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.Published versio

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.NA - Clara Mayo Memorial Research Fellowship, Department of Psychological and Brain Sciences, Boston UniversityPublished versio

Initial investigation of test-retest reliability of home-to-home teleneuropsychological assessment in healthy, English-speaking adults

Prior teleneuropsychological research has assessed the reliability between in-person and remote administration of cognitive assessments. Few, if any, studies have examined the test-retest reliability of cognitive assessments conducted in sequential clinic-to-home or home-to-home teleneuropsychological evaluations - a critical issue given the state of clinical practice during the COVID-19 pandemic. This study examined this key psychometric question for several cognitive tests administered over repeated videoconferencing visits 4-6 months apart in a sample of healthy English-speaking adults. A total of 44 participants (ages 18-75) completed baseline and follow-up cognitive testing 4-6 months apart. Testing was conducted in a home-to-home setting over HIPAA-compliant videoconferencing meetings on participants' audio-visual enabled laptop or desktop computers. The following measures were repeated at both virtual visits: the Controlled Oral Word Association Test (FAS), Category Fluency (Animals), and Digit Span Forward and Backward from the Wechsler Adult Intelligence Scale, Fourth Edition. Intraclass correlation coefficients (ICC), Pearson correlations, root mean square difference (RMSD), and concordance correlation coefficients (CCC) were calculated as test-retest reliability metrics, and practice effects were assessed using paired-samples t-tests. Some tests exhibited small practice effects, and test-retest reliability was marginal or worse for all measures except FAS, which had adequate reliability (based on ICC and r). Reliability estimates with RMSD suggested that change within +/- 1 SD on these measures may reflect typical test-retest variability. The included cognitive measures exhibited questionable reliability over repeated home-to-home videoconferencing evaluations. Future teleneuropsychology test-retest reliability research is needed with larger, more diverse samples and in clinical populations.F31 AG062158 - NIA NIH HHS; R01 AG054671 - NIA NIH HHS; R01 AG066823 - NIA NIH HHSAccepted manuscrip

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

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. Keywords: autosomal dominant Alzheimer's disease; depression; hippocampus; preclinical; presenilin-1

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.HighlightsWe 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