Background
High-quality healthcare for people living with dementia encompasses both patients and care partners (CPs). A framework populated with simple assessment tools is needed to deconstruct this ...complexity into actionable domains that inform assessment and care planning for individuals and dyads, help differentiate care team roles, and can more fully estimate true population burden in health and social care systems.
Design
Researchers used a cross-sectional mixed-methods descriptive study to illustrate the use of an inductive Six Domain framework and simple assessment tools in a sample of dyads selected for complexity.
Setting
Data was collected from three university-affiliated hospitals with a shared electronic medical record (EMR).
Participants
Eighty-eight CPs for people living with dementia (care recipients) newly discharged home after an acute medical hospitalization participated.
Measures
Care recipients' outpatient and inpatient diagnoses, medications, and care were extracted from the EMR. CPs completed an in-home semi-structured interview and study measures. Data were sorted into six domains: three care recipient-focused domains (cognition, emotion/behavior, general and functional health); a single CP-focused domain (mood, cognition, stress, and self-rated health); a health-related social needs domain (enrollment of persons with dementia in low-income insurance, CP-reported financial strain); and a care delivery domain (CP-reported engagement with clinicians in care recipients' care planning, and match between CP-reported knowledge of care recipients' medical care needs and medical records).
Results
As expected, all people living with dementia had significant cognitive, neurobehavioral, and medical complexity requiring extensive oversight and management at home. Over a third of CPs reported high stress, depression, or anxiety. A fifth screened positive for one or more indicators of poor health, cognitive impairment, and/or health-related social needs. CP reports and care recipients' medical records were discordant for chronic conditions in 68% of cases and for prescribed medications in 44%. In 85% of cases, there were gaps in indicators of CP-clinician collaboration in care management.
Conclusion and relevance
The Six Domains of Health framework captures a broad array of challenges that are relevant to providing comprehensive dyadic care and setting individualized health and social care priorities. With further study, it could provide conceptual scaffolding for comparative population research and more equitable, fully integrated pathways for care.
Hearing loss is an important risk factor for the development of dementia, particularly Alzheimer's disease (AD). Mid-life hearing loss increases the risk of developing dementia by double any other ...single factor. However, given this strong connection between hearing loss and AD, the mechanisms responsible for this link are still unknown. Data from observational studies relating hearing loss and cognitive impairment, measured with standardized questionnaires, has shown a strong relationship between them. Similar findings have emerged from animal studies, showing that the induction of hearing loss via prolonged loud sound exposure or ear canal blocking, can impair cognitive abilities. Interestingly, patients with age-related hearing impairment exhibit increased phosphorylated tau in the cerebrospinal fluid, but no such relationship has been identified for amyloid-β. In addition, hearing loss predisposes to social isolation precipitating the development of dementia through a supposed reduction in cognitive load and processing requirements. Given this link between hearing loss and dementia, the question arises whether the restoration of hearing might mitigate against the onset or progress of AD. Indeed, there is a growing body of research that suggests that those who wear hearing aids for age-related hearing problems maintain better cognitive function over time than those who do not. These are compelling findings, as they suggest the use of hearing aids has the potential to be a cost-effective treatment for those with hearing loss both prior (for those at high risk for AD) and after the development of symptoms. This review aims to summarize the current theories that relate hearing loss and cognitive decline, present the key findings of animal studies, observational studies and summarize the gaps and limitations that need to be addressed in this topic. Through this, we suggest directions for future studies to tackle the lack of adequately randomized control trials in the field. This omission is responsible for the inability to provide a conclusive verdict on whether to use hearing interventions to target hearing-loss related cognitive decline.
Dementia is a progressive global cognitive impairment syndrome. In 2010, more than 35 million people worldwide were estimated to be living with dementia. Some people with mild cognitive impairment ...(MCI) will progress to dementia but others remain stable or recover full function. There is great interest in finding good predictors of dementia in people with MCI. The Mini-Mental State Examination (MMSE) is the best-known and the most often used short screening tool for providing an overall measure of cognitive impairment in clinical, research and community settings.
To determine the diagnostic accuracy of the MMSE at various thresholds for detecting individuals with baseline MCI who would clinically convert to dementia in general, Alzheimer's disease dementia or other forms of dementia at follow-up.
We searched ALOIS (Cochrane Dementia and Cognitive Improvement Specialized Register of diagnostic and intervention studies (inception to May 2014); MEDLINE (OvidSP) (1946 to May 2014); EMBASE (OvidSP) (1980 to May 2014); BIOSIS (Web of Science) (inception to May 2014); Web of Science Core Collection, including the Conference Proceedings Citation Index (ISI Web of Science) (inception to May 2014); PsycINFO (OvidSP) (inception to May 2014), and LILACS (BIREME) (1982 to May 2014). We also searched specialized sources of diagnostic test accuracy studies and reviews, most recently in May 2014: MEDION (Universities of Maastricht and Leuven, www.mediondatabase.nl), DARE (Database of Abstracts of Reviews of Effects, via the Cochrane Library), HTA Database (Health Technology Assessment Database, via the Cochrane Library), and ARIF (University of Birmingham, UK, www.arif.bham.ac.uk). No language or date restrictions were applied to the electronic searches and methodological filters were not used as a method to restrict the search overall so as to maximize sensitivity. We also checked reference lists of relevant studies and reviews, tracked citations in Scopus and Science Citation Index, used searches of known relevant studies in PubMed to track related articles, and contacted research groups conducting work on MMSE for dementia diagnosis to try to locate possibly relevant but unpublished data.
We considered longitudinal studies in which results of the MMSE administered to MCI participants at baseline were obtained and the reference standard was obtained by follow-up over time. We included participants recruited and clinically classified as individuals with MCI under Petersen and revised Petersen criteria, Matthews criteria, or a Clinical Dementia Rating = 0.5. We used acceptable and commonly used reference standards for dementia in general, Alzheimer's dementia, Lewy body dementia, vascular dementia and frontotemporal dementia.
We screened all titles generated by the electronic database searches. Two review authors independently assessed the abstracts of all potentially relevant studies. We assessed the identified full papers for eligibility and extracted data to create two by two tables for dementia in general and other dementias. Two authors independently performed quality assessment using the QUADAS-2 tool. Due to high heterogeneity and scarcity of data, we derived estimates of sensitivity at fixed values of specificity from the model we fitted to produce the summary receiver operating characteristic curve.
In this review, we included 11 heterogeneous studies with a total number of 1569 MCI patients followed for conversion to dementia. Four studies assessed the role of baseline scores of the MMSE in conversion from MCI to all-cause dementia and eight studies assessed this test in conversion from MCI to Alzheimer´s disease dementia. Only one study provided information about the MMSE and conversion from MCI to vascular dementia. For conversion from MCI to dementia in general, the accuracy of baseline MMSE scores ranged from sensitivities of 23% to 76% and specificities from 40% to 94%. In relationship to conversion from MCI to Alzheimer's disease dementia, the accuracy of baseline MMSE scores ranged from sensitivities of 27% to 89% and specificities from 32% to 90%. Only one study provided information about conversion from MCI to vascular dementia, presenting a sensitivity of 36% and a specificity of 80% with an incidence of vascular dementia of 6.2%. Although we had planned to explore possible sources of heterogeneity, this was not undertaken due to the scarcity of studies included in our analysis.
Our review did not find evidence supporting a substantial role of MMSE as a stand-alone single-administration test in the identification of MCI patients who could develop dementia. Clinicians could prefer to request additional and extensive tests to be sure about the management of these patients. An important aspect to assess in future updates is if conversion to dementia from MCI stages could be predicted better by MMSE changes over time instead of single measurements. It is also important to assess if a set of tests, rather than an isolated one, may be more successful in predicting conversion from MCI to dementia.
Lewy body diseases share clinical, pathological, genetic and biochemical signatures, and are regarded as a highly heterogeneous group of neurodegenerative disorders. Inclusive of Parkinson's disease ...(PD), Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB), controversy still exists as to whether they should be considered as separate disease entities or as part of the same disease continuum. Here we discuss emerging knowledge relating to both clinical, and neuropathological differences and consider current biomarker strategies as we try to improve our diagnostic capabilities and design of disease modifying therapeutics for this group of debilitating neurodegenerative disorders.
This article is part of the Special Issue “Synuclein”.
We discuss the difficulties and challenges facing researchers when trying to distinguish between Lewy body disorders based on the current clinical, neuropathological and genetic data. It seems clear that to unravel the complex pathogenesis behind the spectrum of diseases within the LBD spectrum, we need to focus our attention on a combined approach which may identify potential targets that are able to be translated into successful clinical trials and subsequent personalised treatment strategies for people affected by these terrible neurodegenerative diseases.
This article is part of the Special Issue “Synuclein”.
In this multicenter study on subjective cognitive decline (SCD) in community-based and memory clinic settings, we assessed the (1) incidence of Alzheimer's disease (AD) and non-AD dementia and (2) ...determinants of progression to dementia.
Eleven cohorts provided 2978 participants with SCD and 1391 controls. We estimated dementia incidence and identified risk factors using Cox proportional hazards models.
In SCD, incidence of dementia was 17.7 (95% Poisson confidence interval 15.2-20.3)/1000 person-years (AD: 11.5 9.6-13.7, non-AD: 6.1 4.7-7.7), compared with 14.2 (11.3-17.6) in controls (AD: 10.1 7.7-13.0, non-AD: 4.1 2.6-6.0). The risk of dementia was strongly increased in SCD in a memory clinic setting but less so in a community-based setting. In addition, higher age (hazard ratio 1.1 95% confidence interval 1.1-1.1), lower Mini–Mental State Examination (0.7 0.66-0.8), and apolipoprotein E ε4 (1.8 1.3-2.5) increased the risk of dementia.
SCD can precede both AD and non-AD dementia. Despite their younger age, individuals with SCD in a memory clinic setting have a higher risk of dementia than those in community-based cohorts.
•A large collaborative study indicates subjective cognitive decline (SCD) is a prodrome of Alzheimer's disease and non-Alzheimer's disease dementia.•Incidence of dementia for SCD is 17.7 (95% confidence interval 15.2-20.3)/1000 person-years.•Risk factors for progression from SCD to dementia are age, lower MMSE, and APOE.•SCD in a memory clinic setting increased the risk of dementia.
Given a long preclinical stage of Alzheimer's disease (AD) continuum before the onset of dementia, there is a growing demand for tools capable of detecting the earliest feature of subtle cognitive ...impairment and optimizing recruitment to clinical trials for potentially disease-modifying therapeutic interventions such as BACE1 inhibitors. Now that all BACE1 inhibitor programs in symptomatic and prodromal AD populations have ended in failure, trials need to shift to target the earlier preclinical stage. However, evaluating cognitive efficacy (if any) in asymptomatic AD individuals is a great challenge. In this context, accelerated long-term forgetting (ALF) is emerging as a sensitive cognitive measure that can discriminate between presymptomatic individuals with high risks for developing AD and healthy controls. ALF is characterized by increased forgetting rates over extended delays (e.g., days, weeks, months) despite normal learning and short-term retention on standard memory assessments that typically use around 30-min delays. This review provides an overview of recent progress in animal model and clinical studies on this topic, focusing on the utility and underlying mechanism of ALF that may be applicable to earlier diagnosis and BACE1 inhibitor efficacy evaluation at a preclinical stage of AD.
Pathologies of the brain microvasculature, often referred to as cerebral small-vessel disease, are important contributors to vascular dementia, the second most common form of dementia in aging ...societies. In addition to their role in acute ischemic and hemorrhagic stroke, they have emerged as major cause of age-related cognitive decline in asymptomatic individuals. A central histological finding in these pathologies is the disruption of the vessel architecture including thickening of the vessel wall, narrowing of the vessel lumen and massive expansion of the mural extracellular matrix. The underlying molecular mechanisms are largely unknown, but from the investigation of several disease forms with defined etiology, high temperature requirement protein A1 (HTRA1), a secreted serine protease degrading primarily matrisomal substrates, has emerged as critical factor and potential therapeutic target. A genetically induced loss of HTRA1 function in humans is associated with cerebral autosomal-recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), a rare, hereditary form of brain microvascular disease. Recently, proteomic studies on cerebral amyloid angiopathy (CAA), a common cause of age-related dementia, and cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most prevalent monogenic small-vessel disease, have provided evidence for an impairment of HTRA1 activity through sequestration into pathological protein deposits, suggesting an alternative mechanism of HTRA1 inactivation and expanding the range of diseases with HTRA1 involvement. Further investigations of the mechanisms of HTRA1 regulation in the brain microvasculature might spawn novel strategies for the treatment of small-vessel pathologies.
Alterations in the immune response that result in inflammation might play a role in the pathology of dementias. In order to analyze changes of the peripheral immune system associated with different ...types of dementias, we determined several innate and adaptive cell populations in whole blood using flow cytometry. We included patients with Alzheimer's disease (AD; n = 60), vascular dementia (VaD; n = 20), and frontotemporal dementia (FTD; n = 12) at the time point of diagnosis and 24 age-matched neuropsychiatric healthy persons. Monocytes and NK cells were diminished in VaD, but not in AD and FTD. B cell and T cell numbers were decreased in all investigated forms of dementia. Changes in the contribution of naïve/memory T cells were only present in AD. Correlation and regression analyses revealed associations between altered immune cell populations and Q Albumin as marker for the integrity of the blood-cerebrospinal fluid-barrier, Mini-Mental State Examination values, and age. The peripheral immune system is altered in AD, VaD, and FTD. However, each disorder presents unique changes in the investigated cell types indicating different mechanisms underlying the pathology.
Alzheimer's disease (AD) takes a more aggressive course in women than men, with higher prevalence and faster progression. Amnestic AD specifically targets the default mode network (DMN), which ...subserves short-term memory; past research shows relative hyperconnectivity in the posterior DMN in aging women. Higher reliance on this network during memory tasks may contribute to women's elevated AD risk. Here, we applied connectome-based predictive modeling (CPM), a robust linear machine-learning approach, to the Lifespan Human Connectome Project-Aging (HCP-A) dataset (
n
= 579). We sought to characterize sex-based predictors of memory performance in aging, with particular attention to the DMN. Models were evaluated using cross-validation both across the whole group and for each sex separately. Whole-group models predicted short-term memory performance with accuracies ranging from ρ = 0.21–0.45. The best-performing models were derived from an associative memory task-based scan. Sex-specific models revealed significant differences in connectome-based predictors for men and women. DMN activity contributed more to predicted memory scores in women, while within- and between- visual network activity contributed more to predicted memory scores in men. While men showed more segregation of visual networks, women showed more segregation of the DMN. We demonstrate that women and men recruit different circuitry when performing memory tasks, with women relying more on intra-DMN activity and men relying more on visual circuitry. These findings are consistent with the hypothesis that women draw more heavily upon the DMN for recollective memory, potentially contributing to women's elevated risk of AD.
Background
Brain-derived neurotrophic factor levels are higher in those who are physically active and lower in people with cognitive dysfunction. This study investigated whether brain-derived ...neurotrophic factor mediated or modified the association of sedentary time to MRI-estimated brain volumes in midlife.
Methods
Baseline (
n
= 612) and five-year follow-up (
n
= 418) data were drawn from the multicenter Coronary Artery Risk Development in Young Adults Brain MRI sub-study, including Black and White participants (aged 50.3 years, 51.6% females, 38.6% Black). Sedentary time (hours per day) was categorized into quartiles with low ≤ 4.3 (reference) and high > 8.4. Outcomes of the study were total brain, white matter, gray matter, hippocampal volumes, and white matter fractional anisotropy at baseline and 5-year percent change from baseline. The study used general linear regression models to examine the mediation and moderation effects of brain-derived neurotrophic factor (natural log transformed) on the associations of sedentary time to brain outcomes. The authors adjusted the regression model for age, sex, race, intracranial volume, education, and vascular factors.
Results
Cross-sectionally, baseline participants with the highest sedentary time had a lower total brain (−12.2 cc; 95%CI: −20.7, −3.7), gray matter (−7.8 cc; 95%CI: −14.3, −1.3), and hippocampal volume (−0.2 cc; 95%CI: −0.3, 0.0) compared with populations with the lowest sedentary time. The brain-derived neurotrophic factor levels did not mediate the associations between brain measures and sedentary time. Brain-derived neurotrophic factor was found to moderate associations of sedentary time to total brain and white matter volume such that the brain volume difference between high and low sedentary time decreased as brain-derived neurotrophic factor levels increased. Longitudinally, higher baseline brain-derived neurotrophic factor level was associated with less brain volume decline. The longitudinal associations did not differ by sedentary time, and brain-derived neurotrophic factor did not mediate or moderate the association of sedentary time to brain measure changes.
Conclusions
Higher brain-derived neurotrophic factor levels may buffer the negative effects of sedentary time on the brain.
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