1367 results
Myth 6 - That Darwin’s Galápagos Finches Inspired His Most Important Evolutionary Insights
- Edited by Kostas Kampourakis, Université de Genève
-
- Book:
- Darwin Mythology
- Published online:
- 30 May 2024
- Print publication:
- 06 June 2024, pp 68-79
-
- Chapter
- Export citation
-
Summary
It is widely believed that Darwin’s Galápagos finches inspired his theory of natural selection. Nothing could be further from the truth. Darwin’s failure to label his Galápagos finch specimens by island, and his lack of useful behavioral observations about the differing diets of these birds, limited his ability to argue that their diverse beaks had evolved by natural selection to fill different ecological niches. For these reasons, these birds are not even mentioned in the Origin of Species. As is well established by historians of science, and as is further supported by Darwin’s own testimony, his revolutionary theory of natural selection was inspired by his reading of Thomas Robert Malthus’s book On Population in September 1838, three years after Darwin’s historic visit to the Galápagos Islands and two years after his return to England on the Beagle. What Darwin’s Galápagos birds, including the famous finches, helped him to understand is that species often grade insensibly into one another and that varieties, as he later argued in the Origin of Species, are “incipient species.” It was the largely underappreciated existence of this variability among species in nature that allowed Darwin to grasp how natural selection might give rise to new species. Inspired in part by David Lack’s (1947) influential book Darwin’s Finches, the pervasive myth associated with these iconic birds is a classic instance of how important scientific discoveries often become telescoped around a dramatic moment of eureka-like insight, obscuring what typically proves to be a more protracted and conceptually multifaceted processes of scientific innovation.
Myth 5 - That Darwin Converted to Evolutionary Theory During His Historic Galápagos Islands Visit
- Edited by Kostas Kampourakis, Université de Genève
-
- Book:
- Darwin Mythology
- Published online:
- 30 May 2024
- Print publication:
- 06 June 2024, pp 56-67
-
- Chapter
- Export citation
-
Summary
It is sometimes said that Darwin was converted to the theory of evolution by the striking evidence provided by his famous Galápagos finches, and, in this connection, that his historic visit to the Galápagos Islands had an immediate impact on his evolutionary thinking. Such was not the case. During his five-week visit to these islands in September and October 1835, Darwin was still under the spell of creationist thinking, so much so that he failed to label most of his Galápagos birds by island—information that was of vital importance for establishing that these species had arisen by geographic isolation on the different islands of the Galápagos group. Moreover, at the time Darwin collected the famous finches that are now named after him, he was misled by their remarkable beak diversity into thinking they were members of different avian families rather than being closely related descendants of a common ancestor. It was not until after Darwin’s return to England, and more particularly during Darwin’s fateful meeting with distinguished ornithologist John Gould in March of 1837, that Darwin finally became convinced that different species of birds indeed inhabited the different islands of the Galápagos group. In addition, Gould’s astute correction of Darwin’s provisional voyage taxonomic assessments of the Galápagos finches allowed Darwin to grasp that these birds were members of a single avian subfamily. Inspired by this new information, Darwin realized that evolution could account for it, and he now generalized these conclusions to other aspects of his Beagle voyage collections.
Shared familial risk for type 2 diabetes mellitus and psychiatric disorders: a nationwide multigenerational genetics study
- Theresa Wimberley, Isabell Brikell, Aske Astrup, Janne T. Larsen, Liselotte V. Petersen, Clara Albiñana, Bjarni J. Vilhjálmsson, Cynthia M. Bulik, Zheng Chang, Giuseppe Fanelli, Janita Bralten, Nina R. Mota, Jordi Salas-Salvadó, Fernando Fernandez-Aranda, Monica Bulló, Barbara Franke, Anders Børglum, Preben B. Mortensen, Henriette T. Horsdal, Søren Dalsgaard
-
- Journal:
- Psychological Medicine , First View
- Published online by Cambridge University Press:
- 27 May 2024, pp. 1-10
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Background
Psychiatric disorders and type 2 diabetes mellitus (T2DM) are heritable, polygenic, and often comorbid conditions, yet knowledge about their potential shared familial risk is lacking. We used family designs and T2DM polygenic risk score (T2DM-PRS) to investigate the genetic associations between psychiatric disorders and T2DM.
MethodsWe linked 659 906 individuals born in Denmark 1990–2000 to their parents, grandparents, and aunts/uncles using population-based registers. We compared rates of T2DM in relatives of children with and without a diagnosis of any or one of 11 specific psychiatric disorders, including neuropsychiatric and neurodevelopmental disorders, using Cox regression. In a genotyped sample (iPSYCH2015) of individuals born 1981–2008 (n = 134 403), we used logistic regression to estimate associations between a T2DM-PRS and these psychiatric disorders.
ResultsAmong 5 235 300 relative pairs, relatives of individuals with a psychiatric disorder had an increased risk for T2DM with stronger associations for closer relatives (parents:hazard ratio = 1.38, 95% confidence interval 1.35–1.42; grandparents: 1.14, 1.13–1.15; and aunts/uncles: 1.19, 1.16–1.22). In the genetic sample, one standard deviation increase in T2DM-PRS was associated with an increased risk for any psychiatric disorder (odds ratio = 1.11, 1.08–1.14). Both familial T2DM and T2DM-PRS were significantly associated with seven of 11 psychiatric disorders, most strongly with attention-deficit/hyperactivity disorder and conduct disorder, and inversely with anorexia nervosa.
ConclusionsOur findings of familial co-aggregation and higher T2DM polygenic liability associated with psychiatric disorders point toward shared familial risk. This suggests that part of the comorbidity is explained by shared familial risks. The underlying mechanisms still remain largely unknown and the contributions of genetics and environment need further investigation.
Thermal and nutrient stress drove Permian-Triassic shallow marine extinctions
- William J. Foster, Anja B. Frank, Qijian Li, Silvia Danise, Xia Wang, Jörn Peckmann
-
- Journal:
- Cambridge Prisms: Extinction / Accepted manuscript
- Published online by Cambridge University Press:
- 13 May 2024, pp. 1-25
-
- Article
-
- You have access Access
- Open access
- Export citation
The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: an individual participant data meta-analysis
- Kuan-Yu Pan, Lonneke van Tuijl, Maartje Basten, Judith J. M. Rijnhart, Alexander de Graeff, Joost Dekker, Mirjam I. Geerlings, Adriaan Hoogendoorn, Adelita V. Ranchor, Roel Vermeulen, Lützen Portengen, Adri C. Voogd, Jessica Abell, Philip Awadalla, Aartjan T. F. Beekman, Ottar Bjerkeset, Andy Boyd, Yunsong Cui, Philipp Frank, Henrike Galenkamp, Bert Garssen, Sean Hellingman, Monika Hollander, Martijn Huisman, Anke Huss, Melanie R. Keats, Almar A. L. Kok, Steinar Krokstad, Flora E. van Leeuwen, Annemarie I. Luik, Nolwenn Noisel, Yves Payette, Brenda W. J. H. Penninx, Susan Picavet, Ina Rissanen, Annelieke M. Roest, Judith G. M. Rosmalen, Rikje Ruiter, Robert A. Schoevers, David Soave, Mandy Spaan, Andrew Steptoe, Karien Stronks, Erik R. Sund, Ellen Sweeney, Alison Teyhan, Emma L. Twait, Kimberly D. van der Willik, Femke Lamers
-
- Journal:
- Psychological Medicine , First View
- Published online by Cambridge University Press:
- 29 April 2024, pp. 1-14
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Background
Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers).
MethodsTwo-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs).
ResultsSmoking (HRs range 1.04–1.10) and physical inactivity (HRs range 1.01–1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03–1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01).
ConclusionsSmoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.
Pediatric Medical Countermeasures: Antidotes and Cytokines for Radiological and Nuclear Incidents and Terrorism
- Thom S. Maciulewicz, Ziad Kazzi, Irene L. Navis, Gregory J. Nelsen, Theodore J. Cieslak, Christopher Newton, Anna Lin, Doneen J. West, Frank G. Walter
-
- Journal:
- Disaster Medicine and Public Health Preparedness / Volume 18 / 2024
- Published online by Cambridge University Press:
- 23 April 2024, e76
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
The war in Ukraine raises concerns for potential hazards of radiological and nuclear incidents. Children are particularly vulnerable in these incidents and may need pharmaceutical countermeasures, including antidotes and cytokines. Searches found no published study comparing pediatric indications and dosing among standard references detailing pediatric medications for these incidents. This study addresses this gap by collecting, tabulating, and disseminating this information to healthcare professionals caring for children. Expert consensus chose the following references to compare their pediatric indications and dosing of medical countermeasures for radiation exposure and internal contamination with radioactive materials: Advanced Hazmat Life Support (AHLS) for Radiological Incidents and Terrorism, DailyMed, Internal Contamination Clinical Reference, Medical Aspects of Radiation Incidents, and Medical Management of Radiological Casualties, as well as Micromedex, POISINDEX, and Radiation Emergency Medical Management (REMM). This is the first study comparing pediatric indications and dosing for medical countermeasures among commonly used references for radiological and nuclear incidents.
Relationship Between Severity and Length of Exposure to COVID-19 Parameters and Resulting Government Responses and the Suicide Crisis Syndrome (SCS)
- Lisa J. Cohen, Yinan Liang, Devon Peterkin, Kamryn McGibbon, Frank Rappa, Megan L. Rogers, Sungeun You, Ksenia Chistopolskaya, Sergey Enikolopov, Shira Barzilay, Vikas Menon, M. Ishrat Husain, Manuela Dudeck, Judith Streb, Elif Çinka, Fatma Kantas Yilmaz, Oskar Kuśmirek, Samira S. Valvassori, Yarden Blum, Igor Galynker
-
- Journal:
- Disaster Medicine and Public Health Preparedness / Volume 18 / 2024
- Published online by Cambridge University Press:
- 15 April 2024, e68
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Objective:
The COVID-19 pandemic has had a globally devastating psychosocial impact. A detailed understanding of the mental health implications of this worldwide crisis is critical for successful mitigation of and preparation for future pandemics. Using a large international sample, we investigated in the present study the relationship between multiple COVID-19 parameters (both disease characteristics and government responses) and the incidence of the suicide crisis syndrome (SCS), an acute negative affect state associated with near-term suicidal behavior.
Methods:Data were collected from 5528 adults across 10 different countries in an anonymous web-based survey between June 2020 and January 2021.
Results:Individuals scoring above the SCS cut-off lived in countries with higher peak daily cases and deaths during the first wave of the pandemic. Additionally, the longer participants had been exposed to markers of pandemic severity (eg, lockdowns), the more likely they were to screen positive for the SCS. Findings reflected both country-to-country comparisons and individual variation within the pooled sample.
Conclusion:Both the pandemic itself and the government interventions utilized to contain the spread appear to be associated with suicide risk. Public policy should include efforts to mitigate the mental health impact of current and future global disasters.
Holocene climate variability – CORRIGENDUM
- Paul A. Mayewski, Eelco E. Rohling, J. Curt Stager, Wibjörn Karlén, Kirk A. Maasch, L. David Meeker, Eric A. Meyerson, Francoise Gasse, Shirley van Kreveld, Karin Holmgren, Julia Lee-Thorp, Gunhild Rosqvist, Frank Rack, Michael Staubwasser, Ralph R. Schneider, Eric J. Steig
-
- Journal:
- Quaternary Research / Volume 119 / May 2024
- Published online by Cambridge University Press:
- 19 March 2024, p. 162
-
- Article
-
- You have access Access
- HTML
- Export citation
Towards a Non-Use Regime on Solar Geoengineering: Lessons from International Law and Governance
- Aarti Gupta, Frank Biermann, Ellinore van Driel, Nadia Bernaz, Dhanasree Jayaram, Rakhyun E. Kim, Louis J. Kotzé, Dana Ruddigkeit, Stacy D. VanDeveer, Margaretha Wewerinke-Singh
-
- Journal:
- Transnational Environmental Law , First View
- Published online by Cambridge University Press:
- 27 February 2024, pp. 1-32
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
In recent years, some scientists have called for research into and potential development of ‘solar geoengineering’ technologies as an option to counter global warming. Solar geoengineering refers to a set of speculative techniques to reflect some incoming sunlight back into space, for example, by continuously spraying reflective sulphur aerosols into the stratosphere over several generations. Because of the significant ecological, social, and political risks posed by such technologies, many scholars and civil society organizations have urged governments to take action to prohibit the development and deployment of solar geoengineering techniques. In this article we take such calls for a prohibitory or a non-use regime on solar geoengineering as a starting point to examine existing international law and governance precedents that could guide the development of such a regime. The precedents we examine include international prohibitory and restrictive regimes that impose bans or restrictions on chemical weapons, biological weapons, weather modification technologies, anti-personnel landmines, substances that deplete the ozone layer, trade in hazardous wastes, deep seabed mining, and mining in Antarctica. We also assess emerging norms and soft law in anticipatory governance of novel technologies, such as human cloning and gene editing. While there is no blueprint for a solar geoengineering non-use regime in international law, our analysis points to numerous specific elements on which governments could draw to constrain or impose an outright prohibition on the development of technologies for solar geoengineering, should they opt to do so.
Prospects for a high-field, compact break-even axisymmetric mirror (BEAM) and applications
- Part of
- C.B. Forest, J.K. Anderson, D. Endrizzi, J. Egedal, S. Frank, K. Furlong, M. Ialovega, J. Kirch, R.W. Harvey, B. Lindley, Yu.V. Petrov, J. Pizzo, T. Qian, K. Sanwalka, O. Schmitz, J. Wallace, D. Yakovlev, M. Yu
-
- Journal:
- Journal of Plasma Physics / Volume 90 / Issue 1 / June 2024
- Published online by Cambridge University Press:
- 17 January 2024, 975900101
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
This paper explores the feasibility of a break-even-class mirror referred to as BEAM (break-even axisymmetric mirror): a neutral-beam-heated simple mirror capable of thermonuclear-grade parameters and $Q\sim 1$ conditions. Compared with earlier mirror experiments in the 1980s, BEAM would have: higher-energy neutral beams, a larger and denser plasma at higher magnetic field, both an edge and a core and capabilities to address both magnetohydrodynamic and kinetic stability of the simple mirror in higher-temperature plasmas. Axisymmetry and high-field magnets make this possible at a modest scale enabling a short development time and lower capital cost. Such a $Q\sim 1$ configuration will be useful as a fusion technology development platform, in which tritium handling, materials and blankets can be tested in a real fusion environment, and as a base for development of higher-$Q$ mirrors.
Do financial constraint and perceived stress modify the effects of food tax schemes on food purchases: moderation analyses in a virtual supermarket experiment
- Sanne K Djojosoeparto, Maartje P Poelman, Michelle Eykelenboom, Mariëlle A Beenackers, Ingrid HM Steenhuis, Maartje M van Stralen, Margreet R Olthof, Carry M Renders, Frank J van Lenthe, Carlijn BM Kamphuis
-
- Journal:
- Public Health Nutrition / Volume 27 / Issue 1 / 2024
- Published online by Cambridge University Press:
- 15 January 2024, e38
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Objective:
To investigate whether financial constraint and perceived stress modify the effects of food-related taxes on the healthiness of food purchases.
Design:Moderation analyses were conducted with data from a trial where participants were randomly exposed to: a control condition with regular food prices, an sugar-sweetened beverage (SSB) tax condition with a two-tiered levy on the sugar content in SSB (5–8 g/100 ml: €0·21 per l and ≥8 g/100 ml: €0·28 per l) or a nutrient profiling tax condition where products with Nutri-Score D or E were taxed at a 20 percent level. Outcome measures were overall healthiness of food purchases (%), energy content (kcal) and SSB purchases (litres). Effect modification was analysed by adding interaction terms between conditions and self-reported financial constraint or perceived stress in regression models. Outcomes for each combination of condition and level of effect modifier were visualised.
Setting:Virtual supermarket.
Participants:Dutch adults (n 386).
Results:Financial constraint or perceived stress did not significantly modify the effects of food-related taxes on the outcomes. Descriptive analyses suggest that in the control condition, the overall healthiness of food purchases was lowest, and SSB purchases were highest among those with moderate/high levels of financial constraint. Compared with the control condition, in a nutrient profiling tax condition, the overall healthiness of food purchases was higher and SSB purchases were lower, especially among those with moderate/high levels of financial constraint. Such patterns were not observed for perceived stress.
Conclusion:Further studies with larger samples are recommended to assess whether food-related taxes differentially affect food purchases of subgroups.
27 Assessing Differences in Academic Achievement Among a National Sample of Children with Epilepsy Before and During the COVID-19 Pandemic
- Brandon Almy, Lauren Scimeca, David Marshall, Brittany L. Nordhaus, Erin Fedak Romanowski, Nancy McNamara, Elise Hodges, Madison M. Berl, Alyssa Ailion, Donald J. Bearden, Katrina Boyer, Crystal M. Cooper, Amanda M. Decrow, Priscilla H. Duong, Patricia Espe-Pfeifer, Marsha Gabriel, Jennifer I. Koop, Kelly A. McNally, Andrew Molnar, Emily Olsen, Kim E. Ono, Kristina E. Patrick, Brianna Paul, Jonathan Romain, Leigh N. Sepeta, Rebecca L.H. Stilp, Greta N. Wilkening, Mike Zaccariello, Frank Zelko
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 28-29
-
- Article
-
- You have access Access
- Export citation
-
Objective:
The COVID-19 pandemic significantly disrupted schools and learning formats. Children with epilepsy are at-risk for generalized academic difficulties. We investigated the potential impact of COVID-19 on learning in those with epilepsy by comparing achievement on well-established academic measures among school-age children with epilepsy referred prior to the COVID-19 pandemic and those referred during the COVID-19 pandemic.
Participants and Methods:This study included 466 children [52% male, predominately White (76%), MAge=10.75 years] enrolled in the Pediatric Epilepsy Research Consortium Epilepsy (PERC) Surgery database project who were referred for surgery and seen for neuropsychological testing. Patients were divided into two groups based on a proxy measure of pandemic timing completed by PERC research staff at each site (i.e., “were there any changes to typical in-person administration [of the evaluation] due to COVID?”). 31% of the sample (N = 144) were identified as having testing during the pandemic (i.e., “yes” response), while 69% were identified as having testing done pre-pandemic (i.e., “no” response). Of the 31% who answered yes, 99% of administration changes pertained to in-person testing or other changes, with 1% indicating remote testing. Academic achievement was assessed by performance measures (i.e., word reading, reading comprehension, spelling, math calculations, and math word problems) across several different tests. T-tests compared the two groups on each academic domain. Subsequent analyses examined potential differences in academic achievement among age cohorts that approximately matched grade level [i.e., grade school (ages 5-10), middle school (ages 11-14), and high school (ages 15-18)].
Results:No significant differences were found between children who underwent an evaluation before the pandemic compared to those assessed during the pandemic based on age norms across academic achievement subtests (all p’s > .34). Similarly, there were no significant differences among age cohorts. The average performance for each age cohort generally fell in the low average range across academic skills. Performance inconsistently varied between age cohorts. The youngest cohort (ages 5-10) scored lower than the other cohorts for sight-word reading, whereas this cohort scored higher than the middle cohort (ages 11-14) for math word problems and reading comprehension. There were no significant differences between the two pandemic groups on demographic variables, intellectual functioning, or epilepsy variables (i.e., age of onset, number of seizure medications, seizure frequency).
Conclusions:Academic functioning was generally equivalent between children with epilepsy who underwent academic testing as part of a pre-surgical evaluation prior to the pandemic compared to those who received testing during the pandemic. Additionally, academic functioning did not significantly differ between age cohorts. Children with epilepsy may have entered the pandemic with effective academic supports and/or were accustomed to school disruptions given their seizure history. Replication is needed as findings are based on a proxy measure of pandemic timing and the extent to which children experienced in-person, remote, and hybrid learning is unknown. Children tested a year into the pandemic, after receiving instruction through varying educational methods, may score differently than those tested earlier. Future research can address these gaps. Although it is encouraging that academic functioning was not disproportionately impacted during the pandemic in this sample, children with epilepsy are at-risk for generalized academic difficulties and continued monitoring of academic functioning is necessary.
4 Evaluating Plasma GFAP for the Detection of Alzheimer’s Disease Dementia
- Madeline Ally, Henrik Zetterberg, Kaj Blennow, Nicholas J. Ashton, Thomas K. Karikari, Hugo Aparicio, Michael A. Sugarman, Brandon Frank, Yorghos Tripodis, Ann C. McKee, Thor D. Stein, Brett Martin, Joseph N. Palmisano, Eric G. Steinberg, Irene Simkina, Lindsay Farrer, Gyungah Jun, Katherine W. Turk, Andrew E. Budson, Maureen K. O’Connor, Rhoda Au, Wei Qiao Qiu, Lee E. Goldstein, Ronald Killiany, Neil W. Kowall, Robert A. Stern, Jesse Mez, Michael L. Alosco
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 408-409
-
- Article
-
- You have access Access
- Export citation
-
Objective:
Blood-based biomarkers represent a scalable and accessible approach for the detection and monitoring of Alzheimer’s disease (AD). Plasma phosphorylated tau (p-tau) and neurofilament light (NfL) are validated biomarkers for the detection of tau and neurodegenerative brain changes in AD, respectively. There is now emphasis to expand beyond these markers to detect and provide insight into the pathophysiological processes of AD. To this end, a reactive astrocytic marker, namely plasma glial fibrillary acidic protein (GFAP), has been of interest. Yet, little is known about the relationship between plasma GFAP and AD. Here, we examined the association between plasma GFAP, diagnostic status, and neuropsychological test performance. Diagnostic accuracy of plasma GFAP was compared with plasma measures of p-tau181 and NfL.
Participants and Methods:This sample included 567 participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC) Longitudinal Clinical Core Registry, including individuals with normal cognition (n=234), mild cognitive impairment (MCI) (n=180), and AD dementia (n=153). The sample included all participants who had a blood draw. Participants completed a comprehensive neuropsychological battery (sample sizes across tests varied due to missingness). Diagnoses were adjudicated during multidisciplinary diagnostic consensus conferences. Plasma samples were analyzed using the Simoa platform. Binary logistic regression analyses tested the association between GFAP levels and diagnostic status (i.e., cognitively impaired due to AD versus unimpaired), controlling for age, sex, race, education, and APOE e4 status. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate diagnostic groups compared with plasma p-tau181 and NfL. Linear regression models tested the association between plasma GFAP and neuropsychological test performance, accounting for the above covariates.
Results:The mean (SD) age of the sample was 74.34 (7.54), 319 (56.3%) were female, 75 (13.2%) were Black, and 223 (39.3%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having cognitive impairment (GFAP z-score transformed: OR=2.233, 95% CI [1.609, 3.099], p<0.001; non-z-transformed: OR=1.004, 95% CI [1.002, 1.006], p<0.001). ROC analyses, comprising of GFAP and the above covariates, showed plasma GFAP discriminated the cognitively impaired from unimpaired (AUC=0.75) and was similar, but slightly superior, to plasma p-tau181 (AUC=0.74) and plasma NfL (AUC=0.74). A joint panel of the plasma markers had greatest discrimination accuracy (AUC=0.76). Linear regression analyses showed that higher GFAP levels were associated with worse performance on neuropsychological tests assessing global cognition, attention, executive functioning, episodic memory, and language abilities (ps<0.001) as well as higher CDR Sum of Boxes (p<0.001).
Conclusions:Higher plasma GFAP levels differentiated participants with cognitive impairment from those with normal cognition and were associated with worse performance on all neuropsychological tests assessed. GFAP had similar accuracy in detecting those with cognitive impairment compared with p-tau181 and NfL, however, a panel of all three biomarkers was optimal. These results support the utility of plasma GFAP in AD detection and suggest the pathological processes it represents might play an integral role in the pathogenesis of AD.
48 Educational Differences in Digital Clock Drawing for the Command Condition: A Bayesian Network Analysis
- Emily F Matusz, Brandon E Frank, Catherine Dion, Udell Holmes III, Yonah Joffe, Sabyasachi Bandyopadhyay, Parisa Rashidi, Patrick Tighe, David J Libon, Catherine C Price
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 727-728
-
- Article
-
- You have access Access
- Export citation
-
Objective:
Research shows that highly educated individuals have at least 20 graphomotor features associated with clock drawing with hands set for '10 after 11' (Davoudi et al., 2021). Research has yet to understand clock drawing features in individuals with fewer years of education. In the current study, we compared older adults with < 8 years of education to those with > 9 years of education on number and pattern of graphomotor feature relationships in the clock drawing command condition.
Participants and Methods:Participants age 65+ from the University of Florida (UF) and UF Health (N= 10,491) completed both command and copy conditions of the digital Clock Drawing Test (dCDT) as a part of a federally-funded investigation. Participants were categorized into two education groups: < 8 years of education (n= 304) and > 9 years of education (n= 10,187). Propensity score matching was then used to match participants from each subgroup (n= 266 for each subgroup) on the following demographic characteristics: age, sex, race, and ethnicity (n= 532, age= 74.99±6.21, education= 10.41±4.45, female= 42.7%, non-white= 32.0%). Network models were derived using Bayesian Structure Learning (BSL) with the hill-climbing algorithm to obtain optimal directed acyclic graphs (DAGs) from all possible solutions in each subgroup for the dCDT command condition.
Results:Both education groups retained 13 of 91 possible edges (14.29%). For the < 8 years of education group (education= 6.65±1.74, ASA= 3.08±0.35), the network included 3 clock face (CF), 7 digit, and 3 hour hand (HH) and minute hand (MH) independent, or “parent,” features connected to the retained edges (BIC= -7395.24). In contrast, the > 9 years of education group (education= 14.17±2.88, ASA= 2.90±0.46) network retained 1 CF, 6 digit, 5 HH and MH, and 1 additional parent features representing the total number of pen strokes (BIC= -6689.92). Both groups showed that greater distance from the HH to the center of the clock also had greater distance from the MH to the center of the clock [ßz(< 8 years)= 0.73, ßz(> 9 years)= 0.76]. Groups were similar in the size of the digit height relative to the distance of the digits to the CF [ßz(< 8 years)= 0.27, ßz(> 9 years)= 0.56]. Larger HH angle was associated with larger MH angle across groups [ßz(< 8 years)= 0.28, ßz(> 9 years)= 0.23].
Conclusions:Education groups differed in the ratio of dCDT parent feature types. Specifically, copy clock production in older adults with < 8 years of education relied more heavily on CF parent features. In contrast, older adults with > 9 years of education relied more heavily on HH and MH parent features. Individuals with < 8 years of education may more infrequently present the concept of time in the clock drawing command condition. This study highlights the importance of considering education level in interpreting dCDT scores and features.
5 Antemortem Plasma GFAP Predicts Alzheimer’s Disease Neuropathological Changes
- Madeline Ally, Henrik Zetterberg, Kaj Blennow, Nicholas J. Ashton, Thomas K. Karikari, Hugo Aparicio, Michael A. Sugarman, Brandon Frank, Yorghos Tripodis, Brett Martin, Joseph N. Palmisano, Eric G. Steinberg, Irene Simkina, Lindsay Farrer, Gyungah Jun, Katherine W. Turk, Andrew E. Budson, Maureen K. O’Connor, Rhoda Au, Wei Qiao Qiu, Lee E. Goldstein, Ronald Killiany, Neil W. Kowall, Robert A. Stern, Jesse Mez, Bertran R. Huber, Ann C. McKee, Thor D. Stein, Michael L. Alosco
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 409-410
-
- Article
-
- You have access Access
- Export citation
-
Objective:
Blood-based biomarkers offer a more feasible alternative to Alzheimer’s disease (AD) detection, management, and study of disease mechanisms than current in vivo measures. Given their novelty, these plasma biomarkers must be assessed against postmortem neuropathological outcomes for validation. Research has shown utility in plasma markers of the proposed AT(N) framework, however recent studies have stressed the importance of expanding this framework to include other pathways. There is promising data supporting the usefulness of plasma glial fibrillary acidic protein (GFAP) in AD, but GFAP-to-autopsy studies are limited. Here, we tested the association between plasma GFAP and AD-related neuropathological outcomes in participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC).
Participants and Methods:This sample included 45 participants from the BU ADRC who had a plasma sample within 5 years of death and donated their brain for neuropathological examination. Most recent plasma samples were analyzed using the Simoa platform. Neuropathological examinations followed the National Alzheimer’s Coordinating Center procedures and diagnostic criteria. The NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Measures of GFAP were log-transformed. Binary logistic regression analyses tested the association between GFAP and autopsy-confirmed AD status, as well as with semi-quantitative ratings of regional atrophy (none/mild versus moderate/severe) using binary logistic regression. Ordinal logistic regression analyses tested the association between plasma GFAP and Braak stage and CERAD neuritic plaque score. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate autopsy-confirmed AD status. All analyses controlled for sex, age at death, years between last blood draw and death, and APOE e4 status.
Results:Of the 45 brain donors, 29 (64.4%) had autopsy-confirmed AD. The mean (SD) age of the sample at the time of blood draw was 80.76 (8.58) and there were 2.80 (1.16) years between the last blood draw and death. The sample included 20 (44.4%) females, 41 (91.1%) were White, and 20 (44.4%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having autopsy-confirmed AD (OR=14.12, 95% CI [2.00, 99.88], p=0.008). ROC analysis showed plasma GFAP accurately discriminated those with and without autopsy-confirmed AD on its own (AUC=0.75) and strengthened as the above covariates were added to the model (AUC=0.81). Increases in GFAP levels corresponded to increases in Braak stage (OR=2.39, 95% CI [0.71-4.07], p=0.005), but not CERAD ratings (OR=1.24, 95% CI [0.004, 2.49], p=0.051). Higher GFAP levels were associated with greater temporal lobe atrophy (OR=10.27, 95% CI [1.53,69.15], p=0.017), but this was not observed with any other regions.
Conclusions:The current results show that antemortem plasma GFAP is associated with non-specific AD neuropathological changes at autopsy. Plasma GFAP could be a useful and practical biomarker for assisting in the detection of AD-related changes, as well as for study of disease mechanisms.
3 Stricker Learning Span criterion validity: remote self-administration of a computer adaptive word list memory test shows similar ability to differentiate PET-defined biomarker groups as in-person Rey Auditory Verbal Learning Test performance in cognitively unimpaired individuals on the Alzheimer’s continuum
- Nikki H. Stricker, John L. Stricker, Aimee J. Karstens, Jay S. Patel, Teresa J. Christianson, Winnie Z. Fan, Sabrina M. Albertson, Ryan D. Frank, Mary M. Machulda, Walter K. Kremers, Julie A. Fields, Jonathan Graff-Radford, Clifford R. Jack, Jr, David S. Knopman, Michelle M. Mielke, Ronald C. Petersen
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 407-408
-
- Article
-
- You have access Access
- Export citation
-
Objective:
The Stricker Learning Span (SLS) is a computer-adaptive word list memory test specifically designed for remote assessment and self-administration on a web-based multi-device platform (Mayo Test Drive). Given recent evidence suggesting the prominence of learning impairment in preclinical Alzheimer’s disease (AD), the SLS places greater emphasis on learning than delayed memory compared to traditional word list memory tests (see Stricker et al., Neuropsychology in press for review and test details). The primary study aim was to establish criterion validity of the SLS by comparing the ability of the remotely-administered SLS and inperson administered Rey Auditory Verbal Learning Test (AVLT) to differentiate biomarkerdefined groups in cognitively unimpaired (CU) individuals on the Alzheimer’s continuum.
Participants and Methods:Mayo Clinic Study of Aging CU participants (N=319; mean age=71, SD=11; mean education=16, SD=2; 47% female) completed a brief remote cognitive assessment (∼0.5 months from in-person visit). Brain amyloid and brain tau PET scans were available within 3 years. Overlapping groups were formed for 1) those on the Alzheimer’s disease (AD) continuum (A+, n=110) or not (A-, n=209), and for 2) those with biological AD (A+T+, n=43) vs no evidence of AD pathology (A-T-, n=181). Primary neuropsychological outcome variables were sum of trials for both the SLS and AVLT. Secondary outcome variables examined comparability of learning (1-5 total) and delay performances. Linear model ANOVAs were used to investigate biomarker subgroup differences and Hedge’s G effect sizes were derived, with and without adjusting for demographic variables (age, education, sex).
Results:Both SLS and AVLT performances were worse in the biomarker positive relative to biomarker negative groups (unadjusted p’s<.05). Because biomarker positive groups were significantly older than biomarker negative groups, group differences were attenuated after adjusting for demographic variables, but SLS remained significant for A+ vs A- and for A+T+ vs A-T- comparisons (adjusted p’s<.05) and AVLT approached significance (p’s .05-.10). The effect sizes for the SLS were slightly better (qualitatively, no statistical comparison) for separating biomarker-defined CU groups in comparison to AVLT. For A+ vs A- and A+T+ vs A-T- comparisons, unadjusted effect sizes for SLS were -0.53 and -0.81 and for AVLT were -0.47 and -0.61, respectively; adjusted effect sizes for SLS were -0.25 and -0.42 and for AVLT were -0.19 and -0.26, respectively. In secondary analyses, learning and delay variables were similar in terms of ability to separate biomarker groups. For example, unadjusted effect sizes for SLS learning (-.80) was similar to SLS delay (.76), and AVLT learning (-.58) was similar to AVLT 30-minute delay (-.55) for the A+T+ vs AT- comparison.
Conclusions:Remotely administered SLS performed similarly to the in-person-administered AVLT in its ability to separate biomarker-defined groups in CU individuals, providing evidence of criterion validity. The SLS showed significantly worse performance in A+ and A+T+ groups (relative to A- and A-T-groups) in this CU sample after demographic adjustment, suggesting potential sensitivity to detecting transitional cognitive decline in preclinical AD. Measures emphasizing learning should be given equal consideration as measures of delayed memory in AD-focused studies, particularly in the preclinical phase.
10 Pupil Dilation During the Stroop Task Offers a Sensitive and Scalable Biomarker of Locus Coeruleus Integrity
- Alexandra J Weigand, Jeremy A Elman, Seraphina K Solders, Alyssa J Macomber, Lawrence R Frank, Eric L Granholm, Mark W Bondi
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 802-803
-
- Article
-
- You have access Access
- Export citation
-
Objective:
Neuronal dysfunction of the locus coeruleus (LC), the primary producer of norepinephrine, has been identified as a biomarker of early Alzheimer's disease (AD) pathophysiology. Norepinephrine has been implicated in attentional control, and its reduced cortical circulation in AD may be associated with selective attentional difficulties. Additionally, greater pupil dilation indicates greater effort needed to perform a cognitive task, and greater compensatory effort to perform the digit span task has been found in individuals at risk for AD. In this study, we examined associations between a neuroimaging biomarker of the LC and pupil dilation during the Stroop task as a sensitive measure of attentional control.
Participants and Methods:64 older adults without dementia were recruited from the San Diego community (mean [SD] age = 74.3 [6.3]; 39 cognitively unimpaired and 25 with mild cognitive impairment). All participants underwent magnetic resonance imaging of the LC and generated behavioral data from a computerized Stroop task that included 36 incongruent trials (e.g., GREEN presented in red ink), 36 congruent trials (e.g., GREEN presented in green ink), and 32 neutral trials (e.g., LEGAL presented in green ink) in a randomized presentation. Mean pupil dilation for each trial (change relative to baseline at the start of each trial) was measured at 30 Hz using the Tobii X2-30 system (Tobii, Stockholm, Sweden) and averaged within each Stroop condition. Paired t-tests assessed for differences in mean pupil dilation across incongruent and congruent Stroop conditions. Iterative re-weighted least squares regression was used to assess the association between a rostral LC contrast ratio measure derived from manually marked ROIs and mean pupil dilation during incongruent trials divided by congruent trials, adjusting for age, sex, and education. Follow-up analyses also assessed the association of these variables with mean reaction time (RT) for incongruent trials divided by congruent trials.
Results:Mean pupil dilation significantly differed across conditions (t = 3.74, mean difference = .13, 95% CI [.06, .20]) such that dilation was higher during the incongruent condition (mean [SD] dilation = .18 [.38] mm) relative to the congruent condition (mean [SD] dilation = .05 [.35] mm). A significant association was observed between pupil dilation and LC contrast ratio, such that increased levels of mean dilation during incongruent trials relative to congruent trials were observed at lower levels of LC contrast ratio (i.e., lower LC integrity; r = -.37, 95% CI [-.55, -.13]). This association was not observed for mean dilation during only congruent trials (r = -.08, 95% CI [-.31, .18]). Additionally, neither LC contrast ratio [r = .24, 95% CI [-.02, .46]) nor mean incongruent/congruent pupil dilation (r = .14, 95% CI [-.13, .37]) were associated with incongruent/congruent RT.
Conclusions:Findings suggest that increased pupil dilation during a demanding attentional task is indicative of increased compensatory effort needed to achieve the same level of performance for individuals with reduced LC biomarker integrity. Pupillometry assessment offers a low-cost, non-invasive, and scalable biomarker of LC dysfunction that may be indicative of preclinical AD.
65 Mayo Test Drive raw composite criterion validity: a brief remote self-administered digital cognitive composite shows similar ability to differentiate PET-defined biomarker groups as a global composite from a person-administered neuropsychological battery in cognitively unimpaired individuals on the Alzheimer’s continuum
- Nikki H. Stricker, Aimee J. Karstens, Teresa J. Christianson, John L. Stricker, Winnie Z. Fan, Sabrina M. Albertson, Ryan D. Frank, Mary M. Machulda, Walter K. Kremers, Jason Hassenstab, Julie A. Fields, Jonathan Graff-Radford, Clifford R. Jack, Jr., David S. Knopman, Michelle M. Mielke, Ronald C. Petersen
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 371-372
-
- Article
-
- You have access Access
- Export citation
-
Objective:
Mayo Test Drive (MTD): Test Development through Rapid Iteration, Validation and Expansion, is a web-based multi-device (smartphone, tablet, personal computer) platform optimized for remote self-administered cognitive assessment that includes a computer-adaptive word list memory test (Stricker Learning Span; SLS; Stricker et al., 2022; Stricker et al., in press) and a measure of processing speed (Symbols Test: Wilks et al., 2021). Study aims were to determine criterion validity of MTD by comparing the ability of the MTD raw composite and in-person administered cognitive measures to differentiate biomarkerdefined groups in cognitively unimpaired (CU) individuals on the Alzheimer’s continuum.
Participants and Methods:Mayo Clinic Study of Aging CU participants (N=319; mean age=71, SD=11, range=37-94; mean education=16, SD=2, range=6-20; 47% female) completed a brief remote cognitive assessment (∼0.5 months from in-person visit). Brain amyloid and brain tau PET scans were available within 3 years. Overlapping groups were formed for 1) those on the Alzheimer’s disease (AD) continuum (A+, n=110) or not (A-, n=209), and for 2) those with biological AD (A+T+, n=43) or with no evidence of AD pathology (A-T-, n=181). Primary outcome variables were MTD raw composite (SLS sum of trials + an accuracy-weighted Symbols response time measure), Global-z (average of 9 in-person neuropsychological measures) and an in-person screening measure (Kokmen Short Test of Mental Status, STMS; which is like the MMSE). Linear model ANOVAs were used to investigate biomarker subgroup differences and Hedge’s G effect sizes were derived, with and without adjusting for demographic variables (age, education, sex).
Results:Remotely administered MTD raw composite showed comparable to slightly larger effect sizes compared to Global-z. Unadjusted effect sizes for MTD raw composite for differentiating A+ vs. A- and A+T+ vs. A-T- groups, respectively, were -0.57 and -0.84 and effect sizes for Global-z were -0.54 and -0.73 (all p’s<.05). Because biomarker positive groups were significantly older than biomarker negative groups, group differences were attenuated after adjusting for demographic variables, but MTD raw composite remained significant for A+T+ vs A-T- (adjusted effect size -0.35, p=.007); Global-z did not reach significance for A+T+ vs A-T- (adjusted effect size -0.19, p=.08). Neither composite reached significance for adjusted analyses for the A+ vs A- comparison (MTD raw composite adjusted effect size= -.22, p=.06; Global-z adjusted effect size= -.08, p=.47). Results were the same for an alternative MTD composite using traditional z-score averaging methods, but the raw score method is preferred for comparability to other screening measures. The STMS screening measure did not differentiate biomarker groups in any analyses (unadjusted and adjusted p’s>.05; d’s -0.23 to 0.05).
Conclusions:Remotely administered MTD raw composite shows at least similar ability to separate biomarker-defined groups in CU individuals as a Global-z for person-administered measures within a neuropsychological battery, providing evidence of criterion validity. Both the MTD raw composite and Global-z showed greater ability to separate biomarker positive from negative CU groups compared to a typical screening measure (STMS) that was unable to differentiate these groups. MTD may be useful as a screening measure to aid early detection of Alzheimer’s pathological changes.
3 Latent Wechsler Profiles in Presurgical Pediatric Epilepsy
- Madison M Berl, Erin T Kaseda, Jennifer I Koop, Brandon Almy, Alyssa Ailion, Donald J Bearden, Katrina Boyer, Crystal M Cooper, Amanda M DeCrow, Priscilla H Duong, Patricia Espe-Pfeifer, Marsha Gabriel, Elise Hodges, David Marshall, Kelly A McNally, Andrew Molnar, Emily Olsen, Kim E Ono, Kristina E Patrick, Brianna Paul, Jonathan Romain, Leigh N Sepeta, Rebecca LH Stilp, Greta Wilkening, Michael Zaccariello, Frank Zelko, PERC Epilepsy Surgery Database Project
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 308-310
-
- Article
-
- You have access Access
- Export citation
-
Objective:
The Pediatric Epilepsy Research Consortium (PERC) Epilepsy Surgery Database Project is a multisite collaborative that includes neuropsychological evaluations of children presenting for epilepsy surgery. There is some evidence for specific neuropsychological phenotypes within epilepsy (Hermann et al, 2016); however, this is less clear in pediatric patients. As a first step, we applied an empirically-based subtyping approach to determine if there were specific profiles using indices from the Wechsler scales [Verbal IQ (VIQ), Nonverbal IQ (NVIQ), Processing Speed Index (PSI), Working Memory Index (WMI)]. We hypothesized that there would be at least four profiles that are distinguished by slow processing speed and poor working memory as well as profiles with significant differences between verbal and nonverbal reasoning abilities.
Participants and Methods:Our study included 372 children (M=12.1 years SD=4.1; 77.4% White; 48% male) who completed an age-appropriate Wechsler measure, enough to render at least two index scores. Epilepsy characteristics included 84.4% with focal epilepsy (evenly distributed between left and right focus) and 13.5% with generalized or mixed seizure types; mean age of onset = 6.7 years, SD = 4.5; seizure frequency ranged from daily to less than monthly; 53% had structural etiology; 71% had an abnormal MRI; and mean number of antiseizure medications was two. Latent profile analysis was used to identify discrete underlying cognitive profiles based on intellectual functioning. Demographic and epilepsy characteristics were compared among profiles.
Results:Based on class enumeration procedures, a 3-cluster solution provided the best fit for the data, with profiles characterized by generally Average, Low Average, or Below Average functioning. 32.8% were in the Average profile with mean index scores ranging from 91.7-103.2; 47.6% were in the Low Average profile with mean index ranging from 80.7 to 84.5; and 19.6% were in the Below Average profile with mean index scores ranging from 55.0-63.1. Across all profiles, the lowest mean score was the PSI, followed by WMI. VIQ and NVIQ represented relatively higher scores for all three profiles. Mean discrepancy between indices within a profile was as large as 11.5 IQ points. No demographics or epilepsy characteristics were significantly different across cognitive phenotypes.
Conclusions:Latent cognitive phenotypes in a pediatric presurgical cohort were differentiated by general level of functioning; however, across profiles, processing speed was consistently the lowest index followed by working memory. These findings across phenotypes suggest a common relative weakness which may result from a global effect of antiseizure medications and/or the widespread impact of seizures on neural networks even in a largely focal epilepsy cohort; similar to adult studies with temporal lobe epilepsy (Hermann et al, 2007). Future work will use latent profile analysis to examine phenotypes across other domains relevant to pediatric epilepsy including attention, naming, motor, and memory functioning. These findings are in line with collaborative efforts towards cognitive phenotyping which is the aim of our PERC Epilepsy Surgery Database Project that has already established one of the largest pediatric epilepsy surgery cohorts.
49 Educational Differences in Digital Clock Drawing for the Copy Condition: A Bayesian Network Analysis
- Emily F Matusz, Brandon E Frank, Catherine Dion, Udell Holmes III, Yonah Joffe, Sabyasachi Bandyopadhyay, Parisa Rashidi, Patrick Tighe, David J Libon, Catherine C Price
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, p. 728
-
- Article
-
- You have access Access
- Export citation
-
Objective:
Research shows that highly educated individuals have at least 20 graphomotor features associated with clock drawing with hands set for '10 after 11' (Davoudi et al., 2021). Research has yet to understand clock drawing features in individuals with fewer years of education. In the current study, we compared older adults with < 8 years of education to those with > 9 years of education on number and pattern of graphomotor feature relationships in the clock drawing copy condition.
Participants and Methods:Participants age 65+ from the University of Florida (UF) and UF Health (N= 10,491) completed command and copy digital Clock Drawing Tests (dCDT) as a part of a federally-funded investigation. Participants were categorized into two groups: < 8 years of education (n= 304) and > 9 years of education (n= 10,187). Propensity score matching was used to match participants from each subgroup (n= 266 for each subgroup) on the following: age, sex, race, and ethnicity (n= 532, age= 74.99±6.21, education= 10.41±4.45, female= 42.7%, non-white= 32.0%). Network models were derived using Bayesian Structure Learning (BSL) with the hill-climbing algorithm to obtain optimal directed acyclic graphs (DAGs) from all possible solutions in each subgroup for the dCDT copy condition.
Results:The < 8 years of education group (education= 6.65±1.74, ASA= 3.08±0.35), retained 12 of 91 possible edges (13.19%, BIC= -7775.50). The network retained 2 clock face (CF), 5 digit, and 5 hour hand (HH) and minute hand (MH) independent, or “parent,” features connected to the retained edges. In contrast, the > 9 years of education group (education= 14.17±2.88, ASA= 2.90±0.46) network retained 15 of 91 possible edges (16.48%, BIC= -8261.484). The network retained 2 CF, 6 digit, 4 HH and MH, and an additional 3 total stroke parent features. Both groups showed that greater distance from the HH to the clock center also had greater distance from the MH to the clock center (ßz= 0.73, both). Groups were similar in digit width size relative to digit height [ßz(< 8 years)= 0.72, ßz(> 9 years)= 0.74]. Digit height size related to CF area [ßz(< 8 years)= 0.44, ßz(> 9 years)= 0.62] and CF area related to the digit distance to the CF across groups [ßz(< 8 years)= 0.39, ßz(> 9 years)= 0.46]. Greater distance from the MH to the clock center was associated with smaller MH angle [ßz(< 8 years)= -0.35, ßz(> 9 years)= -0.31], whereas greater digit misplacement was associated with larger MH angle across groups [ßz(< 8 years)= 0.14, ßz(> 9 years)= 0.29].
Conclusions:Education groups differed in the ratio of dCDT parent feature types. Specifically, copy clock production in older adults with < 8 years of education relied more evenly across CF, digit, and MH and HH parent features. In contrast, those with > 9 years of education differed in the additional reliance on total stroke parent features. Individuals with < 8 years of education may more heavily rely upon visual referencing when copying a clock. This study highlights the importance of considering education level in interpreting dCDT scores and features.