Dementia Assessment Research Articles

Plasma level of alpha-synuclein oligomers as a biomarker for isolated rapid eye movement sleep behavior disorder diagnosis and progression: a prospective cohort study.

Alpha-synuclein oligomers (o-α-syn) are pivotal in the pathogenesis of α-synucleinopathy. Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) serves as an early indicator of the disease, offering insights into disease mechanisms and early intervention. Nevertheless, the diagnostic and predictive potential of o-α-syn in iRBD remains largely unexplored. This study aimed to evaluate the plasma levels of o-α-syn in patients and investigate their utility as biomarkers for diagnosis of and predicting phenoconversion in iRBD. A total of 143 participants, including 77 polysomnography-confirmed iRBD patients and 66 normal controls (NC), were recruited for this longitudinal observational study. Baseline clinical assessments and plasma collection were conducted for all iRBD patients, with 72 of them undergoing regularly prospective follow-up assessments for parkinsonism or dementia. Plasma levels of o-α-syn were quantified using enzyme-linked immunosorbent assay, and were compared between groups using a general linear model adjusted for age and sex. The diagnostic performance of plasma o-α-syn in iRBD was evaluated by area under the receiver operating characteristic curve (AUC) with 95% CI. Cox regression analysis and Kaplan-Meier survival curves were employed to assess the predictive value of plasma o-α-syn for phenoconversion in iRBD. Plasma o-α-syn levels did not exhibit statistically significant differences among iRBD converter patients, iRBD nonconverter patients, and NC. The AUC for distinguishing NC from iRBD was 0.52 (95% CI: 0.42-0.62, p = 0.682). Spearman correlation analysis revealed a significant positive correlation between plasma o-α-syn levels and MOCA scores in the iRBD group (p < 0.001). Subgroup analyses indicated that iRBD patients with cognitive decline (p = 0.058) and depressive symptoms (p = 0.017) had notably lower o-α-syn levels compared to those without such symptoms. Over a median follow-up period of 5.83 years, 26 iRBD patients developed neurodegenerative synucleinopathies. Cox regression and Kaplan-Meier survival curve analyses indicated that plasma level of o-α-syn lacked a predictive value for disease conversion in iRBD patients. Despite a potential role in the pathophysiology of iRBD, o-α-syn are not appropriate biomarkers for diagnosing or predicting disease progression. While this study offers insights into the pathogenesis of iRBD and neurodegenerative synucleinopathies, further large-scale longitudinal studies are warranted to validate these findings.

Younger people with dementia registered to public mental health services in Victoria, Australia.

Objectives Individuals living with young-onset dementia fall through the gaps of adult and geriatric services. Given that non-cognitive symptoms of dementia in younger people are often psychiatric and behavioural in nature, these people may contact mental health services. There is sparse information investigating the frequency of people with young-onset dementia who contact mental health triage in Victoria. Methods Triage data were obtained from the Victorian Agency for Health Information. The data contained demographics for people registered with Victorian mental health services. Consumers who had an International Classification for Diseases code for dementia and were aged less than 65 years were identified as people with young-onset dementia. Using information of the frequency of people with young-onset dementia who were registered with each area-based mental health service, population census statistics were used to make estimates of the frequency of young-onset dementia. Results Of the 6172 people who had a dementia diagnosis, 1020 of them were aged less than 65 years and had young-onset dementia. There were proportionally more men who had young-onset dementia compared to women. There were more people with young-onset dementia registered to rural mental health services compared to metropolitan services. Conclusion Findings provide important information for service planning in Victoria. Recommendations include upskilling and education for the assessment of dementia for those clinicians who work in mental health services, particularly in rural regions.

Confiabilidade e validade de construto da Escala de Avaliação de Incapacidade na Demência - Versão Longa (DADL-BR)

Abstract Objectives Evaluate the reliability test-retest (intra and inter-examiner) and construct validity of the Long Version of Disability Assessment for Dementia (Brazilian Version - DADL-BR). Methods The DADL-BR was applied to 58 caregivers/family of older adults with dementia. The inter-examiner (n = 30) and intra-examiner (n = 28) reliability was assessed using the kappa test and Pearson’s correlation coefficient, and the internal consistency was assessed using Cronbach’s alpha. The construct validity (n = 48) was performed by comparing DADL-BR with MMSE. Results The results of the intra and inter-examiner demonstrated good reliability (0.72 and 0.74), as well as nearly perfect correlations (0.99) for both inter- and intra-examiner reliability. The internal consistency was excellent (0.87) and the results demonstrated a good correlation (0.74) between DADL-BR and MMSE in construct validity analysis. Conclusions DADL-BR can be considered reliable instrument and with good construct validity, considering internal consistency and test-retest reliability and may be constitute a useful instrument for assessing the occupational performance profile of older adults with dementia.

Higher Dynamic Balance Performance Was Associated With Cognitive Function Among U.S. Community-Dwelling Low-Income Older Adults.

Multiple studies have reported the association between balance performance and cognitive function among older adults. However, few studies have been conducted in low-income settings. This cross-sectional study examined the relationships of dynamic and static balance with cognitive function in community-dwelling low-income older adults in Orlando, Florida. Dynamic balance was assessed with a Short Physical Performance Battery (SPPB) and static balance with BTracks Balance System. Rowland Universal Dementia Assessment Scale (RUDAS) assessed cognition and Patient Health Questionnaire-9 assessed depressive symptoms. Multiple regression analysis showed dynamic balance was significantly associated with cognition, but static balance was not, controlling for depressive symptoms (N = 89, M age = 72.70, SD ± 6.95; females = 79). Specifically, higher dynamic balance was associated with better cognitive function. Cognitively healthy participants (RUDAS scores ≥23) scored 2.526 points higher in SPPB than those with possible cognitive impairment (RUDAS scores <23). Findings provide the evidence to suggest dynamic balance and cognitive function health disparities affecting older adults from low-income community. By implication, dynamic balance and cognitive function should be part of routine screening with older adults living in low-income communities.

Subjective Difficulty with Higher-Level Functional Capacity in Community-Dwelling Older People withMild Cognitive Impairment.

Mild cognitive impairment (MCI) is a predictor of future age-related dementia. We herein investigated associations of MCI with higher-level functional capacities, as well as with subjective difficulty regarding these functions, in community-dwelling older people, to identify a simple method for early MCI detection. We administered a test battery to 118 community-dwelling older people living in an urban area. The battery consisted of three tests;the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC), the Touch Panel-type Dementia Assessment Scale (TDAS), and the Geriatric Depression Scale-15. We then excluded participants with possible dementia or depression symptoms, and divided the remainder (n = 67) into an MCI group (n = 16) and a non-MCI group (n = 51), according to TDAS performance. Logistic regression analysis with the MCI and non-MCI groups as dependent variables indicated that TMIG-IC was a significant variable. Male sex and the perception that preparing meals and filling out pension forms had become more difficult were significantly associated with MCI, each independently increasing the probability of MCI. Subjective difficulty with higher-level functions and impairment in higher-level functional capacity may serve as indices for mass screening for MCI.

SEVERE ALZHEIMER’S DEMENTIA ALTERS THE RELATIONSHIP BETWEEN EXECUTIVE FUNCTION AND FALLS

Abstract Falls are a public health concern for older adults, particularly those with cognitive impairments, like mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia. Executive function (EF) is linked to falls in older adults, but little is known about the relationship between individual EF assessments and falls in individuals with varying cognitive statuses. Using cross-sectional secondary data analyses with binary logistic regression, we examined the associations between EF assessments (Trail Making Test (ΔTMT), Digit Span (DS), Stroop test, Clock Drawing Test, and phonemic/semantic fluency tests) and falls (fall history and subsequent falls) in 466 participants (aged 66-103) with either intact cognition, MCI, or AD dementia. Surprisingly, a significant interaction effect emerged with AD dementia and EF assessments (ΔTMT, DS, and semantic fluency), revealing that individuals with AD dementia with worse EF had a lower probability of prior fall history. These findings were influenced by a low percentage of reported falls in people with severe AD dementia. Further stratified analysis of the interaction effects showed that DS and semantic fluency were significantly associated with fall history in people without AD dementia. While some EF assessments were individually associated with falls, interpretations should be made cautiously, especially considering the appropriateness of the assessments for specific populations. The counterintuitive result may stem from factors specific to severe AD dementia. In conclusion, this study uncovers complex interactions between cognitive status, EF assessments, and fall history, and the potential for further investigation to enhance our understanding of falls in individuals with severe AD dementia.

A CROSS-NATIONAL COMPARISON OF RISK FACTORS ASSOCIATED WITH THE MOTORIC COGNITIVE RISK (MCR) SYNDROME

Abstract The Motoric Cognitive Risk (MCR) syndrome predicts risk of Alzheimer’s disease and vascular dementia. Cross-national comparisons of risk factors for MCR are important for identifying region-specific factors to design regionally tailored preventive interventions. We examined risk factors associated with MCR in 20,468 adults aged ≥65 years from the U.S Health and Retirement Study (HRS), English Longitudinal Study of Ageing (ELSA), Mexican Health and Aging Study (MHAS), China Health and Retirement Study (CHARLES), Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD), Survey of Health, Ageing and Retirement in Europe (SHARE) and Brazilian Longitudinal Study of Aging (ELSI-Brazil). MCR was defined as the presence of cognitive complaints and slow gait with no mobility disability and dementia. Associations between demographic [sex, education], medical [hypertension, diabetes, Parkinson’s, heart disease, stroke, obesity, depression, multiple falls], sensorimotor [grip strength, hearing] and behavioral factors [smoking, sedentariness, sleep quality], and prevalent MCR were examined using logistic models. Despite some overlap, cohort-specific risk factors for MCR were identified with relative risk ratios ranging as: 0.4-2.8 for education and multiple falls in HRS, 2.3-7.4 for poor hearing and sedentariness in ELSA, 2.3-2.6 for poor grip and diabetes in MHAS, 1.9-2.2 for depression and sedentariness in CHARLES, 0.5-5.3 for education and stroke in LASI-DAD, 0.3-2.4 for education and depression in SHARE and 2.4-4.0 for multiple falls and stroke in ELSI-Brazil. In this cross-sectional, cross-national comparison of 21 countries, MCR associated risk factors were region-specific, laying the foundation for tailored interventions to prevent MCR and subsequently dementia.

THE ASSOCIATION OF CAREGIVER STRAIN AND NEEDS OF CAREGIVERS AND PEOPLE LIVING WITH DEMENTIA

Abstract Caregivers play a vital part of dementia care management and are key to keeping people living with dementia at home. Providing this care can result in caregiver strain, especially among those who live in low or under resourced communities, such as rural or impoverished areas. One instrument for measuring caregiver strain among this population is the BRI caregiver strain instrument, which includes four dimensions of strain including caregiver mastery, relationship strain, health strain and social isolation. To date, little research assessing the validity of the instrument. We assessed the validity using confirmatory factor analysis in a cohort of 930 caregivers providing care to people undergoing assessment for dementia representing four diverse regions in Georgia (Atlanta, Albany, Augusta, and Macon). Then, we examined the associations of the lack of caregiver knowledge of dementia, care recipient function, and challenging behaviors using univariate and multivariate linear regression. We found that the four-factor solution showed good model fit and was appropriate for subsequent analysis with this population. In our regression models, we found that caregiver lack of understanding of dementia significantly predicted caregiver strain (β=2.09, P&amp;lt;.001). When controlling for care recipient function, lack of knowledge decreased in strength, but remained significant (β=1.86, P&amp;lt;.001). When adding challenging behaviors, lack of dementia knowledge lost significance and challenging behaviors became the strongest predictor of caregiver strain (β=2.03, P&amp;lt;.001). Caregiver strain is a multifactorial process and tools to reduce challenging behaviors and increase caregiver knowledge are promising points of intervention early in the diagnostic process.

THE RELATIONSHIP BETWEEN ORAL HEALTH AND COGNITIVE FUNCTION: EVIDENCE FROM THE LASI

Abstract The present study aimed to examine the association between oral health and cognitive function among older adults in India. Data for the study were selected from the Longitudinal Aging Survey of India (LASI, 2017-2019) and the LASI Diagnostic Assessment of Dementia (LASI-DAD) and 4,096 respondents aged 60 and above were included. Oral health was measured by self-reported physician-diagnosed oral health problems including presence of painful teeth, ulcers for more than two weeks, bleeding gums, swelling gums, loose teeth, dental cavities or caries, soreness or cracks in the corners of the mouth, or other problems as well as edentulism (i.e., losing all natural teeth, some natural teeth, or no teeth). A higher number of these problems indicated a more complex oral health condition. Cognitive function was measured by the standardized total score of all cognitive tests in the Harmonized Cognitive Assessment Protocol (HCAP). Binomial logistic regression models were used to analyze the relationship between the diagnosis of oral health problems and cognitive function. Results showed that having one or more oral health problems was associated with lower scores on cognitive function (β=-0.16, p=0.04), after controlling for sociodemographic characteristics and health status. There was no significant association between edentulism and cognitive function. Findings of the study suggest that oral health is integral to long-term overall health, specifically cognitive function. Our findings highlight the importance of educating older individuals about the connection between oral health and cognitive function along with the need for broadening their access to oral health care in India.

Propensity score analysis of red cell distribution width to serum calcium ratio in acute myocardial infarction as a predictor of in-hospital mortality.

Red cell distribution width (RDW) and serum calcium (Ca) levels are predictors of in-hospital mortality in acute myocardial infarction (AMI) patients. However, their sensitivity and specificity are limited. Therefore, this study aimed to determine whether the RDW to Ca ratio (RCR) acquired on admission can be used to predict the in-hospital mortality of AMI patients. This retrospective cohort study extracted clinical information from the Medical Information Market for Intensive IV (MIMIC-IV) database on 2,910 AMI patients enrolled via propensity score matching (PSM). Prognostic values were assessed using a multivariate logistic model and three PSM approaches. Analysis was performed based on stratified variables and interactions among sex, age, ethnicity, anemia, renal disease, percutaneous transluminal coronary intervention (PCI), coronary artery bypass grafting (CABG), atrial fibrillation, congestive heart failure, dementia, diabetes, paraplegia, hypertension, cerebrovascular disease, and Sequential Organ Failure Assessment (SOFA) score. A total of 4,105 ICU-admitted AMI patients were analyzed. The optimal cut-off value of the RCR for in-hospital mortality was 1.685. The PSM was performed to identify 1,455 pairs (2,910) of score-matched patients, with balanced differences exhibited for nearly all variables.The patients' median age was 72 years (range, 63-82 years) and 60.9% were male. The risk of in-hospital mortality incidence increased with increasing RCR levels. After adjusting for confounders, the risk ratio for the incidence of in-hospital mortality for high RCR was 1.75 [95% confidence interval (CI): 1.60-1.94, P = 0.0113] compared to that associated with low RCR in the PSM cohort. High RCR was also substantially implicated in in-hospital mortality incidence in the weighted cohorts [odds ratio (OR) = 1.76, 95% CI: 1.62-1.94, P = 0.0129]. Assessment of RCR in three groups showed that patients with high RCR also had a higher risk of in-hospital mortality (OR = 3.04; 95% CI, 2.22-4.16; P < 0.0001) than in patients with RCR in the adjusted model. In the sensitivity analysis, both the original and weighted groups showed similar results. The RCR at admission may be useful for predicting in-hospital mortality in ICU-admitted AMI patients.

Caring for persons with Dementia: a qualitative study of the needs of carers following care recipient discharge from hospital

BackgroundA randomised clinical trial titled the Carer End of Life Planning Intervention (CELPI) in people dying with dementia evaluated the effect of carer education and support about palliative care on care recipient outcomes. We present a pre-planned qualitative analysis of data collected during the CELPI trial in which needs of carers randomised to the study intervention group were assessed using a novel instrument (Carer Needs Directed Assessment in Dementia (CANDID). This tool aimed to identify carers’ perceptions of their own and their care-recipients’ needs and is an important step in identifying support provision for dementia-specific, palliative cares services upon hospital discharge.MethodsThe CANDID tool was designed to identify the needs and experiences of primary carers and of their care recipients during the last twelve months of the care recipient’s life. The tool consisted of 33 open-ended questions evaluating: symptom management, emergency contacts, advance care planning, carer’s perception of the care recipient’s future needs, carer’s current needs, and a proposed current and future care plan. The researcher’s philosophical assumption of interpretative phenomenology informed the study and approach to data collection and analysis. Qualitative data collected during interviews using this tool were thematically analysed in five steps: compiling, disassembling, reassembling, interpreting and concluding. An interpretation of participants’ reality emerged from their common experiences and the subjective meanings assigned to actions attached to the phenomena studied.ResultsThirty carer participants were included. Analysis identified three major themes: Carers’ perceived stressors, systemic barriers to care provision, and future planning. Issues identified included barriers to accessing supports, carer health and division between roles, financial burden, familial conflicts, adquate care in hospital and aged care facilities, concern about future needs, and end-of-life discussions.ConclusionThe CANDID tool enabled an evaluation of carer needs and concerns. Identifying those needs may inform a referral to palliative care services where the level of management required may be benenficial for both the person living with dementia and their primary carer.Trial RegistrationAustralian Clinical Trials Registration: (ACTRN12619001187134).

Suitability of Neuropsychological Tests for Assessments of Dementia in Africa

AbstractBackgroundNeuropsychological assessment is a centerpiece element for detecting, diagnosing, and following‐up the evolution of a dementia syndrome. It should be based on valid, reliable, standardized, and culturally suitable tests. However, the majority of the available tests were developed in western countries, and little is known about how these tests were translated and adapted in Africa in concordance with the international guidelines of psychological measurement. The aim of this review is to inspect closely the available neuropsychological tests used in Africa during the last three decades, examine their psychometric qualities, and analyze their cultural appropriateness to the local populations.MethodWe performed a systematic review on published articles dealing with the neuropsychological assessment of dementia in the 54 African countries during the latest 30 years on main scientific search databases (Web of Science, Academic Search Ultimate (Ebsco), ScienceDirect, Scopus, PubMed, APA PsycArticles, Embase, Cochran). The search keywords were: dement* and (neuropsych* or *cognit*) and (assessment or evaluation or test*) and country, without restrictions about the language of publication. Our approach is fourfold: i) papers' extraction, ii) tests identification, iii) concordance analysis, and iv) appropriateness evaluation.ResultWe identified a list of different tests used in each country and estimated the level of their concordance with the international guidelines of psychological measurement regarding the translation and adaptation procedures as well as the type of validity, reliability, and the availability of local standardized data. More than the two‐thirds of the identified tests did not respect the international guidelines of psychological measurement in developing, translating and adapting neuropsychological tests for the screening and assessment of dementia in Africa.ConclusionWe focused on the importance to fix measurement’s issues in the neuropsychological assessment of dementia in Africa. A suggested list of recommendations was provided to improve it especially that Africa is the second most populous continent after Asia and its elderly population is showing the most rapid increase in the world.

Peripheral and central markers of inflammation increased in frontotemporal dementia and related conditions

AbstractBackgroundNeuroinflammation is an important pathogenic mechanism in frontotemporal dementia (FTD) and related disorders. Postmortem and in vivo imaging studies have shown brain inflammation early in these conditions, and as proportionate to symptom severity and rate of progression. However, data on inflammation blood markers of inflammation and their relationship with central inflammation are limited. Here we assess inflammatory patterns of 41 serum cytokines from patients with FTD and related conditions, and their association with regional microglial activation (TSPO PET).MethodBlood samples were obtained from 29 healthy controls, and 214 patients with a clinical diagnosis of behavioural variant FTD (bvFTD = 52), primary progressive aphasia (PPA = 51), progressive supranuclear palsy (PSP = 58) and corticobasal syndrome (CBS = 53). Serum assays used the MesoScale Discovery V‐Plex‐Human Cytokine 36 plex panel plus five additional cytokine assays. A Principal Component Analysis (PCA) across all participants was used to reduce dimensionality of cytokine data. A sub‐group of patients (bvFTD = 10, PPA = 17, PSP = 17) underwent PET imaging with [11C]PK11195 PET, as index of microglial activation. Kruskal‐Wallis and pairwise t‐tests were performed on the resulting components to compare each patient cohort to controls. [11C]PK11195 non‐displaceable binding potential (BPND) was calculated in 83 regions of interest (ROIs) across the whole brain. Spearman correlations tested associations between cytokine components and regional [11C]PK11195 BPND.ResultSixteen cytokines were undetectable in &gt;50% of participants and thus excluded. The first component identified by the PCA on the remaining 25 cytokines (explaining 19.7%) was strongly loaded by pro‐inflammatory cytokines (Figure 1, left). Kruskal–Wallis one‐way analyses of variance on detected significant differences across the groups (χ2(4) = 11.0, p = 0.027), and the pairwise t‐tests identified significant differences between each patient cohort and controls (Figure 1, right). Spearman correlations identified regional positive associations between individual cytokine‐component scores and microglial activation in frontal and brainstem regions across the whole group (R≥0.25), and syndrome‐specific regional patterns (Figure 2).ConclusionThis data‐driven approach identified a pro‐inflammatory profile across FTD and related conditions, which is positively associated with higher levels of microglial activation in syndrome‐related key brain regions. Blood‐based tests could greatly increase the scalability and access to neuroinflammatory assessment in dementia and experimental medicine studies.

Peripheral and central markers of inflammation increased in frontotemporal dementia and related conditions

AbstractBackgroundNeuroinflammation is an important pathogenic mechanism in frontotemporal dementia (FTD) and related disorders. Postmortem and in vivo imaging studies have shown brain inflammation early in these conditions, and as proportionate to symptom severity and rate of progression. However, data on inflammation blood markers of inflammation and their relationship with central inflammation are limited. Here we assess inflammatory patterns of 41 serum cytokines from patients with FTD and related conditions, and their association with regional microglial activation (TSPO PET).MethodBlood samples were obtained from 29 healthy controls, and 214 patients with a clinical diagnosis of behavioural variant FTD (bvFTD = 52), primary progressive aphasia (PPA = 51), progressive supranuclear palsy (PSP = 58) and corticobasal syndrome (CBS = 53). Serum assays used the MesoScale Discovery V‐Plex‐Human Cytokine 36 plex panel plus five additional cytokine assays. A Principal Component Analysis (PCA) across all participants was used to reduce dimensionality of cytokine data. A sub‐group of patients (bvFTD = 10, PPA = 17, PSP = 17) underwent PET imaging with [11C]PK11195 PET, as index of microglial activation. Kruskal‐Wallis and pairwise t‐tests were performed on the resulting components to compare each patient cohort to controls. [11C]PK11195 non‐displaceable binding potential (BPND) was calculated in 83 regions of interest (ROIs) across the whole brain. Spearman correlations tested associations between cytokine components and regional [11C]PK11195 BPND.ResultSixteen cytokines were undetectable in &gt;50% of participants and thus excluded. The first component identified by the PCA on the remaining 25 cytokines (explaining 19.7%) was strongly loaded by pro‐inflammatory cytokines (Figure 1, left). Kruskal–Wallis one‐way analyses of variance on detected significant differences across the groups (χ2(4) = 11.0, p = 0.027), and the pairwise t‐tests identified significant differences between each patient cohort and controls (Figure 1, right). Spearman correlations identified regional positive associations between individual cytokine‐component scores and microglial activation in frontal and brainstem regions across the whole group (R≥0.25), and syndrome‐specific regional patterns (Figure 2).ConclusionThis data‐driven approach identified a pro‐inflammatory profile across FTD and related conditions, which is positively associated with higher levels of microglial activation in syndrome‐related key brain regions. Blood‐based tests could greatly increase the scalability and access to neuroinflammatory assessment in dementia and experimental medicine studies.

Attitudes and Practices towards the use of technology‐screening tools, diagnosis, and management of cognitive impairment in primary care

AbstractBackgroundPrevious studies in the Cuban population suggest that Alzheimer’s Disease and related dementias (ADRD) are under‐diagnosed at primary care relative to population estimates. Recent interventions aimed to introduce the use of technology based cognitive assessments have been validated for primary care (e.g., Brain Health Assessment).However, the implementation of newly develop tools depends on the Primary care providers’ (PCPs) barrier and attitudes toward the diagnosis and management of patients with ADRD at a primary care level. Here we aimed to assess PCPs’ attitudes towards ADRD diagnosis, and the use of technology based cognitive assessments.Method84 PCPs were randomly selected form 10 primary care clinics. Sample size include a wide range of PCPs, including: family medicine (n = 54), neurologist (n = 2), psychiatrists(n = 13), psychologists(n = 10), clinicians (n = 3) and geriatricians (n = 2)). A questionnaire on Dementia assessment and management in primary care settings was administered to the participants. Descriptive statistics were employed for summarizing the data. Kruskal Wallis association test was utilized for determining associations between provider characteristics and outcomes.ResultsMost participants were female (n = 64, 76.2%), over 50 years old (n = 36, 52.9%) and family medicine practitioners (64.3%). The average number of patients consulted per month by PCPs were 250 (CI95% 250‐367) and over 60% of them were 55 years or older. Most of the PCPs (n = 63, 75.0%) will not refer patients with suspected ADRD if they had the training and instruments and technologies for the diagnosis at a primary care level. Lack of time (n = 59, 70.2%) and lack of confidence in their abilities (n = 68, 81.0%) were the most cited barriers for the diagnosis and management of ADRD . Around 80.0% of the interviewed practitioners considered the use of technology based cognitive assessments as important or very important tool for ADRD diagnosis. The positive attitudes of the PCPs for using technologies were correlated with the municipalities where they work (p = 0.01) and the continuous professional development of the PCPs (p = 0.03).ConclusionThere are still barriers for the diagnosis of ADRD at a primary care level. Though PCPs are willing to implement technology based cognitive assessments in their daily practice, addressing existing barriers is key for success

P208: The activities of Initial- phase Intensive Support Team for Dementia (IPIST) in Japan

Objective:The Intensive Initial Support Team for Dementia (IPIST) is a multidisciplinary outreach team that provides intensive initial assessment and support for dementia in Japan, introduced based on the Memory Service in the UK. All municipalities are required to establish at least one team, which consists of at least one physician and two professional staffs such as public health nurses and care workers. IPIST usually complete the work within approximately six months, including consultation with medical specialists and introduction of public supports. IPIST sometimes faces “complex case” that is difficult to manage. Because complex cases often have psychiatric problems, accessibility to psychiatric resources is important for IPIST. This study investigated the percentage of psychiatric professionals among IPIST members and the characteristics of complex cases they face.Methods:Through all 1741 municipalities in Japan, a questionnaire was distributed to each IPIST regarding the complex cases they experienced during April-September 2020. The questionnaire asked for the characteristics of each IPIST (e.g., specialty of the team physician, availability of staff with psychiatric expertise, etc.) and which of the 12 categories each complex case fit into, allowing multiple choice.Results:We could collect responses from 1291 IPISTs. 43.3% of IPISTs had a psychiatrist, 43.1% had an internal medicine physician, 13.4% had a neurologist, and 17.0% had some other physician as their team physician. In addition, 59.4% of the teams had medical staff members with psychiatric experience, including psychiatrists. A total of 7340 cases were reported as complex cases. While the most common category for difficulties in case management was “refusal of services” (19.5%), factors requiring psychiatric intervention such as “behavioral and psychological symptoms of dementia” (16.0%), “co-occurring mental illness” (7.3%), “complaints from neighbors” (7.1%), and “trash-house” (4.3%) were also frequently observed.Conclusion:The survey revealed that many IPISTs already had psychiatrists and other professionals with clinical psychiatric experience, and that they managed a lot of complex cases with issues that would be the target of psychiatric intervention. We believe early psychiatric engagement is important in many complex cases in outreach support for community residents with suspected dementia.

The utility of neuropsychological process scores in verbal recall and verbal fluency in persons with or at risk for dementia: Data from COMPASS‐ND

AbstractBackgroundSubjective cognitive decline (SCD) is considered a risk state for decline to mild cognitive impairment (MCI) or dementia due to Alzheimer’s disease (AD). By definition, individuals with SCD report concerns about changes in cognitive function but perform within normal limits on formal testing. This study examined whether neuropsychology process scores on tests of auditory learning and memory (the Rey Auditory Verbal Learning Test, RAVLT) and semantic and phonemic oral fluency were able to distinguish subtle difficulties in cognition, over and above total scores.MethodWe used data from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS‐ND) study to examine performance in 60 cognitively normal (CN) older adults with no cognitive complaints (mean age = 69 years; mean education = 16 years), 55 participants with SCD (age = 70; education = 17), 102 with MCI (age = 72; education = 16), and 47 with AD (age = 75; education = 15). Participants were matched on age and education, except for AD participants who were older. Age and education were co‐variates in all analyses. For the RAVLT, we examined delayed recall total scores, and process measures of primacy and recency recall on the second learning trial. For fluency, we examined total scores, and process measures of clustering, switching, word frequency, and age of acquisition.ResultRAVLT: An item position by group interaction revealed that primacy scores better distinguished all participant groups (CU&gt;SCD&gt;MCI&gt;AD) than delayed recall (CU = SCD = MCI&gt;AD). The left subiculum hippocampal subfield volume was positively associated with primacy scores in the MCI group, controlling for intracranial volume and age. Oral fluency: Both phonemic and semantic total scores discriminated CN, MCI, and AD participants in a stepwise manner; there was a non‐significant trend for SCD participants to perform more poorly than CN. Process scores did not provide additional discrimination.ConclusionThese findings indicate that primacy scores for episodic recall are sensitive to subtle memory deficits in SCD and may reflect hippocampal atrophy, supporting the clinical use of using serial position effects in the assessment of MCI and SCD.Learning Objective(s): Participants will learn about more detailed scoring methods for common neuropsychological tests, their sensitivity to subtle cognitive deficits in SCD, and their relationship with neuroanatomical structures.

Co‐morbidity of sensory loss (hearing, vision, olfaction) in persons with or at risk for dementia: Implications for brain structure and function

AbstractBackgroundHearing, vision, and olfactory loss have each independently been associated with cognitive decline and increased risk for dementia. Research has examined their individual relationships with brain structure and function, but these predictors have not been examined together in older adults who vary along a spectrum of risk for dementia. We examined groups who range from relatively low risk (those with normal cognition and no cognitive complaints (NC)), to those with higher risk, namely individuals with subjective reports of cognitive decline (SCD) but normal cognition and those with mild cognitive impairment (MCI).MethodWe used data from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS‐ND) study. Hearing loss was assessed with a pure‐tone screening protocol and a speech‐in‐noise test, vision was assessed with the MNRead for visual acuity and the MARS test for contrast sensitivity, and olfaction was assessed with the Brief Smell Identification Test (BSIT). We examined the frequency of sensory deficits in 60 NC (mean age = 69 years; mean education = 16 years), 55 participants with SCD (age = 70; education = 17), 102 with MCI (age = 72; education = 16), and 47 with Alzheimer’s disease (AD, age = 75; education = 15). Participants were matched on age and education, except for AD participants who were older.ResultsThe frequency of having at least one impairment in at least one sensory domain increased across groups (55% NC, 62% SCD, 75% MCI, 96% AD). A deficit in olfaction was the most common single deficit. Sensory deficits became increasing more co‐morbid across the risk spectrum. Hearing loss and olfaction loss were each associated with lower hippocampal volume and hearing loss was associated with alterations in functional brain connectivity in the default mode network.ConclusionThese analyses indicate that sensory loss is highly frequent and co‐morbid in persons with or at risk for dementia. These findings have implications for cognition, brain function, functional activities, and care delivery for persons with or at risk for dementia.

An exploratory pilot study on diffusion MRI measurement of cortical microstructural neurodegeneration for the assessment of dementia in a Japanese hospital setting

AbstractBackgroundThe use of diffusion MRI (dMRI) to assess cortical microstructure has demonstrated promise for measuring neurodegeneration in Alzheimer’s disease (PMID:33174658, PMID:36281682) and frontotemporal dementia (PMID:32641807, PMID:34686217) using retrospective research datasets. The ultimate translation of research findings to clinical practice requires prospective studies in hospital settings. A pilot study at the National Hospital Organization, Niigata, was designed and successfully delivered.MethodThe study was registered on Oct 5th 2021 (jRCT1032210367). Scanning took place between Oct 13th 2021 and June 30th 2022, on a 1.5T Philips Ingenia. MRI data was transferred using a secure cloud gateway (Cimar). A total of 10 healthy controls (HC), 10 Alzheimer’s disease (AD) patients, and 5 frontotemporal dementia (FTD) patients were recruited.Structural (3D T1‐weighted) and dMRI (2mm isotropic, 32 directions at b = 1000 s/mm2) scans were used to calculate cortical mean diffusivity and three neuropathologically‐inspired cortical diffusivity measures: the angle between the radial minicolumnar direction and the principal diffusion direction (AngleR); the principal diffusion component parallel with the minicolumns (ParlPD), and the diffusion components perpendicular to the minicolumns (PerpPD+). Metrics were also summarized over AD signature regions (Ridgway et al., CTAD 2022).ResultOf the n = 25 cases, 18 had clear clinical diagnoses after neurological and radiological assessment, while 7 were more complex (including focal bleeding, focal ischemia, meningioma, supra‐sellar tumour). Characteristics are given in Table 1.Figure 1 plots two whole‐brain measures: PerpPD+ and AngleR. A threshold of PerpPD+ &gt; 1.325 has 100% sensitivity to the 8 clear AD cases, with 86% specificity for 7 controls vs AD. Results were less clear for FTD using whole‐brain measures alone.The Cohen’s d effect size for clear AD versus clear HC was 2.82 using whole‐brain PerpPD+. Using signature regions (Figure 2b) improved separation to d = 3.08 for PerpPD+, compared to d = 1.87 for the cortical thickness signature (Figure 2a).ConclusionThe pilot study demonstrated practical feasibility and good performance for distinguishing AD from HC using cortical diffusivity measures acquired at the 1.5T field‐strength common in hospitals in Japan. Future work will investigate FTD signature regions. A larger multicentre study assessing diagnostic accuracy using additional AD biomarkers is warranted.

Gene‐Based Analysis with Functional Annotation in 2680 South Asians from the LASI‐DAD Study

AbstractBackgroundThe prevalence of dementia among South Asians across India is as high as 10% in those 55 years and older, yet little is known about the risk dementia factors in this population. To date, most known genetic risk loci of Alzheimer’s disease (AD) were identified from studies conducted in European Ancestry (EA) participants. The full mutational spectrum and the functional relevance of those loci in South Asians remains unknown. Analyzing DNA sequence data poses challenges due to the large number of rare variants tested, with most variants likely not associated with dementia. These challenges can be addressed with an annotation‐informed gene‐based analysis.MethodUsing whole‐genome sequence data from 2680 participants from the Diagnostic Assessment of Dementia for the Longitudinal Aging Study of India (LASI‐DAD), we performed a gene‐based analysis of 84 genes known to be associated with AD in EA. We investigated associations with the Hindi Mental State Examination (HMSE) score, general cognitive function, and five cognitive domains. For each gene, we examined missense/loss‐of‐function (LoF) variants and brain‐specific promoter/enhancer variants, separately, both with and without incorporating additional annotation weights (e.g., deleteriousness, conservation scores) using the variant‐Set Test for Association using Annotation infoRmation (STAAR).ResultIn the missense/LoF analysis, when controlling for age, sex, state/territory, and the first 10 principal components, 16 genes were nominally associated with at least one cognitive outcome (p&lt;0.05). Three genes (APOE, PICALM, TSPOAP1) were significant after multiple testing correction (FDR q&lt;0.1). In the brain‐specific promoter/enhancer analysis, 21 genes were nominally significant, but none were significant at FDR q&lt;0.1. Results remained similar after adding annotation weights. The most strongly associated variants in each gene were rs429358 (APOE), rs779406084 (PICALM), and rs9913145 (TSPOAP1). rs779406084 is a missense mutation that is more prevalent in this Indian sample (MAF = 0.075%) compared to EA (MAF = 0.0015%).ConclusionSome genes associated with AD in EA are also associated with cognitive outcomes in South Asians in India. Analyzing sequence data in South Asians provides opportunities to identify potential novel causal variants that are enriched in this population.