Potentially inappropriate prescribing for people with dementia in ambulatory care: a cross-sectional observational study.

BACKGROUND: Studies have shown that potentially inappropriate prescribing (PIP) is highly prevalent among people with dementia (PwD) and linked to negative outcomes, such as hospitalisation and mortality. However, there are limited data on prescribing appropriateness for PwD in Saudi Arabia. Therefore, we aimed to estimate the prevalence of PIP and investigate associations between PIP and other patient characteristics among PwD in an ambulatory care setting. METHODS: A cross-sectional, retrospective analysis was conducted at a tertiary hospital in Saudi Arabia. Patients who were ≥ 65 years old, had dementia, and visited ambulatory care clinics between 01/01/2019 and 31/12/2021 were included. Prescribing appropriateness was evaluated by applying the Screening Tool of Older Persons Potentially Inappropriate Prescriptions (STOPP) criteria. Descriptive analyses were used to describe the study population. Prevalence of PIP and the prevalence per each STOPP criterion were calculated as a percentage of all eligible patients. Logistic regression analysis was used to investigate associations between PIP, polypharmacy, age and sex; odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Analyses were conducted using SPSS v27. RESULTS: A total of 287 PwD were identified; 56.0% (n = 161) were female. The mean number of medications prescribed was 9.0 [standard deviation (SD) ± 4.2]. The prevalence of PIP was 61.0% (n = 175). Common instances of PIP were drugs prescribed beyond the recommended duration (n = 90, 31.4%), drugs prescribed without an evidence-based clinical indication (n = 78, 27.2%), proton pump inhibitors (PPIs) for > 8 weeks (n = 75, 26.0%), and acetylcholinesterase inhibitors with concurrent drugs that reduce heart rate (n = 60, 21.0%). Polypharmacy was observed in 82.6% (n = 237) of patients and was strongly associated with PIP (adjusted OR 24.1, 95% CI 9.0-64.5). CONCLUSIONS: Findings have revealed a high prevalence of PIP among PwD in Saudi Arabia that is strongly associated with polypharmacy. Future research should aim to explore key stakeholders' experiences and perspectives of medicines management to optimise medication use for this vulnerable patient population.

Barriers and facilitators to care for agitation and/or aggression among persons living with dementia in long-term care.

BACKGROUND: Agitation and/or aggression affect up to 60% of persons living with dementia in long-term care (LTC). It can be treated via non-pharmacological and pharmacological interventions, but the former are underused in clinical practice. In the literature, there is currently a lack of understanding of the challenges to caring for agitation and/or aggression among persons living with dementia in LTC. This study assesses what barriers and facilitators across the spectrum of care exist for agitation and/or aggression among people with dementia in LTC across stakeholder groups. METHODS: This was a qualitative study that used semi-structured interviews among persons involved in the care and/or planning of care for people with dementia in LTC. Participants were recruited via purposive and snowball sampling, with the assistance of four owner-operator models. Interviews were guided by the Theoretical Domains Framework and transcribed and analyzed using Framework Analysis. RESULTS: Eighteen interviews were conducted across 5 stakeholder groups. Key identified barriers were a lack of agitation and/or aggression diagnostic measures, limited training for managing agitation and/or aggression in LTC, an overuse of physical and chemical restraints, and an underuse of non-pharmacological interventions. Facilitators included using an interdisciplinary team to deliver care and having competent and trained healthcare providers to administer non-pharmacological interventions. CONCLUSIONS: This study advances care for persons living with dementia in LTC by drawing attention to unique and systemic barriers present across local and national Canadian LTC facilities. Findings will support future implementation research endeavours to eliminate these identified barriers across the spectrum of care, thus improving care outcomes among people with dementia in LTC.

Living with dementia: Exploring the intersections of culture, race, and dementia, stigma.

Research documents the presence of stigma and discrimination as key components in the lived experience of dementia. However, to date, there is limited understanding regarding how social location, particularly as it relates to culture and race, may shape this experience of stigma and discrimination. In this qualitative exploratory study, personal interviews were held with ten Chinese Canadians living with dementia focused on better understanding how culture, race, and dementia stigma influence their experiences. From the onset, themes related to stigma and discrimination were woven into the participants' stories about living with dementia. Consistent with other research, all participants described an increased sense of vulnerability and invisibility related to how both they and others responded to their diagnosis of dementia. Participants also provided examples of how this experience of stigma was compounded by culture, race, and immigration status. Importantly, these acts of stigma and discrimination were both externally and internally imposed, resulting in feelings of lack of safety and insecurity. This research draws attention to the increased vulnerability that accompanies a diagnosis of dementia and illustrates how this may be heightened by one's culture and racism.

Understanding the influence of different proxy perspectives in explaining the difference between self-rated and proxy-rated quality of life in people living with dementia: a systematic literature review and meta-analysis.

PURPOSE: Proxy assessment can be elicited via the proxy-patient perspective (i.e., asking proxies to assess the patient's quality of life (QoL) as they think the patient would respond) or proxy-proxy perspective (i.e., asking proxies to provide their own perspective on the patient's QoL). This review aimed to identify the role of the proxy perspective in explaining the differences between self-rated and proxy-rated QoL in people living with dementia. METHODS: A systematic literate review was conducted by sourcing articles from a previously published review, supplemented by an update of the review in four bibliographic databases. Peer-reviewed studies that reported both self-reported and proxy-reported mean QoL estimates using the same standardized QoL instrument, published in English, and focused on the QoL of people with dementia were included. A meta-analysis was conducted to synthesize the mean differences between self- and proxy-report across different proxy perspectives. RESULTS: The review included 96 articles from which 635 observations were extracted. Most observations extracted used the proxy-proxy perspective (79%) compared with the proxy-patient perspective (10%); with 11% of the studies not stating the perspective. The QOL-AD was the most commonly used measure, followed by the EQ-5D and DEMQOL. The standardized mean difference (SMD) between the self- and proxy-report was lower for the proxy-patient perspective (SMD: 0.250; 95% CI 0.116; 0.384) compared to the proxy-proxy perspective (SMD: 0.532; 95% CI 0.456; 0.609). CONCLUSION: Different proxy perspectives affect the ratings of QoL, whereby adopting a proxy-proxy QoL perspective has a higher inter-rater gap in comparison with the proxy-patient perspective.

Clinical characteristics of older patients with suspected or diagnosed dementia during hospitalization.

AIM: In Japan, an additional system for patients with suspected or diagnosed dementia during hospitalization for physical illness began in 2016. We examined the clinical characteristics of older patients with suspected or diagnosed dementia during hospitalization. METHODS: The study participants consisted of 569 patients. Current age, sex, comorbidities, causative disease for admission, body mass index (BMI), blood tests, environment before admission, prescription history before admission and rate of delirium were examined. Simple regression analysis for high-frequency diseases was carried out with the respective risk factors as independent variables. Multiple regression analysis was then carried out. RESULTS: Infection had the highest frequency in the causative diseases for admission. A total of 48% of patients had delirium during hospitalization. The delirium group had the highest frequency of being at home. In the infection group, BMI and serum albumin were lower in the non-infection group (BMI 19.0 ± 3.7 vs 20.4 ± 4.1; P < 0.001, albumin 2.1 ± 0.7 vs 3.3 ± 0.6 g/dL; P < 0.001 respectively). White blood cell count and C-reactive protein were higher than in the non-infection group, respectively (white blood cell count 11181.4 ± 6533.3 vs 8765.8 ± 111 424.3/µL; P = 0.007, C-reactive protein 8.6 ± 8.6 vs 3.0 ± 5.2 mg/dL; P < 0.001 respectively). Using independent factors associated with infection, multiple regression analysis was performed. BMI (P = 0.013), serum albumin (P < 0.001) and nursing home care before admission (P < 0.001) had significant correlations. CONCLUSIONS: Assessment of delirium and the environment before admission of older patients with suspected or diagnosed dementia when hospitalized are necessary. Furthermore, evaluation of nutrition might also contribute to reducing deterioration due to physical illness. Geriatr Gerontol Int 2024; ••: ••-••.

The impact of a hospital-based special care unit on behavioural and psychological symptoms in older people living with dementia.

BACKGROUND: Hospital patients with behavioural and psychological symptoms of dementia (BPSD) are vulnerable to a range of adverse outcomes. Hospital-based Special Care Units (SCUs) are secure dementia-enabling environments providing specialised gerontological care. Due to a scarcity of research, their value remains unconfirmed. OBJECTIVE: To compare hospital based SCU management of BPSD with standard care. DESIGN: Single-case multiple baseline design. SETTING AND PARTICIPANTS: One-hundred admissions to an 8-bed SCU over 2 years in a large Australian public hospital. METHODS: Repeated measures of BPSD severity were undertaken prospectively by specialist dementia nurses for patients admitted to a general ward (standard care) and transferred to the SCU. Demographic and other clinical data, including diagnoses, medication use, and care-related outcomes were obtained from medical records retrospectively. Analysis used multilevel models to regress BPSD scores onto care-setting outcomes, adjusting for time and other factors. RESULTS: When receiving standard care, patients' BPSD severity was 6.8 (95% CI 6.04-7.64) points higher for aggression, 15.6 (95% CI 13.90-17.42) points higher for the neuropsychiatric inventory, and 5.8 (95% CI 5.14-6.50) points higher for non-aggressive agitation compared to SCU. Patients receiving standard care also experienced increased odds for patient-to-nurse violence (OR 2.61, 95% CI 1.67-4.09), security callouts (OR 5.39 95% CI 3.40-8.52), physical restraint (OR 17.20, 95% CI 7.94-37.25) and antipsychotic administration (OR 3.41, 95% CI 1.60-7.24). CONCLUSION: Clinically significant reductions in BPSD and psychotropic administration were associated with SCU care relative to standard ward care. These results suggest more robust investigation of hospital SCUs, and dementia-enabling design are warranted.

Health Information Seeking Using Tech and Non-Tech Sources Among a Diverse Sample of Caregivers in the Deep South.

Caregivers of people living with dementia (PLWD) are often tasked with making decisions about their loved one's daily care and healthcare treatment, causing stress and decision-making fatigue. Many caregivers engage in health information seeking to improve their health literacy for optimal decision-making, though there is limited knowledge about the strategies used to increase their health literacy. This study involved a survey of caregivers in Alabama, most of whom were African American and/or living in rural communities that have historically underserved. The findings shed light on caregivers' experiences in seeking out health-related information and their perceptions of various sources of information.

A mediating role of self-care difficulty in the association between caregiver strain and the impact of caregiving on health: A cross-sectional secondary analysis.

Caregivers of people living with dementia face strain, reduced self-care, and poorer health status. However, research examining the links among those outcomes is limited. We explored the association between caregiver strain and the impact of caregiving on health status and identified the mediating role of self-care difficulty in this association. In the national caregiving dataset "Caregiving in the U.S. 2020," we included 312 caregivers in this study. Demographics, caregiving characteristics, a composite scale for caregiver strain, and single-item questions for the impact of caregiving on health status and self-care difficulty were used. Descriptive statistics and mediation analysis were conducted. Results revealed that higher caregiver strain was associated with higher self-care difficulty (OR 2.054, p < .001) and negative health changes due to caregiving (OR 2.719, p < .001). Self-care difficulty partially mediated this association. These results indicated the need to explore interventions or resources to offer caregivers to encourage their self-care awareness and activities.

A Scoping Review of Dementia Interventions in Home-Based Primary Care.

OBJECTIVES: Home-based primary care (HBPC) provides interdisciplinary, longitudinal, comprehensive care at home to homebound older adults. The prevalence of dementia among HBPC recipients is approximately 50%. To date, little research has been performed to determine whether dementia-specific interventions have been conducted in HBPC or their efficacy. We performed a scoping review to assess the landscape of dementia interventions in HBPC. DESIGN: Systematic scoping review. SETTING AND PARTICIPANTS: Care delivery programs for patients or caregivers of patients with dementia for the purpose of improving the management of dementia in the setting of HBPC. METHODS: The PRISMA-ScR protocol was followed. Literature searches were performed using PubMed, Embase, and Scopus for articles on dementia-focused interventions implemented in HBPC. Articles were excluded if they consisted of abstracts only, were not in English, or were not dementia interventions in HBPC. RESULTS: A total of 1657 unique titles and abstracts were screened. Overall, 1584 titles and abstracts were excluded, resulting in 73 full-text studies to assess for eligibility. Of these 73 full-text studies, 1 study met criteria for inclusion, an observational study assessing the implementation of the Resources for Enhancing Alzheimer's Caregiver Health (REACH) intervention in Veterans Affairs HBPC. That study found the intervention to be effective in reducing caregiver burden, with a decrease of 2 hours on duty per day, trending toward significance. Among the excluded 72 full-text studies, some studies included potentially relevant interventions that could be translated into HBPC care, including dementia interventions that targeted long-term services and supports, office-based primary care and other nonhome settings such as nursing homes, and home-based palliative care. CONCLUSIONS AND IMPLICATIONS: Despite high prevalence of dementia among homebound older adults receiving HBPC, there are a dearth of studies on HBPC-specific dementia interventions. Future studies should consider adapting and testing interventions found to be effective in other settings to HBPC.

Evaluation of Neurodegenerative Disorders with Amyloid-ß, Tau, and Dopaminergic PET Imaging: Interpretation Pitfalls.

Antiamyloid therapies for Alzheimer disease recently entered clinical practice, making imaging biomarkers for Alzheimer disease even more relevant to guiding patient management. Amyloid and tau PET are valuable tools that can provide objective evidence of Alzheimer pathophysiology in living patients and will increasingly be used to complement 18F-FDG PET in the diagnostic evaluation of cognitive impairment and dementia. Parkinsonian syndromes, also common causes of dementia, can likewise be evaluated with a PET imaging biomarker,18F-DOPA, allowing in vivo assessment of the presynaptic dopaminergic neurons. Understanding the role of these PET biomarkers will help the nuclear medicine physician contribute to the appropriate diagnosis and management of patients with cognitive impairment and dementia. To successfully evaluate brain PET examinations for neurodegenerative diseases, knowledge of the necessary protocol details for obtaining a reliable imaging study, inherent limitations for each PET radiopharmaceutical, and pitfalls in image interpretation is critical. This review will focus on underlying concepts for interpreting PET examinations, important procedural details, and guidance for avoiding potential interpretive pitfalls for amyloid, tau, and dopaminergic PET examinations.

Alzheimer's disease prevention: Apolipoprotein e4 moderates the effect of physical activity on brain beta-amyloid deposition in healthy older adults.

OBJECTIVES: To investigate if higher baseline physical activity levels are associated with less ß-amyloid burden and whether the ApoE4 genotype moderates this association cross-sectionally and longitudinally. DESIGN: Prospective cohort study. METHODS: 204 cognitively normal older adults (74.5 ±â€¯6.6 years; 26 % ApoE4-carrier) were analyzed. Baseline physical activity was measured using the Minnesota Physical Activity Questionnaire. Brain ß-amyloid burden was measured with positron emission tomography using 11C-labeled Pittsburgh compound. A subsample of 128 participants underwent longitudinal positron emission tomography (2.0 ±â€¯0.9 scans over 5 ±â€¯3 years). Statistical analysis was run according to physical activity (high/low group) and the ApoE4 genotype (carrier/noncarrier). RESULTS: The ApoE4 genotype moderated the relationship between physical activity and ß-amyloid, such that low physical activity had a greater impact on ß-amyloid deposition in ApoE4-carriers than noncarriers. This ApoE4 × physical activity effect on brain ß-amyloid deposition was also observed when all available ß-amyloid scan timepoints were included in the model. ß-amyloid deposition increased over time (p < 0.001), and ApoE4-carriers had disproportionately greater ß-amyloid accumulation than ApoE4-noncarriers. The lower physical activity group had marginally greater ß-amyloid accumulation than the higher physical activity group (p = 0.099), but there was no significant ApoE4 effect on ß-amyloid accumulation. CONCLUSIONS: Low physical activity in combination with the ApoE4-carrier genotype is associated with increased ß-amyloid burden, suggesting that ApoE4 moderates the effect of physical activity on ß-amyloid load. However, this effect was insufficient for baseline physical activity to modulate the change in ß-amyloid accumulation over time.

Uncovering the extent of dementia prevalence in Iran: a comprehensive systematic review and meta-analysis.

BACKGROUND: Dementia is one of the major causes of disability and dependency among older people worldwide. The formation of an aging population in Iran can be associated with societal problems, including age-related disorders such as dementia. This study aimed to estimate the prevalence of dementia& Alzheimer disease in adults aged 60 years or older and it's its geographical distribution in Iran. METHODS: A systematic review and meta-analysis study included articles published in both English and Persian languages and utilized various databases including: Google Scholar, PubMed, Web of Science, Magiran, and thesis database of medicine universities up to December 2022. The pooled prevalence was calculated using random effects models. The prevalence was reported separately for different geographical locations and types of area sampling, and age adjustment was performed for the selected studies. All statistical analyses were conducted using metaprop package in STATA version 17. The I2 statistic was applied to assess heterogeneity. RESULTS: The meta-analysis considered nine relevant studies that were carried out up to 2023 in Iran. The study found that the prevalence of dementia in central and east counties was estimated to be 0.14 (95% CI; 0.04-0.31), while in western counties, the prevalence was estimated to be 0.1 (95%CI; 0.01-0.27). The estimated overall crude prevalence of dementia was estimated at 0.14 (95% CI; 0.03-0.31). Estimated prevalence-based health centers sampling and hospital-based studies were 0.02 (95% CI; 0.02-0.03), 0.05 (95% CI 0.06-0.11), respectively. One study used nursing home sampling as the sampling method, and the estimated prevalence was 0.43 (95%CI 0.38-0.49). CONCLUSION: This is the first systematic review and meta-analysis of the prevalence of dementia's disease up to 2023 in Iran. The estimated overall prevalence of dementia is lower than the reported prevalence in European countries and similar to other Asian countries.

Effects of risk factors on the development and mortality of early- and late-onset dementia: an 11-year longitudinal nationwide population-based cohort study in South Korea.

BACKGROUND: Early-onset dementia (EOD, onset age < 65) and late-onset dementia (LOD, onset age ≥ 65) exhibit distinct features. Understanding the risk factors for dementia development and mortality in EOD and LOD respectively is crucial for personalized care. While risk factors are known for LOD development and mortality, their impact on EOD remains unclear. We aimed to investigate how hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, and osteoporosis influence the development and mortality of EOD and LOD, respectively. METHODS: Using the Korean National Health Insurance Service (NHIS) database, we collected 546,709 dementia-free individuals and followed up for 11 years. In the two study groups, the Younger group (< 65 years old) and the Older group (≥ 65 years old), we applied Cox proportional hazard models to assess risk factors for development of EOD and LOD, respectively. Then, we assessed risk factors for mortality among EOD and LOD. RESULTS: Diabetes mellitus and osteoporosis increased the risk of EOD and LOD development. Hypertension increased the risk of EOD, while atrial fibrillation increased the risk of LOD. Conversely, hyperlipidemia exhibited a protective effect against LOD development. Additionally, diabetes mellitus increased mortality in EOD and LOD. Hypertension and atrial fibrillation increased mortality in LOD, while hyperlipidemia decreased mortality in EOD and LOD. CONCLUSIONS: Risk factors influencing dementia development and mortality differed in EOD and LOD. Targeted public health interventions addressing age-related risk factors may reduce dementia incidence and mortality.

Association of midlife body-weight variability and cycles with earlier dementia onset: a nationwide cohort study.

BACKGROUND: Given the rising awareness of health-related lifestyle modifications, the impact of changes in body weight (BW) on cognitive function and dementia generates significant concern. This study aimed to investigate the association between BW changes and dementia in a middle-aged Korean population. METHODS: A retrospective, population-based longitudinal study was conducted utilizing data from the National Health Insurance Service (NHIS) database. Participants aged 40 years or older in 2011 who underwent at least five health checkups between 2002 and 2011 were followed-up for dementia until 2020. A total of 3,635,988 dementia-free Korean aged < 65 at baseline were examined. We analyzed the association between BW variability independent of the mean (VIM) with BW cycle, defined as either an upward or a downward direction of BW, and the risk of incident dementia. RESULTS: The results showed an increased risk of dementia in the highest quartile of VIM quartile (hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.47-1.58) compared to the lowest quartile of VIM. Additionally, the results showed an even higher increased risk of dementia in the highest BW cycle (≥ 2 cycles of 10% BW = HR 2.00, 95% CI 1.74-1.29). Notably, the combined concept of VIM with BW cycle showed an even higher dementia risk (highest quartile of VIM with ≥ 2 cycles of 10% BW = HR 2.37, 95% CI 2.05-2.74) compared to the baseline group (lowest quartile of VIM with < 3% BW cycle). CONCLUSIONS: The present study highlights the importance of considering BW changes with BW variability along with the BW cycle to assess dementia risk in detail, providing valuable insights for preventive strategies.

Unpaid carers of people with dementia and information communication technology: Use, impact and ideas for the future.

OBJECTIVES: Several 100,000s of people living with dementia in the UK are cared for at home by a spouse or relative. Few studies have considered the ICT needs and experiences of unpaid carers. This study explores the types of ICT unpaid carers use, the ways they use ICT, the impact of ICT-use, and their ideas for how ICT could be more supportive of their role as a carer. METHODS: Six focus groups with 32 unpaid carers of people living with dementia discussed their experiences of - and barriers to - using ICT. Transcripts were analysed thematically according to three types of ICT (mainstream, accessible and formal) and five functions (supporting domestic tasks, care management, monitoring, communication and information and education). RESULTS: Participants predominantly used mainstream ICT devices such as laptops and smartphones and internet-enabled applications including videoconferencing and social media platforms to support their daily activities and assist them in their caring role. A few participants discussed using accessible devices such as memory clocks and formal telecare and care-phone services for care management and monitoring functions. Participants' ideas for improvements centred on personalised communication applications that facilitate remote interactions and promote persons living with dementia's independence. Others expressed concerns about the growing need to use ICT to access formal care services and the inadequacy of the ICT infrastructure in some care homes. CONCLUSIONS: Unpaid carers mostly turn to readily available mainstream ICT to support their personal and care activities. Further research is required to understand the social impact of the increasing reliance of ICT across health, social and residential care service sectors. Improved cooperation between unpaid carers, technology developers and care services providers could align ICT development to the needs and experiences of families living with dementia and assist unpaid carers with identifying ICTs that optimally support their personal circumstances.

Molecular dissection of an immunodominant epitope in Kv1.2-exclusive autoimmunity.

Introduction: Subgroups of autoantibodies directed against voltage-gated potassium channel (Kv) complex components have been associated with immunotherapy-responsive clinical syndromes. The high prevalence and the role of autoantibodies directly binding Kv remain, however, controversial. Our objective was to determine Kv autoantibody binding requirements and to clarify their contribution to the observed immune response. Methods: Binding epitopes were studied in sera (n = 36) and cerebrospinal fluid (CSF) (n = 12) from a patient cohort positive for Kv1.2 but negative for 32 common neurological autoantigens and controls (sera n = 18 and CSF n = 5) by phospho and deep mutational scans. Autoantibody specificity and contribution to the observed immune response were resolved on recombinant cells, cerebellum slices, and nerve fibers. Results: 83% of the patients (30/36) within the studied cohort shared one out of the two major binding epitopes with Kv1.2-3 reactivity. Eleven percent (4/36) of the serum samples showed no binding. Fingerprinting resolved close to identical sequence requirements for both shared epitopes. Kv autoantibody response is directed against juxtaparanodal regions in peripheral nerves and the axon initial segment in central nervous system neurons and exclusively mediated by the shared epitopes. Discussion: Systematic mapping revealed two shared autoimmune responses, with one dominant Kv1.2-3 autoantibody epitope being unexpectedly prevalent. The conservation of the molecular binding requirements among these patients indicates a uniform autoantibody repertoire with monospecific reactivity. The enhanced sensitivity of the epitope-based (10/12) compared with that of the cell-based detection (7/12) highlights its use for detection. The determined immunodominant epitope is also the primary immune response visible in tissue, suggesting a diagnostic significance and a specific value for routine screening.

Immunotherapy with an antibody against CD1d modulates neuroinflammation in an α-synuclein transgenic model of Lewy body like disease.

The neuroinflammatory process in synucleinopathies of the aging population such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB) involves microglial activation as well as infiltration of the CNS by T cells and natural killer T cells (NKTs). To evaluate the potential of targeting NKT cells to modulate neuroinflammation, we treated α-syn transgenic (tg) mice (e.g.: Thy1 promoter line 61) with an antibody against CD1d, which is a glycoprotein expressed in antigen presenting cells (APCs). CD1d-presented lipid antigens activate NKT cells through the interaction with T cell receptor in NKTs, resulting in the production of cytokines. Thus, we hypothesized that blocking the APC-NKT interaction with an anti-CD1d antibody might reduce neuroinflammation and neurodegeneration in models of DLB/PD. Treatment with the anti-CD1d antibody did not have effects on CD3 (T cells), slightly decreased CD4 and increased CD8 lymphocytes in the mice. Moreover, double labeling studies showed that compared to control (IgG) treated α-syn tg mice, treatment with anti-CD1d decreased numbers of CD3/interferon γ (IFN γ)-positive cells, consistent with NKTs. Further double labeling studies showed that CD1d-positive cells co-localized with the astrocytes marker GFAP and that anti-CD1d antibody reduced this effect. While in control α-syn tg mice CD3 positive cells were near astrocytes, this was modified by the treatment with the CD1d antibody. By qPCR, levels of IFN γ, CCL4, and interleukin-6 were increased in the IgG treated α-syn tg mice. Treatment with CD1d antibody blunted this cytokine response that was associated with reduced astrocytosis and microgliosis in the CNS of the α-syn tg mice treated with CD1d antibody. Flow cytometric analysis of immune cells in α-syn tg mice revealed that CD1d-tet + T cells were also increased in the spleen of α-syn tg mice, which treatment with the CD1d antibody reduced. Reduced neuroinflammation in the anti-CD1d-treated α-syn tg mice was associated with amelioration of neurodegenerative pathology. These results suggest that reducing infiltration of NKT cells with an antibody against CD1d might be a potential therapeutical approach for DLB/PD.

Extending the phenotypic spectrum assessed by the CDR plus NACC FTLD in genetic frontotemporal dementia.

INTRODUCTION: We aimed to expand the range of the frontotemporal dementia (FTD) phenotypes assessed by the Clinical Dementia Rating Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains (CDR plus NACC FTLD). METHODS: Neuropsychiatric and motor domains were added to the standard CDR plus NACC FTLD generating a new CDR plus NACC FTLD-NM scale. This was assessed in 522 mutation carriers and 310 mutation-negative controls from the Genetic Frontotemporal dementia Initiative (GENFI). RESULTS: The new scale led to higher global severity scores than the CDR plus NACC FTLD: 1.4% of participants were now considered prodromal rather than asymptomatic, while 1.3% were now considered symptomatic rather than asymptomatic or prodromal. No participants with a clinical diagnosis of an FTD spectrum disorder were classified as asymptomatic using the new scales. DISCUSSION: Adding new domains to the CDR plus NACC FTLD leads to a scale that encompasses the wider phenotypic spectrum of FTD with further work needed to validate its use more widely. Highlights: The new Clinical Dementia Rating Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains neuropsychiatric and motor (CDR plus NACC FTLD-NM) rating scale was significantly positively correlated with the original CDR plus NACC FTLD and negatively correlated with the FTD Rating Scale (FRS).No participants with a clinical diagnosis in the frontotemporal dementia spectrum were classified as asymptomatic with the new CDR plus NACC FTLD-NM rating scale.Individuals had higher global severity scores with the addition of the neuropsychiatric and motor domains.A receiver operating characteristic analysis of symptomatic diagnosis showed nominally higher areas under the curve for the new scales.

Risk of depression in persons with Alzheimer's disease: A national cohort study.

INTRODUCTION: Depression is a risk factor and possible prodromal symptom of Alzheimer's disease (AD), but little is known about subsequent risk of developing depression in persons with AD. METHODS: National matched cohort study was conducted of all 129,410 persons diagnosed with AD and 390,088 with all-cause dementia during 1998-2017 in Sweden, and 3,900,880 age- and sex-matched controls without dementia, who had no prior depression. Cox regression was used to compute hazard ratios (HRs) for major depression through 2018. RESULTS: Cumulative incidence of major depression was 13% in persons with AD and 3% in controls. Adjusting for sociodemographic factors and comorbidities, risk of major depression was greater than two-fold higher in women with AD (HR, 2.21; 95% confidence interval [CI], 2.11-2.32) or men with AD (2.68; 2.52-2.85), compared with controls. Similar results were found for all-cause dementia. DISCUSSION: Persons diagnosed with AD or related dementias need close follow-up for timely detection and treatment of depression. Highlights: In a large cohort, women and men with AD had >2-fold subsequent risk of depression.Risks were highest in the first year (>3-fold) but remained elevated ≥3 years later.Risk of depression was highest in persons aged ≥85 years at AD diagnosis.Persons with AD need close follow-up for detection and treatment of depression.

Relationship of plasma biomarkers to digital cognitive tests in Alzheimer's disease.

INTRODUCTION: A major limitation in Alzheimer's disease (AD) research is the lack of the ability to measure cognitive performance at scale-robustly, remotely, and frequently. Currently, there are no established online digital platforms validated against plasma biomarkers of AD. METHODS: We used a novel web-based platform that assessed different cognitive functions in AD patients (N = 46) and elderly controls (N = 53) who were also evaluated for plasma biomarkers (amyloid beta 42/40 ratio, phosphorylated tau ([p-tau]181, glial fibrillary acidic protein, neurofilament light chain). Their cognitive performance was compared to a second, larger group of elderly controls (N = 352). RESULTS: Patients with AD were significantly impaired across all digital cognitive tests, with performance correlating with plasma biomarker levels, particularly p-tau181. The combination of p-tau181 and the single best-performing digital test achieved high accuracy in group classification. DISCUSSION: These findings show how online testing can now be deployed in patients with AD to measure cognitive function effectively and related to blood biomarkers of the disease. Highlights: This is the first study comparing online digital testing to plasma biomarkers.Alzheimer's disease patients and two independent cohorts of elderly controls were assessed.Cognitive performance correlated with plasma biomarkers, particularly phosphorylated tau (p-tau)181.Glial fibrillary acidic protein and neurofilament light chain, and less so the amyloid beta 42/40 ratio, were also associated with performance.The best cognitive metric performed at par to p-tau181 in group classification.