Changes in iPSC-Astrocyte morphology reflect Alzheimer's disease patient clinical markers.

Human induced pluripotent stem cells (iPSCs) provide powerful cellular models of Alzheimer's disease (AD) and offer many advantages over non-human models, including the potential to reflect variation in individual-specific pathophysiology and clinical symptoms. Previous studies have demonstrated that iPSC-neurons from individuals with Alzheimer's disease (AD) reflect clinical markers, including β-amyloid (Aβ) levels and synaptic vulnerability. However, despite neuronal loss being a key hallmark of AD pathology, many risk genes are predominantly expressed in glia, highlighting them as potential therapeutic targets.

Patterns of tau, amyloid and synuclein pathology in ageing, Alzheimer's disease and synucleinopathies.

Alzheimer's disease (AD) is neuropathologically defined by deposits of misfolded hyperphosphorylated tau (HP-tau) and β-amyloid. Lewy body (LB) dementia, which includes dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is characterised pathologically by α-synuclein aggregates. HP-tau and β-amyloid can also occur as copathologies in LB dementia, and a diagnosis mixedAD/DLB can be made if present in sufficient quantities.

Cost-utility analysis of adapted problem adaptation therapy for depression in mild-to-moderate dementia caused by Alzheimer's disease: PATHFINDER randomised controlled trial.

Background: Depression is common in people with dementia, and negatively affects quality of life.

Aims: This paper aims to evaluate the cost-effectiveness of an intervention for depression in mild and moderate dementia caused by Alzheimer's disease over 12 months (PATHFINDER trial), from both the health and social care and societal perspectives.

Method: A total of 336 participants were randomised to receive the adapted PATH intervention in addition to treatment as usual (TAU) ( = 168) or TAU alone ( = 168).

EEG Functional Connectivity Differences Predict Future Conversion to Dementia in Mild Cognitive Impairment With Lewy Body or Alzheimer Disease.

Background: Predicting which individuals may convert to dementia from mild cognitive impairment (MCI) remains difficult in clinical practice. Electroencephalography (EEG) is a widely available investigation but there is limited research exploring EEG connectivity differences in patients with MCI who convert to dementia.

Methods: Participants with a diagnosis of MCI due to Alzheimer's disease (MCI-AD) or Lewy body disease (MCI-LB) underwent resting state EEG recording.

An alternative method of SNP inclusion to develop a generalized polygenic risk score analysis across Alzheimer's disease cohorts.

Introduction: Polygenic risk scores (PRSs) have great clinical potential for detecting late-onset diseases such as Alzheimer's disease (AD), allowing the identification of those most at risk years before the symptoms present. Although many studies use various and complicated machine learning algorithms to determine the best discriminatory values for PRSs, few studies look at the commonality of the Single Nucleotide Polymorphisms (SNPs) utilized in these models.

Methods: This investigation focussed on identifying SNPs that tag blocks of linkage disequilibrium across the genome, allowing for a generalized PRS model across cohorts and genotyping panels.

Outcomes of Patients With Mild Cognitive Impairment With Lewy Bodies or Alzheimer Disease at 3 and 5 Years After Diagnosis.

Background And Objectives: Retrospective studies indicate that dementia with Lewy bodies (DLB) may be preceded by a mild cognitive impairment (MCI) prodrome. Research criteria for the prospective identification of MCI with Lewy bodies (MCI-LB) have been developed. We aimed to assess the prognosis of a prospectively identified MCI-LB cohort at 2 key milestones, 3- and 5 years after diagnosis, to examine classification stability over time and rates of adverse outcomes (dementia or death).

Associations between multimorbidity and neuropathology in dementia: consideration of functional cognitive disorders, psychiatric illness and dementia mimics.

Background: Multimorbidity, the presence of two or more health conditions, has been identified as a possible risk factor for clinical dementia. It is unclear whether this is due to worsening brain health and underlying neuropathology, or other factors. In some cases, conditions may reflect the same disease process as dementia (e.

Dementias Platform UK: Bringing genetics into life.

Introduction: The Dementias Platform UK (DPUK) Data Portal is a data repository bringing together a wide range of cohorts. Neurodegenerative dementias are a group of diseases with highly heterogeneous pathology and an overlapping genetic component that is poorly understood. The DPUK collection of independent cohorts can facilitate research in neurodegeneration by combining their genetic and phenotypic data.

Adapted problem adaptation therapy for depression in mild to moderate Alzheimer's disease dementia: A randomized controlled trial.

Introduction: Trials of effectiveness of treatment options for depression in dementia are an important priority.

Methods: Randomized controlled trial to assess adapted Problem Adaptation Therapy (PATH) for depression in mild/moderate dementia caused by Alzheimer's disease.

Results: Three hundred thirty-six participants with mild or moderate dementia, >7 on Cornell Scale for Depression in Dementia (CSDD), randomized to adapted PATH or treatment as usual.

Prevalence, distribution, and severity of cerebral amyloid angiopathy differ between Lewy body diseases and Alzheimer's disease.

Dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), and Parkinson's disease (PD) collectively known as Lewy body diseases (LBDs) are neuropathologically characterised by α-synuclein deposits (Lewy bodies and Lewy neurites). However, LBDs also exhibit pathology associated with Alzheimer's disease (AD) (i.e.

Regional AT-8 reactive tau species correlate with intracellular Aβ levels in cases of low AD neuropathologic change.

The amyloid cascade hypothesis states that Aβ aggregates induce pathological changes in tau, leading to neurofibrillary tangles (NFTs) and cell death. A caveat with this hypothesis is the spatio-temporal divide between plaques and NFTs. This has been addressed by the inclusion of soluble Aβ and tau species in the revised amyloid cascade hypothesis.

Long-term impact of the COVID-19 pandemic on the quality of life of people with dementia and their family carers.

Introduction: Few studies have longitudinally mapped quality of life (QoL) trajectories of newly diagnosed people with dementia and their carers, particularly during coronavirus disease-2019 (COVID-19).

Methods: In a UK cohort study, 261 newly diagnosed people with dementia and 206 family carers were assessed prior to the pandemic (July 2019-March 2020), followed up after the first lockdown (July-October 2020) and then again a year and 2 years later. Latent growth curve modelling examined the level and change of QoL over the four time-points using dementia-specific QoL measures (DEMQOL and C-DEMQOL).

Plasma metabolites distinguish dementia with Lewy bodies from Alzheimer's disease: a cross-sectional metabolomic analysis.

Background: In multifactorial diseases, alterations in the concentration of metabolites can identify novel pathological mechanisms at the intersection between genetic and environmental influences. This study aimed to profile the plasma metabolome of patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), two neurodegenerative disorders for which our understanding of the pathophysiology is incomplete. In the clinical setting, DLB is often mistaken for AD, highlighting a need for accurate diagnostic biomarkers.

Sustained attention in mild cognitive impairment with Lewy bodies and Alzheimer's disease.

Objective: Attentional impairments are common in dementia with Lewy bodies and its prodromal stage of mild cognitive impairment (MCI) with Lewy bodies (MCI-LB). People with MCI may be capable of compensating for subtle attentional deficits in most circumstances, and so these may present as occasional lapses of attention. We aimed to assess the utility of a continuous performance task (CPT), which requires sustained attention for several minutes, for measuring attentional performance in MCI-LB in comparison to Alzheimer's disease (MCI-AD), and any performance deficits which emerged with sustained effort.

A pragmatic, multicentre, double-blind, placebo-controlled randomised trial to assess the safety, clinical and cost-effectiveness of mirtazapine and carbamazepine in people with Alzheimer's disease and agitated behaviours: the HTA-SYMBAD trial.

Background: Agitation is common and impacts negatively on people with dementia and carers. Non-drug patient-centred care is first-line treatment, but we need other treatment when this fails. Current evidence is sparse on safer and effective alternatives to antipsychotics.

Functional connectivity in Lewy body disease with visual hallucinations.

Background And Purpose: Visual hallucinations are a common, potentially distressing experience of people with Lewy body disease (LBD). The underlying brain changes giving rise to visual hallucinations are not fully understood, although previous models have posited that alterations in the connectivity between brain regions involved in attention and visual processing are critical.

Methods: Data from 41 people with LBD and visual hallucinations, 48 with LBD without visual hallucinations and 60 similarly aged healthy comparator participants were used.

Age-related hearing loss and dementia-related neuropathology: An analysis of the United Kingdom brains for dementia research cohort.

Age-related hearing loss frequently precedes or coexists with mild cognitive impairment and dementia. The role specific neuropathologies play in this association, as either a cause or a consequence, is unclear. We therefore aimed to investigate whether specific dementia related neuropathologies were associated with hearing impairment in later life.

Plasma biomarkers of neurodegeneration in mild cognitive impairment with Lewy bodies.

Background: Blood biomarkers of Alzheimer's disease (AD) may allow for the early detection of AD pathology in mild cognitive impairment (MCI) due to AD (MCI-AD) and as a co-pathology in MCI with Lewy bodies (MCI-LB). However not all cases of MCI-LB will feature AD pathology. Disease-general biomarkers of neurodegeneration, such as glial fibrillary acidic protein (GFAP) or neurofilament light (NfL), may therefore provide a useful supplement to AD biomarkers.

Associations Between Local Area Deprivation and Physical Activity Participation in People with Cognitive Impairment in the North East of England.

Background: Promoting physical activity, such as habitual walking behaviors, in people with cognitive impairment may support their ability to remain independent with a good quality of life for longer. However, people with cognitive impairment participate in less physical activity compared to cognitively unimpaired older adults. The local area in which people live may significantly impact abilities to participate in physical activity.