Emerging drugs for dementia with Lewy Bodies: a review of Phase II & III trials.

INTRODUCTION: Despite faster cognitive decline and greater negative impact on patients and family caregivers, drug development efforts in Dementia with Lewy Bodies (DLB) fall behind those for Alzheimer's Disease (AD). Current off-label drug DLB treatment options are limited to symptomatic agents developed to address cognitive deficits in AD, motor deficits in Parkinson's Disease, or behavioral symptoms in psychiatric disease. Aided by recent improvements in DLB diagnosis, a new focus on the development of disease-modifying agents (DMA) is emerging. AREAS COVERED: Driven by evidence supporting different pathological mechanisms in DLB and PDD, this review assesses the evidence on symptomatic drug treatments and describes current efforts in DMA development in DLB. Specifically, our goals were to: (1) review evidence supporting the use of symptomatic drug treatments in DLB; (2) review the current DMA pipeline in DLB with a focus on Phase II and III clinical trials; and (3) identify potential issues with the development of DMA in DLB. Included in this review were completed and ongoing drug clinical trials in DLB registered on ClinicalTrials.gov (no time limits set for the search) or disseminated at the 2023 international conference on Clinical Trials in AD. Drug clinical trials registered in non-US clinical trial registries were not included. EXPERT OPINION: Adoption of current symptomatic drug treatments used off-label in DLB relied on efficacy of benefits in other disorders rather than evidence from randomized controlled clinical trials. Symptoms remain difficult to manage. Several DMA drugs are currently being evaluated as either repurposing candidates or novel small molecules. Continued improvement in methodological aspects including development of DLB-specific outcome measures and biomarkers is needed to move the field of DMA drug development forward.

Global rural health disparities in Alzheimer's disease and related dementias: State of the science.

INTRODUCTION: Individuals living in rural communities are at heightened risk for Alzheimer's disease and related dementias (ADRD), which parallels other persistent place-based health disparities. Identifying multiple potentially modifiable risk factors specific to rural areas that contribute to ADRD is an essential first step in understanding the complex interplay between various barriers and facilitators. METHODS: An interdisciplinary, international group of ADRD researchers convened to address the overarching question of: "What can be done to begin minimizing the rural health disparities that contribute uniquely to ADRD?" In this state of the science appraisal, we explore what is known about the biological, behavioral, sociocultural, and environmental influences on ADRD disparities in rural settings. RESULTS: A range of individual, interpersonal, and community factors were identified, including strengths of rural residents in facilitating healthy aging lifestyle interventions. DISCUSSION: A location dynamics model and ADRD-focused future directions are offered for guiding rural practitioners, researchers, and policymakers in mitigating rural disparities. HIGHLIGHTS: Rural residents face heightened Alzheimer's disease and related dementia (ADRD) risks and burdens due to health disparities. Defining the unique rural barriers and facilitators to cognitive health yields insight. The strengths and resilience of rural residents can mitigate ADRD-related challenges. A novel "location dynamics" model guides assessment of rural-specific ADRD issues.

Characterization of dementia with Lewy bodies (DLB) and mild cognitive impairment using the Lewy body dementia module (LBD-MOD).

INTRODUCTION: The National Institute on Aging Alzheimer's Disease Research Center program added the Lewy body dementia module (LBD-MOD) to the Uniform Data Set to facilitate LBD characterization and distinguish dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). We tested the performance of the LBD-MOD. METHODS: The LBD-MOD was completed in a single-site study in 342 participants: 53 controls, 78 AD, and 110 DLB; 79 mild cognitive impairment due to AD (MCI-AD); and 22 MCI-DLB. RESULTS: DLB differed from AD in extrapyramidal symptoms, hallucinations, apathy, autonomic features, REM sleep behaviors, daytime sleepiness, cognitive fluctuations, timed attention tasks, and visual perception. MCI-DLB differed from MCI-AD in extrapyramidal features, mood, autonomic features, fluctuations, timed attention tasks, and visual perception. Descriptive data on LBD-MOD measures are provided for reference. DISCUSSION: The LBD-MOD provided excellent characterization of core and supportive features to differentiate DLB from AD and healthy controls while also characterizing features of MCI-DLB.

Perceived Benefits of Using Nonpharmacological Interventions in Older Adults With Alzheimer's Disease or Dementia With Lewy Bodies.

The current qualitative research explored perceived effects of three nonpharmacological interventions (chair yoga [CY], participatory music intervention [MI], and chair-based exercise [CBE]) in managing symptoms in older adults with Alzheimer's disease or dementia with Lewy bodies from family caregivers' perspectives. Three focus groups were conducted following completion of the 12-week interventions. Constant comparative analysis determined whether each intervention had perceived effects on symptoms, based on caregivers' perspectives. Three major themes emerged: (a) Changes in Cognitive Symptoms, (b) Changes in Physical Function, and (c) Changes in Mood, Behavioral Symptoms, and Sleep Disturbance. Results can be integrated into treatment plans for older adults with dementia. Future research should focus on CY or CBE with support from caregivers to manage dementia symptoms and compare CY or CBE practiced with caregivers against CBE or CY practiced solely by participants with dementia. [Journal of Gerontological Nursing, 46(1), 37-46.].

Intention to Be Screened for Alzheimer's Disease in Nondemented Older Adults: Integrated Behavioral Model and Self-Efficacy as Mediation Effect.

The study explored factors associated with intention to be screened for Alzheimer's disease (AD). The study also examined whether self-efficacy mediates the relationship between knowledge about screening and the intention to be screened for AD. A population-based, random-digit dialing survey was performed and 1,043 responses were collected from a sample of nondemented persons (50 years or older) living in urban, suburban, and rural areas in a Midwestern state. The findings showed that participants who were younger and who had higher levels of (a) perceived benefits and barriers, (b) social support, and (c) self-efficacy reported higher levels of intention to be screened for AD. Older adults with positive life orientation reported greater intention to be screened for AD, whereas depressed participants were more likely to report a plan to be screened for AD. Self-efficacy mediated the relationship between knowledge about screening and intention to be screened. Older adults were more likely to report intention to be screened when they had positive attitudes about the screen and believed that they could receive the screen. The intention to be screened for AD could serve public awareness by defining effective ways to assist older adults to seek a cognitive screen.

Improving data collection, documentation, and workflow in a dementia screening study.

BACKGROUND: A clinical study team performing three multicultural dementia screening studies identified the need to improve data management practices and facilitate data sharing. A collaboration was initiated with librarians as part of the National Library of Medicine (NLM) informationist supplement program. The librarians identified areas for improvement in the studies' data collection, entry, and processing workflows. CASE PRESENTATION: The librarians' role in this project was to meet needs expressed by the study team around improving data collection and processing workflows to increase study efficiency and ensure data quality. The librarians addressed the data collection, entry, and processing weaknesses through standardizing and renaming variables, creating an electronic data capture system using REDCap, and developing well-documented, reproducible data processing workflows. CONCLUSIONS: NLM informationist supplements provide librarians with valuable experience in collaborating with study teams to address their data needs. For this project, the librarians gained skills in project management, REDCap, and understanding of the challenges and specifics of a clinical research study. However, the time and effort required to provide targeted and intensive support for one study team was not scalable to the library's broader user community.

The Relationship Between Mobility Dysfunction Staging and Global Cognitive Performance.

OBJECTIVES: To assess the relationship and the directionality between mobility and cognitive performance. METHOD: A cross-sectional analysis of a racially/ethnically diverse sample of 327 community-dwelling adults (mean age=68.9±9.9 y; range, 40 to 100 y) categorized as having no mobility dysfunction, upper-extremity (UE) impairment, lower-extremity (LE) impairment, or mobility limitation (both UE and LE impairments), and compared by global cognition with multiple hierarchical linear regression adjusted for sociodemographic, health, and mood factors. A bootstrapping mediation analysis investigated the directionality of the mobility-cognition association. RESULTS: LE (Est.=-2.95±0.77, P=0.001) but not UE impairment (Est.=-1.43±1.05, P=0.175) was associated with a poorer global cognitive performance/impairment. The presence of mobility limitation had the strongest effect on cognition (Est.=-3.78±1.09, P<0.001) adjusting for sociodemographic factors, body composition, comorbidities, and mood. Mediation analysis indicated that the relationship between cognition and mobility likely operates in both directions. DISCUSSION: The association between cognitive function and mobility follows a dose-response pattern in which the likelihood of poor global cognition increases with the progression of mobility dysfunction, with evidence that LE impairments may be better indicators of an impaired cognitive status than UE impairments. Using brief, valid tools to screen older patients for early signs of mobility dysfunction, especially when the LE is affected, is feasible, and may provide the first detectable stage of future cognitive impairment and provide actionable steps for interventions to improve performance, reduce burden, and prevent the development of physical disability and loss of independence.

Trajectory of Mobility Decline by Type of Dementia.

Cognitive and physical aspects of functionality are closely related. However, whether physical decline differs by dementia type and progression rate is debatable. To address these issues, we conducted a longitudinal study of 766 older adults whose physical performance and cognitive status were assessed annually with standard assessment tools [eg, Physical Performance Test, Clinical Dementia Rate (CDR)] for 8 years. Compared with participants who remained cognitively normal, those progressing to later-stage dementia (CDR=1) declined in their mobility by a factor of 2.82 (P<0.001), followed by those who maintained a later-stage diagnosis (slope=-1.84, P<0.001), those progressing from early-stage to later-stage (CDR=0.5 to CDR=1) dementia (slope=-1.20, P<0.001), and those who progressed to early-stage dementia (slope=-0.39, P=0.038) suggesting a steeper physical decline with dementia progression, particularly in those with the fastest disease progression. Although all types of dementia experienced mobility decline, those progressing to non-Alzheimer disease (AD) dementias, especially vascular dementia declined faster than those who remained normal (slope=-2.70, P<0.001) or progressed to AD (slope=-2.18, P<0.001). These associations were better captured by the gait/balance component of physical functionality. Our findings suggest that rapidly progressing dementia patients particularly those with non-AD subtypes should be targeted for interventions to maintain or improve gait/balance and prevent functional decline and disability although AD patients may also benefit.

Anosognosia increases caregiver burden in mild cognitive impairment.

OBJECTIVE: Our aim is to determine the clinical correlates of impaired insight in patients with mild cognitive impairment (MCI) by examining its impact on cognition, functional status, neuropsychiatric symptoms, and caregiver burden. METHODS: The study involved 75 patients with MCI and their caregivers. Patients and caregivers underwent a comprehensive evaluation including the Clinical Dementia Rating, memory tests, and the Functional Assessment Questionnaire. Behavioral symptoms were assessed by the Neuropsychiatric Inventory, caregiver burden by the Zarit Burden Inventory, and insight by comparing self-report on the AD8 dementia screening tool to informant collateral. Patients were asked about their perceptions of their memory, and answers were compared with informants' responses. Patient mood was assessed with the Hospital Anxiety Depression Scale. RESULTS: There was a significant difference in AD8 scores among patients who retained versus lacked insight. Zarit Burden Inventory scores showed a significant rise as patient insight declined; the burden appeared greater on spouse versus non-spouse caregivers. Patients with poor insight had significantly worse ratings in Clinical Dementia Rating domains of personal care and judgment, while patients who retained insight had significantly higher depression and anxiety. Insight impairment was associated with worse caregiver mood. CONCLUSIONS: Decreased patient awareness for cognitive problems was significantly associated with higher caregiver burden, independent of neuropsychiatric symptoms, functional abilities, and cognition. Personal care, judgment, and problem-solving skills could contribute to caregiver burden. Increased awareness seemed a source of patient depression and anxiety. The research highlights the need to focus on the needs of MCI caregivers and to incorporate psychosocial assessments of caregiver-patient dyads into office visits.

Comparison of 2 informant questionnaire screening tools for dementia and mild cognitive impairment: AD8 and IQCODE.

BACKGROUND: Dementia and mild cognitive impairment (MCI) are underrecognized in community settings. This may be due in part to the lack of brief dementia screening tools available to clinicians. We compared 2 brief, informant-based screening tests: the AD8 and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) in a community-based neurology practice in the midwestern United States. METHODS: We examined 186 consecutive patients (44 controls, 13 with MCI, and 129 with dementia). Receiver operator characteristic curves were used to examine the ability of AD8 and IQCODE to discriminate between controls and MCI or dementia. Sensitivity, specificity, predictive values, and likelihood ratios were reported. RESULTS: AD8 differentiated healthy controls from MCI (P<0.001) or dementia (P<0.001), and MCI from dementia (P=0.008). The IQCODE differentiated controls and MCI from dementia (both P<0.001), and between controls and MCI (P=0.002). Both AD8 (AUC=0.953; 95% confidence interval, 0.92-0.99) and IQCODE (AUC=0.930, 95% confidence interval, 0.88-0.97) provided discrimination between controls and patients with dementia; however, the AD8 had superior sensitivity detecting dementia (99.2%) and MCI (100%) compared with the IQCODE (79.1% for dementia, 46.1% for MCI) with nonoverlapping confidence intervals. Using published cut-offs (AD8≥2, IQCODE≥3.4), only 1 case of dementia was missed with the AD8, whereas the IQCODE failed to detect dementia in 27 individuals. The AD8 detected MCI in all 13 individuals, whereas the IQCODE misclassified 7 individuals. CONCLUSIONS: Both the AD8 and IQCODE were able to detect dementia in a community setting. The AD8, however, was more successful than IQCODE in detecting MCI. If simple and efficient screening for early cognitive impairment is the goal, particularly in the early stages (e.g., for prevention trials or public screening), the combination of an informant interview (the AD8) and a brief performance measure could be considered as they meet the basic requirements of the Personalized Prevention Plan for Medicare beneficiaries.

Objective estimation of m-CTSIB balance test scores using wearable sensors and machine learning.

Accurate balance assessment is important in healthcare for identifying and managing conditions affecting stability and coordination. It plays a key role in preventing falls, understanding movement disorders, and designing appropriate therapeutic interventions across various age groups and medical conditions. However, traditional balance assessment methods often suffer from subjectivity, lack of comprehensive balance assessments and remote assessment capabilities, and reliance on specialized equipment and expert analysis. In response to these challenges, our study introduces an innovative approach for estimating scores on the Modified Clinical Test of Sensory Interaction on Balance (m-CTSIB). Utilizing wearable sensors and advanced machine learning algorithms, we offer an objective, accessible, and efficient method for balance assessment. We collected comprehensive movement data from 34 participants under four different sensory conditions using an array of inertial measurement unit (IMU) sensors coupled with a specialized system to evaluate ground truth m-CTSIB balance scores for our analysis. This data was then preprocessed, and an extensive array of features was extracted for analysis. To estimate the m-CTSIB scores, we applied Multiple Linear Regression (MLR), Support Vector Regression (SVR), and XGBOOST algorithms. Our subject-wise Leave-One-Out and 5-Fold cross-validation analysis demonstrated high accuracy and a strong correlation with ground truth balance scores, validating the effectiveness and reliability of our approach. Key insights were gained regarding the significance of specific movements, feature selection, and sensor placement in balance estimation. Notably, the XGBOOST model, utilizing the lumbar sensor data, achieved outstanding results in both methods, with Leave-One-Out cross-validation showing a correlation of 0.96 and a Mean Absolute Error (MAE) of 0.23 and 5-fold cross-validation showing comparable results with a correlation of 0.92 and an MAE of 0.23, confirming the model's consistent performance. This finding underlines the potential of our method to revolutionize balance assessment practices, particularly in settings where traditional methods are impractical or inaccessible.

Social Determinants of Health, Risk and Resilience against Alzheimer's Disease and Related Dementias: The Healthy Brain Initiative.

Background: Few studies have investigated associations between perceived social determinants of health (SDOH) and Alzheimer's disease and related dementia (ADRD) biomarkers or between SDOH and resilience against ADRD. Objective: To examine associations between perceived and objective SDOH and ADRD-related outcomes. Methods: We used cross-sectional data on≥50-year-olds without dementia in the Healthy Brain Initiative (n = 162). Questionnaires captured trust in neighbors and indices of perceived neighborhood greenspace access, time spent in neighborhood greenspaces, and interpersonal discrimination. Residential addresses were linked to 2021 Area Deprivation Index scores. The Vulnerability Index (VI) is based on 12 dementia risk factors (e.g., age, race/ethnicity, diabetes) and Resilience Index (RI) is based on 6 protective factors (e.g., diet, mindfulness, physical activity). Cognitive measured included number symbol coding task and Montreal Cognitive Assessment. Biomarkers included Aß42/40 and pTau-217/npTau-217, hippocampal and white matter hyperintensity volume, lipoprotein A, and high-sensitivity c-reactive protein. Results: Perceived greater access to greenspaces (estimate = 2.83, 95% CI = 1.40-4.26) and greater time in neighborhood greenspaces were associated with greater RI scores (estimate = 2.30, 95% CI = 1.24-3.35). Reporting greater discrimination (estimate = 0.10, 95% CI = 0.04-0.16) and living in higher deprivation neighborhoods were associated with greater VI scores (estimate = 0.017, 95% CI = 0.003-0.032). Greater discrimination was associated with greater white matter hyperintensity volume (estimate = 0.27, 95% CI = 0.04-0.51). Conclusions: Perceived greenspace access and time spent in greenspaces were associated with resilience against ADRD, and interpersonal discrimination was associated with vulnerability to ADRD. Future work needs to validate perceived SDOH measures, examine associations in racially/ethnic diverse populations, and investigate longitudinal associations between SDOH and ADRD-related biomarkers.

The Mediating Role of Cortical Atrophy on the Relationship between the Resilience Index and Cognitive Function: Findings from the Healthy Brain Initiative.

Background: Lifestyle factors are linked to differences in brain aging and risk for Alzheimer's disease, underscored by concepts like 'cognitive reserve' and 'brain maintenance'. The Resilience Index (RI), a composite of 6 factors (cognitive reserve, physical and cognitive activities, social engagement, diet, and mindfulness) provides such a holistic measure. Objective: This study aims to examine the association of RI scores with cognitive function and assess the mediating role of cortical atrophy. Methods: Baseline data from 113 participants (aged 45+, 68% female) from the Healthy Brain Initiative were included. Life course resilience was estimated with the RI, cognitive performance with Cognivue®, and brain health using a machine learning derived Cortical Atrophy Score (CAS). Mediation analysis probed the relationship between RI, cognitive outcomes, and cortical atrophy. Results: In age and sex adjusted models, the RI was significantly associated with CAS (ß= -0.25, p = 0.006) and Cognivue® scores (ß= 0.32, p < 0.001). The RI-Cognivue® association was partially mediated by CAS (ß= 0.07; 95% CI [0.02, 0.14]). Conclusions: Findings revealed that the collective effect of early and late-life lifestyle resilience factors on cognition are partially explained by their association with less brain atrophy. These findings underscore the value of comprehensive lifestyle assessments in understanding the risk and progression of cognitive decline and Alzheimer's disease in an aging population.

Mindfulness and Care Experience in Family Caregivers of Persons Living with Dementia.

Background: Greater mindfulness, the practice of awareness and living in the moment without judgement, has been linked to positive caregiving outcomes in dementia caregivers and its impact attributed to greater decentering and emotion regulation abilities. Whether the impact of these mindfulness-based processes varies across caregiver subgroups is unclear. Objective: Analyze cross-sectional associations between mindfulness and caregiver psychosocial outcomes, considering different caregiver and patient characteristics. Methods: A total of 128 family caregivers of persons living with Alzheimer's disease and related disorders were assessed on several mindfulness measures (i.e., global; decentering, positive emotion regulation, negative emotion regulation) and provided self-reported appraisals of caregiving experience; care preparedness; confidence, burden, and depression/anxiety. Bivariate relationships between mindfulness and caregiver outcomes were assessed with Pearson's correlations and stratified by caregiver (women versus men; spouse versus adult child) and patient (mild cognitive impairment (MCI) versus Dementia; AD versus dementia with Lewy bodies; low versus high symptom severity) characteristics. Results: Greater mindfulness was associated with positive outcomes and inversely associated with negative outcomes. Stratification identified specific patterns of associations across caregiver groups. Significant correlations were found between all mindfulness measures and caregiving outcomes in male and MCI caregivers while the individual mindfulness component of positive emotion regulation was significantly correlated to outcomes in most caregiver groups. Conclusion: Our findings support a link between caregiver mindfulness and improved caregiving outcomes and suggest directions of inquiry into whether the effectiveness of dementia caregiver-support interventions may be improved by targeting specific mindfulness processes or offering a more inclusive all-scope approach depending on individual caregiver or patient characteristics.

The Healthy Brain Initiative (HBI): A prospective cohort study protocol.

BACKGROUND: The Health Brain Initiative (HBI), established by University of Miami's Comprehensive Center for Brain Health (CCBH), follows racially/ethnically diverse older adults without dementia living in South Florida. With dementia prevention and brain health promotion as an overarching goal, HBI will advance scientific knowledge by developing novel assessments and non-invasive biomarkers of Alzheimer's disease and related dementias (ADRD), examining additive effects of sociodemographic, lifestyle, neurological and biobehavioral measures, and employing innovative, methodologically advanced modeling methods to characterize ADRD risk and resilience factors and transition of brain aging. METHODS: HBI is a longitudinal, observational cohort study that will follow 500 deeply-phenotyped participants annually to collect, analyze, and store clinical, cognitive, behavioral, functional, genetic, and neuroimaging data and biospecimens. Participants are ≥50 years old; have no, subjective, or mild cognitive impairment; have a study partner; and are eligible to undergo magnetic resonance imaging (MRI). Recruitment is community-based including advertisements, word-of-mouth, community events, and physician referrals. At baseline, following informed consent, participants complete detailed web-based surveys (e.g., demographics, health history, risk and resilience factors), followed by two half-day visits which include neurological exams, cognitive and functional assessments, an overnight sleep study, and biospecimen collection. Structural and functional MRI is completed by all participants and a subset also consent to amyloid PET imaging. Annual follow-up visits repeat the same data and biospecimen collection as baseline, except that MRIs are conducted every other year after baseline. ETHICS AND EXPECTED IMPACT: HBI has been approved by the University of Miami Miller School of Medicine Institutional Review Board. Participants provide informed consent at baseline and are re-consented as needed with protocol changes. Data collected by HBI will lead to breakthroughs in developing new diagnostics and therapeutics, creating comprehensive diagnostic evaluations, and providing the evidence base for precision medicine approaches to dementia prevention with individualized treatment plans.

The Healthy Brain Initiative (HBI): A prospective cohort study protocol.

Background: The Health Brain Initiative (HBI), established by University of Miami's Comprehensive Center for Brain Health (CCBH), follows racially/ethnically diverse older adults without dementia living in South Florida. With dementia prevention and brain health promotion as an overarching goal, HBI will advance scientific knowledge by developing novel assessments and non-invasive biomarkers of Alzheimer's disease and related dementias (ADRD), examining additive effects of sociodemographic, lifestyle, neurological and biobehavioral measures, and employing innovative, methodologically advanced modeling methods to characterize ADRD risk and resilience factors and transition of brain aging. Methods: HBI is a longitudinal, observational cohort study that will follow 500 deeply-phenotyped participants annually to collect, analyze, and store clinical, cognitive, behavioral, functional, genetic, and neuroimaging data and biospecimens. Participants are ≥50 years old; have no, subjective, or mild cognitive impairment; have a study partner; and are eligible to undergo magnetic resonance imaging (MRI). Recruitment is community-based including advertisements, word-of-mouth, community events, and physician referrals. At baseline, following informed consent, participants complete detailed web-based surveys (e.g., demographics, health history, risk and resilience factors), followed by two half-day visits which include neurological exams, cognitive and functional assessments, an overnight sleep study, and biospecimen collection. Structural and functional MRI is completed by all participants and a subset also consent to amyloid PET imaging. Annual follow-up visits repeat the same data and biospecimen collection as baseline, except that MRIs are conducted every other year after baseline. Ethics and expected impact: HBI has been approved by the University of Miami Miller School of Medicine Institutional Review Board. Participants provide informed consent at baseline and are re-consented as needed with protocol changes. Data collected by HBI will lead to breakthroughs in developing new diagnostics and therapeutics, create comprehensive diagnostic evaluations, and provide the evidence base for precision medicine approaches to dementia prevention with individualized treatment plans.

Personality typology in relation to muscle strength.

BACKGROUND: Physical inactivity plays a central role in the age-related decline in muscle strength, an important component in the process leading to disability. Personality, a significant determinant of health behaviors including physical activity, could therefore impact muscle strength throughout adulthood and affect the rate of muscle strength decline with aging. Personality typologies combining "high neuroticism" (N ≥ 55), "low extraversion" (E < 45), and "low conscientiousness" (C < 45) have been associated with multiple risky health behaviors but have not been investigated with regards to muscle strength. PURPOSE: The purpose of this study is to investigate associations between individual and combined typologies consisting of high N, low E, and low C and muscle strength, and whether physical activity and body mass index act as mediators. METHOD: This cross-sectional study includes 1,220 participants from the Baltimore Longitudinal Study of Aging. RESULTS: High N was found among 18%, low E among 31%, and low C among 26% of the sample. High levels of N, particularly when combined with either low E or low C, were associated with lower muscle strength compared with having only one or none of these personality types. Facet analyses suggest an important role for the N components of depression and hostility. Physical activity level appears to partly explain some of these associations. CONCLUSION: Findings provide support for the notion that the typological approach to personality may be useful in identifying specific personality types at risk of low muscle strength and offer the possibility for more targeted prevention and intervention programs.

Vascular Cognitive Impairment (VCI).

Vascular cognitive impairment (VCI) is predominately caused by vascular risk factors and cerebrovascular disease. VCI includes a broad spectrum of cognitive disorders, from mild cognitive impairment to vascular dementia caused by ischemic or hemorrhagic stroke, and vascular factors alone or in a combination with neurodegeneration including Alzheimer's disease (AD) and AD-related dementia. VCI accounts for at least 20-40% of all dementia diagnosis. Growing evidence indicates that cerebrovascular pathology is the most important contributor to dementia, with additive or synergistic interactions with neurodegenerative pathology. The most common underlying mechanism of VCI is chronic age-related dysregulation of CBF, although other factors such as inflammation and cardiovascular dysfunction play a role. Vascular risk factors are prevalent in VCI and if measured in midlife they predict cognitive impairment and dementia in later life. Particularly, hypertension, high cholesterol, diabetes, and smoking at midlife are each associated with a 20 to 40% increased risk of dementia. Control of these risk factors including multimodality strategies with an inclusion of lifestyle modification is the most promising strategy for treatment and prevention of VCI. In this review, we present recent developments in age-related VCI, its mechanisms, diagnostic criteria, neuroimaging correlates, vascular risk determinants, and current intervention strategies for prevention and treatment of VCI. We have also summarized the most recent and relevant literature in the field of VCI.

The Cognitive & Leisure Activity Scale (CLAS): A new measure to quantify cognitive activities in older adults with and without cognitive impairment.

INTRODUCTION: Potentially modifiable dementia risk factors include diet and physical and cognitive activity. However, there is a paucity of scales to quantify cognitive activities. To address this, we developed the Cognitive & Leisure Activity Scale (CLAS). METHODS: The CLAS was validated in 318 consecutive individuals with and without cognitive impairment. Psychometric properties were compared with sample characteristics, disease stage, and etiology. RESULTS: The CLAS has very good data quality (Cronbach alpha: 0.731; 95% confidence interval: 0.67-0.78). CLAS scores correlated with gold standard measures of cognition, function, physical functionality, behavior, and caregiver burden. CLAS scores were positively correlated with other resilience factors (eg, diet, physical activity) and negatively correlated with vulnerability factors (eg, older age, frailty). DISCUSSION: The CLAS is a brief inventory to estimate dosage of participation in cognitive activities. The CLAS could be used in clinical care to enhance cognitive activity or in research to estimate dosage of activities prior to an intervention.

The Effect of Baseline Patient and Caregiver Mindfulness on Dementia Outcomes.

BACKGROUND: Mindfulness is the practice of awareness and living in the present moment without judgment. Mindfulness-based interventions may improve dementia-related outcomes. Before initiating interventions, it would be beneficial to measure baseline mindfulness to understand targets for therapy and its influence on dementia outcomes. OBJECTIVE: This cross-sectional study examined patient and caregiver mindfulness with patient and caregiver rating scales and patient cognitive performance and determined whether dyadic pairing of mindfulness influences patient outcomes. METHODS: Individuals (N = 291) underwent comprehensive evaluations, with baseline mindfulness assessed using the 15-item Applied Mindfulness Process Scale (AMPS). Correlation, regression, and mediation models tested relationships between patient and caregiver mindfulness and outcomes. RESULTS: Patients had a mean AMPS score of 38.0±11.9 and caregivers had a mean AMPS score of 38.9±11.5. Patient mindfulness correlated with activities of daily living, behavior and mood, health-related quality of life, subjective cognitive complaints, and performance on episodic memory and attention tasks. Caregiver mindfulness correlated with preparedness, care confidence, depression, and better patient cognitive performance. Patients in dyads with higher mindfulness had better cognitive performance, less subjective complaints, and higher health-related quality of life (all p-values<0.001). Mindfulness effects on cognition were mediated by physical activity, social engagement, frailty, and vascular risk factors. CONCLUSION: Higher baseline mindfulness was associated with better patient and caregiver outcomes, particularly when both patients and caregivers had high baseline mindfulness. Understanding the baseline influence of mindfulness on the completion of rating scales and neuropsychological test performance can help develop targeted interventions to improve well-being in patients and their caregivers.