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Understanding and guiding technology use in dementia : a pan-European mapping and consensus studyIntroduction: Dementia is a leading cause of disability worldwide, and its prevalence is expected to rise significantly by the year 2050. Assistive technologies (AT) have emerged as promising tools to promote independence and quality of life. The COVID-19 pandemic prompted an increased uptake of AT among people with dementia, exposing important limitations in digital literacy, accessibility, and support.MethodsThis pan-European study mapped recent research initiatives involving digital technology use by people with dementia during the pandemic and synthesised a set of recommendations for supporting the use of AT by people with dementia, and its development, using the Delphi method.ResultsThe mapping exercise identified 28 relevant projects, highlighting the types of technologies used during the pandemic and the settings in which they were implemented. Video-conferencing platforms were the most reported projects. More than half of the projects and initiatives (n = 17) were adapted to include digital technologies due to the pandemic. The subsequent Delphi consensus study incorporated input from experts by experience and produced 18 evidence-based recommendations, adapted from this mapping exercise and a previous scoping review.DiscussionKey findings emphasise involving people with dementia in technology design, ensuring equitable access, and providing adequate training and support. The recommendations offer a practical, consensus-based framework to improve the efficacy of AT adoption, with implications extending beyond pandemic contexts to improve dementia care globally.
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Mind the Gap : a systematic review of barriers, facilitators, and experiences of care transitions for people living with dementia and their informal caregiversBACKGROUND AND OBJECTIVES: Care transitions for people living with dementia are critical periods requiring coordinated, person-centered support. Effective transitions can reduce caregiver burden, prevent adverse outcomes, and improve care quality. However, the barriers, facilitators, and lived experiences during transitions remain poorly understood. This systematic review synthesizes evidence on these factors from the perspectives of people with dementia and their informal caregivers. RESEARCH DESIGN AND METHODS: A comprehensive search across MEDLINE, CINAHL, PsycINFO, ProQuest, and Web of Science identified 67 eligible English-language studies published from 2018 to 2023. Quality appraisal used Joanna Briggs Institute tools. The protocol was registered on PROSPERO: CRD42023452669. RESULTS: Four themes captured the barriers, facilitators, and experiences shaping care transitions for people with dementia and their caregivers. Systemic influences included fragmented governance, funding and policy inconsistencies, and structural challenges in care coordination and delivery, mitigated by proactive planning and integrated care. Health and social care workforce factors highlighted gaps in dementia training, staffing, and communication, with empathetic, informed staff improving transitions. Emotions and decision-making reflected caregiver burden, uncertainty, and advocacy, eased by early guidance and peer support. Cultural, social and situational influences showed how values, socioeconomic status, and rurality affected transition choices, underscoring the need for culturally sensitive, person-centered support. DISCUSSION AND IMPLICATIONS: Care transitions remain complex, shaped by systemic, workforce, emotional, and cultural factors. Addressing inequities and coordination gaps is critical for more integrated transitional care. Strengthening dementia-specific training, home-based care models, and culturally responsive communication may improve continuity, person-centeredness, and caregiver support.
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Mri changes following treatment of Glp-1 analogue, liraglutide in Alzheimer's diseaseBackground: Preclinical evidence in transgenic models of Alzheimer's disease (AD) suggests that liraglutide, a GLP1 analogue, exerts neuroprotective effects by reducing amyloid oligomers, normalising synaptic plasticity and reducing insulin resistance, and increasing the proliferation of neuronal progenitor cells. ELAD is a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase IIb trial of liraglutide in participants with mild to moderate AD conducted at 24 centres in the UK. Method(s): As a part of this study, a total of 204 Alzheimer's participants were randomised to receive either liraglutide or placebo as a daily subcutaneous injection for 12 months. All subjects underwent volumetric MRI scans at baseline and during follow up. Volumetric changes from baseline to follow up in MRI scans were evaluated using both regional volume analysis and voxel based morphometric analysis Result: MRI analysis demonstrated that temporal lobe volume, total grey matter volume and frontoparietal volume change was lower in liraglutide treated patients compared to the placebo group. Voxel based morphometry (VBM) analysis demonstrated that liraglutide-treated participants showed a slower reduction in whole cortical grey matter, frontal, temporal and parietal lobe volume in participants treated with liraglutide compared to placebo. Conclusion(s): In the ELAD study, participants with mild to moderate AD who received liraglutide had slower reduction in MRI volume and cognition compared to the placebo demonstrating a potential benefit of liraglutide in the treatment of Alzheimer's disease. These findings highlight the potential of GLP-1 analogues in the treatment of Alzheimer's disease.
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Evaluation of liraglutide in the treatment of Alzheimer's diseaseBackground Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue licensed for the treatment of type 2 diabetes. 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. Methods ELAD is a 12-month, 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 – (NCT01843075). [18F]FDG-PET and MRI brain scans of all patients will be performed at baseline and after 12 months treatment with liraglutide or matching placebo. Once enrolled, all subjects had a neuropsychological battery of tests All scans and tests will be repeated after 12 months. A total of 204 participants were randomised to receive either liraglutide or placebo as a daily subcutaneous injection for 12 months. The primary objective was to evaluate the change in cerebral glucose metabolic rate in the cortical regions (hippocampus, medial temporal lobe, and posterior cingulate) from baseline to 12-month follow-up in participants with Alzheimer’s disease receiving treatment with liraglutide compared to those receiving placebo. The key secondary outcomes were the change from baseline to 12 months in z scores for clinical and cognitive measures (Alzheimer’s Disease Assessment Scale – Cognitive Subscale and Executive domain scores of the Neuropsychological Test Battery, Clinical Dementia Rating Sum of Boxes, and Alzheimer’s Disease Cooperative Study – Activities of Daily Living) and the incidence and severity of treatment-emergent adverse events or clinically important changes in safety assessments. Other secondary outcomes were 12-month change in magnetic resonance imaging volume, diffusion tensor imaging parameters, and changes in composite scores using support machine vector analysis in the treatment group compared with the placebo group. Results The study demonstrated that liraglutide treated patients performed significantly better than placebo arm in temporal lobe and whole cortical MRI volume and cognitive function measured by ADAS-EXEC (ADAS-Cog with Executive domains of the Neuropsychological Test Battery). Conclusion This demonstrates that GLP1 analogues can improve cognitive function and MRI volume in AD subjects and could be a potential treatment for treatment for Alzheimer's
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Early onset dementia : clinical utility of cerebrospinal fluid amyloidbeta and tau measures in diagnosing mild cognitive impairmentBackground: The differentiation of a preclinical or prodromal Alzheimer's disease (AD) is challenging particularly in patients with Early Onset Alzheimer's or Related Dementias (EOARD). The first clinical symptoms of AD during the prodromal phase are mild cognitive impairment (MCI), with some younger adults presenting with depression or anxiety. We report a local practice on utilising diagnostic lumbar puncture to investigate the cause of MCI for the diagnosis of EOARD at a tertiary neurocognitive referral centre. Method(s): The study was approved by the Ethic Committee (Ref:18/EM/0292). 30 participants aged 32-68 years old at the onset of symptoms (mean 62 years; 61% female) from the Nottingham EOARD clinics (UK) were included. Clinical diagnosis was based on clinical presentation, neurocognitive profile, radiological features (MRI, FDG-PET CT) and CSF amyloidbeta1-42/1-40 (Abeta), total tau and Thr181-phosphorylated tau measurements. Patients were classified into three groups according to the clinical diagnosis: a)MCI secondary to Alzheimer's disease as defined by NIA-AA Research Framework [n=16]. b)Subjective Cognitive impairment, stable impairment in cognitive battery with no evidence of neurodegeneration on neuroimaging or abnormal levels of Amyloidb/tau in the CSF [n=9]. c)Other neurodegenerative conditions [n=5] (Table). Result(s): In patients with MCI, the CSF total tau and Thr181-phosphorylated tau levels showed a non-linear relationship with age, with an inverse U-shaped curve reaching the highest level at the age of 55 years, followed by a significant decline in the following decade (Figure). In contrast, the CSF Abeta level decreased in the MCI group, independently of age, and was associated with the neuropsychological measures of memory impairment (p=0.037). In contrast, total and phosphorylated CSF tau levels did not correlate with the cognitive performance measures. Similarly, the principal component analysis confirmed that the clinical diagnosis of Alzheimer's MCI (as per the NIA-AA criteria) correlated with the CSF Abeta loss. Conclusion(s): In Early Onset Alzheimer's disease, the low levels of CSF Abeta appear to be more sensitive than the total and 181Thr-phosphorylated tau measures in differentiating Alzheimer's MCI from other forms of dementia. Further work on larger samples of EOARD in clinical practice will address the cost effectiveness due to making an earlier diagnosis.
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Dysfunctional cerebral glucose transport in Alzheimer’s diseaseBackground: Glucose is the primary energy source required for the homeostatic function of the brain. Glucose transporter 1 (GLUT1) present at the blood-brain barrier is a key regulator of glucose transport into the brain. Reduced GLUT1 expression is shown to exacerbate Alzheimer's pathology in rodent models. Here we aimed to establish whether there are regional differences in ineffective glucose transport amongst people living with Alzheimer's disease. Method(s): 125 participants diagnosed with Alzheimer's dementia, with an [18F]FDG scan with atrial input were enrolled. All participants underwent 3-tesla magnetic resonance imaging and [18F]FDG scan with continuous and discrete arterial sampling. Spectral analysis was performed to create 1-minute input-response function parametric maps. To produce glucose transfer maps we applied the following equation; K1 * Ca / tau (K1 = 1-minute IRF map, Ca = Plasma glucose concentration, tau = 1.48 a lumped constant). Glucose transfer maps were then coregistered to the participants' structural MRI and normalised to MNI space. Regional mean glucose transfer was then calculated for the anterior cingulate cortex, frontal lobe, hippocampus, parahippocampus, occipital lobe, parietal lobe, posterior cingulate cortex, striatum, temporal lobe, and thalamus. A within-subject ANOVA was then performed to evaluate the regional differences in cerebral glucose transport. Result(s): The parahippocampus exhibited the lowest rate of glucose transfer in comparison to all other regions (p < 0.001), followed by the hippocampus. The striatum and occipital lobe demonstrated the regions of the highest mean glucose transportation from blood to the brain. In terms of brain lobes, the temporal lobe showed the lowest rates of glucose transfer, followed by the parietal lobe, then frontal and occipital (p < 0.001). Conclusion(s): We demonstrate dysfunctional BBB glucose transport in Alzheimer's disease, with prominent glucose transport abnormalities localised in the parahippocampus. Impaired glucose transport was most apparent within temporal lobe structures. Targeting glucose transfer may be an effective way of treating Alzheimer's disease.
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Differential expression of 5mC epigenomic regulators in Alzheimer's diseaseBackground Epigenetic processes are molecular mechanisms that contribute to the pathogenesis of neurodegenerative diseases. 5-methylcytosine (5mC) and the oxidised state, 5-formilcytosine (5fC), are known transcriptional regulators moderated by sets of writer, reader, and eraser effector proteins. We propose that gene expression variation in DNA effector proteins may contribute to Alzheimer’s Disease (AD) neuropathology. We also aimed to characterize the distribution of 5fC modifications across brain regions and within cellular compartments to better understand the role of 5mC/5fC modifications in AD. Methods RNA sequencing data for 17 effector proteins obtained from the Aging, Dementia and Traumatic Brain Injury Study was analysed to assess variation in abundance of 5mC writers, readers, and erasers. Gene expression data were compared across four brain regions in 51 AD and 56 healthy control samples, and between Braak and CERAD neuropathological scales. In addition, we examined the presence and distribution of 5fC by immunofluorescence (IF) across four brain regions in sections from healthy individuals. Results Transcripts of DNA methylation writers DNMT1, DNMT3A and DNMT3B were found increased in the AD cohort across 3 brain regions, whilst the reader UHRF1 mRNA was decreased in the same assessment. GADD45B and AICDA, DNA methylation erasers, showed changes in mRNA abundance across Braak and CERAD neuropathological load groupings. IF analysis indicated 5fC modification to be highly abundant in dentate gyrus and within the cytoplasm of hippocampal mossy cells and of neurons in cortical layer III. Within neuronal cells, we observed 5fC partially colocalizing with mitochondria especially within hippocampal neurons. Conclusion Our findings indicate that changes in 5mC/5hmC/5fC effector protein expression are associated with AD and its neuropathology. The characterisation of 5fC localisation in human brain indicates high abundance within the cytoplasm of hippocampal cells suggesting that 5fC may be involved in pre- and post-transcriptional control of memory processing pathways and, when disrupted, may lead to neurodegenerative disease. References: Sanchez-Mut JV, et al. Transl Psychiatry. 2016; Miller JA, et al. Elife. 2017; Bachman, M., et al. Nat Chem Biol. 2015; Zhang Y, Zhou C. DNA Repair (Amst). 2019; Aging, Dementia and TBI Study (2017) Available from Allen Brain Atlas
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Liraglutide in mild to moderate Alzheimer’s disease : a phase 2b clinical trialLiraglutide, a glucagon-like peptide 1 (GLP-1) agonist and antidiabetic drug, has shown neuroprotective effects in animal models. In this study, we aimed to evaluate the safety and efficacy of liraglutide in mild to moderate Alzheimer’s disease syndrome. ‘Evaluating liraglutide in Alzheimer’s disease’ (ELAD) is a multicenter, randomized, double-blind, placebo-controlled phase 2b trial in 204 participants with mild to moderate Alzheimer’s disease syndrome with no diabetes. Participants received daily injections of liraglutide or placebo for 52 weeks. They underwent fluorodeoxyglucose positron emission tomography, magnetic resonance imaging and detailed neuropsychometric evaluations. The primary outcome was a change in cerebral glucose metabolic rate. Secondary outcomes were safety and tolerability and cognitive changes. The primary outcome showed no significant differences in cerebral glucose metabolism (difference = −0.17; 95% confidence interval: −0.39 to 0.06; P = 0.14) between the two groups. The secondary outcome—score on the Alzheimer’s Disease Assessment Scale-Executive domain (ADAS-Exec)—performed better in liraglutide-treated patients compared to placebo (0.15; 95% confidence interval: 0.03−0.28; unadjusted P = 0.01). No significant differences were observed in Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) (−0.58; 95% confidence interval: −3.13 to 1.97; unadjusted P = 0.65) or Clinical Dementia Rating-Sum of Boxes (CDR-SoB) (−0.06; 95% confidence interval: −0.57 to 0.44; unadjusted P = 0.81) scores. Liraglutide was generally safe and well tolerated in non-diabetic patients with Alzheimer’s disease. ClinicalTrials.gov identifier: NCT01843075.
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Transcriptomic analysis of plasma small extracellular vesicles identifies potential diagnostic biomarkers for Parkinson's disease dementiaIntroductionBlood-based biomarkers that can aid diagnosis of Parkinson's Disease (PD) dementia (PDD), and predict PDD onset in people with PD are urgently needed. Plasma small extracellular vesicles (SEV) reflect molecular changes in living human brain. Next-generation RNA-sequencing (RNA-Seq) of PDD plasma SEV can advance our understanding of PDD molecular pathology, and identify blood-based biomarkers. Hence, we conducted the first comprehensive transcriptomic analysis of PDD plasma SEV.
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Clinical effectiveness of music interventions for dementia and depression in older people (MIDDEL) : a multinational, cluster-randomised controlled trialBackground: Dementia and depression are among the leading causes of global disease burden. Effective and scalable interventions are needed to address the effect of these conditions, and music interventions are a promising non-pharmacological approach. The aim of this study was to determine the effectiveness of music interventions on depressive symptoms among care home residents with dementia in Australia, Germany, the Netherlands, Norway, Türkiye, and the UK.
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Impact of music interventions on depression in care home residents with dementia : UK results from music interventions for depression and dementia in elderly care RCTBackground: We report UK findings from Music Interventions for Depression and Dementia in Elderly care (MIDDEL), a cross-national, clustered, randomised trial undertaken in 2018–2023 to evaluate the effectiveness of music interventions for depression symptoms in care home residents living with dementia (NCT03496675, clinicaltrials.gov (accessed on 1 December 2024)). The trial compared the effects of Group Music Therapy (GMT) with Recreational Choir Singing (RCS); GMT and RCS combined; and treatment as usual (TAU). Methods: In the intervention arms, the protocolized music interventions were delivered in care home units twice per week for three months, then once per week for three months. The primary outcome was depressive symptoms after six months, measured by MADRS. Secondary outcomes included well-being—EQ-5D-5L, Visual Analogue Scale (VAS); quality of life—QOL-AD; symptoms of dementia—SIB-8, NPI-Q; and caregiver distress—NPI-Q. The change in MADRS score from baseline to 6 months was assessed using a linear mixed-effects model. We report the multivariate model having both treatments as predictors, both unadjusted and adjusted, for the interaction between the treatments. Results: The UK trial started in 2022 after the pandemic lockdown, when 16 care home units were recruited and randomised, four per arm; 192 residents aged over 65 with depression and dementia participated. An ITT analysis of 146 participants retained at 6 months found neither intervention had a significant positive effect on any outcome. Significant unfavourable effects were found for RCS participants on MADRS, NPI symptom severity, and EQ-VAS. The combination of RCS + GMT had a detrimental effect on caregiver distress. Conclusions: MIDDEL UK findings do not support the use of GMT or RCS to alleviate depression in care home residents with dementia.
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Cellular and extracellular MicroRNA dysregulation in LRRK2-Linked Parkinson’s diseaseCell-free microRNAs in body fluids have emerged as promising biomarker candidates in neurodegenerative diseases. While several studies have identified dysregulated miRNAs in sporadic Parkinson’s disease, it remains unclear whether distinguishable alterations of cell-free miRNAs occur in genetic forms of the disease, such as those associated with the LRRK2 G2019S mutation. In this proof-of-concept study, we used a human induced pluripotent stem cell-derived dopaminergic neuron model to investigate whether the LRRK2 G2019S mutation induces detectable changes in the intra- and extracellular miRNAome, and whether miRNA signatures identified in vitro can be validated in patient-derived cerebrospinal fluid. We differentiated dopaminergic neurons from induced pluripotent stem cells carrying the LRRK2 G2019S mutation and an isogenic gene-corrected control. Extracellular vesicles were isolated from the culture medium and used as a source of cell-free miRNA. Next, small RNA libraries were generated and analyzed. Differentially expressed microRNAs were validated in an independent batch using RT-qPCR. We further quantified candidate microRNAs in cerebrospinal fluid samples from five LRRK2 G2019S patients and matching healthy controls. The patient cohort included the fibroblast donor from whom the stem cells were originally derived. We successfully isolated extracellular vesicles from induced pluripotent stem cell-derived human dopaminergic neurons. We identified a distinct set of differentially expressed miRNAs in cellular and cell-free RNA, among which let-7g-5p and miR-21-5p were consistently upregulated and validated across independent replicates. These alterations were reflected in the cerebrospinal fluid of the original donor and partially reproduced in additional LRRK2 patients, supporting the concept of patient-specific signatures. A strong correlation between intra- and extracellular miRNA expression was observed. Our findings demonstrate that induced pluripotent stem cell-derived dopaminergic neurons can serve as a model to identify individualized, cell-free microRNA signatures associated with the LRRK2 G2019S mutation. The dysregulated miRNAs detected in vitro were mirrored in patient cerebrospinal fluid, supporting their potential as accessible molecular readouts. These results lay the groundwork for personalized biomarker strategies in genetic forms of Parkinson’s disease and warrant further validation in larger patient cohorts.
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Magnetic resonance spectroscopy metabolites as biomarkers of Alzheimer’s DiseaseAbstract Background Magnetic resonance spectroscopy (MRS) is a non-invasive method of evaluating metabolite levels in the cerebral cortex. Measurable metabolites can provide markers of neuronal damage, glial activation and, neurotransmission, pathological features of Alzheimer’s disease. Here we sought to establish the effectiveness of several metabolites as biomarkers for Alzheimer’s disease. Method 198 participants with a single-voxel 1H MRS scan were enrolled (n = 170 participants living with Alzheimer’s disease, n = 28 healthy controls). All participants underwent 3-tesla magnetic resonance imaging and cognitive assessment with the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-cog). An experienced radiographer placed an 8cm3 voxel within the posterior cingulate cortex for single-voxel 1H MRS acquisition. Scans were then processed to evaluate levels of N-acetylaspartate, myo-inositol, choline, and glutamate. Creatine peak was additionally evaluated as a reference. N-acetylaspartate/creatine, myo-inositol /creatine, choline/creatine ratios and glutamate were compared between Alzheimer’s participants and controls to calculate the effect size. Correlations were then performed between metabolite ratios and ADAS-cog scores. Result N-acetylaspartate/creatine effectively distinguished between Alzheimer’s patients and healthy controls (Cohens D = 0.83) with a lowered ratio in Alzheimer’s participants. Elevated glutamate signal and myo-inositol/creatine ratios were also displayed in Alzheimer’s patients (Cohens D = 0.62 and 0.69, respectively). Choline/creatine ratio displayed no significant difference between groups (Cohens D = 0.26). Lower N-acetylaspartate /creatine and glutamate correlated with higher ADAS-cog scores (r = -0.29, p < 0.001, CIs: -0.42 to -0.14 and r = -0.30, p < 0.001, CIs: -0.44 to -0.16, respectively). Myo-inositol and choline failed to correlate with cognitive impairment. Conclusion N-acetylaspartate, a signature of neuronal damage, is an effective biomarker of Alzheimer’s disease and associated cognitive decline. Enhanced glial activity, measured with myo-inositol, was shown in Alzheimer’s disease, suggesting that glial-reactivity markers deserve consideration in the diagnosis of Alzheimer’s disease. Glutamate demonstrated the strongest association with cognitive impairment, despite showing a smaller effect size than N-acetylaspartate and myo-inositol in distinguishing between Alzheimer’s patients and controls. Together we establish MRS is a useful, non-invasive biomarker of several pathological processes involved in the development of Alzheimer’s. Evaluation of N-acetylaspartate, glutamate, and myo-inositol may aid in the diagnosis of neurodegenerative disease, detecting markers undetectable by conventional MRI methodology.
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Do glial-reactivity and cerebral blood flow modulate cerebral glucose metabolism in Alzheimer’s disease?Background Alzheimer’s disease is a devastating neurodegenerative disorder with a complex pathogenesis. One main pathological feature utilised in diagnosis is neurodegeneration or neuronal injury, which is reflected in reductions in cerebral glucose metabolism measured by [18F]Fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET). Here we evaluated the involvement of glial reactivity measured with magnetic resonance spectroscopy (MRS) and cerebral blood flow measured with arterial spin labelling (ASL) on [18F]FDG PET as a measure of cerebral glucose metabolism. Method 123 people living with early Alzheimer’s disease who completed baseline evaluations on the evaluating liraglutide in Alzheimer’s disease trial were enrolled. Participants completed [18F]FDG PET scans with arterial input, T1 weighted MRI, single-voxel 1HMRS, and pulsed ASL scans at Imperial College London Clinical Imaging Facility. The Totally Automatic Robust Quantitation in NMR (TARQUIN) package was used to process MRS scans and identify the concentration of myo-inositol within the posterior cingulate cortex (PCC), a marker of glial activation. Oxford-ASL was utilised to process ASL and quantify cerebral blood flow in the PCC. Finally, spectral analysis was performed on the [18F]FDG PET scans to assess the cerebral metabolic rate of glucose in the PCC. Result Pearson’s correlations were performed between the cerebral metabolic rate of glucose, cerebral blood flow and glial activity measured by the level of myo-inositol in the PCC. Increased cerebral glucose metabolism was correlated with higher myo-inositol in this sample of Alzheimer’s disease participants. In contrast, cerebral blood flow was not associated with cerebral glucose metabolism. Conclusion Here we demonstrate that increased glial reactivity contributes to [18F]FDG PET signal in the early stages of Alzheimer’s disease. In response to early neuronal injury, astrocytes and microglia may become activated and enhance regional rates of glucose consumption. Hence, the contribution from these cells in addition to neurons should be considered in interpreting [18F]FDG PET as a measure of cerebral glucose metabolism. Interestingly, cerebral blood flow did not influence glucose metabolism. Microglia and astrocyte reactivity may contribute to an increase the cerebral glucose metabolism while neuronal loss and synaptic function may contribute to lower glucose metabolism measured by [18F]FDG in the early stages of Alzheimer's disease.
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Temporal dynamics in the association between depression and dementia : an umbrella review and meta-analysisBACKGROUND: Identifying modifiable risk factors is crucial for dementia prevention, a global health concern. Depression is considered a risk factor for dementia, but the temporal dynamics across the life course remain inconclusive. Therefore, we aimed to systematically assess the relationship between the timing of depression assessment and risk of all-cause late-life dementia. METHODS: We conducted an umbrella review and meta-analysis to assess incident dementia in individuals with non-current history of depression. PubMed and Ovid Embase, MEDLINE, and PsycInfo were searched from inception up to February 17, 2025. Systematic reviews with meta-analyses investigating the association between depression and incident late-life dementia were included. From eligible reviews, we also extracted data from studies reporting dementia risk as hazard ratios (HRs), analysing the timing of depression measurement using random-effects models for meta-analysis. This study is registered with PROSPERO, CRD42021249706. FINDINGS: Of the 7763 records identified, nine reviews were eligible for inclusion of the umbrella review. One review was judged to be of moderate quality, while the others were either low (n = 3) or critically low (n = 5). For our meta-analyses, 18 studies reporting depression onset in later life (n = 901,762 participants, n = 7595 incident dementia cases) and seven studies on depression assessed during midlife (n ≥ 2,501,269 participants, n ≥ 276,929 incident dementia cases) were included. All studies in the meta-analyses were deemed to be of good quality, with no strong evidence of publication bias. Pooled HRs indicated depression present in late-life (HR 1.95, 95% CI: 1.68-2.26; I (2) = 77.5%) and midlife (HR 1.56, 95% CI: 1.12-2.18; I (2) = 97.5%) significantly increased risk of all-cause dementia. INTERPRETATION: The findings suggest that depression across the life course may increase dementia risk; however, substantial heterogeneity and review quality should be considered when interpreting the strength of this evidence. A life course approach to the treatment and prevention of depression may help reduce the burden of dementia, but this will require scaling up access to effective mental health care for vulnerable populations. Further research is needed to clarify if the stronger late-life association reflects depression as an immediate risk factor or an early manifestation of neurodegenerative processes. FUNDING: National Institute for Health and Care Research, UK Research and Innovation, and Saudi Arabian Cultural Mission.
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Implementation of dementia communication skills training in acute hospitals : a longitudinal, mixed-methods case study evaluationPurpose People with dementia occupy c.25% of acute hospital beds. Being in hospital can lead to distress in people with dementia, exacerbated by the difficult acute hospital environment and lack of staff preparedness to meet their often-complex needs. Acute hospital staff identify supporting distressed patients with dementia as a practice challenge. Communication skills training can improve interaction quality and staff confidence, however little communication research to date has been conducted in acute hospitals. This study aimed to implement a communication skills training programme for preventing and responding to distress in patients with dementia in acute hospitals, and to assess its impact. Methods A longitudinal, mixed-methods, multiple case study design was employed in six wards across three English acute hospitals. The Kirkpatrick training evaluation framework (reaction to training, impact on knowledge and confidence, behaviours and outcomes for patients and staff) underpinned the study, with qualitative observational and interview, and quantitative survey and outcomes data collected immediately pre, post and 1-3 months post training. The [redacted] communication skills training programme included three communication trainables identified in an earlier conversation analysis study phase. It was delivered over two half-days, by local clinical educators, upskilled via a train-the-trainer programme. Findings A total of 145 staff attended at least one half-day of training. Delivery was feasible, however practical challenges with training organisation and freeing up staff to attend occurred. Staff who found it engaging and relevant to their role, valued its interactive content and the opportunity for reflection and implementation of skills between sessions. A statistically significant increase was found pre- to immediate post-training on staff communication knowledge (CI 0.01-1.2) and confidence in caring for people with dementia (CI 4.9-7.3). Staff reported a range of areas of learning aligned to the trainables. Over 90% of staff said they planned to implement the training in practice and many provided concrete examples of application. Challenges in applying the specific communication principals taught to wider practice situations were identified by some staff. Impact on observed patient agitation levels and staff communication practices were challenging to evidence objectively in the context of the acute hospital environment. Conclusion/original contribution It is feasible, although challenging, to deliver empirically based communication skills training to support acute hospital staff to better care for patients with dementia who may become distressed. It can lead to perceived increases in knowledge and confidence to support distress in this population. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Cognitive and neuroimaging for neurodegenerative disorders : a cohort study design with initial findings [In Press]Introduction: Dementia presents with significant heterogeneity across age groups, particularly in early-onset cognitive decline (EOCD), which poses diagnostic and management challenges. The Cognitive and Neuroimaging for Neurodegenerative Disorders (CogNID) study aims to characterise clinical, cognitive, neuroimaging, and biomarker features across a diverse cohort of individuals with cognitive impairment, with a focus on diagnostic complexity, biomarker utility, and mortality. Methods: Out of 680 study participants within this prospective cohort enrolled from the real-world clinics within the National Health Service, who consented to take part in the study, we analysed data from 429 individuals recruited between December 2018 and November 2024 from the Memory Clinics, including the young-onset dementia service and associated services. Participants underwent structured cognitive assessments, neuroimaging (MRI/CT), and Cerebrospinal fluid (CSF) biomarker evaluation, where available. Diagnoses were made by multidisciplinary consensus. Group comparisons were conducted between early-onset (EOCD, <65 years) and late-onset cognitive decline (LOCD, ≥65 years). Results: Of the 429 participants, 349 (81.4%) had EOCD and 80 (18.6%) had LOCD. The mean age was 60.05 years, with no significant difference in sex or ethnicity across groups. Depression and anxiety were common (29.6%), as were cardiovascular risk factors. Lumbar punctures were more frequently performed in EOCD (p = 0.03), with 36.4% of tested participants demonstrating biomarker profiles consistent with Alzheimer’s disease (A+T+). Functional cognitive disorder (FCD) was more common in EOCD (22.3% vs. 5.0%, p < 0.001). Subgroup analysis revealed significantly lower ACE-III scores and higher pathological CSF findings in Alzheimer’s disease versus FCD. Mortality was higher in the LOCD group (11.3% vs. 4.6%, p = 0.03). Conclusion: The CogNID study highlights the clinical and diagnostic heterogeneity of individuals with cognitive impairment, particularly in younger adults. Incorporating neuroimaging and CSF biomarkers into routine clinical pathways enhances diagnostic precision and reveals distinct phenotypic profiles between EOCD and LOCD. These findings underscore the need for harmonised diagnostic protocols, broader biomarker accessibility, and inclusive recruitment strategies in dementia research and clinical services.
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A content review of national dementia plans : are human rights considered?The World Health Organization has set a target for 75% of member states to have national dementia plans by 2025. These plans should align with human rights standards, such as the Convention on the Rights of Persons with Disabilities. The aim of this study was to complete a review of global national dementia plans and their human rights content according to the convention's principles. A categorization matrix of preidentified human rights themes was produced prior to data collection and extensive inclusion criteria were adopted to ensure thorough assessment using deductive content analysis. Each dementia plan was reviewed by at least two independent assessors. Forty plans were included in the final analysis. We found that basic human rights were covered by the plans, with community inclusion acknowledged in 39 plans (97.5%). However, there was less coverage of non-coercive practices and the participation of people with dementia in the design and delivery of services or policies, with only 24 plans (60%) mentioning these aspects. This is the first global review of human rights content within national dementia plans. More must be done to ensure that all such plans align with human rights standards so that the human rights of persons with dementia are respected, protected, and promoted.
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Cognitive impairment, depressive symptoms, and demographic characteristics of care home residents living with dementia in six countriesOBJECTIVES: As the prevalence of dementia and depression continues to increase globally, understanding the interplay between these conditions becomes important for effective diagnosis, treatment, and tailoring of interventions. We investigate the relationship between depressive symptoms and cognitive impairment and the potential role of sociodemographic characteristics, among care home residents in Australia, Germany, the Netherlands, Norway, Türkiye, and the United Kingdom. METHOD: The study used baseline data from an international cluster-randomised controlled trial comprising 1021 residents with dementia and depressive symptoms in 86 care home units. The relationship between cognitive impairment and depressive symptoms was investigated using linear mixed effects models, with country, age, sex, marital status, and education level as possible predictors. RESULTS: Higher severity of cognitive impairment was related to more severe depressive symptoms in all countries. The association was especially strong in Türkiye. Marital status was a significant predictor for depressive symptoms and education level predicted cognitive ability. CONCLUSION: Findings confirm that lower cognitive ability is associated with more depressive symptoms across different contexts in a large international sample. As thresholds to long-term care are likely to be set even higher in the future, interventions to alleviate depressive symptoms among older adults with dementia become even more important.
