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Comparing neuropsychological, typical, and ADNI criteria for the diagnosis of mild cognitive impairment in Vietnam-era veterans
- Monica T. Ly, Jennifer Adler, Adan F. Ton Loy, Emily C. Edmonds, Mark W. Bondi, Lisa Delano-Wood, for the Department of Defense Alzheimer’s Disease Neuroimaging Initiative
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- Journal of the International Neuropsychological Society , First View
- Published online by Cambridge University Press:
- 24 January 2024, pp. 1-9
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Objective:
Neuropsychological criteria for mild cognitive impairment (MCI) more accurately predict progression to Alzheimer’s disease (AD) and are more strongly associated with AD biomarkers and neuroimaging profiles than ADNI criteria. However, research to date has been conducted in relatively healthy samples with few comorbidities. Given that history of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are risk factors for AD and common in Veterans, we compared neuropsychological, typical (Petersen/Winblad), and ADNI criteria for MCI in Vietnam-era Veterans with histories of TBI or PTSD.
Method:267 Veterans (mean age = 69.8) from the DOD-ADNI study were evaluated for MCI using neuropsychological, typical, and ADNI criteria. Linear regressions adjusting for age and education assessed associations between MCI status and AD biomarker levels (cerebrospinal fluid [CSF] p-tau181, t-tau, and Aβ42) by diagnostic criteria. Logistic regressions adjusting for age and education assessed the effects of TBI severity and PTSD symptom severity simultaneously on MCI classification by each criteria.
Results:Agreement between criteria was poor. Neuropsychological criteria identified more Veterans with MCI than typical or ADNI criteria, and were associated with higher CSF p-tau181 and t-tau. Typical and ADNI criteria were not associated with CSF biomarkers. PTSD symptom severity predicted MCI diagnosis by neuropsychological and ADNI criteria. History of moderate/severe TBI predicted MCI by typical and ADNI criteria.
Conclusions:MCI diagnosis using sensitive neuropsychological criteria is more strongly associated with AD biomarkers than conventional diagnostic methods. MCI diagnostics in Veterans would benefit from incorporation of comprehensive neuropsychological methods and consideration of the impact of PTSD.
2 Cognitive Heterogeneity and Risk of Progression in Data-Driven Subtle Cognitive Decline Phenotypes
- Kelsey R Thomas, Katherine J Bangen, Alexandra J Weigand, Gema Ortiz, Kayla S Walker, David P Salmon, Mark W Bondi, Emily C Edmonds
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 103-104
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Objective:
There is increasing recognition of cognitive and pathological heterogeneity in early-stage Alzheimer’s disease and other dementias. Data-driven approaches have demonstrated cognitive heterogeneity in those with mild cognitive impairment (MCI), but few studies have examined this heterogeneity and its association with progression to MCI/dementia in cognitively unimpaired (CU) older adults. We identified cluster-derived subgroups of CU participants based on comprehensive neuropsychological data and compared baseline characteristics and rates of progression to MCI/dementia or a Dementia Rating Scale (DRS) of <129 across subgroups.
Participants and Methods:A hierarchical cluster analysis was conducted using 11 baseline neuropsychological test scores from 365 CU participants in the UCSD Shiley-Marcos Alzheimer’s Disease Research Center (age M=71.93 years, SD=7.51; 55.9% women; 15.6% Hispanic/Latino/a/x/e). A discriminate function analysis was then conducted to test whether the individual neuropsychological scores predicted cluster-group membership. Cox regressions examined the risk of progression to consensus diagnosis of MCI or dementia, or to DRS score <129, by cluster group.
Results:Cluster analysis identified 5 groups: All-Average (n=139), Low-Visuospatial (n=46), Low-Executive (n=51), Low-Memory/Language (n=83), and Low-All Domains (n=46). The discriminant function analysis using the neuropsychological measures to predict group membership into these 5 clusters correctly classified 85.2% of the participants. Subgroups had unique demographic and clinical characteristics. Relative to the All-Average group, the Low-Visuospatial (hazard ratio [HR] 2.39, 95% CI [1.03, 5.56], p=.044), Low-Memory/Language (HR 4.37, 95% CI [2.24, 8.51], p<.001), and Low-All Domains (HR 7.21, 95% CI [3.59, 14.48], p<.001) groups had greater risk of progression to MCI/dementia. The Low-Executive group was also twice as likely to progress to MCI/dementia compared to the AllAverage group, but did not statistically differ (HR 2.03, 95% CI [0.88,4.70], p=.096). A similar pattern of results was found for progression to DRS score <129, with the Low-Executive (HR 2.82, 95% CI [1.26, 6.29], p=.012), Low-Memory/Language (HR 3.70, 95% CI [1.80, 7.56], p<.001) and Low-All Domains (HR 5.79, 95% CI [2.74, 12.27], p<.001) groups at greater risk of progression to a DRS score <129 than the All-Average group. The Low-Visuospatial group was also twice as likely to progress to DRS <129 compared to the All-Average group, but did not statistically differ (HR 2.02, 95% CI [0.80, 5.06], p=.135).
Conclusions:Our results add to a growing literature documenting heterogeneity in the earliest cognitive and pathological presentations associated with Alzheimer’s disease and related disorders. Participants with subtle memory/language, executive, and visuospatial weaknesses all declined at faster rates than the All-Average group, suggesting that there are multiple pathways and/or unique subtle cognitive decline profiles that ultimately lead to a diagnosis of MCI/dementia. These results have important implications for early identification of individuals at risk for MCI/dementia. Given that the same classification approach may not be optimal for everyone, determining profiles of subtle cognitive difficulties in CU individuals and implementing neuropsychological test batteries that assess multiple cognitive domains may be a key step towards an individualized approach to early detection and fewer missed opportunities for early intervention.
6 Pulse Pressure and APOE ε4 Dose Interact to Affect Cerebral Blood Flow in Older Adults Without Dementia
- Lauren Edwards, Kelsey R Thomas, Alexandra J Weigand, Emily C Edmonds, Alexandra L Clark, Einat K Brenner, Daniel A Nation, Lisa Delano-Wood, Mark W Bondi, Katherine J Bangen
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 107-108
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Objective:
Alterations in cerebral blood flow (CBF) are associated with risk of cognitive decline and Alzheimer’s disease (AD). Although apolipoprotein E (APOE) ε4 and greater vascular risk burden have both been linked to reduced CBF in older adults, less is known about how APOE ε4 status and vascular risk may interact to influence CBF. We aimed to determine whether the effect of vascular risk on CBF varies by gene dose of APOE ε4 alleles (i.e., number of e4 alleles) in older adults without dementia.
Participants and Methods:144 older adults without dementia from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) underwent arterial spin labeling (ASL) and T1-weighted MRI, APOE genotyping, fluorodeoxyglucose positron emission tomography (FDG-PET), lumbar puncture, and blood pressure assessment. Vascular risk was assessed using pulse pressure (systolic blood pressure -diastolic blood pressure), which is thought to be a proxy for arterial stiffening. Participants were classified by number of APOE ε4 alleles (n0 alleles = 87, m allele = 46, n2 alleles = 11). CBF in six FreeSurfer-derived a priori regions of interest (ROIs) vulnerable to AD were examined: entorhinal cortex, hippocampus, inferior temporal cortex, inferior parietal cortex, rostral middle frontal gyrus, and medial orbitofrontal cortex. Linear regression models tested the interaction between categorical APOE ε4 dose (0, 1, or 2 alleles) and continuous pulse pressure on CBF in each ROI, adjusting for age, sex, cognitive diagnosis (cognitively unimpaired vs. mild cognitive impairment), antihypertensive medication use, cerebral metabolism (FDG-PET composite), reference CBF region (precentral gyrus), and AD biomarker positivity defined using the ADNI-optimized phosphorylated tau/ß-amyloid ratio cut-off of > 0.0251 pg/ml.
Results:A significant pulse pressure X APOE ε4 dose interaction was found on CBF in the entorhinal cortex, hippocampus, and inferior parietal cortex (ps < .005). Among participants with two e4 alleles, higher pulse pressure was significantly associated with lower CBF (ps < .001). However, among participants with zero or one ε4 allele, there was no significant association between pulse pressure and CBF (ps > .234). No significant pulse pressure X APOE ε4 dose interaction was found in the inferior temporal cortex, rostral middle frontal gyrus, or medial orbitofrontal cortex (ps > .109). Results remained unchanged when additionally controlling for general vascular risk assessed via the modified Hachinski Ischemic Scale.
Conclusions:These findings demonstrate that the cross-sectional association between pulse pressure and region-specific CBF differs by APOE ε4 dose. In particular, a detrimental effect of elevated pulse pressure on CBF in AD-vulnerable regions was found only among participants with the e4/e4 genotype. Our findings suggest that pulse pressure may play a mechanistic role in neurovascular unit dysregulation for those genetically at greater risk for AD. Given that pulse pressure is just one of many potentially modifiable vascular risk factors for AD, future studies should seek to examine how these other factors (e.g., diabetes, high cholesterol) may interact with APOE genotype to affect cerebrovascular dysfunction.
51 Pupillary Responses During Verbal Fluency Tasks as a Biomarker of Risk for Alzheimer's Disease
- Veronica Gandara, Mark Bondi, Jeremy Elman, William Kremen, David Salmon, Jason Holden, Alexandra Weigand, Seraphina Solders, Peter Link, Eric Granholm
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 258-259
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We examined the use of pupillometry as an early risk marker of Alzheimer's disease (AD). Pupil dilation during a cognitive task has been shown to be an index of cognitive effort and may provide a marker of early change in cognition even before performance begins to decline. Individuals who require more effort to successfully perform a task may be closer to decline. We previously found greater compensatory effort to perform the digit span task in individuals with amnestic mild cognitive impairment (aMCI) who may be at greater risk for AD than individuals with non-amnestic MCI (naMCI). Task evoked pupil dilation is linked to increased norepinephrine output from the locus coeruleus (LC), a structure affected early in the AD pathological process. In this study, we measured pupil dilation during verbal fluency tasks in participants with aMCI or naMCI, and cognitively normal (CN) individuals. Based on our findings using the digit span task, we hypothesized that participants with aMCI would show greater compensatory cognitive effort than the other two groups.
Participants and Methods:This study included 101 older adults without dementia recruited from the UC San Diego Shiley-Marcos Alzheimer's Disease Research Center and San Diego community (mean [SD] age = 74.7 [5.8]; education = 16.6 [2.5]; N=58 female; N=92 White); 62 CN, 20 aMCI and 19 naMCI participants. Pupillary responses (change relative to baseline at the start of each trial) were recorded at 30 Hz using a Tobii X2-30 (Tobii, Stockholm, Sweden) during semantic (animals, fruits, vegetables) and phonemic (letters F, A, S) fluency tasks. Participants generated as many words as possible in a category (semantic) or starting with a given letter (phonemic) in 60 seconds.
Results:Repeated measures ANOVA (3 groups X 2 fluency conditions) with age, education and sex as covariates showed a significant main effect of group (F(2,95)=3.64, p=.03), but no group X condition interaction (F<1). Pairwise comparisons showed significantly greater fluency task-evoked dilation for aMCI relative to CN (p=.015) and naMCI (p=.019) participants. When controlling for performance (total letter or category words produced), pupil dilation (cognitive effort) remained significantly greater in aMCI relative to the other two groups in both fluency conditions, suggesting pupil dilation informs risk beyond information provided by task performance.
Conclusions:In a previous sample of community-dwelling men who were an average of 13 years younger than the present sample, we found significantly greater pupil dilation during a digit span task in aMCI relative to naMCI and CN groups. In the present study, we replicated those findings in an older sample using a different cognitive task. Significantly greater pupil dilation was found in individuals with aMCI on verbal fluency tasks, indicating greater compensatory cognitive effort to maintain performance. Pupillometry provides a promising biomarker that might be used as an inexpensive and noninvasive additional screening tool for risk of AD.
17 Education Moderates the Association Between Hippocampal CBF and Memory in Women but Not Men
- Einat K Brenner, Alexandra J Weigand, Lauren C Edwards, Amanda T Calcetas, Maria Bordyug, Sarah J Banks, Erin E Sundermann, Kelsey R Thomas, Mark W Bondi, Katherine J Bangen
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 227-228
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Higher educational attainment is associated with reduced risk for Alzheimer's disease (AD) dementia, and its protective effect may act through alterations in cerebral blood flow (CBF) that allow for better coping with accumulating neuropathology. Additionally, there are sex differences in both the risk of developing AD as well as the potential protective effects of education. We therefore sought to investigate whether education moderates the association of hippocampal CBF and memory in cognitively unimpaired older adults, and to examine if these interactions were moderated by sex.
Participants and Methods:Cognitively unimpaired older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI; 51 men, 50 women) underwent neuropsychological evaluation and arterial spin labeling MRI, which was used to quantify bilateral hippocampal CBF. Sex was defined as sex at birth. Multiple linear regressions assessed (1) the independent associations among education, CBF, and memory performance separately in men and women and (2) the three-way interactions among CBF, sex, and education, followed by sex-stratified analyses. Three outcome measures were examined: Logical Memory Story A immediate and delayed recall, and Rey Auditory Verbal Learning Test (RAVLT) intrusions. All models adjusted for age and APOE epsilon-4 allele frequency, and all models with CBF additionally adjusted for cerebral metabolism (baseline FDG-PET composite) and pulse pressure.
Results:CBF was not associated with education or memory in either women or men. There was a positive association between education and delayed memory in women (ß=0.14, t=2.64, p=0.008) as well as trending, positive associations between education and immediate memory in women (ß=0.09, t=1.79, p=0.074) and education and delayed memory in men (ß=0.09, t=1.94, p=0.054). Three-way interactions among sex, CBF, and education were significant on immediate recall (ß=2.55, t=2.53, p=0.013), delayed recall (ß=2.56, t=2.44, p=0.017), and RAVLT intrusions (ß=-2.28, t=-2.27, p=0.026). In women, there were interactions between education and hippocampal CBF on both immediate (ß=2.49, t=2.90, p=0.006) and delayed recall (ß=2.30, t=2.78, p=0.009), such that as education increased, the strength of the association between CBF and immediate memory increased. There was also an interaction between education and hippocampal CBF on RAVLT intrusions in women (ß=-2.42, t=-3.05, p=0.004), such that as education increased, the strength of the association between CBF and number of intrusions decreased; there was a main effect where in women with lower education, as CBF increased, the number of intrusions increased (ß=0.76, t=2.59, p=0.032); in women with higher education, there was no association between CBF and intrusions. In men, none of these two-way interactions were significant.
Conclusions:These results suggest that, in cognitively unimpaired older women, the relationship between hippocampal CBF and memory is moderated by education level, even when adjusting for several other factors. Specifically, higher education may serve as a protective factor in the hippocampal CBF-memory relationship, and this relationship was sex-dependent, occurring in women only. Further research is needed to examine these relationships longitudinally across the clinical continuum of AD. Additionally, this work needs to be conducted in more diverse samples to allow for analyses investigating the impact of education on the intersection of race/ethnicity and sex/gender.
5 From Advantage to Disadvantage: Women’s Clinical Trajectory in Early-Stage Alzheimer’s Disease
- Erin E. Sundermann, Sarah J. Banks, Mark W. Bondi, Anat Biegon, Thomas Hildebrandt
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 101-102
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There are critical and perplexing sex/gender differences in Alzheimer’s disease (AD). Women show a more favorable clinical profile in preclinical AD particularly with verbal memory, but a steeper decline post mild cognitive impairment (MCI) diagnosis and, ultimately, higher rates of AD. Longitudinal studies are needed to understand sex differences across the AD trajectory. Using data from the Alzheimer’s Disease Neuroimaging Initiative, we identified profiles of memory trajectories among those with evidence of preclinical AD or MCI at baseline and how these trajectories differ by sex.
Participants and Methods:In our sample of 659 participants (age range: 55-90, mean age=72.9 [SD=7.4], 95% non-Hispanic White; mean follow-up=41.2 [SD=32.3] months), 233 were labelled “preclinical” AD (51% women) at baseline based on a cognitively normal status but positivity for either the cerebrospinal fluid p-Tau/Aß42, Amyloid PET or Tau PET biomarkers, and 426 participants (44% women) were MCI at baseline based on Jak/Bondi criteria. We applied latent class growth curve modeling to the heterogeneous change in the Rey Auditory Verbal Learning Test (RAVLT) Immediate and Delayed Recall within preclinical and MCI groups separately. Models in MCI group included Non-Linear Spline to account for differential change rates within subgroups. Models were compared on Bayesian Information Criterion, Entropy, and Class distribution to determine a best-fitting model. Effects of sex on trajectories were the primary outcomes. All models included APOE4 carrier status and age.
Results:Women outperformed men on Immediate and Delayed Recall at baseline in the preclinical and MCI groups (ps<.05). Within the preclinical group, 3-class models representing stable, decline, and accelerated decline provided optimal fit for both Immediate and Delayed Recall. Whereas, on average, preclinical women showed more stable Immediate Recall than men (beta=6.24, SE=.82, p<.0001), they were more likely to be in the Immediate Recall accelerated decline class (23.4% vs. 16.25%; female:male; Chi-square=36.29, p<.00001). On average, preclinical women and men did not differ in Delayed Recall trajectories (beta=.31, SE=.30, p=.28); however, preclinical women were more likely to be in the stable Delayed Recall class (11.04% vs. 6.5%; Chi-Square=19.19, p<.0001). Within the MCI group, 2-class models representing a stable decline group and an accelerated decline group provided optimal fit for both outcomes. Whereas, on average, MCI women showed more stable Immediate Recall than men (beta=3.55, SE=.79, p<.0001), they were more likely to be in the Immediate Recall accelerated decline class, although not significantly. Women and men did not differ, on average, in their Delayed Recall trajectories; however, women were significantly more likely to be in the Delayed Recall accelerated decline class (Chi-square=32.24, p<.0001).
Conclusions:Our findings indicate that sex is an important determinant of the variability observed in early-stage AD trajectories; however, sex differences varied by Immediate versus Delayed Recall likely due, in-part, to psychometric test properties. Our results suggest that, when looking at sex differences in AD trajectories on average, women’s superior stability in verbal learning masks their higher likelihood of rapid decline. Our findings have implications for our ability to optimally diagnose and track disease progression in both sexes.
57 CSF Markers of AD-Related Pathology Relate to aMCI among People with HIV
- Judith D. Lobo, Erin E. Sundermann, Laura M. Campbell, Ben Gouaux, Scott Letendre, Mark W. Bondi, David J. Moore
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 53-54
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Older people with HIV (PWH) are at-risk for Alzheimer’s disease (AD) and its precursor, amnestic mild cognitive impairment (aMCI). Identifying aMCI among PWH is challenging because memory impairment is also common in HIV-associated neurocognitive disorders (HAND). The neuropathological hallmarks of aMCI/AD are amyloid-ß42 (Aß42) plaque and phosphorylated tau (p-tau) accumulation. Neurofilament light chain protein (NfL) is a marker of neuronal injury in AD and other neurodegenerative diseases. In this study, we assessed the prognostic value of the CSF AD pathology markers of lower Aß42, and higher p-tau, p-tau/Aß42 ratio, and NfL levels to identify an aMCI-like profile among older PWH and differentiating it from HAND. We assessed the relationship between aMCI and HAND diagnosis and AD biomarker levels
Participants and Methods:Participants included 74 PWH (Mean age=48 [SD=8.5]; 87.4% male, 56.5% White) from the National NeuroAIDS Tissue Consortium (NNTC). CSF Aß42, Aß40, p-tau and NfL were measured by commercial immunoassay. Participants completed a neurocognitive evaluation assessing the domains of learning, recall, executive function, speed of information processing, working memory, verbal fluency, and motor. Memory domains were assessed with the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised, and aMCI was defined as impairment (<1.0 SD below normative mean) on two or more memory outcomes among HVLT-R and BVMT-R learning, delayed recall and recognition with at-least one recognition impairment required. HAND was defined as impairment (<1.0 SD below normative mean) in 2 or more cognitive domains. A series of separate linear regression models were used to examine how the levels of CSF p-tau, Aß42, p-tau/Aß42 ratio, and NfL relate to aMCI and HAND status while controlling for demographic variables (age, gender, race and education). Covariates were excluded from the model if they did not reach statistical significance.
Results:58% percent of participants were diagnosed with HAND, 50.5% were diagnosed with aMCI. PWH with aMCI had higher levels of CSF p-tau/Aß42 ratio compared to PWH without aMCI (ß=.222, SE=.001, p=.043) while controlling for age (ß=.363, p=.001). No other AD biomarker significantly differed by aMCI or HAND status.
Conclusions:Our results indicate that the CSF p-tau/Aß42 ratio relates specifically to an aMCI-like profile among PWH with high rates of cognitive impairment across multiple domains in this advanced HIV disease cohort. Thus, the p-tau/Aß42 ratio may have utility in disentangling aMCI from HAND and informing the need for further diagnostic procedures and intervention. Further research is needed to fully identify, among a broader group of PWH, who is at greatest risk for aMCI/AD and whether there is increased risk for aMCI/AD among PWH as compared to those without HIV.
41 Examining the independent and additive effects of family history of dementia and apolipoprotein e4 on neurocognitive performance among people with HIV
- Maulika Kohli, Laura M Campbell, Erin Sundermann, Mark W Bondi, Paul Gilbert, Donald Franklin, Scott Letendre, Robert K Heaton, Payal Patel, Susan Morgello, Benjamin Gelman, David Clifford, Raeanne C Moore, David J Moore
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 249-250
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Among people with HIV (PWH), the apolipoprotein e4 (APOE-e4) allele, a genetic marker associated with Alzheimer’s disease (AD), and self-reported family history of dementia (FHD), considered a proxy for higher AD genetic risk, are independently associated with worse neurocognition. However, research has not addressed the potential additive effect of FHD and APOE-e4 on global and domain-specific neurocognition among PWH. Thus, the aim of the current investigation is to examine the associations between FHD, APOE-e4, and neurocognition among PWH.
Participants and Methods:283 PWH (Mage=50.9; SDage=5.6) from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study completed comprehensive neuropsychological and neuromedical evaluations and underwent APOE genotyping. APOE status was dichotomized into APOE-e4+ and APOE-e4-. APOE-e4+ status included heterozygous and homozygous carriers. Participants completed a free-response question capturing FHD of a first- or second-degree relative (i.e., biologic parent, sibling, children, grandparent, grandchild, uncle, aunt, nephew, niece, half-sibling). A dichotomized (yes/no), FHD variable was used in analyses. Neurocognition was measured using global and domain-specific demographically corrected (i.e., age, education, sex, race/ethnicity) T-scores. t-tests were used to compare global and domain-specific demographically-corrected T-scores by FHD status and APOE-e4 status. A 2x2 factorial analysis of variance (ANOVA) was used to model the interactive effects of FHD and APOE-e4 status. Tukey’s HSD test was used to follow-up on significant ANOVAs.
Results:Results revealed significant differences by FHD status in executive functioning (t(281)=-2.3, p=0.03) and motor skills (t(278)=-2.0, p=0.03) such that FHD+ performed worse compared to FHD-. Differences in global neurocognition by FHD status approached significance (t(281)=-1.8, p=.069). Global and domain-specific neurocognitive performance were comparable among APOE-e4 carriers and noncarriers (ps>0.05). Results evaluating the interactive effects of FHD and APOE-e4 showed significant differences in motor skills (F(3)=2.7, p=0.04) between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups such that the FHD+/APOE-e4- performed worse than the FHD-/APOE-e4+ group (p=0.02).
Conclusions:PWH with FHD exhibited worse neurocognitive performance within the domains of executive functioning and motor skills, however, there were no significant differences in neurocognition between APOE-e4 carriers and noncarriers. Furthermore, global neurocognitive performance was comparable across FHD/APOE-e4 groups. Differences between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups in motor skills were likely driven by FHD status, considering there were no independent effects of APOE-e4 status. This suggests that FHD may be a predispositional risk factor for poor neurocognitive performance among PWH. Considering FHD is easily captured through self-report, compared to blood based APOE-e4 status, PWH with FHD should be more closely monitored. Future research is warranted to address the potential additive effect of FHD and APOE-e4 on rates of global and domain-specific neurocognitive decline and impairment over time among in an older cohort of PWH, where APOE-e4 status may have stronger effects.
4 Risk Factor and Biomarker Correlates of FLAIR White Matter Hyperintensities in Former American Football Players
- Monica T Ly, Fatima Tuz-Zahra, Yorghos Tripodis, Charles H Adler, Laura J Balcer, Charles Bernick, Elaine Peskind, Megan L Mariani, Rhoda Au, Sarah J Banks, William B Barr, Jennifer V Wethe, Mark W Bondi, Lisa Delano-Wood, Robert C Cantu, Michael J Coleman, David W Dodick, Michael D McClean, Jesse Mez, Joseph N Palmisano, Brett Martin, Kaitlin Hartlage, Alexander P Lin, Inga K Koerte, Jeffrey L Cummings, Eric M Reiman, Martha E Shenton, Robert A Stern, Sylvain Bouix, Michael L Alosco
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 608-610
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White matter hyperintensity (WMH) burden is greater, has a frontal-temporal distribution, and is associated with proxies of exposure to repetitive head impacts (RHI) in former American football players. These findings suggest that in the context of RHI, WMH might have unique etiologies that extend beyond those of vascular risk factors and normal aging processes. The objective of this study was to evaluate the correlates of WMH in former elite American football players. We examined markers of amyloid, tau, neurodegeneration, inflammation, axonal injury, and vascular health and their relationships to WMH. A group of age-matched asymptomatic men without a history of RHI was included to determine the specificity of the relationships observed in the former football players.
Participants and Methods:240 male participants aged 45-74 (60 unexposed asymptomatic men, 60 male former college football players, 120 male former professional football players) underwent semi-structured clinical interviews, magnetic resonance imaging (structural T1, T2 FLAIR, and diffusion tensor imaging), and lumbar puncture to collect cerebrospinal fluid (CSF) biomarkers as part of the DIAGNOSE CTE Research Project. Total WMH lesion volumes (TLV) were estimated using the Lesion Prediction Algorithm from the Lesion Segmentation Toolbox. Structural equation modeling, using Full-Information Maximum Likelihood (FIML) to account for missing values, examined the associations between log-TLV and the following variables: total cortical thickness, whole-brain average fractional anisotropy (FA), CSF amyloid ß42, CSF p-tau181, CSF sTREM2 (a marker of microglial activation), CSF neurofilament light (NfL), and the modified Framingham stroke risk profile (rFSRP). Covariates included age, race, education, APOE z4 carrier status, and evaluation site. Bootstrapped 95% confidence intervals assessed statistical significance. Models were performed separately for football players (college and professional players pooled; n=180) and the unexposed men (n=60). Due to differences in sample size, estimates were compared and were considered different if the percent change in the estimates exceeded 10%.
Results:In the former football players (mean age=57.2, 34% Black, 29% APOE e4 carrier), reduced cortical thickness (B=-0.25, 95% CI [0.45, -0.08]), lower average FA (B=-0.27, 95% CI [-0.41, -.12]), higher p-tau181 (B=0.17, 95% CI [0.02, 0.43]), and higher rFSRP score (B=0.27, 95% CI [0.08, 0.42]) were associated with greater log-TLV. Compared to the unexposed men, substantial differences in estimates were observed for rFSRP (Bcontrol=0.02, Bfootball=0.27, 994% difference), average FA (Bcontrol=-0.03, Bfootball=-0.27, 802% difference), and p-tau181 (Bcontrol=-0.31, Bfootball=0.17, -155% difference). In the former football players, rFSRP showed a stronger positive association and average FA showed a stronger negative association with WMH compared to unexposed men. The effect of WMH on cortical thickness was similar between the two groups (Bcontrol=-0.27, Bfootball=-0.25, 7% difference).
Conclusions:These results suggest that the risk factor and biological correlates of WMH differ between former American football players and asymptomatic individuals unexposed to RHI. In addition to vascular risk factors, white matter integrity on DTI showed a stronger relationship with WMH burden in the former football players. FLAIR WMH serves as a promising measure to further investigate the late multifactorial pathologies of RHI.
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
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- 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
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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.
3 The Relationship Between Apolipoprotein-E4 Genotype, Memory, and the Medial Temporal Lobe and How These Relationships Vary by Race in Middle-Aged Persons with HIV
- Laura M Campbell, Maulika Kohli, Erin E Sundermann, Christine Fennema-Notestine, Averi Barrett, Cinnamon Bloss, Mark W Bondi, David B Clifford, Ronald J Ellis, Donald Franklin, Benjamin Gelman, Igor Grant, Robert K Heaton, Scott Letendre, Payal B Patel, David J Moore, Susan Morgello, Raeanne C Moore
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 683-684
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Objective:
Many people with HIV (PWH) are at risk for age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Studies on the association between cognition, neuroimaging outcomes, and the Apolipoprotein E4 (APOE4) genotype, which is associated with greater risk of AD, have yielded mixed results in PWH; however, many of these studies have examined a wide age range of PWH and have not examined APOE by race interactions that are observed in HIV-negative older adults. Thus, we examined how APOE status relates to cognition and medial temporal lobe (MTL) structures (implicated in AD pathogenesis) in mid- to older-aged PWH. In exploratory analyses, we also examined race (African American (AA)/Black and non-Hispanic (NH) White) by APOE status interactions on cognition and MTL structures.
Participants and Methods:The analysis included 88 PWH between the ages of 45 and 68 (mean age=51±5.9 years; 86% male; 51% AA/Black, 38% NH-White, 9% Hispanic/Latinx, 2% other) from the CNS HIV Antiretroviral Therapy Effects Research multi-site study. Participants underwent APOE genotyping, neuropsychological testing, and structural MRI; APOE groups were defined as APOE4+ (at least one APOE4 allele) and APOE4- (no APOE4 alleles). Eighty-nine percent of participants were on antiretroviral therapy, 74% had undetectable plasma HIV RNA (<50 copies/ml), and 25% were APOE4+ (32% AA/Black/15% NH-White). Neuropsychological testing assessed seven domains, and demographically-corrected T-scores were calculated. FreeSurfer 7.1.1 was used to measure MTL structures (hippocampal volume, entorhinal cortex thickness, and parahippocampal thickness) and the effect of scanner was regressed out prior to analyses. Multivariable linear regressions tested the association between APOE status and cognitive and imaging outcomes. Models examining cognition covaried for comorbid conditions and HIV disease characteristics related to global cognition (i.e., AIDS status, lifetime methamphetamine use disorder). Models examining the MTL covaried for age, sex, and
relevant imaging covariates (i.e., intracranial volume or mean cortical thickness).
Results:APOE4+ carriers had worse learning (ß=-0.27, p=.01) and delayed recall (ß=-0.25, p=.02) compared to the APOE4- group, but APOE status was not significantly associated with any other domain (ps>0.24). APOE4+ status was also associated with thinner entorhinal cortex (ß=-0.24, p=.02). APOE status was not significantly associated with hippocampal volume (ß=-0.08, p=0.32) or parahippocampal thickness (ß=-0.18, p=.08). Lastly, race interacted with APOE status such that the negative association between APOE4+ status and cognition was stronger in NH-White PWH as compared to AA/Black PWH in learning, delayed recall, and verbal fluency (ps<0.05). There were no APOE by race interactions for any MTL structures (ps>0.10).
Conclusions:Findings suggest that APOE4 carrier status is associated with worse episodic memory and thinner entorhinal cortex in mid- to older-aged PWH. While APOE4+ groups were small, we found that APOE4 carrier status had a larger association with cognition in NH-White PWH as compared to AA/Black PWH, consistent with studies demonstrating an attenuated effect of APOE4 in older AA/Black HIV-negative older adults. These findings further highlight the importance of recruiting diverse samples and suggest exploring other genetic markers (e.g., ABCA7) that may be more predictive of AD in some races to better understand AD risk in diverse groups of PWH.
49 Locus Coeruleus MR Signal Interacts with CSF p-tau/AB42 to Predict Attention, Executive Function, and Verbal Memory
- Seraphina K Solders, Tamara R Shabi, Alexandra J Weigand, Jeremy A Elman, Eric L Granholm, Lawrence R Frank, Mark W Bondi
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 921-922
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Objective:
The locus coeruleus (LC) plays a key role in cognitive processes such as attention, executive function, and memory. The LC has been identified as an early site of tau accumulation in Alzheimer’s disease (AD). LC neurons are thought to survive, albeit with limited functionality, until later stages of the disease, though how exactly this limited functionality impacts cognition through the course of AD is still poorly understood. We investigated the interactive effects of an imaging biomarker of the LC and AD-related cerebrospinal fluid (CSF) biomarkers on attention, executive function, and memory.
Participants and Methods:We recruited 67 older adults from the San Diego community (mean age=74.52 years; 38 cognitively normal, 23 with mild cognitive impairment, and 6 with probable AD). Participants had LC-sensitive magnetic resonance imaging (MRI) used to obtain a measure of LC signal relative to surrounding tissue, with lower LC signal possibly indicating limited functionality. Participants also underwent a lumbar puncture to obtain CSF measurements of amyloid-beta 42 (Ab42) and phosphorylated tau (p-tau). We calculated the p-tau/Ab42 ratio, which is positively correlated with AD progression. Finally, participants were administered a comprehensive neuropsychological battery, and cognitive composites were created for attention (Digit Symbol, Digit Span Forward, Trails A), executive function (Digit Span Backward, Trails B, Color-Word Inhibition Switching), and two measures of verbal memory [learning (CVLT List A 1-5, Logical Memory Immediate Recall) and delay (CVLT Long Free Recall, Logical Memory Delayed Recall)]. Four multiple linear regressions modeled the relationship between each composite with age, gender, education, p-tau/Ab42, average LC contrast, and interactions between average LC contrast and p-tau/Ab42. For models that were statistically significant, additional regressions were assessed to determine which segment of the LC (caudal, middle, rostral) contributed to the relationship.
Results:Our model predicted attention (p=.001, R2=.298) with main effects of average LC signal, p-tau/Ab42, and LC by p-tau/Ab42 interaction. Follow-up regressions revealed that each LC segment contributes to this relationship. Our model predicted executive function (p=.006, R2=.262) with a main effect of average LC signal and LC by p-tau/Ab42 interaction. Follow-up regressions revealed that this relationship was limited to the caudal and middle LC. Our models predicted both verbal learning (p<.001, R2=.512) and delayed memory (p<.001, R2=.364); both with main effects of gender and education. Follow-up regressions revealed that the rostral LC signal interacts with p-tau/Ab42 to predict both verbal learning and delayed memory. For all interactions, those with low p-tau/Ab42 exhibited a positive relationship between LC signal and cognition, whereas those with higher p-tau/Ab42 showed a negative relationship.
Conclusions:MR-assessed LC signal relates to attention, executive function, and verbal learning and memory in a manner that depends on CSF levels of p-tau and Ab42. The relationship between LC signal and cognition is positive at low levels and negative at higher levels of p-tau/Ab42. If lower LC signal indicates reduced integrity, these findings imply that MR-assessed LC signal may be a more meaningful marker of AD progression in earlier stages of the disease. Alternatively, this measure may capture a different underlying mechanism depending on tau and amyloid biomarker status.
17 - Lex Arbitri and the Rules of Procedure
- from Part IV - Applicable Law
- Edited by Stefan Kröll, Andrea K. Bjorklund, McGill University, Montréal, Franco Ferrari, New York University
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- Book:
- Cambridge Compendium of International Commercial and Investment Arbitration
- Published online:
- 18 February 2023
- Print publication:
- 02 March 2023, pp 468-481
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Summary
Lex arbitri (or ‘law of the arbitration’) is the law applicable to an international arbitration based upon the legal seat designated by the parties. The content of lex arbitri is dictated not by international law, but rather by the national law on international arbitration of the chosen jurisdiction. Typically, lex arbitri will address issues relating to the constitution of the arbitral tribunal and the conduct of the arbitration, including the extent to which local courts may be called upon to assist the arbitration process or may review and enforce any potential award, and the legal limits of arbitration in a jurisdiction.This chapter will consider the impact of lex arbitri on international commercial arbitration on the one hand and international investment treaty arbitration on the other.ICSID investment arbitrations are substantially ‘delocalized’ through the legal framework of the ICSID Convention, reducing their dependency on lex arbitri.By contrast, non-ICSID investment arbitrations are ‘localized’ in the seat of arbitration, and therefore are subject to lex arbitri.The direction of travel of international investment treaty proceedings, shown by complex bespoke procedural regimes in specific IIAs and negotiations for a Multilateral Investment Court, international investment disputes may ultimately ‘graduate’ out of dependence on lex arbitri.
2 - Ensuring Indonesians Are Safe from COVID-19
- Edited by Sri Mulyani Indrawati, Suahasil Nazara, Titik Anas, Candra Fajri Ananda, Kiki Verico
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- Book:
- Keeping Indonesia Safe from the COVID-19 Pandemic
- Published by:
- ISEAS–Yusof Ishak Institute
- Published online:
- 30 June 2023
- Print publication:
- 31 October 2022, pp 27-64
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Summary
INTRODUCTION
The novel coronavirus 2019 (COVID-19) outbreak has devastating public health consequences and poses a major economic threat. The ongoing pandemic continues to chart the path for global public health and economic activities. The Johns Hopkins University Coronavirus Resource Center reported more than 470 million total confirmed cases worldwide in March 2022. Global economic growth shrank by 3.5 per cent in 2020 (Weiss et al. 2020; World Bank 2021), with a recovery projected to happen in 2021 and 2022. Globally, countries implemented various responses to COVID-19 which can be classified into four key areas: saving lives; protecting the purchasing power of the poor and vulnerable; saving jobs and businesses; restoring countries to become more resilient (World Bank 2020).
The first two confirmed COVID-19 cases in Indonesia emerged on 2 March 2020 and spread exponentially within a short time. By January 2022, the Indonesian National Disaster Management Authority (Badan Nasional Penanggulangan Bencana, or BNPB) reported more than 4.2 million cases. Indonesia had already faced three large waves of COVID-19 cases between 2020 and early 2022: the original Wuhan coronavirus variant in 2020, the Delta variant in mid-2021, and the Omicron variant in early 2022. The Indonesian government took various significant steps to reduce the spread of the virus and protect the poor and vulnerable families, jobs and businesses, and maintain economic recovery.
To reduce the spread of COVID-19 in the early days of the pandemic, Indonesia introduced international travel restrictions on 1 January 2020 before the first COVID-19 cases were detected in the country. The government introduced the Work, Study, and Worship at Home policy on 16 March 2020 and implemented large-scale social restrictions (Pembatasan Sosial Berskala Besar, or PSBB) on 31 March 2020 as recommended by many studies and international organizations (Glass et al. 2006; Gottlieb et al. 2020; Maharaj and Kleczkowski 2012; Reluga 2020).
Later, on 11 May 2020, Indonesia launched comprehensive health, economic and social containment measures, the National Economic Recovery (Pemulihan Ekonomi Nasional, or PEN) programme. It covers public health support, social protection for the poor and vulnerable, fiscal incentives and financial support for businesses. The government spent IDR575.9 trillion in 2020 and IDR657.1 trillion in 2021 for the PEN programme. In 2022, the government continued the programme by allocating IDR455.62 trillion.
Dōwa Policy and Japanese Politics By Ian Neary. Routledge, 2021. 276 pages. Hardback, £120.00 GBP, ISBN: 9780367651343. Ebook, £36.99, ISBN: 9781003127994
- Christopher Bondy
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- International Journal of Asian Studies / Volume 20 / Issue 2 / July 2023
- Published online by Cambridge University Press:
- 21 April 2022, pp. 929-931
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11 - Germanic Heritage Varieties in the Americas
- from Part I - Heritage Languages around the World
- Edited by Silvina Montrul, University of Illinois, Urbana-Champaign, Maria Polinsky, University of Maryland, College Park
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- The Cambridge Handbook of Heritage Languages and Linguistics
- Published online:
- 04 November 2021
- Print publication:
- 25 November 2021, pp 252-276
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Summary
Continental West Germanic and North Germanic languages have been spoken in the Americas for several hundred years, and many are alive as heritage languages today, though often used only by elderly speakers. This chapter examines these languages from several perspectives. First, we look at social and historical contexts of bilingualism. Second, we describe the varieties used, e.g., the extent to which people knew a standard language, along with associated language attitudes and ideologies. Third, we look at key structural properties of Germanic heritage languages with examples from phonetics and phonology, morphology, syntax, pragmatics, and the lexicon, revealing parallels in development and change across languages. Finally, we note some patterns and language maintenance and shift.
The experience of northern italy in elderly patients with COVID-19 infection and mental disorders
- G. Serafini, E. Bondi, C. Locatelli, M. Amore
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- Journal:
- European Psychiatry / Volume 64 / Issue S1 / April 2021
- Published online by Cambridge University Press:
- 13 August 2021, p. S260
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Introduction
In December 2019, the first cases of Corona Virus Disease 2019 (COVID-19) outbreak related to acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were reported in the Chinese city of Wuhan. European countries experienced a tragic growth in the number of Covid-19 cases although several restrictions have been imposed.
ObjectivesThe study is aimed to describe the first experience of the Hospital Papa Giovanni XXIII in the city of Bergamo, Northern Italy.
MethodsThe most relevant clinical characteristics of aged patients with COVID-19 and mental disorders have been described.
ResultsAccording to the experience of the Hospital Papa Giovanni XXIII, medical departments, after appropriate training of all healthcare workers, have been rapidly converted into specific units aimed at treating patients with COVID-19 infection. Specifically, we directly observed a rapidly growing request of psychiatric interventions in aged patients with COVID-19 infection due to the emergence of severe delirium (mainly hyperkinetic) which was reported in approximately 30−50% of cases increasing with age, psychomotor agitation, anxiety, and depressive symptoms. When compared with younger subjects, we found that subjects aged 65 or above with prolonged hospitalization in our hospital are more vulnerable to: 1) environmental factors (e.g., social isolation and distance from family members, stay in intensive/subintensive units, communication difficulties due to therapeutic devices); 2) individual factors (e.g., COVID-19 possible neurotropic properties, impairments in insight and cognitive dysfunctions, comorbid medical conditions, and use of multiple medications).
ConclusionsThe main implications of the present findings have been discussed.
Crystalline Ice: Not all bad!
- Laura Koepping, Amy Bondy, Min Su
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- Journal:
- Microscopy and Microanalysis / Volume 27 / Issue S1 / August 2021
- Published online by Cambridge University Press:
- 30 July 2021, pp. 532-537
- Print publication:
- August 2021
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Responding to Natural and Industrial Disasters: Partnerships and Lessons Learned
- Elaine Symanski, Heyreoun An Han, Inkyu Han, Michelle McDaniel, Kristina W. Whitworth, Sheryl McCurdy, William Brett Perkison, Amal Rammah, P. Grace Tee Lewis, George L. Delclos, Elena Craft, Melissa Bondy, Cheryl Lyn Walker, Loren Hopkins, José Guillermo Cedeño Laurent, Daisy James
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- Journal:
- Disaster Medicine and Public Health Preparedness / Volume 16 / Issue 3 / June 2022
- Published online by Cambridge University Press:
- 16 March 2021, pp. 885-888
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Objectives:
The aim of this study was to provide insights learned from disaster research response (DR2) efforts following Hurricane Harvey in 2017 to launch DR2 activities following the Intercontinental Terminals Company (ITC) fire in Deer Park, Texas, in 2019.
Methods:A multidisciplinary group of academic, community, and government partners launched a myriad of DR2 activities.
Results:The DR2 response to Hurricane Harvey focused on enhancing environmental health literacy around clean-up efforts, measuring environmental contaminants in soil and water in impacted neighborhoods, and launching studies to evaluate the health impact of the disaster. The lessons learned after Harvey enabled rapid DR2 activities following the ITC fire, including air monitoring and administering surveys and in-depth interviews with affected residents.
Conclusions:Embedding DR2 activities at academic institutions can enable rapid deployment of lessons learned from one disaster to enhance the response to subsequent disasters, even when those disasters are different. Our experience demonstrates the importance of academic institutions working with governmental and community partners to support timely disaster response efforts. Efforts enabled by such experience include providing health and safety training and consistent and reliable messaging, collecting time-sensitive and critical data in the wake of the event, and launching research to understand health impacts and improve resiliency.
Surviving COVID-19 in Bergamo province: a post-acute outpatient re-evaluation
- Serena Venturelli, Simone Vasilij Benatti, Monica Casati, Francesca Binda, Gianluca Zuglian, Gianluca Imeri, Caterina Conti, Ave Maria Biffi, Maria Simonetta Spada, Emi Bondi, Giorgia Camera, Roberta Severgnini, Andrea Giammarresi, Claudia Marinaro, Alessandro Rossini, Pietro Andrea Bonaffini, Giovanni Guerra, Antonio Bellasi, Simonetta Cesa, Marco Rizzi
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- Journal:
- Epidemiology & Infection / Volume 149 / 2021
- Published online by Cambridge University Press:
- 19 January 2021, e32
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Bergamo province was badly hit by the coronavirus disease 2019 (COVID-19) epidemic. We organised a public-funded, multidisciplinary follow-up programme for COVID-19 patients discharged from the emergency department or from the inpatient wards of ‘Papa Giovanni XXIII’ Hospital, the largest public hospital in the area. As of 31 July, the first 767 patients had completed the first post-discharge multidisciplinary assessment. Patients entered our programme at a median time of 81 days after discharge. Among them, 51.4% still complained of symptoms, most commonly fatigue and exertional dyspnoea, and 30.5% were still experiencing post-traumatic psychological consequences. Impaired lung diffusion was found in 19%. Seventeen per cent had D-dimer values two times above the threshold for diagnosis of pulmonary embolism (two unexpected and clinically silent pulmonary thrombosis were discovered by investigating striking D-dimer elevation). Survivors of COVID-19 exhibit a complex array of symptoms, whose common underlying pathology, if any, has still to be elucidated: a multidisciplinary approach is fundamental, to address the different problems and to look for effective solutions.