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Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by gradual memory loss and declining cognitive and executive functions. AD is the most common cause of dementia, affecting more than 50 million people worldwide, and is a major health concern in society. Despite decades of research, the cause of AD is not well understood and there is no effective curative treatment so far. Therefore, there is an urgent need to increase understanding of AD pathophysiology in the hope of developing a much-needed cure. Dissecting the cellular and molecular mechanisms of AD pathogenesis has been challenging as the most commonly used model systems such as transgenic animals and two-dimensional neuronal culture do not fully recapitulate the pathological hallmarks of AD. The recent advent of three-dimensional human brain organoids confers unique opportunities to study AD in a humanised model system by encapsulating many aspects of AD pathology. In the present review, we summarise the studies of AD using human brain organoids that recapitulate the major pathological components of AD including amyloid-β and tau aggregation, neuroinflammation, mitochondrial dysfunction, oxidative stress and synaptic and circuitry dysregulation. Additionally, the current challenges and future directions of the brain organoids modelling system are discussed.
The classical deficiency diseases have nearly disappeared from the industrialised world and are thought to be found largely in sub-Saharan Africa and South Asia. More than 80 collected medical articles, mostly from Europe and North America, describe more than 9000 people with low concentrations of copper in organs or tissues or impaired metabolic pathways dependent on copper. More than a dozen articles reveal improved anatomy, chemistry or physiology in more than 1000 patients from supplements containing copper. These criteria are diagnostic of deficiency according to The Oxford Textbook of Medicine. Alzheimer's disease, ischaemic heart disease and osteoporosis receive major emphasis here. However, impaired vision, myelodysplastic syndrome and peripheral neuropathy are mentioned. Copper deficiency probably causes some common, contemporaneous diseases. Advice is provided about opportunities for research. Seemingly authoritative statements concerning the rarity of nutritional deficiency in developed countries are wrong.
Dietary patterns (DP) rich in plant foods are associated with improved health and reduced non-communicable disease risk. In October 2021, the Nutrition Society hosted a member-led conference, held online over 2 half days, exploring the latest research findings examining plant-rich DP and health. The aim of the present paper is to summarise the content of the conference and synopses of the individual speaker presentations are included. Topics included epidemiological analysis of plant-rich DP and health outcomes, the effects of dietary interventions which have increased fruit and vegetable (FV) intake on a range of health outcomes, how adherence to plant-rich DP is assessed, the use of biomarkers to assess FV intake and a consideration of how modifying behaviour towards increased FV intake could impact environmental outcomes, planetary health and food systems. In conclusion, although there are still considerable uncertainties which require further research, which were considered as part of the conference and are summarised in this review, adopting a plant-rich DP at a population level could have a considerable impact on diet and health outcomes, as well as planetary health.
Agitation and psychosis are two common distressing symptoms of dementia. The results of this issue's Cochrane Corner review suggest that, if a pharmacological approach is required, the use of risperidone and other atypical antipsychotics for the purpose of managing these symptoms seems questionable. Furthermore, typical antipsychotics, haloperidol in particular, might have a greater impact on agitation and psychosis than already recognised. This commentary critically appraises the evidence on the efficacy of typical and atypical antipsychotics for agitation and psychosis in dementia.
This chapter explores distinct views about the conditions under which life is worth extending. The first section examines the view that whether living longer is good or bad is contingent upon the kind of experience life is. The metaphor of life as an experience machine brings out the philosophical assumptions inherent in variations on this theme. Limitations of the experience view suggest the need to formulate alternative accounts that refer to objective human capabilities, authenticity, or being in synch with reality. The second section explores how these different assessments of life's value inform practical judgments about whether to offer or accept lifesaving interventions for persons with dementia, focusing on surrogate decision-making for individuals with Alzheimer's disease.
This paper aims to contribute to the knowledge about open, co-produced meeting centres for people with dementia, from their own perspective. Services that support people who are newly diagnosed with dementia are often insufficient. Co-produced services have the potential to address the need of people with dementia to be useful and productive, while reducing the stigma. In this study, we applied a qualitative design. Data were collected at a meeting centre for people with newly diagnosed dementia, and consisted of fieldwork (13 days for about two hours at a time), written materials, and semi-structured interviews (mean length 30 minutes) with five attendees with dementia and two staff persons. The analysis was inspired by situational analysis. The findings showed that the meeting centre provided a place for human encounters, a break from everyday life, and a place to share knowledge and develop new skills. Further, challenges were described. Co-production consisted of the attendees being encouraged to take part in the planning of activities, learning from each other and providing mutual support. The study adds to previous knowledge about co-produced services for people with dementia. Future studies can clarify how co-production can be developed in services for people with newly diagnosed dementia in countries and regions where there is a dearth of this kind of support.
We examined the association between bilingualism, executive function (EF), and brain volume in older monolinguals and bilinguals who spoke English, Spanish, or both, and were cognitively normal (CN) or diagnosed with Mild Cognitive Impairment (MCI) or dementia. Gray matter volume (GMV) was higher in language and EF brain regions among bilinguals, but no differences were found in memory regions. Neuropsychological performance did not vary across language groups over time; however, bilinguals exhibited reduced Stroop interference and lower scores on Digit Span Backwards and category fluency. Higher scores on Digit Span Backwards were associated with a younger age of English acquisition, and a greater degree of balanced bilingualism was associated with lower scores in category fluency. The initial age of cognitive decline did not differ between language groups. The influence of bilingualism appears to be reflected in increased GMV in language and EF regions, and to a lesser degree, in EF.
With growing and ageing populations, the incidence of dementia is expected to triple globally by 2050. In the absence of effective drugs to treat or reverse the syndrome, dietary approaches which prevent or delay disease onset have considerable population health potential. Prospective epidemiological studies and mechanistic insight from experimental models strongly support a positive effect of a high fish and long chain n-3 fatty acid (EPA and DHA) intake on a range of cognitive outcomes and dementia risk, with effect sizes equivalent to several years of ageing between the highest and lowest consumers. As reviewed here, an effect of EPA and DHA on neuroinflammation and oxylipin production is likely to in part mediate the neurophysiological benefits. However, randomised controlled trials (RCTs) with EPA and DHA supplementation have produced mixed findings. Insight into the likely modulators of response to intervention and factors which should be considered for future RCTs are given. Furthermore, the impact of APOE genotype on disease risk and response to EPA and DHA supplementation is summarised. The prevalence of dementia is several-fold higher in APOE4 females (about 13% Caucasian populations) relative to the general population, who are emerging as a subgroup who may particularly benefit from DHA intervention, prior to the development of significant pathology.
In 2017, personal genetics company 23andMe announced that it had received FDA approval to provide people with their apolipoprotein E (APOE) genotype and nine other genes linked with health risks. The APOE gene is associated with late-onset Alzheimer’s disease (AD), the leading cause of dementia. In this chapter, I argue that APOE testing is of limited clinical significance given the present lack of disease-modifying therapies for AD and the fact that preventive measures are the same regardless of an individual’s APOE status. Nevertheless, an APOE result can have great personal and legal significance to individuals–for instance, influencing decision-making around insurance, employment, end-of-life care. One way to reconcile the obvious tension between paternalism and the individual’s right to know their genetic risk for late-onset AD is to provide genetic information in the context of robust information about the personal and legal ramifications of the result. This, I argue, is an area were 23andMe and other DTC genetic testing companies fall short.
Individuals with Alzheimer's disease and related dementias often require substantial support from other people. Much of the care-giving is from family members who eventually experience physical, emotional and financial stress, depression and fatigue. In Uganda, families are a cornerstone in providing care to individuals with dementia. However, little is known about the psychosocial supports available to the care-givers in their care-giving role. We assessed the psychosocial supports available to care-givers of individuals with Alzheimer's disease and related dementias in southwestern Uganda. We conducted 34 in-depth interviews at three referral hospitals at which care-givers identified by the treating clinicians were approached for informed consent. The interviews were conducted until thematic saturation was reached, and the interviews were translated and transcribed. Thematic content analysis was used to analyse the data. Care-giver supports were structured into two major themes: medical supports utilised and supports beyond the medical care system. Medical supports highlighted information provided by medical professionals. Supports beyond the medical care system included emotional and instrumental supports provided by religious leaders, the local communities and family members. Care-givers for individuals with dementia in southwestern Uganda receive educational support from medical practitioners, and unstructured emotional and instrumental supports from the family and community.
There is emerging evidence linking fruit and vegetable consumption and cognitive function. However, studies focusing on the nutrients underlying this relationship are lacking. We aim to examine the association between plasma nutrients and cognition in a population at risk for cognitive decline with a suboptimal diet. The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) trial is a randomized controlled intervention that examines the effects of the MIND diet to prevent cognitive decline. The primary outcome is global cognition. A multivariate linear model was used to investigate the association between blood nutrients and global and/or domain-specific cognition. The model was adjusted for age, sex, education, study site, smoking status, cognitive activities and physical activities. High plasma α-carotene was associated with better global cognition. Participants in the highest tertile of plasma α-carotene had a higher global cognition z score of 0⋅17 when compared with individuals in the lowest tertile (P 0⋅002). Circulating α-carotene levels were also associated with higher semantic memory scores (P for trend 0⋅007). Lutein and zeaxanthin (combined) was positively associated with higher semantic memory scores (P for trend 0⋅009). Our study demonstrated that higher α-carotene levels in blood were associated with higher global cognition scores in a US population at risk for cognitive decline. The higher α-carotene levels in blood reflected greater intakes of fruits, other types of vegetables and lesser intakes of butter and margarine and meat. The higher circulating levels of lutein plus zeaxanthin reflected a dietary pattern with high intakes of fruits, green leafy, other vegetables and cheese, and low consumption of fried foods. Objective nutrient markers in the blood can better characterize dietary intake, which may facilitate the implementation of a tailored dietary intervention for the prevention of cognitive decline.
This study aimed to understand stigma in relation to people living with dementia in São Paulo, Brazil. A critical narrative inquiry methodology was used. Home-based semi-structured interviews were conducted between January and March 2020 with six people living with dementia and 15 family carers. Data analysis was conducted using inductive and deductive techniques. The latter was informed by Link and Phelan's sociological theory of stigma. We found that dementia was commonly viewed by people living with dementia as part of ageing and carers reported low levels of knowledge and awareness about the condition. To avoid negative reactions from people, people living with dementia managed the negative views of dementia by minimising and normalising the condition, by expressing their ability to live an active life, and by emphasising the positive impacts of dementia in their lives. Fear of negative reactions appeared to lead to a selective disclosure of their diagnosis. Among carers, stigmatising attitudes coincided with a strong willingness to provide good care, to protect the person cared for, as well as to understand and validate their own caring experiences, rather than to cause any harm. In doing so, however, carers ended up depersonalising and infantilising people living with dementia, underestimating their capacities, demanding ‘obedience’ and restricting the person's freedom. There is a need to increase awareness about dementia and to provide support and training on person-centred and ethical care for carers in Brazil.
Diagnosis of prodromal Alzheimer's disease and Alzheimer's disease dementia in people with Down syndrome is a major challenge. The Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS) has been validated for diagnosing prodromal Alzheimer's disease and Alzheimer's disease dementia, but the diagnostic process lacks guidance.
To derive CAMDEX-DS informant interview threshold scores to enable accurate diagnosis of prodromal Alzheimer's disease and Alzheimer's disease dementia in adults with Down syndrome.
Psychiatrists classified participants with Down syndrome into no dementia, prodromal Alzheimer's disease and Alzheimer's disease dementia groups. Receiver operating characteristic analyses assessed the diagnostic accuracy of CAMDEX-DS informant interview-derived scores. Spearman partial correlations investigated associations between CAMDEX-DS scores, regional Aβ binding (positron emission tomography) and regional cortical thickness (magnetic resonance imaging).
Diagnostic performance of CAMDEX-DS total scores were high for Alzheimer's disease dementia (area under the curve (AUC), 0.998; 95% CI 0.953–0.999) and prodromal Alzheimer's disease (AUC = 0.954; 95% CI 0.887–0.982) when compared with healthy adults with Down syndrome. When compared with those with mental health conditions but no Alzheimer's disease, CAMDEX-DS Section B scores, denoting memory and orientation ability, accurately diagnosed Alzheimer's disease dementia (AUC = 0.958; 95% CI 0.892–0.984), but were unable to diagnose prodromal Alzheimer's disease. CAMDEX-DS total scores exhibited moderate correlations with cortical Aβ (r ~ 0.4 to 0.6, P ≤ 0.05) and thickness (r ~ −0.4 to −0.44, P ≤ 0.05) in specific regions.
CAMDEX-DS total score accurately diagnoses Alzheimer's disease dementia and prodromal Alzheimer's disease in healthy adults with Down syndrome.
Life expectancy in most developed countries has been rising over the past century. In the UK alone, there are about 12 million people over 65 years old and centenarians have increased by 85% in the past 15 years. As a result of the ageing population, which is due mainly to improvements in medical treatments, public health, improved housing and lifestyle choices, there is an associated increase in the prevalence of pathological conditions, such as metabolic disorders, type 2 diabetes, cardiovascular and neurodegenerative diseases, many types of cancer and others. Statistics suggest that nearly 54% of elderly people in the UK live with at least two chronic conditions, revealing the urgency for identifying interventions that can prevent and/or treat such disorders. Non-pharmacological, dietary interventions such as energetic restriction (ER) and methionine restriction (MR) have revealed promising outcomes in increasing longevity and preventing and/or reversing the development of ageing-associated disorders. In this review, we discuss the evidence and mechanisms that are involved in these processes. Fibroblast growth factor 1 and hydrogen sulphide are important molecules involved in the effects of ER and MR in the extension of life span. Their role is also associated with the prevention of metabolic and cognitive disorders, highlighting these interventions as promising modulators for improvement of health span.
Alzheimer's disease (AD) is a major health concern as the world population ages. Yet, few studies have examined what the public over the age of 50 knows about AD. This qualitative study, based on 40 in-depth interviews, examines the knowledge of AD by Flemish people between 50 and 80 years old and their cross-source engagement with information sources. Building on AD media representations and theories on media complementarity and health information behaviour, we find that respondents mostly encounter AD information non-purposively via traditional mass media and interpersonal communication, while the internet is occasionally used to purposefully seek information. Novels, personal experiences/social proximity, public figures and particularly film stand out as channels and sources of AD information, suggesting that fictional narratives, personal experiences and being able to identify with others leave lasting impressions and help to communicate and disperse AD information. However, common misconceptions and gaps in knowledge persist, including AD being considered part of the normal ageing process and old age as well as confusing AD with Parkinson's disease. The biomedical perspective and the tragedy discourse prevail among the majority of respondents, who describe AD in terms of decline, loss and death and as ‘the beginning of the end’. Only a few, typically female respondents, appear aware of the role of individual health behaviour and lifestyle choices to prevent dementia or delay its onset. The misconceptions of AD and gaps in knowledge, as well as the fact that a third of all cases of dementia might be delayed or prevented by managing lifestyle and other risk factors, stress the importance of public educational programmes and the need to emphasise and raise awareness of preventative behaviour. Overall, the findings from this study can be of help to public health communicators and dementia-awareness campaigns, as well as AD training programmes for health-care professionals and family care-givers.
The efficacy of acetylcholinesterase inhibitors and memantine in the symptomatic treatment of Alzheimer's disease is well-established. Randomised trials have shown them to be associated with a reduction in the rate of cognitive decline.
To investigate the real-world effectiveness of acetylcholinesterase inhibitors and memantine for dementia-causing diseases in the largest UK observational secondary care service data-set to date.
We extracted mentions of relevant medications and cognitive testing (Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores) from de-identified patient records from two National Health Service (NHS) trusts. The 10-year changes in cognitive performance were modelled using a combination of generalised additive and linear mixed-effects modelling.
The initial decline in MMSE and MoCA scores occurs approximately 2 years before medication is initiated. Medication prescription stabilises cognitive performance for the ensuing 2–5 months. The effect is boosted in more cognitively impaired cases at the point of medication prescription and attenuated in those taking antipsychotics. Importantly, patients who are switched between agents at least once do not experience any beneficial cognitive effect from pharmacological treatment.
This study presents one of the largest real-world examination of the efficacy of acetylcholinesterase inhibitors and memantine for symptomatic treatment of dementia. We found evidence that 68% of individuals respond to treatment with a period of cognitive stabilisation before continuing their decline at the pre-treatment rate.
The aim of this study was to contribute with knowledge about how a sense of home and belonging is enacted and can be supported in everyday life, with a particular focus on the relationships that connect everyday life and the environment in nursing home contexts. The concepts ‘a sense of home’ and ‘belonging’ were chosen with the ambition to grasp values grounded in experiences and everyday practices, with an openness for various aspects that can support an enjoyable life and comfort for nursing home residents. The study focused on communal areas, e.g. dining room, kitchen, corridors and gardens, that serve as arenas where nursing home residents’ everyday lives expand beyond the private room. Ethnographic methods were applied to identify and explore situations where a sense of home and belonging were enacted in nursing homes that had been acknowledged as good examples of nursing home environments. Through the analytic process, four qualities were identified: (a) a cornerstone for stability and everydayness, (b) the beating heart, (c) spatial dynamics, and (d) magnetic places. Following from the chosen methodology, the findings provide a situated understanding of how communal areas in nursing homes can invite a sense of home and belonging for the residents.
Neurodegenerative disorders, including Alzheimer's (AD) and Parkinson's diseases (PD), are characterised by the formation of aberrant assemblies of misfolded proteins. The discovery of disease-modifying drugs for these disorders is challenging, in part because we still have a limited understanding of their molecular origins. In this review, we discuss how biophysical approaches can help explain the formation of the aberrant conformational states of proteins whose neurotoxic effects underlie these diseases. We discuss in particular models based on the transgenic expression of amyloid-β (Aβ) and tau in AD, and α-synuclein in PD. Because biophysical methods have enabled an accurate quantification and a detailed understanding of the molecular mechanisms underlying protein misfolding and aggregation in vitro, we expect that the further development of these methods to probe directly the corresponding mechanisms in vivo will open effective routes for diagnostic and therapeutic interventions.