Neighborhood disadvantage reduces cognitive reserve independent of neuropathologic change.

INTRODUCTION: Individuals in socioeconomically disadvantaged neighborhoods exhibit increased risk for impaired cognitive function. Whether this association relates to the major dementia-related neuropathologies is unknown. METHODS: This cross-sectional study included 469 autopsy cases from 2011 to 2023. The relationships between neighborhood disadvantage measured by Area Deprivation Index (ADI) percentiles categorized into tertiles, cognition evaluated by the last Mini-Mental State Examination (MMSE) scores before death, and 10 dementia-associated proteinopathies and cerebrovascular disease were assessed using regression analyses. RESULTS: Higher ADI was significantly associated with lower MMSE score. This was mitigated by increasing years of education. ADI was not associated with an increase in dementia-associated neuropathologic change. Moreover, the significant association between ADI and cognition remained even after controlling for changes in major dementia-associated proteinopathies or cerebrovascular disease. DISCUSSION: Neighborhood disadvantage appears to be associated with decreased cognitive reserve. This association is modified by education but is independent of the major dementia-associated neuropathologies.

Epigenetic age and socioeconomic status contribute to racial disparities in cognitive and functional aging between Black and White older Americans.

Epigenetic age, a biological aging marker measured by DNA methylation, is a potential mechanism by which social factors drive disparities in age-related health. Epigenetic age gap is the residual between epigenetic age measures and chronological age. Previous studies showed associations between epigenetic age gap and age-related outcomes including cognitive capacity and performance on some functional measures, but whether epigenetic age gap contributes to disparities in these outcomes is unknown. We use data from the Health and Retirement Study to examine the role of epigenetic age gap in racial disparities in cognitive and functional outcomes and consider the role of socioeconomic status (SES). Epigenetic age measures are GrimAge or Dunedin Pace of Aging methylation (DPoAm). Cognitive outcomes are cross-sectional score and two-year change in Telephone Interview for Cognitive Status (TICS). Functional outcomes are prevalence and incidence of limitations performing Instrumental Activities of Daily Living (IADLs). We find, relative to White participants, Black participants have lower scores and greater decline in TICS, higher prevalence and incidence rates of IADL limitations, and higher epigenetic age gap. Age- and gender-adjusted analyses reveal that higher GrimAge and DPoAm gap are both associated with worse cognitive and functional outcomes and mediate 6-11% of racial disparities in cognitive outcomes and 19-39% of disparities in functional outcomes. Adjusting for SES attenuates most DPoAm associations and most mediation effects. These results support that epigenetic age gap contributes to racial disparities in cognition and functioning and may be an important mechanism linking social factors to disparities in health outcomes.

Linked Patient and Provider Impressions of Outpatient Teleneurology Encounters.

Background and Objectives: Teleneurology is common in clinical practice partly due to the SARS CoV-2 pandemic. Impressions about teleneurology from patients and providers alike are generally favorable; some of the reported benefits include ease of access to specialized health care, savings of time and money, and similar quality of care as an in-person visit. However, comparisons between patient and provider impressions about the same teleneurology encounter have not been described. In this study, we describe patient impressions about a teleneurology encounter and evaluate concordance with provider impressions about the same encounter. Methods: Patients and providers at the University of Pennsylvania Hospital Neurology Department were surveyed about their impressions of teleneurology between April 27, 2020, and June 16, 2020. A convenience sample of patients, whose providers completed a questionnaire, were contacted by telephone to solicit their impressions about the same encounter. Unique questionnaires for patients and providers focused on similar themes, such as adequacy of technology, assessment of history obtained, and overall quality of the visit. Summaries of patient responses are reported with the raw percent agreement between patients and providers for similar questions. Results: One hundred thirty-seven patients completed the survey; 64 (47%) were male and 73 (53%) were female. Sixty-six (47%) patients had a primary diagnosis of PD, 42 (30%) a non-PD/parkinsonism movement disorder, and 29 (21%) a nonmovement disorder neurologic disease. One hundred one (76%) were established patient visits and 36 (26%) were new patient visits. Provider responses from 8 different physicians were included. Most of the patients responded that the ease of joining their visit, their comfort engaging with their physicians during their visit, understanding their plan of care after their visit, and the quality of care from their teleneurology visit were satisfactory. Patients and providers agreed about their impressions of the quality of the history obtained (87% agreement), patient-provider relationship (88% agreement), and overall quality of their experience (70% agreement). Discussion: Patients had favorable impressions about their clinical experience with teleneurology and expressed an interest in incorporating telemedicine visits into their ongoing care. Patients and providers were highly concordant for the history obtained, patient-provider relationship, and overall quality.

Multisite Assessment of Aging-Related Tau Astrogliopathy (ARTAG).

Aging-related tau astrogliopathy (ARTAG) is a recently introduced terminology. To facilitate the consistent identification of ARTAG and to distinguish it from astroglial tau pathologies observed in the primary frontotemporal lobar degeneration tauopathies we evaluated how consistently neuropathologists recognize (1) different astroglial tau immunoreactivities, including those of ARTAG and those associated with primary tauopathies (Study 1); (2) ARTAG types (Study 2A); and (3) ARTAG severity (Study 2B). Microphotographs and scanned sections immunostained for phosphorylated tau (AT8) were made available for download and preview. Percentage of agreement and kappa values with 95% confidence interval (CI) were calculated for each evaluation. The overall agreement for Study 1 was >60% with a kappa value of 0.55 (95% CI 0.433-0.645). Moderate agreement (>90%, kappa 0.48, 95% CI 0.457-0.900) was reached in Study 2A for the identification of ARTAG pathology for each ARTAG subtype (kappa 0.37-0.72), whereas fair agreement (kappa 0.40, 95% CI 0.341-0.445) was reached for the evaluation of ARTAG severity. The overall assessment of ARTAG showed moderate agreement (kappa 0.60, 95% CI 0.534-0.653) among raters. Our study supports the application of the current harmonized evaluation strategy for ARTAG with a slight modification of the evaluation of its severity.

The Penn Parkinson's Daily Activities Questionnaire-15: Psychometric properties of a brief assessment of cognitive instrumental activities of daily living in Parkinson's disease.

INTRODUCTION: To describe the psychometric properties of the Penn Parkinson's Daily Activities Questionnaire-15 (PDAQ-15), a 15-item measure of cognitive instrumental activities of daily living for Parkinson's disease (PD) patients derived from the original 50-item PDAQ. METHODS: PDAQ-15 items were chosen by expert consensus. Knowledgeable informants of PD participants (n = 161) completed the PDAQ-15. Knowledgeable informants were defined as an individual having regular contact with the PD participant. PD participants were assigned a diagnosis of normal cognition, mild cognitive impairment, or dementia based on expert consensus. RESULTS: PDAQ-15 scores correlated strongly with global cognition (Dementia Rating Scale-2, r = 0.71, p < 0.001) and a performance-based functional measure (Direct Assessment of Functional Status, r = 0.83; p < 0.001). PDAQ-15 scores accurately discriminated between non-demented PD participants (normal cognition/mild cognitive impairment) and PD with dementia (ROC curve area = 0.91), participants with and without any cognitive impairment (normal cognition versus mild cognitive impairment/dementia, ROC curve area = 0.85) and between participants with mild cognitive impairment and dementia (ROC curve area = 0.84). CONCLUSIONS: The PDAQ-15 shows good discriminant validity across cognitive stages, correlates highly with global cognitive performance, and appears suitable to assess daily cognitive functioning in PD.

Predictors of emergent feeding tubes and tracheostomies in amyotrophic lateral sclerosis (ALS).

Predictable decline in ALS makes unplanned gastrostomy and tracheostomy avoidable. We determined whether gastrostomy or tracheostomy insertion during emergent hospitalization is associated with patient or hospital characteristics, changed Medicare policy in 2001, or proximity to specialized ALS care. We performed a retrospective analysis of hospitalizations and procedures for ALS/MND patients in Pennsylvania between 1996 and 2009. We identified predictors of gastrostomy/tracheostomy during emergent hospitalization and trends over time. Patients underwent 1748 gastrostomies and 373 tracheostomies. Thirty-two percent of gastrostomies and 67% of tracheostomies were placed emergently. Emergent hospitalizations involving gastrostomy were more expensive with fewer home discharges. Black patients and Medicaid patients had higher odds of emergent gastrostomy placement. Conversely, academic hospital affiliation decreased odds of emergent gastrostomy or tracheostomy placement (AOR 0.49, AOR 0.37, p < 0.001). After Medicare policy changes, gastrostomy use increased, while emergent gastrostomies decreased. Surprisingly, proximity to specialized care was associated with increased emergent gastrostomy placement. In conclusion, black patients and Medicaid patients were more likely to undergo emergent gastrostomy insertion. Patients receiving gastrostomy during emergent admissions had fewer home discharges and higher costs. Academic hospital affiliation decreased odds of emergent gastrostomy or tracheostomy. After Medicare changes broadening access, while gastrostomy use increased, the proportion of emergent procedures decreased.

The Philadelphia Brief Assessment of Cognition (PBAC): a validated screening measure for dementia.

The Philadelphia Brief Assessment of the Cognition (PBAC) is a brief dementia-screening instrument. The PBAC assesses five cognitive domains: working memory/executive control; lexical retrieval/language; visuospatial/visuoconstructional operations; verbal/visual episodic memory; and behavior/social comportment. A revised version of the PBAC was administered to 198 participants including patients with Alzheimer's disease (AD) (n=46) and four groups of patients with frontotemporal dementia (FTD) syndromes: behavioral-variant FTD (bvFTD; n=65), semantic-variant primary progressive aphasia (PPA) (svPPA; n=22), non-fluent/agrammatic-variant PPA (nfaPPA; n=23), and corticobasal syndrome (CBS; n=42), and a group of normal controls (n=15). The total PBAC score was highly correlated with the MMSE. The criterion validity of the PBAC was assessed relative to standard neuropsychological test performance. Using standard neuropsychological test performance as a criterion, the total PBAC score accurately identified the presence and severity of dementia. Intra-class correlations between PBAC subscales and standard neuropsychological tests were highly significant. PBAC subscales demonstrated good clinical utility in distinguishing AD and FTD subtypes using receiver operating characteristic analysis and standard diagnostic performance statistics to determine optimal subscale cut scores. The PBAC is a valid tool and able to assesses differential patterns neuropsychological/behavioral impairment in a broad range of neurodegenerative conditions.

Genetic testing and Parkinson disease: assessment of patient knowledge, attitudes, and interest.

The most common genetic contributor to late-onset Parkinson disease (PD) is the LRRK2 gene. In order to effectively integrate LRRK2 genetic testing into clinical practice, a strategy tailored to the PD population must be developed. We assessed 168 individuals with PD for baseline knowledge of genetics, perceived risk, and interest and opinions regarding genetic counseling and testing. Most participants felt that they were familiar with general genetics terms but overall knowledge levels were low, with an average score of 55%. The majority of participants thought it was likely they inherited a PD gene (72%), believed genetic testing for PD would be useful (86%), and were interested in genetic testing (59%) and genetic counseling (56%). However, only a few participants had heard of any genetic tests for PD (29%) or LRRK2 (10%). There appears to be a significant level of interest in genetics and genetic testing within the PD population, but a considerable deficit in genetics knowledge and an over-estimation of risk. Genetic education and counseling tools to address these needs were developed to provide patients with the ability to make informed and knowledgeable genetic testing decisions.

Design of comprehensive Alzheimer's disease centers to address unmet national needs.

The problem of Alzheimer's disease (AD) exemplifies the challenges of dealing with a broad range of aging-related chronic disorders that require long-term, labor-intensive, and expensive care. As the baby boom generation ages and brain diseases become more prevalent, the need to confront the pending health care crisis is more urgent than ever before. Indeed, there is now a critical need to expand significantly the national effort to solve the problem of AD, with special focus on prevention. The Campaign to Prevent Alzheimer's Disease by 2020 (PAD2020) aims to create a new paradigm for planning and supporting the organization of worldwide cooperative research networks to develop new technologies for early detection and treatments of aging-related memory and motor impairments. PAD 2020 is developing an implementation plan to justify (1) increasing the federal budget for research, (2) developing novel national resources to discover new interventions for memory and motor disorders, and (3) creating innovative and streamlined decision-making processes for selecting and supporting new ideas. Since 1978 the National Institute on Aging or National Institute of Health (NIH) established an extensive national network of AD research facilities at academic institutions including AD Centers (ADCs), Consortium to Establish a Registry for AD, AD Cooperative Study (ADCS), AD Drug Discovery Program, National Alzheimer's Coordinating Center, National Cell Repository for AD, and AD Neuroimaging Initiative. However, despite the success of these programs and their critical contributions, they are no longer adequate to meet the challenges presented by AD. PAD 2020 is designed to address these changes by improving the efficiency and effectiveness of these programs. For example, the ADCs (P30s and P50s) can be enhanced by converting some into Comprehensive Alzheimer's Disease Centers (CADCs) to support not only research, but also by being demonstration projects on care/treatment, clinical trials, and education as well as by seamlessly integrating multisite collaborative studies (ADCS, AD Neuroimaging Initiative, Patient Registries, Clinical Data Banks, etc) into a cohesive structure that further enhances the original mission of the National Institute on Aging ADCs. Regional CADCs offer greater efficiency and cost savings while serving as coordinating hubs of existing ADCs, thereby offering greater economies of scale and programmatic integration. The CADCs also broaden the scope of ADC activities to include research on interventions, diagnosis, imaging, prevention trials, and other longitudinal studies that require long-term support. Thus, CADCs can address the urgent need to identify subjects at high risk of AD for prevention trials and very early in the course of AD for clinical trials of disease modification. The enhanced CADCs will allow more flexibility among ADCs by supporting collaborative linkages with other institutions and drawing on a wider expertise from different locations. This perspective article describes the University of Pennsylvania (Penn) CADC Model as an illustrative example of how an existing ADC can be converted into a CADC by better utilization of Penn academic resources to address the wide range of problems concerning AD. The intent of this position paper is to stimulate thinking and foster the development of other or alternative models for a systematic approach to the study of dementia and movement disorders.

Would caregivers of Alzheimer disease patients involve their relative in a decision to use an AD-slowing medication?

OBJECTIVES: The authors examined the factors associated with 1) caregivers' willingness to involve a relative with Alzheimer disease (AD) in a decision to use an AD-slowing treatment; and 2) how caregivers would resolve a disagreement over this decision with the their relative. METHODS: This was a cross-sectional interview study of 102 caregivers of patients with mild-to-severe-stage AD, enrolled in a University Memory Disorders Clinic. RESULTS: Forty-four percent of caregivers (45/102) said that his or her relative would participate in a decision to use an AD-slowing treatment. Logistic regression showed that having less dementia severity, being a female caregiver, and a spousal relationship were all associated with caregivers' involving their relative in this decision. Among the caregivers who said they would involve their relative, the majority said they would resolve disagreements over whether to use the treatment in favor of what the patient wanted, versus what the family wanted for the patient. Male caregivers were less likely to resolve disagreements in favor of the patients' preferences. CONCLUSION: Although most caregivers of patients in mild-to-moderate stages would include these patients in an AD treatment decision, certain caregiver characteristics, such as gender and relationship, are associated with not involving patients in this decision. Physicians working with dementia patients and their family members should take these characteristics into account when discussing treatment options and work with patient-caregiver dyads to improve the communication of preferences.