Stages Of Dementia Research Articles

Carers and professionals' views on using virtual reality in dementia care: A qualitative study.

Virtual reality (VR) interventions provide immersive, interactive computer-simulated virtual environments. There is interest in their use for people with dementia as they may provide stimulating experiences and improve dementia symptoms and quality of life. However, as more insight is needed about carers' and clinical professionals' perspectives to understand how VR may be implemented successfully, we elicited their views on the benefits of, and challenges to, using VR in dementia care. We conducted five qualitative focus groups involving 25 healthcare professionals and informal carers with experience of dementia care. Participants received a demonstration of a VR headset and content and were then questioned following a topic guide asking for views on benefits of, and challenges to, using VR for dementia care. The main findings addressed the benefits of, and concerns about, the impact and implications of VR on wellbeing, ethics, implementation, caregivers and services. Overall, participants had a positive attitude toward VR and made several suggestions for its future use to enable enjoyable and immersive experiences. Examples included suggestions to personalise VR content to accommodate heterogenous profiles and stages of dementia, co-developing protocols to address health risks and side effects and further investigating shared experiences of VR with caregivers. Healthcare professionals and informal carers thought that VR had potential to enhance a holistic and personalised approach to dementia care. They suggested changes which could guide future implementation of VR interventions for dementia patients and their caregivers.

2248 Clinical relevance of Donanemab treatment

Abstract Objective To assess in Alzheimer’s disease (ad), the treatment impact of donanemab, an amyloid plaque-reducing monoclonal antibody, on readily interpretable item-measures and constructs that matter to patients, care-partners, and clinicians. Background Positive outcomes were reported from TRAILBLAZER-ALZ2, a randomised, double-blind, placebo-controlled, 18-month, phase 3 study evaluating donanemab as an investigational treatment for mild cognitive impairment (MCI) or mild dementia due to ad. In 1736 participants, donanemab significantly slowed the rate of clinical decline (by 22–36%) as measured by the integrated ad Rating Scale (iADRS) and the Clinical Dementia Rating Scale—Sum-of-Boxes (CDR-SB); both measures of cognition and function as indications of global clinical severity. In these subsequent post-hoc exploratory analyses, the impact of donanemab treatment on individual iADRS cognition and function items, CDR domains, and risks of advancing to greater disease severity were assessed. Methods Mixed model repeated measures and Cox proportional hazard modelling methodology assessed treatment effects on iADRS items and CDR domains. Results Donanemab treatment was associated with significant beneficial effects on: 1) iADRS cognitive items related to episodic memory and executive function, and instrumental activities of daily living items related to communication and others (e.g. being left alone, making a meal, using household appliances); 2) all CDR-SB cognitive and functional domains (i.e. memory, orientation, judgement/problem solving, community affairs, home/hobbies, and personal care); and 3) lowering risk of progression to a more advanced clinical stage of disease. Conclusions These analyses explored the impact of donanemab treatment on constructs that matter to and are considered more readily interpretable by patients, care-partners, and clinicians. These results provide further support that treating those with MCI or mild dementia due to ad with donanemab can meaningfully reduce risk of progression to more severe clinical stages (e.g. moderate stage dementia), and potentially allow greater independence for a longer period of time.

An Exploration of the Peri-Diagnostic Experiences of Lesbian, Gay and Bisexual People With Dementia Using the Candidacy Framework.

How dementia affects lesbian, gay, bisexual, trans, queer people or those with other minoritised sexual/gender identities (LGBTQ+) is not well understood. Furthermore, existing research often excludes the voices of LGBTQ+ people living with dementia and focuses instead on their care partners. This study addresses this evidence gap by drawing on the ESRC/NIHR funded DETERMIND cohort, consisting of 940 newly diagnosed people with dementia, to explore the peri-diagnostic experiences of people living with dementia who identify as LGBTQ+. We recruited five people (who identified as lesbian, gay or bisexual [LGB]) and completed semi-structured interviews with them and their partner caregivers (n=3) discussing their experiences of (1) engaging with dementia health care services, (2) receiving a dementia diagnosis, and (3) the support they were offered after diagnosis. Interviews were shaped by the Candidacy Framework, a theoretical model for understanding accessibility of health services, and an inductive thematic analysis was employed to develop common themes. Participants did not routinely disclose their LGBTQ+ identities to health service professionals, despite feeling this was an essential aspect of who they are. They relied on their resilience of overcoming previous experiences of lifetime discrimination to navigate complicated dementia care systems. The importance of 'chosen families' as informal support networks for LGBTQ+ people living with dementia was highlighted, particularly given the lack of formal care services they felt comfortable accessing. All participants were concerned about their future care needs and whether they would receive home-based or community-based support that respected their LGBTQ+ identities. This study adds to the limited evidence base that can be used to inform future research, policy and practice seeking to address inequalities across the dementia care pathway. We only interviewed people who identified as LGB so generalizability to the whole LGBTQ+ population is limited, however our data suggest dementia health care professionals should encourage and support disclosures of LGBTQ+ identities so that inclusive care and support planning can be provided to LGBTQ+ people at every stage of dementia.

Identification of profiles associated with conversions between the Alzheimer’s disease stages, using a machine learning approach

BackgroundThe identification of factors involved in the conversion across the different Alzheimer’s disease (AD) stages is crucial to prevent or slow the disease progression. We aimed to assess the factors and their combination associated with the conversion across the AD stages, from mild cognitive impairment to dementia, at a mild, moderate or severe stage and to identify profiles associated with earliest/latest conversion across the AD stages.MethodsIn this study conducted on the real-life MEMORA cohort data collected from January 1, 2013, and December 31, 2019, three cohorts were selected depending on the baseline neurocognitive stage from a consecutive sample of patients attending a memory center, aged between 50 and 90 years old, with a diagnosis of AD during the follow-up, and with at least 2 visits at 6 months to 1 year of interval. A machine learning approach was used to assess the relationship between factors including socio-demographic characteristics, comorbidities and history of diseases, prescription of drugs, and geriatric hospitalizations, and the censored time to conversion from mild cognitive impairment to AD dementia, from the mild stage of dementia to the moderate or severe stages of AD dementia, and from the moderate stage of AD dementia to the severe stage. Profiles of earliest/latest conversion compared to median time to conversion across stages were identified. The median time to conversion was estimated with a Kaplan-Meier estimator.ResultsOverall, 2891 patients were included (mean age 77±9 years old, 65% women). The median time of follow-up was 28 months for mild cognitive impairment (MCI) patients, 33 months for mild AD dementia and 30 months for moderate AD dementia. Among the 1264 patients at MCI stage, 61% converted to AD dementia (median time to conversion: 25 months). Among the 1142 patients with mild AD dementia, 59% converted to moderate/severe stage (median time: 23 months) and among the 1332 patients with moderate AD dementia, 23% converted to severe stage (Q3 time to conversion: 22 months). Among the studied factors, cardiovascular comorbidities, anxiety, social isolation, osteoporosis, and hearing disorders were identified as being associated with earlier conversion across stages. Symptomatic treatment i.e. cholinesterase inhibitors for AD was associated with later conversion from mild stage of dementia to moderate/severe stages.ConclusionThis study based on a machine learning approach allowed to identify potentially modifiable factors associated with conversion across AD stages for which timely interventions may be implemented to delay disease progression.

Comparative Characteristics of Inflammatory Markers in Alzheimer’s Disease in Males and Females

Background: the role of the sex factor in the differences between the manifestations of normality and pathology is not limited to the phenomenon of sexual dimorphism. It is known that the prevalence of certain diseases in males and females is different, in particular, there is a multiple increase in the incidence of dementia in females compared to males in Alzheimer’s disease (AD). Taking into account the role of neuroinflammation in the pathogenesis of neurodegenerative diseases, there is reason to assume gender differences in inflammation indicators at different stages of dementia in AD. The aim of the study was to conduct comparative analysis of indicators of the inflammatory system in the blood plasma of males and females at different stages of Alzheimer’s disease. Patients, control group and methods: a total of 210 patients with AD (101 males and 109 females) aged 49 to 94 years (average age 72.3 ± 8.2) with varying degrees of dementia severity, i.e. mild, moderate, severe, were examined. In peripheral blood plasma, the enzymatic activity of leukocyte elastase (LE) and the functional activity of α1-proteinase inhibitor (α1-PI) were determined by the spectrophotometric method, and the level of C-reactive protein (CRP) and IL-6 were determined by the enzyme-linked immunosorbent method (ELISA). The control group consisted of 52 healthy people, who did not differ from the patients in age and gender. Results and discussion: in the blood of patients with varying severity of dementia in AD, a statistically significant increase in α1-PI activity was observed compared to controls (p < 0.0001), regardless of gender. For all subgroups of patients with AD, the indicators of LE enzymatic activity were within the control range or beyond its lower limit. Low LE activity was observed in males compared to females both in the general group and in moderate dementia (p = 0.005105, p = 0.028672, respectively). In severe dementia, a significant decrease in LE activity compared to the controls did not depend on gender. Low LE activity in the blood of patients with AD, along with elevated levels of other inflammatory markers, may reflect a critical violation of the permeability of the blood-brain barrier and/or functional exhaustion of neutrophils due to a long-term inflammatory process. In males, compared with females, an increase in the level of the pro-inflammatory cytokine IL-6 was detected in the general group and in moderate dementia (p = 0.021238, p = 0.027894, respectively). A highly significant increase in CRP levels was only detected in males in subgroups with different severity of dementia. CRP levels in males were significantly higher than in females at the stage of moderate and severe dementia (p = 0.000906, p = 0.000049, respectively). Conclusion: distinctive features of inflammatory markers spectrum were identified, depending on gender and severity of dementia in AD. These results can be used to develop sex-specific preventive or therapeutic strategies for patients with mild cognitive impairment to determine risk and resistance to developing dementia.

Two-Year Longitudinal Outcomes of Subjective Cognitive Decline in Hispanics Compared to Non-hispanic Whites.

Subjective cognitive decline (SCD), considered a preclinical dementia stage, is less understood in Hispanics, a high-risk group for dementia. We investigated SCD to mild cognitive impairment (MCI) progression risk, as well as baseline and longitudinal features of depressive symptoms, SCD complaints, and objective cognitive performance among Hispanics compared to non-Hispanic Whites (NHW). Hispanic (n = 23) and NHW (n = 165) SCD participants were evaluated at baseline and 2-year follow-up. Evaluations assessed function, depressive symptoms, SCD, and objective cognitive performance. Hispanics were at increased risk of progression to MCI (OR: 6.10, 95% CI 1.09-34.20, P = .040). Hispanic participants endorsed more depressive symptoms at baseline (P = .048) that worsened more longitudinally (OR: 3.16, 95% CI 1.18-8.51, P = .023). Hispanic participants had increased SCD complaints on the Brief Cognitive Rating Scale (BCRS) (β = .40 SE: .17, P = .023), and in specific BCRS domains: concentration (β = .13, SE: .07, P = .047), past memory (β = .13, SE: .06, P = .039) and functional abilities (β = .10, SE: .05, P = .037). In objective cognitive performance, Hispanic ethnicity associated with decline in MMSE (β = -.27, SE: .13, P = .039), MoCA (β = -.80 SE: .34, P = .032), Trails A (β = 2.75, SE: .89, P = .002), Trails B (β = 9.18, SE: 2.71, P = .001) and Guild Paragraph Recall Delayed (β = -.80 SE: .28, P = .005). Conclusions: Hispanic ethnicity associated with a significantly increased risk of 2-year progression of SCD to MCI compared to NHW. This increased risk associated with increased depressive symptoms, distinctive SCD features, and elevated amnestic and non-amnestic objective cognitive decline. This supports further research to refine the assessment of preclinical dementia in this high-risk group.

Association of Basal Forebrain Atrophy With Cognitive Decline in Early Alzheimer Disease.

In early Alzheimer disease (AD), β-amyloid (Aβ) deposition is associated with volume loss in the basal forebrain (BF) and cognitive decline. However, the extent to which Aβ-related BF atrophy manifests as cognitive decline is not understood. This study sought to characterize the relationship between BF atrophy and the decline in memory and attention in patients with early AD. Participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study who completed Aβ-PET imaging and repeated MRI and cognitive assessments were included. At baseline, participants were classified based on their clinical dementia stage and Aβ status, yielding groups that were cognitively unimpaired (CU) Aβ-, CU Aβ+, and mild cognitive impairment (MCI) Aβ+. Linear mixed-effects models were used to assess changes in volumetric measures of BF subregions and the hippocampus and changes in AIBL memory and attention composite scores for each group compared with CU Aβ- participants. Associations between Aβ burden, brain atrophy, and cognitive decline were evaluated and explored further using mediation analyses. The cohort included 476 participants (72.6 ± 5.9 years, 55.0% female) with longitudinal data from a median follow-up period of 6.1 years. Compared with the CU Aβ- group (n = 308), both CU Aβ+ (n = 107) and MCI Aβ+ (n = 61) adults showed faster decline in BF and hippocampal volumes and in memory and attention (Cohen d = 0.73-1.74). Rates of atrophy in BF subregions and the hippocampus correlated with cognitive decline, and each individually mediated the impact of Aβ burden on memory and attention decline. When all mediators were considered simultaneously, hippocampal atrophy primarily influenced the effect of Aβ burden on memory decline (β [SE] = -0.139 [0.032], proportion mediated [PM] = 28.0%) while the atrophy of the posterior nucleus basalis of Meynert in the BF (β [SE] = -0.068 [0.029], PM = 13.1%) and hippocampus (β [SE] = -0.121 [0.033], PM = 23.4%) distinctively influenced Aβ-related attention decline. These findings highlight the significant role of BF atrophy in the complex pathway linking Aβ to cognitive impairment in early stages of AD. Volumetric assessment of BF subregions could be essential in elucidating the relationships between the brain structure and behavior in AD.

Borderline-DEMNET: A Workflow for Detecting Alzheimer’s and Dementia Stage by Solving Class Imbalance Problem

Alzheimer’s Disease (AD) is the leading cause of dementia, a broad term encompassing memory loss and other cognitive impairments. Although there is no known cure for dementia, managing specific symptoms associated with it can be effective. Mild dementia stages, including AD, can be treated, and computer-based techniques have been developed to aid in early diagnosis. This paper presents a new workflow called Borderline-DEMNET, designed to classify various stages of Alzheimer’s/dementia with more than three classes. Borderline-SMOTE is employed to address the issue of imbalanced datasets. A comparison is made between the proposed Borderline-DEMNET workflow and the existing DEMNET model, which focuses on classifying different dementia and AD stages. The evaluation metrics specified in the paper are used to assess the results. The framework is trained, tested, and validated using the Kaggle dataset, while the robustness of the work is checked using the ADNI dataset. The proposed workflow achieves an accuracy of 99.17% for the Kaggle dataset and 99.14% for the ADNI dataset. In conclusion, the proposed workflow outperforms previously identified models, particularly in terms of accuracy. It also proves that selecting a proper class balancing technique will increase accuracy.

Borderline-DEMNET: A Workflow for Detecting Alzheimer’s and Dementia Stage by Solving Class Imbalance Problem

Alzheimer’s Disease (AD) is the leading cause of dementia, a broad term encompassing memory loss and other cognitive impairments. Although there is no known cure for dementia, managing specific symptoms associated with it can be effective. Mild dementia stages, including AD, can be treated, and computer-based techniques have been developed to aid in early diagnosis. This paper presents a new workflow called Borderline-DEMNET, designed to classify various stages of Alzheimer’s/dementia with more than three classes. Borderline-SMOTE is employed to address the issue of imbalanced datasets. A comparison is made between the proposed Borderline-DEMNET workflow and the existing DEMNET model, which focuses on classifying different dementia and AD stages. The evaluation metrics specified in the paper are used to assess the results. The framework is trained, tested, and validated using the Kaggle dataset, while the robustness of the work is checked using the ADNI dataset. The proposed workflow achieves an accuracy of 99.17% for the Kaggle dataset and 99.14% for the ADNI dataset. In conclusion, the proposed workflow outperforms previously identified models, particularly in terms of accuracy. It also proves that selecting a proper class balancing technique will increase accuracy.

The Effectiveness of an Exercise Program on Muscle Strength and Range of Motion on Upper Limbs, Functional Ability and Depression at Early Stage of Dementia.

Background: Dementia involves the loss of cognitive abilities and represents a decline from the prior level of function, which impairs functional abilities in day-to-day life. The purpose of the present study is to examine the effectiveness of an exercise program on the muscle strength and range of motion of the upper limbs, the functional status, and the depression of elderly people with early stage dementia. Methods: The sample consisted of 60 elderly people with early stage dementia who were randomly divided into a control and an experimental group of 30 participants each. The experimental group received a 12-week Otago exercise program with 45 min duration of each session. The control group received usual care without doing exercise. The outcome measures of muscle strength and range of motion of the upper limbs, the functional status, and the depression were assessed by valid instruments and tests at the beginning and at the end of the intervention program. Repeated measures one-way ANOVA and Mann-Whitney tests examined the differences between the two groups at the end of the 12-week exercise program. Results: Statistically significant differences were found between the experimental and control groups in the entire outcome measures (functional ability F = 9.35 p < 0.05; muscle strength right hand F = 32.33, p < 0.05 left hand U = 95.50 p < 0.01; e.g., range of motion shoulder extension U = 104.00 p < 0.01), except depression. Conclusions: Both muscle strength and range of motion of the upper limbs, as well as the functional ability, were improved by the exercise program. Further research is needed to investigate the present results, in particular to explore the long-term cognitive, behavioral, and functional status outcomes of exercise in the early stages of dementia.

The relationship between anxiety and levels of Alzheimer's disease plasma biomarkers.

Anxiety is highly prevalent in Alzheimer's disease (AD), correlating with CSF/PET biomarkers and disease progression. Relationships to plasma biomarkers are unclear. Herein, we compare levels of plasma biomarkers in research participants with and without anxiety at cognitively normal, mild cognitive impairment, and AD dementia stages. We observed significantly higher plasma tau/Aβ42 ratio in AD participants with anxiety versus those without, but did not observe differences at other stages or plasma biomarkers. No such relationships were evident with depression. These results support a unique pathophysiological relationship between anxiety and AD that can be reflected in plasma biomarkers, suggestive of heightened neurodegeneration.

Medicare expenditures among spouses of persons with dementia.

Spouses of persons living with dementia face intense strains on their well-being compared with similarly aged adults and spouses of partners with no dementia. This strain can impact spouses' health and healthcare needs, and therefore affect their healthcare utilization and expenditures. Using data from the Health and Retirement Study linked with Medicare claims, we matched dyads of spouses and their partners with dementia (SPWD) to a comparison group of similar spouses and their partners with no dementia (SPWND). We then examined Medicare expenditures for spouses in the 5 years following their partner's dementia onset month using a two-part regression model. SPWD cumulative total Medicare expenditures were, on average, $60,043 in the 5 years post dementia onset, compared to $56,068 for SPWND. This difference ($3974, 95% CI = [-$3,199; $11,477]) was not significant. However, there were significant differences in the 5th year's total expenditures (+$2,748 [$321; $5,447]), driven by inpatient expenditures ($1,562 [$22; $3,277]). Despite the differences in partner's dementia status, we found no significant difference in the 5-year cumulative Medicare expenditures between SPWD and SPWND. Compared to previous studies, we likely captured an earlier stage of dementia more consistently for a broader population which may be less straining on spouses. Further research should examine patterns of expenditures in later years and around critical timepoints in caregiving, such as partner transitions to formal long-term care settings and death, to better understand healthcare expenditures for spouses of persons living with dementia.

Efficacy of COMPAs, an App Designed to Support Communication Between Persons Living With Dementia in Long-Term Care Settings and Their Caregivers: Mixed Methods Implementation Study.

Persons living with dementia experience autonomy loss and require caregiver support on a daily basis. Dementia involves a gradual decline in communication skills, leading to fewer interactions and isolation for both people living with dementia and their caregivers, negatively impacting the quality of life for both members of the dyad. The resulting stress and burden on caregivers make them particularly susceptible to burnout. This study aims to examine the efficacy of Communication Proches Aidants (COMPAs), an app designed following the principles of person-centered and emotional communication, which is intended to improve well-being in persons living with dementia and caregivers and reduce caregiver burden. In this implementation study, volunteer caregivers in 2 long-term care facilities (n=17) were trained in using COMPAs and strategies to improve communication with persons living with dementia. Qualitative and quantitative analyses, semistructured interviews, and questionnaires were completed before and after 8 weeks of intervention with COMPAs. Semistructured interviews revealed that all caregivers perceived a positive impact following COMPAs interventions, namely, improved quality of communication and quality of life among persons living with dementia and caregivers. Improved quality of life was also supported by a statistically significant reduction in the General Health Questionnaire-12 scores (caregivers who improved: 9/17, 53%; z=2.537; P=.01). COMPAs interventions were also associated with a statistically significant increased feeling of personal accomplishment (caregivers improved: 11/17, 65%; t15=2.430; P=.03; d=0.61 [medium effect size]). COMPAs intervention improved well-being in persons living with dementia and their caregivers by developing person-centered communication within the dyad, increasing empathy, and reducing burden in caregivers although most caregivers were unfamiliar with technology. The results hold promise for COMPAs interventions in long-term care settings. Larger group-controlled studies with different populations, in different contexts, and at different stages of dementia will provide a clearer picture of the benefits of COMPAs interventions.

Brain structure, amyloid, and behavioral features for predicting clinical progression in subjective cognitive decline.

As a potential preclinical stage of Alzheimer's dementia, subjective cognitive decline (SCD) reveals a higher risk of future cognitive decline and conversion to dementia. However, it has not been clear whether SCD status increases the clinical progression of older adults in the context of amyloid deposition, cerebrovascular disease (CeVD), and psychiatric symptoms. We identified 99 normal controls (NC), 15 SCD individuals who developed mild cognitive impairment in the next 2 years (P-SCD), and 54 SCD individuals who did not (S-SCD) from ADNI database with both baseline and 2-year follow-up data. Total white matter hyperintensity (WMH), WMH in deep (DWMH) and periventricular (PWMH) regions, and voxel-wise grey matter volumes were compared among groups. Furthermore, using structural equation modelling method, we constructed path models to explore SCD-related brain changes longitudinally and to determine whether baseline SCD status, age, and depressive symptoms affect participants' clinical outcomes. Both SCD groups showed higher baseline amyloid PET SUVR, baseline PWMH volumes, and larger increase of PWMH volumes over time than NC. In contrast, only P-SCD had higher baseline DWMH volumes and larger increase of DWMH volumes over time than NC. No longitudinal differences in grey matter volume and amyloid was observed among NC, S-SCD, and P-SCD. Our path models demonstrated that SCD status contributed to future WMH progression. Further, baseline SCD status increases the risk of future cognitive decline, mediated by PWMH; baseline depressive symptoms directly contribute to clinical outcomes. In conclusion, both S-SCD and P-SCD exhibited more severe CeVD than NC. The CeVD burden increase was more pronounced in P-SCD. In contrast with the direct association of depressive symptoms with dementia severity progression, the effects of SCD status on future cognitive decline may manifest via CeVD pathologies. Our work highlights the importance of multi-modal longitudinal designs in understanding the SCD trajectory heterogeneity, paving the way for stratification and early intervention in the preclinical stage. PRACTITIONER POINTS: Both S-SCD and P-SCD exhibited more severe CeVD at baseline and a larger increase of CeVD burden compared to NC, while the burden was more pronounced in P-SCD. Baseline SCD status increases the risk of future PWMH and DWMH volume accumulation, mediated by baseline PWMH and DWMH volumes, respectively. Baseline SCD status increases the risk of future cognitive decline, mediated by baseline PWMH, while baseline depression status directly contributes to clinical outcome.

The characteristic pattern of functional connectivity density influenced by postmenopausal females in the preclinical stage of dementia.

Subjective cognitive decline (SCD) is considered an early indicator of Alzheimer's disease. Previous evidence suggests that postmenopausal females are at heightened risk for developing dementia. However, the potential effects of gender (i.e. postmenopausal female) on functional connectivity density (FCD) in individuals with SCD are not well understood. A total of 56 healthy controls and 57 subjects with SCD were included. The short-range and long-range FCD (srFCD and lrFCD) mapping of each participant was calculated. The interactive effect of gender × diagnosis on the FCD was explored by two-way analysis of variance. The interaction effect of gender × diagnosis on lrFCD was primarily in the right middle frontal gyrus (MFG). The older males with SCD exhibited significantly enhanced lrFCD in the right MFG relative to other subgroups. The lrFCD of the right MFG was positively associated with cognitive performance in older females with SCD. Cognition-related functional terms were significantly related to the right MFG. Decreased lrFCD of the right MFG in cognitively normal older women may explain why postmenopausal females have a higher risk for progression to dementia than men. Furthermore, this altered pattern could be applied to identify individuals with a high risk for dementia.

Neurovascular coupling, functional connectivity, and cerebrovascular endothelial extracellular vesicles as biomarkers of mild cognitive impairment.

Mild cognitive impairment (MCI) is a prodromal stage of dementia. Understanding the mechanistic changes from healthy aging to MCI is critical for comprehending disease progression and enabling preventative intervention. Patients with MCI and age-matched controls (CN) were administered cognitive tasks during functional near-infrared spectroscopy (fNIRS) recording, and changes in plasma levels of extracellular vesicles (EVs) were assessed using small-particle flow cytometry. Neurovascular coupling (NVC) and functional connectivity (FC) were decreased in MCI compared to CN, prominently in the left-dorsolateral prefrontal cortex (LDLPFC). We observed an increased ratio of cerebrovascular endothelial EVs (CEEVs) to total endothelial EVs in patients with MCI compared to CN, correlating with structural MRI small vessel ischemic damage in MCI. LDLPFC NVC, CEEV ratio, and LDLPFC FC had the highest feature importance in the random Forest group classification. NVC, CEEVs, and FC predict MCI diagnosis, indicating their potential as markers for MCI cerebrovascular pathology. Neurovascular coupling (NVC) is impaired in mild cognitive impairment (MCI). Functional connectivity (FC) compensation mechanism is lost in MCI. Cerebrovascular endothelial extracellular vesicles (CEEVs) are increased in MCI. CEEV load strongly associates with cerebral small vessel ischemic lesions in MCI. NVC, CEEVs, and FC predict MCI diagnosis over demographic and comorbidity factors.

Effects of Errorless Learning-based Semantic Feature Analysis Treatment on Naming and Cognitive Abilities for Individuals with Alzheimer’s Disease

Objectives: Alzheimer’s Disease (AD) patients characteristically show a decline in various cognitive functions, including memory and language skills. Additionally, naming deficits are evident from the early stages of dementia in AD patients. This study aimed to consider these characteristics of AD patients and develop a semantic feature analysis based on errorless learning. The effect of this naming treatment on the language and cognitive abilities of AD patients was examined, with participants divided into treatment group and control groups. Methods: Ten patients with early to severe AD were divided into a treatment group and a control group. The noun list was individualized for each participant, and to prevent the production of errors, the researcher provided the names and semantic features of the nouns, which the AD patients then learned. Results: The treatment group showed statistically significant improvements in naming trained nouns, semantically related non-treatment nouns, and semantically unrelated non-treatment nouns. The control group did not show statistically significant improvements in overall noun naming. In the treatment group, the performance in the Controlled Oral Word Association Test (COWAT), specifically in naming animals, significantly increased post-treatment compared to pretreatment. In contrast, the control group showed a significant decrease in digit span test performance post-treatment compared to pre-treatment. Conclusion: A semantic feature analysis based on errorless learning was effective in improving naming performance in AD patients. It also had a positive impact on the enhancement and maintenance of performance in language and cognitive tests.

Using FRAME to adapt an evidence‐based dyadic intervention program for people living with dementia in residential aged care: A pilot feasibility study

AbstractIntroductionThe purpose of this study was to examine the feasibility of adapting and translating an evidence‐based occupational therapist‐delivered program shown to be effective in the community to residential aged care (RAC). The program aims to improve quality of care and quality of life for people living with dementia and the wellbeing of the family care partner.MethodsThis study took place in a not‐for‐profit RAC home in Adelaide, South Australia. Mixed methods, specifically questionnaires, activity logs, focus group, and one‐on‐one interviews were used to evaluate the feasibility of the program implementation. Staff working in the participating home, occupational therapists trained to deliver the program, and residents and their family carer partners were included. Quantitative data were analysed using proportions, means, and standard deviations. Qualitative data were analysed using a thematic approach.Consumer and Community InvolvementThis study was conducted together with a consumer (person living with dementia) and a carer representative (family member of someone residing in RAC). These representatives provided input towards the study design, interpretation of study data, discussion of results, and recommendations for future consideration.ResultsSmall changes to the program improved feasibility and acceptability for delivery in RAC. While the care home staff required added support during implementation, the intervention therapists felt that the program could be delivered in this setting. Family care partners of residents with dementia felt that the program may be better suited if provided upon entry to RAC or in early stages of dementia.ConclusionAdapting a community‐based dementia care program to RAC can be safe and feasible. Program adaptations are necessary for feasibility. Further adaptations and evaluations of associated outcomes (related to residents with dementia and their family care partners) are needed to assess the program effectiveness in larger scale.Plain language summarySpending quality time with family members in residential aged care is important. However, many struggle to know what to say or do when visiting a family member who lives with dementia. Programs that teach families about how to communicate with people living with dementia, how to support them to take part in important everyday living activities, or how to understand why changes in behaviours may occur have not been available in residential aged care. This paper describes how we adapted one such evidence‐based program from community to residential aged care settings. We consulted with people living with dementia, carers, and families and found that the program could also be valuable in this care setting. Residential aged care staff described how the program is very different to what is usually available in residential aged care, but they were optimistic that with the right support, it could be a valuable way to support residents with dementia and their families. Family members of residents with dementia and therapists delivering the program felt that residents in early stages of living in residential aged care and/or early stages of dementia could benefit the most from these programs. We found that including family members in the intervention process can be useful and empowering for families and residents. Future work should also focus on involving other staff members caring for residents in the process. Communication between staff and families is the key for program delivery and success and treating each person as an individual.

Cardiovascular risk factors among older persons with cognitive frailty in middle income country

BACKGROUND Cognitive frailty, characterized by the coexistence of cognitive impairment and physical frailty, represents a multifaceted challenge in the aging population. The role of cardiovascular risk factors in this complex interplay is not yet fully understood. AIM To investigate the relationships between cardiovascular risk factors and older persons with cognitive frailty by pooling data from two cohorts of studies in Malaysia. METHODS A comprehensive approach was employed, with a total of 512 community-dwelling older persons aged 60 years and above, involving two cohorts of older persons from previous studies. Datasets related to cardiovascular risks, namely sociodemographic factors, and cardiovascular risk factors, including hypertension, diabetes, hypercholesterolemia, anthropometric characteristics and biochemical profiles, were pooled for analysis. Cognitive frailty was defined based on the Clinical Dementia Rating scale and Fried frailty score. Cardiovascular risk was determined using Framingham risk score. Statistical analyses were conducted using SPSS version 21. RESULTS Of the study participants, 46.3% exhibited cognitive frailty. Cardiovascular risk factors including hypertension (OR:1.60; 95%CI: 1.12-2.30), low fat-free mass (OR:0.96; 95%CI: 0.94-0.98), high percentage body fat (OR:1.04; 95%CI: 1.02-1.06), high waist circumference (OR:1.02; 95%CI: 1.01-1.04), high fasting blood glucose (OR:1.64; 95%CI: 1.11-2.43), high Framingham risk score (OR:1.65; 95%CI: 1.17-2.31), together with sociodemographic factors, i.e. , being single (OR 3.38; 95%CI: 2.26-5.05) and low household income (OR 2.18; 95%CI: 1.44-3.30) were found to be associated with cognitive frailty. CONCLUSION Cardiovascular-risk specific risk factors and sociodemographic factors were associated with risk of cognitive frailty, a prodromal stage of dementia. Early identification and management of cardiovascular risk factors, particularly among specific group of the population might mitigate the risk of cognitive frailty, hence preventing dementia.

Impaired glymphatic system in genetic frontotemporal dementia: a GENFI study.

The glymphatic system is an emerging target in neurodegenerative disorders. Here, we investigated the activity of the glymphatic system in genetic frontotemporal dementia with a diffusion-based technique called diffusion tensor image analysis along the perivascular space. We investigated 291 subjects with symptomatic or presymptomatic frontotemporal dementia (112 with chromosome 9 open reading frame 72 [C9orf72] expansion, 119 with granulin [GRN] mutations and 60 with microtubule-associated protein tau [MAPT] mutations) and 83 non-carriers (including 50 young and 33 old non-carriers). We computed the diffusion tensor image analysis along the perivascular space index by calculating diffusivities in the x-, y- and z-axes of the plane of the lateral ventricle body. Clinical stage and blood-based markers were considered. A subset of 180 participants underwent cognitive follow-ups for a total of 640 evaluations. The diffusion tensor image analysis along the perivascular space index was lower in symptomatic frontotemporal dementia (estimated marginal mean ± standard error, 1.21 ± 0.02) than in old non-carriers (1.29 ± 0.03, P = 0.009) and presymptomatic mutation carriers (1.30 ± 0.01, P < 0.001). In mutation carriers, lower diffusion tensor image analysis along the perivascular space was associated with worse disease severity (β = -1.16, P < 0.001), and a trend towards a significant association between lower diffusion tensor image analysis along the perivascular space and higher plasma neurofilament light chain was reported (β = -0.28, P = 0.063). Analysis of longitudinal data demonstrated that worsening of disease severity was faster in patients with low diffusion tensor image analysis along the perivascular space at baseline than in those with average (P = 0.009) or high (P = 0.006) diffusion tensor image analysis along the perivascular space index. Using a non-invasive imaging approach as a proxy for glymphatic system function, we demonstrated glymphatic system abnormalities in the symptomatic stages of genetic frontotemporal dementia. Such measures of the glymphatic system may elucidate pathophysiological processes in human frontotemporal dementia and facilitate early phase trials of genetic frontotemporal dementia.