Stages Of Dementia Research Articles

Early Changes in the Locus Coeruleus in Mild Cognitive Impairment with Lewy Bodies.

Although neuromelanin-sensitive magnetic resonance imaging (NM-MRI) has been used to evaluate early neurodegeneration in Parkinson's disease, studies concentrating on the locus coeruleus (LC) in pre-dementia stages of dementia with Lewy bodies (DLB) are lacking. The aims were to evaluate NM-MRI signal changes in the LC in patients with mild cognitive impairment with Lewy bodies (MCI-LB) compared to healthy controls (HC) and to identify the cognitive correlates of the changes. We also aimed to test the hypothesis of a caudal-rostral α-synuclein pathology spread using NM-MRI of the different LC subparts. A total of 38 MCI-LB patients and 59 HCs underwent clinical and cognitive testing and NM-MRI of the LC. We calculated the contrast ratio of NM-MRI signal (LC-CR) in the whole LC as well as in its caudal, middle, and rostral MRI slices, and we compared the LC-CR values between the MCI-LB and HC groups. Linear regression analyses were performed to assess the relationship between the LC-CR and cognitive outcomes. The MCI-LB group exhibited a significant reduction in the right LC-CR compared to HCs (P = 0.021). The right LC-CR decrease was associated with impaired visuospatial memory in the MCI-LB group. Only the caudal part of the LC exhibited significant LC-CR decreases in MCI-LB patients compared to HCs on both sides (P < 0.0001). This is the first study that focuses on LC-CRs in MCI-LB patients and analyzes the LC subparts, offering new insights into the LC integrity alterations in the initial stages of DLB and their clinical correlates. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The Narrowing of Self as Perceived by People in the Early Stages of Dementia-The Second Report.

The purpose of this study is to shed light on the sense of self that occurs amongst those who have been diagnosed with the early stages of dementia, where the individual attempts narrowing their world. The research was conducted using qualitative induction research methods, and data were collected using semi-structured interview methods. The interviews were conducted between 2017 and 2019. The 15 participants were residents with families in a Japanese city of about 950,000 people. The diagnosis was Alzheimer's disease in all cases. Of the 15 participants, six were male and nine female. The average age was 69.9 years. The average score on the MMSE was 19.8 points. The average period since the first diagnosis was 2 years. The average interview time was 51 minutes. The narrowing self perceived by these people diagnosed with mild dementia was composed of the "neglected self" and "closed self." While living in a safe world in which they had given up on their own possibilities and experienced narrowing, they were unable to give up and harbored regret, anger, resentment, and feelings of absurdity. We believe that this study will help us understand the experiences of people in the early stages of dementia and contribute to providing nursing care that is more tailored to the individuals involved.

Alzheimer's Disease : Current Landscape and Future Directions

Introduction: Alzheimer's disease (AD) is the most prevalent form of dementia, constituting up to 72% of cases, and poses a significant financial burden on global healthcare. The aging population is expected to triple the cost of dementia to over $600 billion in the US alone by 2050. Dementia, a major cause of dependency and dysfunction, accounted for 11.4% of all reported deaths in Britain and Wales in 2022. Recent studies suggest a potential decline in dementia incidence, especially in males in Occident countries, possibly linked to better management of vascular risk. While 89% of dementia costs are attributed to high-income countries, middle and low-income nations face significant challenges in addressing the epidemiology of dementia. The prevalence of AD in developing nations is estimated at 3.4%, varying widely. Women exhibit a 1.17 times higher age-specific global prevalence compared to men, and their age-normalized death rate is also higher, suggesting factors beyond life expectancy contribute to their vulnerability. AD primarily affects individuals aged 75 or older, with 80% of cases in this age group. Acetylcholinesterase inhibitors are commonly used in all stages of dementia, though their efficacy in mild cognitive impairment and prodromal AD is uncertain. Distinguishing AD from depression symptoms can be challenging. The pathological features of AD involve neurofibrillary tangles (NFTs) and senile plaques, leading to neural and synaptic loss. Multiple mechanisms contribute to AD pathogenesis, including amyloid/tau toxicity and oxidative stress. Diagnosis : traditionally relies on clinical criteria, but biomarkers like CSF Aβ and tau proteins, as well as blood-based biomarkers, have shown promise in early detection. Noveltrearment: Promising treatment options include anti-amyloid monoclonal antibodies like aducanumab, lecanemab, and gantenerumab, with varying degrees of success in clinical trials. Donanemab, targeting a specific type of Aβ, has shown significant slowing of mental degradation in early-stage patients.

Mild behavioral impairment in people with mild cognitive impairment: Are the two conditions related?

Mild cognitive impairment (MCI) and mild behavioral impairment (MBI) are both considered potential prodromal stages of dementia, especially Alzheimer's disease. Previous literature has lacked specific information about MBI in individuals with MCI and associations of several aspects of both, MBI and MCI. Our aim was to investigate whether associations exist between aspects of MBI and aspects of cognitive performance in certain dimensions of the Montreal Cognitive Assessment (MoCA). We used baseline data from the double-blind randomized controlled intervention MCI-CCT-study. Current cognitive performance of individuals with MCI was measured with the MoCA. MBI was assessed with the MBI Shortscale (MBI short), which was administered through a self-report interview. Associations were assessed with Pearson correlations. Sensitivity analyses were conducted for gender and cognition. Group differences were examined with independent samples t-tests or Welch test. Significant correlations were considered in binary logistic regressions under control of covariates. There was no significant correlation between the current MoCA and MBI short scores in the total sample or in the gender-related analysis. Using dichotomized cognitive performance, significant correlations between MCI and MBI were revealed for individuals with lower MoCA scores. On the task level, several significant associations were identified between MoCA dimensions and MBI dimensions in the total sample and in the sensitivity analyses, also under control of covariates. Our findings support the hypothesis that with increasing cognitive decline, the association between MCI and MBI becomes stronger. Furthermore, a certain cut-off on the MoCA must be reached to identify a correlation.

Assessing palliative care needs in patients with dementia: A cross-sectional analysis of an predominantly oldest-old population from a geriatric memory clinic.

In this cross-sectional study, we assessed palliative care (PC) needs in older adults with dementia. Using the NECPAL CCOMS-ICO© 3.1 tool and comprehensive geriatric assessment, 16.25% of the 554 evaluated patients required PC, which had clinical frailty and a moderate stage of dementia. Advanced frailty was associated with the poorest prognosis, according to the PC-based stratification. Our findings support the use of PC assessment in dementia care, which focuses on a person-centered approach while minimizing unnecessary or ineffective treatments and meeting the real-world patient's needs. PC care may fulfill the multidimensional nature of dementia, shifting towards personalized palliative approaches.

Anthropometric and Demographic Features Affect the Interpretation of Cerebrospinal Fluid Biomarkers in Patients with Different Dementia Syndromes and Cognitively Healthy Adults.

Clinical distinction between dementia with Lewy bodies (DLB) and late-onset Alzheimer's disease (AD) is difficult, while several features might affect the analyses of biomarkers. This study aimed to verify associations of anthropometric and demographic features with cerebrospinal fluid biomarkers, their ratios, and restructured traditional regression formulas in patients with DLB and AD, as well as in cognitively healthy controls. Consecutive outpatients with DLB were paired with outpatients with AD according to sex, dementia stage, and cognitive status, and with controls according to sex and age to investigate associations of sex, age, dementia duration, total sleep time, body mass index, alcohol use, smoking, sanitation, and APOE-ε4 alleles on the measurement of cerebrospinal fluid α-synuclein, biomarker ratios, and restructured traditional regression formulas involving amyloid-β (Aβ42,Aβ40,Aβ38), tau, and phospho-tau Thr181. Overall, 81 participants were included with DLB (n = 27;11 APOE-ε4 +) or AD (n = 27;12 APOE-ε4 +), and controls (n = 27;4 APOE-ε4 +); two thirds were women. Cerebrospinal fluid evidence of amyloidosis and tauopathy was more prevalent among women with AD, while Aβ42/Aβ38 could also discriminate men with DLB from men with AD. Restructured traditional regression formulas had higher diagnostic accuracy for women with AD. Aging, higher body mass index, and APOE-ε4 alleles were associated with amyloidosis in DLB, while only in AD were higher body mass index associated with lower tau pathology load, and more alcohol use associated with higher phospho-tau Thr181/Aβ42. These findings confirm the effects of anthropometric and demographic features on cerebrospinal fluid biomarkers, and also differences in aberrant amyloidosis and tauopathy between DLB and AD.

"Mr. Smith Has No Mealtimes": Minimal Comfort Feeding for Patients with Advanced Dementia.

While Comfort Feeding Only is appropriate for patients with advanced dementia, its emphasis on assiduous hand-feeding that may prolong life for years fails to accommodate the preferences of those who do not want to continue living with this illness. Some have proposed advance directives to completely halt the provision of oral nutrition and hydration once a person has reached an advanced stage of dementia. However, these directives may fail to address patients' discomfort, caregivers' obligations, or current care and regulatory standards when patients reside in facilities. In response to these dilemmas, we introduce Minimal Comfort Feeding (MCF). Rather than offering food and liquids proactively as with Comfort Feeding Only, caregivers provide nutrition and hydration only in response to signs of hunger and thirst. While further study is required to define and negotiate challenges in operationalizing this approach, MCF provides a framework that resolves competing ethical and clinical considerations in caring for those with advanced dementia.

Evaluation of the Interdisciplinary Care Home-bAsed Reablement Program (I-CHARP) for People Living With Cognitive Impairment and Dementia in Care Homes.

Major knowledge and practice gaps exist in aged care home services to support independence of older people with dementia. This research evaluates an adaptation of a community-based rehabilitation model for care homes, namely Interdisciplinary Care Home-bAsed Reablement Program (I-CHARP), by examining whether (and, if so, how) I-CHARP produces its intended effects and how this programme can be practicably implemented, sustained and scaled up across care homes in Australia. I-CHARP is a 4-month bio-behavioural-environmental rehabilitation model of care, integrated in care home services, supported through the deployment of an implementation strategy, the Research Enabled Aged Care Homes (REACH) network. It consists of (1) 8-12 full individual sessions and additional eight brief follow-ups per resident, tailored to the resident's needs, delivered primarily by a team of an occupational therapist, registered nurse and other allied health staff; (2) environmental modifications/assistive devices up to the value of $400 per resident; and (3) engagement of intervention care home staff, managers and regular visitors. An overarching evaluation approach is participatory action research using a cluster quasi-experimental design and mixed methods. It involves testing of the implementation strategy (REACH network and other approaches) while observing/gathering information on the intervention (I-CHARP) and related outcomes in three cycles. Participants include residents (aged ≥ 60 years with early stages of dementia) and care staff from 16 care homes. Care quality indicators, health care costs, field notes and semi-structured interviews/focus groups with intervention site staff, regular visitors and managers will provide further insights into I-CHARP processes and implementation issues. In the final phase of the project, an Agile Implementation Playbook will be developed for the delivery of reablement care that can be used in routine practice across care homes in Australia. The study findings will also inform future policy development and strategic directions for dementia care in care homes. Australian New Zealand Clinical Trial Registry, ACTRN12623000885695 Registered 16 August 2023, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=386088. 1.0 dated 20 July 2023.

Identification of mild cognitive impairment using multimodal 3D imaging data and graph convolutional networks

Abstract Objective. Mild cognitive impairment (MCI) is a precursor stage of dementia characterized by mild cognitive decline in one or more cognitive domains, without meeting the criteria for dementia. MCI is considered a prodromal form of Alzheimer's disease (AD). Early identification of MCI is crucial for both intervention and prevention of AD. To accurately identify MCI, a novel multimodal 3D imaging data integration graph convolutional network model is designed in this paper. Approach. The proposed model utilizes 3D-VGGNet to extract three-dimensional features from multimodal imaging data (such as sMRI and FDG-PET), which are then fused into feature vectors as the node features of a population graph. Non-imaging features of participants are combined with the multimodal imaging data to construct a population sparse graph. Additionally, in order to optimize the connectivity of the graph, we employed the Pairwise Attribute Estimation (PAE) method to compute the edge weights based on non-imaging data, thereby enhancing the effectiveness of the graph structure. Subsequently, a population-based graph convolutional network (GCN) integrates the structural and functional features of different modal images into the features of each participant for MCI classification. Main results. Experiments on the ADNI demonstrated accuracies of 98.57%, 96.03%, and 96.83% for the NC-EMCI, NC-LMCI, and EMCI-LMCI classification tasks, respectively. The AUC, specificity, sensitivity, and F1-score are also superior to state-of-the-art models, demonstrating the effectiveness of the proposed model. Furthermore, the proposed model is applied to the ABIDE dataset for autism diagnosis, achieving an accuracy of 91.43% and outperforming the state-of-the-art models, indicating excellent generalization capabilities of the proposed model. Significance. This study demonstrate the proposed model’s ability to integrate multimodal imaging data and its excellent ability to recognize MCI. This will help achieve early warning for AD and intelligent diagnosis of other brain neurodegenerative diseases.

MRI-Driven Alzheimer’s Disease Diagnosis Using Deep Network Fusion and Optimal Selection of Feature

Alzheimer’s disease (AD) is a degenerative neurological condition characterized by cognitive decline, memory loss, and reduced everyday function, which eventually causes dementia. Symptoms develop years after the disease begins, making early detection difficult. While AD remains incurable, timely detection and prompt treatment can substantially slow its progression. This study presented a framework for automated AD detection using brain MRIs. Firstly, the deep network information (i.e., features) were extracted using various deep-learning networks. The information extracted from the best deep networks (EfficientNet-b0 and MobileNet-v2) were merged using the canonical correlation approach (CCA). The CCA-based fused features resulted in an enhanced classification performance of 94.7% with a large feature vector size (i.e., 2532). To remove the redundant features from the CCA-based fused feature vector, the binary-enhanced WOA was utilized for optimal feature selection, which yielded an average accuracy of 98.12 ± 0.52 (mean ± standard deviation) with only 953 features. The results were compared with other optimal feature selection techniques, showing that the binary-enhanced WOA results are statistically significant (p &lt; 0.01). The ablation study was also performed to show the significance of each step of the proposed methodology. Furthermore, the comparison shows the superiority and high classification performance of the proposed automated AD detection approach, suggesting that the hybrid approach may help doctors with dementia detection and staging.

The Impact of Behavioral and Psychological Symptoms of Dementia on Individual's Autonomy: a Scoping Review.

The purpose of this study was to identify, map, summarize, and clarify the existing literature on the effects of behavioral and psychological symptoms of dementia (BPSD) an individual's autonomy across all types of dementia diagnoses. The study aimed to determine whether there is a correlation between BPSD and a decrease in a person's autonomy, as this relationship is important for improving dementia care through effective interventions. To achieve this goal, a scoping review was conducted using the Joanna Briggs Institute's methodology for scoping reviews and the PRISMA extension for scoping reviews checklist. The inclusion criteria were: (i) population: participants with a clinical diagnosis of any type of dementia; (ii) concept: examining the relationship between one or more neuropsychiatric symptoms or BPSD and the individual's autonomy; (iii) context: the progress of any type and any stage of dementia. The database search yielded 74 records, of which 41 fully met the pre-established eligibility criteria. Most studies in this review focused on participants with Alzheimer's disease and analysed their functional abilities. Most studies in this review showed significant outcomes regarding the impact of BPSD on a person's autonomy. The main BPSD investigated in the studies were depression, apathy, irritability, agitation, aggression, disinhibition, and lability. Apathy had a recurrent association with reduced autonomy in persons with dementia, while depression and psychosis were also found to have an impact on individuals' autonomy.

Unveiling the hippocampal subfield changes across the Alzheimer's disease continuum: a systematic review of neuroimaging studies.

Studies exploring the hippocampal subfield atrophy in Alzheimer's disease (AD) have shown contradictory results. This review aims to disentangle such heterogeneity by investigating the dynamic changes of hippocampal subfields across the AD continuum. We systematically searched the PubMed and EMBASE databases for case-control studies. Selected studies included investigations of biomarker-based amyloid status and reported data on hippocampal subfield atrophy using advanced MRI techniques. Twelve studies were included. Despite high heterogeneity, a distinguishable pattern of vulnerability of hippocampal subfields can be recognized from the cognitively unimpaired phase to the dementia stage, shedding light on hippocampal changes with disease progression. Consistent findings revealed atrophy in the subiculum and presubiculum, along with a potential increase in volume in the cornu ammonis (CA) among the cognitively unimpaired group, a feature not observed in patients experiencing subjective cognitive decline. Atrophy in the subiculum, presubiculum, CA 1-4, and the dentate gyrus characterized the mild cognitive impairment stage, with a more pronounced severity in the progression to dementia.

Symptom- and function-based trajectories of patients with dementia in hospital and community palliative care settings in the last two weeks of life: a retrospective cohort study

BackgroundThe prevalence of dementia is increasing worldwide and many people with the condition require some level of palliative care. However, the trajectories of function and symptom burden in palliative care services at the end of life remain unclear. This study aimed to describe and compare the longitudinal trajectories of function and symptom burden among patients with dementia between hospital versus palliative community care services in the last two weeks of life.MethodsA retrospective cohort study used data from the Australian Palliative Care Outcomes Collaboration. Patients with dementia who died between 1 January 2013 and 31 December 2020 from the Australian Palliative Care Outcomes Collaboration. Four validated clinical instruments were used to collect outcomes on each individual’s function and symptom distress and severity. Multilevel models were used to estimate the differences in clinical trajectories between hospital and community-based palliative care in the last two weeks of life.ResultsPatients with dementia tended to have low levels of distress for most symptoms but increasing levels of functional impairment. There were no or only marginally significant differences in the symptom trajectories between the community and hospital groups (OR ranged from 0.57 to 1.97). Although clinical trajectories of function were relatively similar between two groups, statistically higher functional indicators were observed for people when admitted to community palliative care services (OR = 0.42 and 2.27, respectively).ConclusionsOur findings suggest that community-based palliative care services can be as effective as hospital-based care for many patients with dementia nearing the end of life. With appropriate support for families, community-based care could serve as a viable alternative to hospital-based care for some patients in the final stages of dementia.

Perceived partner responsiveness alters the association between marital distress and well-being in dementia spousal caregivers

Caregivers for spouses with Alzheimer's disease and related dementias (ADRD) experience drastic changes in the marital relationship that may put them at risk for worsening well-being. Perceived partner responsiveness, or feeling cared for, understood, and appreciated by one's spouse, may help mitigate these effects. In this study, we investigated the associations between marital distress, perceived partner responsiveness, and psychological and physiological well-being indicators among ADRD spousal caregivers. MethodA sample of 161 caregivers provided blood samples and completed self-report measures of marital distress, perceived partner responsiveness, and depressive symptoms. We tested hypotheses in our sample cross-sectionally based on two theoretical frameworks. ResultsTesting the marital discord model of depression, caregivers who reported greater marital distress also reported more depressive symptoms, and this association was stronger as participants reported lower perceived partner responsiveness. Caregivers who reported greater marital distress exhibited elevated proinflammatory cytokine production by in vitro lipopolysaccharide (LPS)-stimulated peripheral blood leukocytes at low levels of perceived partner responsiveness, but not mean or high levels. Testing the vulnerability-stress-adaptation model, caregivers who reported more depressive symptoms also reported greater marital distress. Further, caregivers who exhibited elevated LPS-stimulated proinflammatory cytokine production reported greater marital distress at mean and high levels of perceived partner responsiveness, but not low levels. These patterns of results held even when accounting for the dementia stage and reported hours of caregiving per day. DiscussionThis study's findings contribute to the body of research examining interpersonal factors that shape health and well-being among the caregiver population.

Neuropsychological Profiles in Genetic Frontotemporal Dementia: A Meta-Analysis and Systematic Review.

Characterization of cognitive profiles across genetic FTD gene mutations is crucial for the identification of sensitive endpoints for clinical trials targeting specific pathologies. However, no systematic overview of the literature describing cognitive profiles in different FTD gene mutations has been made thus far. We performed a meta-analysis and systematic review to characterize cognitive profiles across the different FTD gene mutations and clinical disease stages of familial frontotemporal dementia (FTD). We included 27 studies comparing presymptomatic (n=1027), and/or symptomatic (n=574) mutation carriers (GRN, MAPT, C9orf72) with controls (n=1296). We extracted cognitive data and grouped them into six cognitive domains (language, attention and mental processing speed, executive function (EF), memory, social cognition, and visuospatial abilities). These domains were further subdivided into specific cognitive sub-processes. We calculated Hedges' g and performed multilevel meta-analyses per cognitive domain and FTD gene mutation comparing presymptomatic and symptomatic mutation carriers to controls. Moderator analyses were performed to the effect of age, education, sex, and cognitive subprocess. Eleven studies into rarer FTD mutations were included in the systematic review. Presymptomatic GRN mutation carriers showed deficits in EF, and presymptomatic C9orf72 mutation carriers in language, EF, and attention. Presymptomatic MAPT mutation carriers did not differ from controls on any of the cognitive domains. All symptomatic mutation carriers had deficits in language, EF, attention, and memory. Both in the presymptomatic and symptomatic stage cognitive sub-processes for language, attention and mental processing speed, EF, and memory were differentially affected in GRN, MAPT, and C9orf72. Cognitive decline was present in the presymptomatic stage of GRN and C9orf72 mutation carriers, but not MAPT mutation carriers. Unique cognitive sub-processes were affected in GRN, MAPT, and C9orf72. This study increased our knowledge of the cognitive deficits in familial FTD, which can aid in differential diagnosis and selection of endpoints for clinical trials.

Mild to moderate cognitive impairment does not bias the Geriatric Depression Scale in a large US sample of older adults.

The Geriatric Depression Scale (GDS) is widely used to screen for depression in clinical practice and to assess symptoms of depression in research about older adults. To determine whether the 15-item GDS can be used in adults with dementia, this study investigated whether item- or test-level bias in the GDS-15 is associated with the respondent's level of cognitive impairment. Using a large U.S. sample of 24,674 adults, we first conducted sample matching procedures between the five groups defined by CDR® Dementia Staging Instrument scores to control for potential confounding effects of common demographic variables. Then, we employed confirmatory factor analysis (for single-group and configural-invariance models only) and item response theory models to test potential differential item/test functioning effects associated with the GDS-15 across the five CDR groups. Practical consequences of the identified biases were quantified using sample-based Cohen's d effect sizes and misclassification rates. In general, people with higher CDR scores were older and had fewer years of education. In comparison to the normal cognition group (CDR-0), negligible biases in GDS-15 scores were found for the groups with questionable, mild, or moderate cognitive impairment (CDR-0.5/1/2). For individuals with severe cognitive impairment (CDR-3), their responses were inconsistent with the normal cognition group and their depression scores were significantly biased with a small-to-medium effect size. The GDS-15 can be used to assess depression in individuals with mild or moderate cognitive impairment, but not in individuals with severe cognitive impairment.

Knowledge, competence and educational needs of mental health staff on palliative care for the elderly with dementia.

Dementia is a clinical syndrome for which the benefits of palliative care have been recognized. The aim of this study was to investigate the knowledge and educational needs of mental health physicians and nurses and also their perceptions of their competence regarding palliative care for the elderly with dementia. A total of 96 mental health professionals (doctors, nurses) working in a public psychiatric hospital and its allied community mental health settings participated in the study. The Palliative Care Quiz for Nursing (PCQN) was used to detect their knowledge on palliative care as well as a questionnaire to collect participants' demographics, their perceptions about their competence on palliative care provision and their educational needs on the basics domains of palliative care for the elderly with dementia. Results revealed participants' significant lack of knowledge (PCQN =7.79/20) and low perception of competence regarding palliative care for aged persons with dementia. Participants who were psychiatrists, who had work experience between 16-20 years and provided care to more than ten patients with terminal dementia per year, showed higher PCQN scores in statistically significant level (p=0.001). The majority (93.6%) of participants considered training in palliative care for dementia patients as necessary, particularly in providing information to family/carers, relieving the psychosocial burden of family/carers, managing the terminal stage of dementia, providing information to dementia patients and planning their advanced care. Findings of this study could inform the design of training programs on palliative care for the elderly with dementia in Greece.

Moving Towards Ethical-Practical Recommendations for Alzheimer's Disease Prediction: Addressing Interindividual, Interprofessional, and Societal Aspects.

Biomarkers for predicting Alzheimer's disease (AD) are advancing and their implementation in various healthcare systems is imminent. There is a need for ethical standards addressing information needs, socio-ethical concerns, and expectations of healthy and at-risk persons. We present an ethical approach that integrates different existing ethical frameworks and discussion of our empirical, cross-cultural findings in a multi-layered perspective by addressing three levels. The micro-level focuses on the communication between counseling professionals, persons at risk or in an early stage of dementia, and family members. The meso-level addresses interprofessional cooperation and exchange as a key element for best person-centered care. The macro-level considers public health promotion, the media, and public-funded research. This approach allows to address key ethical concepts including beneficence, non-maleficence, autonomy, informational self-determination, empowerment, and justice. Our contribution specifically examines the ethical challenges associated with AD prediction by means of biomarkers, based on insights from a German-Israeli comparison, and promotes a transdisciplinary discussion across different healthcare contexts. We propose a reflection on three levels to go beyond the clinical counseling context and to consider the rapidly evolving field of biomarkers in the coming years. Our ethical-practical recommendations should not be considered final, but rather procedural and will require continuous adaptation regarding culturally varying practices, new algorithms, meta-analyses, and re-evaluation of established recommendations.

Automated Volumetric Software in Dementia: Help or Hindrance to the Neuroradiologist?

Brain atrophy occurs in the late stage of dementia, yet structural MRI is widely used in the work-up. Atrophy patterns can suggest a diagnosis of Alzheimer disease (AD) or frontotemporal dementia (FTD) but are difficult to assess visually. We hypothesized that the availability of a quantitative volumetric brain MRI report would increase neuroradiologists' accuracy in diagnosing AD, FTD, or healthy controls compared with visual assessment. Twenty-two patients with AD, 17 with FTD, and 21 cognitively healthy patients were identified from the electronic health systems record and a behavioral neurology clinic. Four neuroradiologists evaluated T1-weighted anatomic MRI studies with and without a volumetric report. Outcome measures were the proportion of correct diagnoses of neurodegenerative disease versus normal aging ("rough accuracy") and AD versus FTD ("exact accuracy"). Generalized linear mixed models were fit to assess whether the use of a volumetric report was associated with higher accuracy, accounting for random effects of within-rater and within-subject variability. Post hoc within-group analysis was performed with multiple comparisons correction. Residualized volumes were tested for an association with the diagnosis using ANOVA. There was no statistically significant effect of the report on overall correct diagnoses. The proportion of "exact" correct diagnoses was higher with the report versus without the report for AD (0.52 versus 0.38) and FTD (0.49 versus 0.32) and lower for cognitively healthy (0.75 versus 0.89). The proportion of "rough" correct diagnoses of neurodegenerative disease was higher with the report than without the report within the AD group (0.59 versus 0.41), and it was similar within the FTD group (0.66 versus 0.63). Post hoc within-group analysis suggested that the report increased the accuracy in AD (OR = 2.77) and decreased the accuracy in cognitively healthy (OR = 0.25). Residualized hippocampal volumes were smaller in AD (mean difference -1.8; multiple comparisons correction, -2.8 to -0.8; P < .001) and FTD (mean difference -1.2; multiple comparisons correction, -2.2 to -0.1; P = .02) compared with cognitively healthy. The availability of a brain volumetric report did not improve neuroradiologists' accuracy over visual assessment in diagnosing AD or FTD in this limited sample. Post hoc analysis suggested that the report may have biased readers incorrectly toward a diagnosis of neurodegeneration in cognitively healthy adults.

Cognitive synaptopathy: synaptic and dendritic spine dysfunction in age-related cognitive disorders.

Cognitive impairment is a leading component of several neurodegenerative and neurodevelopmental diseases, profoundly impacting on the individual, the family, and society at large. Cognitive pathologies are driven by a multiplicity of factors, from genetic mutations and genetic risk factors, neurotransmitter-associated dysfunction, abnormal connectomics at the level of local neuronal circuits and broader brain networks, to environmental influences able to modulate some of the endogenous factors. Otherwise healthy older adults can be expected to experience some degree of mild cognitive impairment, some of which fall into the category of subjective cognitive deficits in clinical practice, while many neurodevelopmental and neurodegenerative diseases course with more profound alterations of cognition, particularly within the spectrum of the dementias. Our knowledge of the underlying neuropathological mechanisms at the root of this ample palette of clinical entities is far from complete. This review looks at current knowledge on synaptic modifications in the context of cognitive function along healthy ageing and cognitive dysfunction in disease, providing insight into differential diagnostic elements in the wide range of synapse alterations, from those associated with the mild cognitive changes of physiological senescence to the more profound abnormalities occurring at advanced clinical stages of dementia. I propose the term "cognitive synaptopathy" to encompass the wide spectrum of synaptic pathologies associated with higher brain function disorders.