Disease and Alzheimer's Disease-Related Dementia (AD/ADRD) in Africa. Specifically, to develop a culture-sensitive training framework for AD/ADRD caregivers, we explored AD/ADRD caregivers' cultural embeddedness in managing people living with AD/ADRD (PLWAD/ADRD) in Ibadan, Nigeria.

Method: Using hermeneutic phenomenological qualitative research design, we interviewed 23 caregivers providing care to PLWAD/ADRD in Ibadan, a Yoruba-speaking ethnic group of Nigeria.

Dementia Care Research and Psychosocial Factors.

Background: Medical records present a rich potential source of information on the lived experiences of people with dementia. These records are extensive and the work of extracting relevant data is labor-intensive. We sought to determine whether we could use natural language processing (NLP) approaches to sift through medical records to prioritize an enriched subset of notes illuminating the lived experiences of people with dementia.

Dementia Care Research and Psychosocial Factors.

Background: Primary progressive aphasia (PPA) is a dementia syndrome characterized by language and communication impairments, with relative sparing of other cognitive domains. As a relatively rare dementia syndrome, there are few measures developed and validated for individuals with PPA. Development of outcome measures tailored to the communication experiences of persons with PPA (PwPPA) is critical for the accurate assessment of interventions success.

Dementia Care Research and Psychosocial Factors.

Background: Co-creation methods are increasingly being used in the research and development of technologies that support older adults living with dementia and their care partners to live well. Use of collaborative methods to engage with the dementia community helps to ensure that research processes and end solutions are sensitively designed, reflective of needs and values, and responsive to priorities. Engagement also has proximal benefits for older adults: Being involved in purposeful activity has been shown to positively impact health and wellbeing outcomes.

Dementia Care Research and Psychosocial Factors.

Background: Cerebral amyloid angiopathy (CAA) is a significant contributor to hemorrhagic stroke, notably lobar intracerebral hemorrhage (ICH) and convexity subarachnoid hemorrhage (SAH), both of which have been observed in patients with MCI/AD. To evaluate all-cause mortality among veterans with mild cognitive impairment (MCI) and Alzheimer's dementia (AD) with/without Intracerebral hemorrhage and subarachnoid hemorrhage (ICH/SAH) in the United States (US) Veterans Affairs Healthcare System (VAHS).

Method: Veterans with MCI or AD were identified based on having clinical notes or diagnostic codes in the VAHS database (2010-2019).

Dementia Care Research and Psychosocial Factors.

Background: Integrating technology in the cognitive assessment process could help with dementia care and management (Astell et al., 2019). The aim of this research was to assess the sensitivity and specificity, as well as establish regression-based norms, for the digital version of the Neurocognitive Frailty Index (NFI, Pakzad et al.