Amyloid-ß and tau pathologies relate to distinctive brain dysconnectomics in preclinical autosomal-dominant Alzheimer's disease.

The human brain is composed of functional networks that have a modular topology, where brain regions are organized into communities that form internally dense (segregated) and externally sparse (integrated) subnetworks that underlie higher-order cognitive functioning. It is hypothesized that amyloid-ß and tau pathology in preclinical Alzheimer's disease (AD) spread through functional networks, disrupting neural communication that results in cognitive dysfunction. We used high-resolution (voxel-level) graph-based network analyses to test whether in vivo amyloid-ß and tau burden was associated with the segregation and integration of brain functional connections, and episodic memory, in cognitively unimpaired Presenilin-1 E280A carriers who are expected to develop early-onset AD dementia in ∼13 y on average. Compared to noncarriers, mutation carriers exhibited less functional segregation and integration in posterior default-mode network (DMN) regions, particularly the precuneus, and in the retrospenial cortex, which has been shown to link medial temporal regions and cortical regions of the DMN. Mutation carriers also showed greater functional segregation and integration in regions connected to the salience network, including the striatum and thalamus. Greater tau burden was associated with lower segregated and integrated functional connectivity of DMN regions, particularly the precuneus and medial prefrontal cortex. In turn, greater tau pathology was related to higher segregated and integrated functional connectivity in the retrospenial cortex and the anterior cingulate cortex, a hub of the salience network. These findings enlighten our understanding of how AD-related pathology distinctly alters the brain's functional architecture in the preclinical stage, possibly contributing to pathology propagation and ultimately resulting in dementia.

Associations of category fluency clustering performance with in vivo brain pathology in autosomal dominant Alzheimer's disease.

OBJECTIVES: Alzheimer's disease (AD) is known to impact semantic access, which is frequently evaluated using the Category Fluency (Animals) test. Recent studies have suggested that in addition to overall category fluency scores (total number of words produced over time), poor clustering could signal AD-related cognitive difficulties. In this study, we examined the association between category fluency clustering performance (i.e., stating words sequentially that are all contained within a subcategory, such as domestic animals) and brain pathology in individuals with autosomal dominant Alzheimer's disease (ADAD). METHODS: A total of 29 non-demented carriers of the Presenilin1 E280A ADAD mutation and 32 noncarrier family members completed the category fluency test (Animals) and the Mini-Mental State Examination (MMSE). The participants also underwent positron emission tomography (PET) scans to evaluate in vivo amyloid-beta in the neocortex and tau in medial temporal lobe regions. Differences between carriers and noncarriers on cognitive tests were assessed with Mann-Whitney tests; associations between cognitive test performance and brain pathology were assessed with Spearman correlations. RESULTS: Animal fluency scores did not differ between carriers and noncarriers. Carriers, however, showed a stronger association between animal fluency clustering and in vivo AD brain pathology (neocortical amyloid and entorhinal tau) relative to noncarriers. CONCLUSION: This study indicates that using category fluency clustering, but not total score, is related to AD pathophysiology in the preclinical and early stages of the disease.

Depressive symptoms and hippocampal volume in autosomal dominant Alzheimer's disease.

INTRODUCTION: Depressive symptoms are among early behavioral changes in Alzheimer's disease (AD); however, the relationship between neurodegeneration and depressive symptoms remains inconclusive. To better understand this relationship in preclinical AD, we examined hippocampal volume and depressive symptoms in cognitively unimpaired carriers of the presenilin-1 (PSEN1) E280A mutation for autosomal dominant AD. METHODS: A total of 27 PSEN1 mutation carriers and 26 non-carrier family members were included. Linear regression was used to test the relationship between hippocampal volume and 15-item Geriatric Depression Scale. RESULTS: Carriers and non-carriers did not differ in depressive symptoms or hippocampal volume. Within carriers, lower hippocampal volume was associated with greater depressive symptoms, which remained significant after adjusting for age and cognition. This relationship was not significant in non-carriers. DISCUSSION: Hippocampal neurodegeneration may underlie depressive symptoms in preclinical autosomal dominant AD. These findings provide support for the utility of targeting depressive symptoms in AD prevention. HIGHLIGHTS: We compared unimpaired autosomal dominant Alzheimer's disease (AD) mutation carriers and non-carriers. Carriers and non-carriers did not differ in severity of depressive symptoms. In carriers, hippocampal volume was inversely associated with depressive symptoms. Depressive symptoms may be a useful target in AD prevention.

Plasma p-tau217 predicts in vivo brain pathology and cognition in autosomal dominant Alzheimer's disease.

INTRODUCTION: Plasma-measured tau phosphorylated at threonine 217 (p-tau217) is a potential non-invasive biomarker of Alzheimer's disease (AD). We investigated whether plasma p-tau217 predicts subsequent cognition and positron emission tomography (PET) markers of pathology in autosomal dominant AD. METHODS: We analyzed baseline levels of plasma p-tau217 and its associations with amyloid PET, tau PET, and word list delayed recall measured 7.61 years later in non-demented age- and education-matched presenilin-1 E280A carriers (n = 24) and non-carrier (n = 20) family members. RESULTS: Carriers had higher plasma p-tau217 levels than non-carriers. Baseline plasma p-tau217 was associated with subsequent amyloid and tau PET pathology levels and cognitive function. DISCUSSION: Our findings suggest that plasma p-tau217 predicts subsequent brain pathological burden and memory performance in presenilin-1 E280A carriers. These results provide support for plasma p-tau217 as a minimally invasive diagnostic and prognostic biomarker for AD, with potential utility in clinical practice and trials. HIGHLIGHTS: Non-demented presenilin-1 E280A carriers have higher plasma tau phosphorylated at threonine 217 (p-tau217) than do age-matched non-carriers. Higher baseline p-tau217 is associated with greater future amyloid positron emission tomography (PET) pathology burden. Higher baseline p-tau217 is associated with greater future tau PET pathology burden. Higher baseline p-tau217 is associated with worse future memory performance.

Association Between Visual Memory and In Vivo Amyloid and Tau Pathology in Preclinical Autosomal Dominant Alzheimer's Disease.

OBJECTIVE: Visual memory (ViM) declines early in Alzheimer's disease (AD). However, it is unclear whether ViM impairment is evident in the preclinical stage and relates to markers of AD pathology. We examined the relationship between ViM performance and in vivo markers of brain pathology in individuals with autosomal dominant AD (ADAD). METHODS: Forty-five cognitively unimpaired individuals from a Colombian kindred with the Presenilin 1 (PSEN1) E280A ADAD mutation (19 carriers and 26 noncarriers) completed the Rey-Osterrieth Complex Figure immediate recall test, a measure of ViM. Cortical amyloid burden and regional tau deposition in the entorhinal cortex (EC) and inferior temporal cortex (IT) were measured using 11C-Pittsburgh compound B positron emission tomography (PET) and 11F-flortaucipir PET, respectively. RESULTS: Cognitively unimpaired carriers and noncarriers did not differ on ViM performance. Compared to noncarriers, carriers had higher levels of cortical amyloid and regional tau in both the EC and IT. In cognitively unimpaired carriers, greater cortical amyloid burden, higher levels of regional tau, and greater age were associated with worse ViM performance. Only a moderate correlation between regional tau and ViM performance remained after adjusting for verbal memory scores. None of these correlations were observed in noncarriers. CONCLUSIONS: Results suggest that AD pathology and greater age are associated with worse ViM performance in ADAD before the onset of clinical symptoms. Further investigation with larger samples and longitudinal follow-up is needed to examine the utility of ViM measures for identifying individuals at high risk of developing dementia later in life.

Associations between plasma neurofilament light, in vivo brain pathology, and cognition in non-demented individuals with autosomal-dominant Alzheimer's disease.

BACKGROUND: Neurofilament light (NfL) is a promising biomarker of early neurodegeneration in Alzheimer's disease (AD). We examined whether plasma NfL was associated with in vivo amyloid beta and tau, and cognitive performance in non-demented presenilin-1 (PSEN1) E280A mutation carriers. METHODS: Twenty-five mutation carriers and 19 non-carriers (age range: 28 to 49 years) were included in this study. Participants underwent 11C Pittsburgh compound B (PiB)-PET (positron emission tomography), flortaucipir-PET, blood sampling, and cognitive testing. RESULTS: Mutation carriers exhibited higher plasma NfL levels than non-carriers. In carriers, higher NfL levels were related to greater regional tau burden and worse cognition, but not amyloid beta load. When we adjusted for age, a proxy of disease progression, elevated plasma NfL levels were only correlated with worse memory recall. CONCLUSIONS: Findings support an association between plasma NfL, cognition, and tau pathology in non-demented individuals at genetic risk for developing AD dementia. Plasma NfL may be useful for selecting individuals at increased risk and tracking disease progression in AD.

A Deep Learning Framework for Predicting Patient Decannulation on Extracorporeal Membrane Oxygenation Devices: Development and Model Analysis Study.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a therapy for patients with refractory respiratory failure. The decision to decannulate someone from extracorporeal membrane oxygenation (ECMO) often involves weaning trials and clinical intuition. To date, there are limited prognostication metrics to guide clinical decision-making to determine which patients will be successfully weaned and decannulated. OBJECTIVE: This study aims to assist clinicians with the decision to decannulate a patient from ECMO, using Continuous Evaluation of VV-ECMO Outcomes (CEVVO), a deep learning-based model for predicting success of decannulation in patients supported on VV-ECMO. The running metric may be applied daily to categorize patients into high-risk and low-risk groups. Using these data, providers may consider initiating a weaning trial based on their expertise and CEVVO. METHODS: Data were collected from 118 patients supported with VV-ECMO at the Columbia University Irving Medical Center. Using a long short-term memory-based network, CEVVO is the first model capable of integrating discrete clinical information with continuous data collected from an ECMO device. A total of 12 sets of 5-fold cross validations were conducted to assess the performance, which was measured using the area under the receiver operating characteristic curve (AUROC) and average precision (AP). To translate the predicted values into a clinically useful metric, the model results were calibrated and stratified into risk groups, ranging from 0 (high risk) to 3 (low risk). To further investigate the performance edge of CEVVO, 2 synthetic data sets were generated using Gaussian process regression. The first data set preserved the long-term dependency of the patient data set, whereas the second did not. RESULTS: CEVVO demonstrated consistently superior classification performance compared with contemporary models (P<.001 and P=.04 compared with the next highest AUROC and AP). Although the model's patient-by-patient predictive power may be too low to be integrated into a clinical setting (AUROC 95% CI 0.6822-0.7055; AP 95% CI 0.8515-0.8682), the patient risk classification system displayed greater potential. When measured at 72 hours, the high-risk group had a successful decannulation rate of 58% (7/12), whereas the low-risk group had a successful decannulation rate of 92% (11/12; P=.04). When measured at 96 hours, the high- and low-risk groups had a successful decannulation rate of 54% (6/11) and 100% (9/9), respectively (P=.01). We hypothesized that the improved performance of CEVVO was owing to its ability to efficiently capture transient temporal patterns. Indeed, CEVVO exhibited improved performance on synthetic data with inherent temporal dependencies (P<.001) compared with logistic regression and a dense neural network. CONCLUSIONS: The ability to interpret and integrate large data sets is paramount for creating accurate models capable of assisting clinicians in risk stratifying patients supported on VV-ECMO. Our framework may guide future incorporation of CEVVO into more comprehensive intensive care monitoring systems.

Use of an Opt-Out vs Opt-In Strategy Increases Use of Residency Mental Health Services.

Background Residents report high levels of distress but low utilization of mental health services. Prior research has shown several barriers that prevent residents from opting into available mental health services. Objective To determine the impact of a mental health initiative centered around an opt-out versus an opt-in approach to help-seeking, on the use of psychotherapy. Methods Resident use of psychotherapy was compared between 2 time frames. During the first time frame (July 1, 2020 to January 31, 2021), residents were offered access to therapy that they could self-initiate by calling to schedule an appointment (opt-in). The second time frame (February 1, 2021 to April 30, 2021) involved the switch to an opt-out structure, during which the same residents were scheduled for a session but could choose to cancel. Additional changes were implemented to reduce stigma and minimize barriers. The outcome was psychotherapy use by residents. Results Of the 114 residents, 7 (6%) self-initiated therapy during the opt-in period. When these same residents were placed in an opt-out context, 59 of the remaining 107 residents (55%) kept their initial appointment, and 23 (39%) self-initiated additional sessions. Altogether, across both phases, a total of 30 of the 114 residents initiated therapy (ie, 7 during the opt-in and 23 during the opt-out). The differences in therapy use between the 2 phases are statistically significant (P<.001 by McNemar's test). Conclusions There was a substantial increase in residents' use of psychotherapy after the opt-out initiative that included efforts to reduce stigma and encourage mental health services.

AAV-based delivery of RNAi targeting Ataxin-2 improves survival, strength, and pathology in mouse models of rapidly and slowly progressive sporadic ALS.

Amyotrophic lateral sclerosis (ALS) is characterized by motor neuron death due to nuclear loss and cytoplasmic aggregation of the splice factor TDP-43. Pathologic TDP-43 associates with stress granules (SGs) and downregulating the SG-associated protein Ataxin-2 (Atxn2) using antisense oligonucleotides (ASO) prolongs survival in the TAR4/4 sporadic ALS mouse model, a strategy now in clinical trials. Here, we used AAV-mediated RNAi delivery to achieve lasting and targeted Atxn2 knockdown after a single injection. To achieve this, a novel AAV with improved transduction potency of our target cells was used to deliver Atxn2 -targeting miRNAs. Mouse dosing studies demonstrated 55% Atxn2 knockdown in frontal cortex and 25% knockdown throughout brainstem and spinal cord after intracerebroventricular injection at a dose 40x lower than used in other recent studies. In TAR4/4 mice, miAtxn2 treatment increased mean and median survival by 54% and 45% respectively (p<0.0003). Mice showed robust improvement across strength-related measures ranging from 24-75%. Interestingly, treated mice showed increased vertical activity above wildtype, suggesting unmasking of an FTD phenotype with improved strength. Histologically, lower motor neuron survival improved with a concomitant reduction in CNS inflammatory markers. Additionally, phosphorylated TDP-43 was reduced to wildtype levels. Bulk RNA sequencing revealed correction of 153 genes in the markedly dysregulated transcriptome of mutant mice, several of which are described in the human ALS literature. In slow progressing hemizygous mice, treatment rescued weight loss and improved gait at late time points. Cumulatively the data support the utility of AAV-mediated RNAi against Atxn2 as a robust and translatable treatment strategy for sporadic ALS.

Connectome-based predictive modeling of brain pathology and cognition in Autosomal Dominant Alzheimer's Disease.

INTRODUCTION: Autosomal Dominant Alzheimer's Disease (ADAD) through genetic mutations can result in near complete expression of the disease. Tracking AD pathology development in an ADAD cohort of Presenilin-1 (PSEN1) E280A carriers' mutation has allowed us to observe incipient tau tangles accumulation as early as 6 years prior to symptom onset. METHODS: Resting-state functional Magnetic Resonance Imaging (fMRI) and Positron-Emission Tomography (PET) scans were acquired in a group of PSEN1 carriers (n=32) and non-carrier family members (n=35). We applied Connectome-based Predictive Modeling (CPM) to examine the relationship between the participant's functional connectome and their respective tau/amyloid-ß levels and cognitive scores (word list recall). RESULTS: CPM models strongly predicted tau concentrations and cognitive scores within the carrier group. The connectivity patterns between the temporal cortex, default mode network, and other memory networks were the most informative of tau burden. DISCUSSION: These results indicate that resting-state fMRI methods can complement PET methods in early detection and monitoring of disease progression in ADAD.

We Hope You're Listening: Qualitative Study of Advice Given by Individuals with Parkinson's Disease.

BACKGROUND: Patient-centered care for persons with Parkinson's disease (PwPD) is associated with positive outcomes, but is lacking in current healthcare systems. OBJECTIVE: In this qualitative study, we solicited advice from PwPD to medical professionals, family members/friends, and newly-diagnosed PwPD. METHODS: Through an online survey, 275 PwPD answered open-ended questions asking for their advice. Responses were analyzed using content analysis. Interrater reliability was 94.5%. RESULTS: Three qualitative themes were identified. First, participants advised enhancing care and communication, with healthcare professionals balancing clinical constraints with compassion, and family/friends balancing support with appreciating autonomy of PwPD. The second theme was empowering PwPD through increasing their knowledge of the disease and care options. The third reflected the importance of focusing on well-being and connection. CONCLUSION: The results highlight several gaps in meeting the needs of PwPD in healthcare settings and personal relationships, underscoring the importance of integrating their perspectives in shaping approaches to care.

Tele-Neuropsychology: From Science to Policy to Practice.

OBJECTIVE: The primary aim of this paper is to accelerate the number of randomized experimental studies of the reliability and validity in-home tele-neuropsychological testing (tele-np-t). METHOD: We conducted a critical review of the tele-neuropsychology literature. We discuss this research in the context of the United States' public and private healthcare payer systems, including the Centers for Medicare & Medicaid Services (CMS) and Current Procedural Terminology (CPT) coding system's telehealth lists, and existing disparities in healthcare access. RESULTS: The number of tele-np publications has been stagnant since the onset of the COVID-19 pandemic. There are less published experimental studies of tele-neuropsychology (tele-np), and particularly in-home tele-np-t, than other tele-np publications. There is strong foundational evidence of the acceptability, feasibility, and reliability of tele-np-t, but relatively few studies of the reliability and validity of in-home tele-np-t using randomization methodology. CONCLUSIONS: More studies of the reliability and validity of in-home tele-np-t using randomization methodology are necessary to support inclusion of tele-np-t codes on the CMS and CPT telehealth lists, and subsequently, the integration and delivery of in-home tele-np-t services across providers and institutions. These actions are needed to maintain equitable reimbursement of in-home tele-np-t services and address the widespread disparities in healthcare access.

Integrating Lifestyle Factor Science into Neuropsychological Practice: A National Academy of Neuropsychology Education Paper.

OBJECTIVE: The primary aim of this paper is to review evidence and clinical implications related to lifestyle activities associated with promoting brain and cognitive health. Our review targets four key lifestyle factors: physical activity and exercise, social engagement, cognitively stimulating activity, and consuming Mediterranean-style diets. METHOD: We conducted a critical review of the lifestyle factor literature in the four domains listed earlier. We contextualize this literature review by translating findings, when possible, into evidence-based recommendations to consider when providing neuropsychological services. RESULTS: There is significant current evidence supporting the role of physical activity and exercise, social engagement, cognitively stimulating activity, and consuming Mediterranean-style diets on positive brain and cognitive health outcomes. While some null findings are present in all four areas reviewed, the weight of the evidence supports the notion that engaging in these activities may promote brain and cognitive functioning. CONCLUSIONS: Clinical neuropsychologists can have confidence in recommending engagement in physical activity, social activity, and cognitively stimulating activity, and adhering to a Mediterranean-style diet to promote brain and cognitive health. We discuss limitations in existing lifestyle factor research and future directions to enhance the existing evidence base, including additional research with historically underrepresented groups and individuals with neurological conditions.

Physical Activity and Neurocognitive Symptoms in Older Adults During COVID-19 Pandemic.

Objectives: Examine whether physical activity (PA) changes during the COVID-19 pandemic were related to subjective cognitive decline (SCD), depression, and anxiety in older adults and whether these varied by sociodemographic variables. Methods: 301 older adults completed an online survey between May and October 2020 and 3 months later, including self-report questionnaires of SCD, depression, and anxiety. PA changes were determined with a question. Results: 60% of participants reported decreased PA. Those who reduced their PA were more likely to be from low to middle income and younger. PA increase was related to less SCD and depressive symptoms compared to those who decreased it. Participants who maintained their PA had fewer SCD concerns, depressive, and anxiety symptoms than those who decreased it. Discussion: Reducing PA was associated with worse neuropsychiatric and cognitive symptoms. Encouraging older adults to increase PA may help mitigate some of the pandemic's adverse effects on psychological well-being.

Comparison of performance on the oral versus written trail making test in patients with movement disorders.

The Oral Trail Making Test (O-TMT) was designed as a clinical analog of the written version (W-TMT). There is debate, however, about whether the measurement of processing speed and set shifting is equivalent between versions. Given the administration advantages of the O-TMT - especially for patients with motor impairments - we examined convergent validity with the W-TMT in patients with movement disorders. Fifty patients (n = 43 idiopathic Parkinson's disease [PD]) were evaluated in a movement disorders clinic. Patients averaged 71 years old (SD = 8.07 years), 16 years of education (SD = 2.30 years), and the majority were non-Hispanic White (n = 46) and male (n = 35). In addition to other neuropsychological measures, patients completed the O-TMT and the W-TMT, counterbalanced and separated by thirty-minutes. Part A scores on O-TMT and W-TMT were not significantly correlated. In contrast, Part B scores were strongly correlated, such that slower performances on O-TMT Part B corresponded with slower performances on W-TMT Part B. Discrepancy scores (Part B minus Part A completion times) were also strongly correlated, such that more time on O-TMT, indicative of slower set shifting speed, corresponded with more time on W-TMT. Better performances on both O-TMT B and W-TMT B were associated with better scores on measures of overall cognitive status, verbal learning, and both phonemic and semantic fluency. Part B of the O-TMT shows promise as an analog for Part B of the W-TMT when evaluating set shifting abilities in patients with movement disorders. Future research with diverse patient populations is recommended to establish generalizability.

Changes in Apathy, Depression, and Anxiety in Parkinson's Disease from before to during the COVID-19 Era.

Apathy, depression, and anxiety are common non-motor symptoms of Parkinson's disease (PD). Tracking the changes in such symptoms over time would be valuable not only to determine their natural course during the disease, but also to establish the effects of unusual historical events interacting with the natural course. Having collected data on apathy (Apathy Scale), depression (Beck Depression Inventory-II), and anxiety (Parkinson's Anxiety Scale) in a large sample of persons with PD (PwPD) before the beginning of the COVID-19 era, we followed up with these individuals to investigate the changes in their prevalence of apathy, depression, and anxiety across two timepoints (T1 and T2). Of the original 347 participants, 111 responded and provided complete data at T2. The data collection at T1, before COVID-19, occurred between 2017-2018. The data collection at T2 occurred in 2021 and included the same measures, with the addition of the Coronavirus Impact Scale to assess the effects of the pandemic on the individual participants. Over this period, there was a significant increase in apathy, but not in depression or anxiety. Anxiety and depression, but not apathy, were correlated with the impact of COVID-19.

Representativeness of samples enrolled in Alzheimer's disease research centers.

To generalize findings on the mechanisms and prognosis in Alzheimer's disease and related dementias (ADRD), it is critical for ADRD research to be representative of the population. Sociodemographic and health characteristics across ethnoracial groups included in the National Alzheimer's Coordinating Center sample (NACC) were compared to the nationally representative Health and Retirement Study (HRS).Baseline NACC data (n = 36,639) and the weighted 2010 HRS wave (N = 52,071,840) were included. We assessed covariate balance by calculating standardized mean differences across harmonized covariates (i.e., sociodemographic, health).NACC participants were older, more educated, with worse subjective memory and hearing, but endorsed fewer depressive symptoms compared to HRS participants. While all racial and ethnic groups in NACC differed from HRS participants in the same way overall, these differences were further amplified between racial and ethnic groups.NACC participants do not represent the U.S. population in key demographic and health factors, which differed by race and ethnicity. HIGHLIGHTS: We examined selection factors included in NACC studies compared to a nationally representative sample.Selection factors included demographic and health factors and self-reported memory concerns.Results suggest that NACC participants are not representative of the U.S. population.Importantly, selection factors differed across racial and ethnic groups.Findings are suggestive of selection bias within NACC studies.

Survey Findings About the Experiences, Challenges, and Practical Advice/Solutions Regarding Teleneuropsychological Assessment in Adults.

OBJECTIVE: In the wake of the coronavirus pandemic, teleneuropsychology utilization has increased. There is a need to characterize the first-hand experiences of individuals using teleneuropsychology, identify the common teleneuropsychology challenges, and devise practical strategies for mitigating/resolving these challenges. METHOD: Survey data were collected from U.S. based neuropsychologists and other individuals (e.g., graduate students and research assistants) who were engaged in remote cognitive assessment with adults (n = 87). Frequency analyses were conducted to examine: how respondents used teleneuropsychology (e.g., duration of use, types of measures and devices/technology platforms used); challenges that were encountered with different technology platforms and teleneuropsychology use; and advice for navigating these challenges. RESULTS: Most respondents began using teleneuropsychology relatively recently in the context of the coronavirus pandemic, with home-to-home or clinic-to-home settings being the most frequently reported teleneuropsychology settings. Zoom®, Doxy.Me®, and MyChart® were the most frequently used platforms, largely due to workplace mandates and/or Health Insurance Portability and Accountability Act-compliant features. Common challenges with teleneuropsychology included internet connection issues and environmental distractions in examinees' homes, and examinees having limited-to-no access to technologies requisite for teleneuropsychology. Providing clear instructions to the examinee prior to the teleneuropsychology visit was the most common advice for ensuring a successful teleneuropsychology evaluation. Similar response patterns were generally noted for those who used TeleNP for clinical or research purposes. CONCLUSIONS: These survey results reflect common experiences and challenges with teleneuropsychology and identify priority targets for increasing its feasibility, reliability, and validity. Findings provide context for the development of formal teleneuropsychology competencies.

A cultural approach to dementia - insights from US Latino and other minoritized groups.

Alzheimer disease and related dementias present considerable challenges to health-care and medical systems worldwide. In the USA, older Black and Latino individuals are more likely than older white individuals to have Alzheimer disease and related dementias. In this Perspective, we leverage our experience and expertise with older US Latino groups to review and discuss the need to integrate cultural factors into dementia research and care. We examine the importance of considering the effects of cultural factors on clinical presentation and diagnosis, dementia risk, clinical research and recruitment, and caregiving practices, with a focus on minoritized groups in the USA. We highlight critical gaps in the literature to stimulate future research aimed at improving the prevention and early detection of Alzheimer disease and related dementias and developing novel treatments and interventions across ethnoracially diverse populations. In addition, we briefly discuss some of our own initiatives to promote research and clinical care among Latino populations living in the USA.

Perceived stigma and quality of life in Parkinson's disease with additional health conditions.

Background: Parkinson's disease (PD) is associated with perceived stigma and affects quality of life (QoL). Additional health conditions may influence these consequences of PD. Aims: This study assessed the impact of health conditions on perceived stigma and QoL in persons with PD. We hypothesised that individuals with more health conditions would report more stigma and poorer QoL. We also examined the contributions of demographic and clinical characteristics to the correlations between health conditions and perceived stigma/QoL. Methods: We identified 196 eligible participants from the Boston University Online Survey Study of Parkinson's Disease and examined their health history, performance on multiple stigma measures, and scores on the 39-item Parkinson's Disease Questionnaire assessing QoL. Results: At least one health condition was reported by 79% of the sample, with a median of 2 and a range of 0-7 health conditions. More perceived stigma and poorer QoL were associated with thyroid disease, depression, anxiety, and the total number of health conditions. These correlations were related to younger age, less education, and earlier disease onset. Other health conditions (high blood pressure, back/leg surgery, headache, cancer/tumours, and heart disease) were not significantly correlated with stigma or QoL. Conclusions: Having more health conditions, or thyroid disease, depression, or anxiety, was associated with more perceived stigma and poorer QoL, with younger age, less education, and earlier disease onset affecting the associations. It is important to consider the burden of health conditions and how they affect persons with PD with specific clinical characteristics.