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Drivers of Memory Loss Underreport in Mild Cognitive Impairment Due to Alzheimer Versus Vascular Disease

Briggs, Anthony Q; Ouedraogo Tall, Sakina; Boza-Calvo, Carolina; Bernard, Mark A; Bubu, Omonigho M; Masurkar, Arjun V
BACKGROUND:We examined drivers of self and study partner reports of memory loss in mild cognitive impairment (MCI) from Alzheimer (AD-MCI) and vascular disease (Va-MCI). METHODS:We performed retrospective cross-sectional analyses of participants with AD-MCI (n=2874) and Va-MCI (n=376) from the National Alzheimer's Coordinating Center data set. Statistical analysis utilized 2-sided t test or the Fisher exact test. RESULTS:Compared with AD-MCI, Va-MCI subjects (24.5% vs. 19.7%, P=0.031) and study partners (31.4% vs. 21.6%, P<0.0001) were more likely to deny memory loss. Black/African Americans were disproportionately represented in the group denying memory loss in AD-MCI (20.0% vs. 13.2%, P<0.0001) and Va-MCI (33.7% vs. 18.0%, P=0.0022). Study partners of participants with these features also disproportionately denied memory loss: female (AD-MCI: 60.1% vs. 51.7%, P=0.0002; Va-MCI: 70.3% vs. 52.3%, P=0.0011), Black/African American (AD-MCI: 23.5% vs. 11.98%, P<0.0001; Va-MCI: 48.8% vs. 26.5%, P=0.0002), and <16 years of education (AD-MCI only: 33.9% vs. 16.3%, P=0.0262). In AD-MCI and Va-MCI, participants with anxiety were disproportionately represented in the group endorsing memory loss (AD: 28.2% vs. 17.4%, P<0.0001; Va: 31.5% vs. 16.1%, P=0.0071), with analogous results with depression. CONCLUSION/CONCLUSIONS:The findings would suggest extra vigilance in interview-based MCI detection of persons at-risk for self-based or informant-based misreport.
PMID: 38755756
ISSN: 1546-4156
CID: 5651692

Complementary and Integrative Medicine for the Treatment of Trigeminal Neuralgia and Trigeminal Autonomic Cephalalgia

Kuruvilla, Deena E; Natbony, Lauren; Chandwani, Brijesh; Jann, Adelene; Bradley, Brooklyn A; Zhang, Niushen
PURPOSE OF REVIEW/OBJECTIVE:Trigeminal neuralgia (TN) and trigeminal autonomic cephalalgias (TACs) are both painful diseases which directly impact the branches of the trigeminal nerve, which supply the face. Patients who have experienced adverse effects, have not responded to mainstream treatments, or have a personal preference for nonmedication options, often turn to complementary and integrative medicine (CIM). The aim of this review is to discuss the efficacy and safety of CIM therapies available for the treatment of TN and TACs. RECENT FINDINGS/RESULTS:Not only are there limited therapeutic options for TN and TAC patients, but also is there a proportion of patients who are intolerant to standard medical treatments. Recent findings have illustrated that 86% of patients with headache disorders utilize CIM modalities in combination with mainstream medical therapy. CIM modalities can be helpful for these diseases and have primarily been studied in combination with standard medical therapy. There is limited evidence for CIM and behavioral therapies in managing these conditions, and more research is needed to confirm which therapies are safe and effective.
PMID: 38285128
ISSN: 1534-3081
CID: 5627362

Clinical Outcomes and Tau Pathology in Retired Football Players: Associations With Diagnosed and Witnessed Sleep Apnea

Banks, Sarah J; Yhang, Eukyung; Tripodis, Yorghos; Su, Yi; Protas, Hillary; Adler, Charles H; Balcer, Laura J; Bernick, Charles; Mez, Jesse B; Palmisano, Joseph; Barr, William B; Wethe, Jennifer V; Dodick, David W; Mcclean, Michael D; Martin, Brett; Hartlage, Kaitlin; Turner, Arlener; Turner, Robert W; Malhotra, Atul; Colman, Michael; Pasternak, Ofer; Lin, Alexander P; Koerte, Inga K; Bouix, Sylvain; Cummings, Jeffrey L; Shenton, Martha E; Reiman, Eric M; Stern, Robert A; Alosco, Michael L
BACKGROUND AND OBJECTIVES/UNASSIGNED:Obstructive sleep apnea (SA) is common in older men and a contributor to negative cognitive, psychiatric, and brain health outcomes. Little is known about SA in those who played contact sports and are at increased risk of neurodegenerative disease(s) and other neuropathologies associated with repetitive head impacts (RHI). In this study, we investigated the frequency of diagnosed and witnessed SA and its contribution to clinical symptoms and tau pathology using PET imaging among male former college and former professional American football players. METHODS/UNASSIGNED:The sample included 120 former National Football League (NFL) players, 60 former college players, and 60 asymptomatic men without exposure to RHI (i.e., controls). Diagnosed SA was self-reported, and all participants completed the Mayo Sleep Questionnaire (MSQ, informant version), the Epworth Sleepiness Scale (ESS), neuropsychological testing, and tau (flortaucipir) PET imaging. Associations between sleep indices (diagnosed SA, MSQ items, and the ESS) and derived neuropsychological factor scores, self-reported depression (Beck Depression Inventory-II [BDI-II]), informant-reported neurobehavioral dysregulation (Behavior Rating Inventory of Executive Function-Adult Version [BRIEF-A] Behavioral Regulation Index [BRI]), and tau PET uptake, were tested. RESULTS/UNASSIGNED:gene carrier status. Higher ESS scores correlated with higher BDI-II and BRIEF-A BRI scores. Continuous positive airway pressure use mitigated all of the abovementioned associations. Among the former college football players, witnessed apnea and higher ESS scores were associated with higher BRIEF-A BRI and BDI-II scores, respectively. No other associations were observed in this subgroup. DISCUSSION/UNASSIGNED:Former elite American football players are at risk of SA. Our findings suggest that SA might contribute to cognitive, neuropsychiatric, and tau outcomes in this population. Like all neurodegenerative diseases, this study emphasizes the multifactorial contributions to negative brain health outcomes and the importance of sleep for optimal brain health.
PMCID:10900387
PMID: 38425491
ISSN: 2163-0402
CID: 5722802

Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study

Yaghi, Shadi; Shu, Liqi; Mandel, Daniel M; Leon Guerrero, Christopher R; Henninger, Nils; Muppa, Jayachandra; Affan, Muhammad; Ul Haq Lodhi, Omair; Heldner, Mirjam R; Antonenko, Kateryna; Seiffge, David J; Arnold, Marcel; Salehi Omran, Setareh; Crandall, Ross Curtiss; Lester, Evan; Lopez Mena, Diego; Arauz, Antonio; Nehme, Ahmad; Boulanger, Marion; Touzé, Emmanuel; Sousa, João André; Sargento-Freitas, Joao; Barata, Vasco; Castro-Chaves, Paulo; Brito, Maria Teresa Álvares Pereira; Khan, Muhib; Mallick, Dania; Rothstein, Aaron; Khazaal, Ossama; Kaufmann, Josefin; Engelter, Stefan T; Traenka, Christopher; Aguiar de Sousa, Diana; Soares, Mafalda; Rosa, Sara Db; Zhou, Lily W; Gandhi, Preet; Field, Thalia S; Mancini, Steven; Metanis, Issa; Leker, Ronen R; Pan, Kelly; Dantu, Vishnu; Baumgartner, Karl Viktor; Burton, Tina M; Freiin von Rennenberg, Regina; Nolte, Christian H; Choi, Richard K; MacDonald, Jason A; Bavarsad Shahripour, Reza; Guo, Xiaofan; Ghannam, Malik; AlMajali, Mohammad; Samaniego, Edgar A; Sanchez, Sebastian; Rioux, Bastien; Zine-Eddine, Faycal; Poppe, Alexandre Y; Fonseca, Ana Catarina; Baptista, Maria; Cruz, Diana; Romoli, Michele; De Marco, Giovanna; Longoni, Marco; Keser, Zafer; Griffin, Kim J; Kuohn, Lindsey; Frontera, Jennifer A; Amar, Jordan; Giles, James A; Zedde, Marialuisa; Pascarella, Rosario; Grisendi, Ilaria; Nzwalo, Hipólito; Liebeskind, David S; Molaie, Amir M; Cavalier, Annie; Kam, Wayneho; Mac Grory, Brian; Al Kasab, Sami; Anadani, Mohammad; Kicielinski, Kimberly P; Eltatawy, Ali Rada; Chervak, Lina M; Chulluncuy-Rivas, Roberto; Aziz, Yasmin Ninette; Bakradze, Ekaterina; Tran, Thanh Lam; Rodrigo-Gisbert, Marc; Requena, Manuel; Saleh Velez, Faddi Ghassan; Ortiz Garcia, Jorge G; Muddasani, Varsha; de Havenon, Adam; Vishnu, Venugopalan Y; Yaddanapudi, Sridhara S; Adams, Latasha; Browngoehl, Abigail; Ranasinghe, Tamra; Dunston, Randy; Lynch, Zachary; Penckofer, Mary; Siegler, James E; Mayer, Silvia V; Willey, Joshua Z; Zubair, Adeel S; Cheng, Yee Kuang; Sharma, Richa; Marto, João Pedro; Mendes Ferreira, Vitor; Klein, Piers; Nguyen, Thanh N; Asad, Syed Daniyal; Sarwat, Zoha; Balabhadra, Anvesh; Patel, Shivam; Secchi, Thais Leite; Martins, Sheila Co; Mantovani, Gabriel Paulo; Kim, Young Dae; Krishnaiah, Balaji; Elangovan, Cheran; Lingam, Sivani; Qureshi, Abid Y; Fridman, Sebastian; Alvarado-Bolaños, Alonso; Khasiyev, Farid; Linares, Guillermo; Mannino, Marina; Terruso, Valeria; Vassilopoulou, Sofia; Tentolouris-Piperas, Vasileios; Martínez-Marino, Manuel; Carrasco Wall, Víctor A; Indraswari, Fransisca; El Jamal, Sleiman; Liu, Shilin; Alvi, Muhammad; Ali, Farman; Sarvath, Mohammed Madani; Morsi, Rami Z; Kass-Hout, Tareq; Shi, Feina; Zhang, Jinhua; Sokhi, Dilraj; Said, Jamil; Simpkins, Alexis N; Gomez, Roberto; Sen, Shayak; Ghani, Mohammad Ravi; Elnazeir, Marwa; Xiao, Han; Kala, Narendra Sharma; Khan, Farhan; Stretz, Christoph; Mohammadzadeh, Nahid; Goldstein, Eric D; Furie, Karen L
PMID: 38335240
ISSN: 1524-4628
CID: 5632012

Leveraging archival cerebrospinal fluid samples for genetic insights from cell-free DNA [Editorial]

Miller, Alexandra M; Bale, Tejus A
PMID: 38427323
ISSN: 1934-6638
CID: 5770612

Alignment of brain embeddings and artificial contextual embeddings in natural language points to common geometric patterns

Goldstein, Ariel; Grinstein-Dabush, Avigail; Schain, Mariano; Wang, Haocheng; Hong, Zhuoqiao; Aubrey, Bobbi; Schain, Mariano; Nastase, Samuel A; Zada, Zaid; Ham, Eric; Feder, Amir; Gazula, Harshvardhan; Buchnik, Eliav; Doyle, Werner; Devore, Sasha; Dugan, Patricia; Reichart, Roi; Friedman, Daniel; Brenner, Michael; Hassidim, Avinatan; Devinsky, Orrin; Flinker, Adeen; Hasson, Uri
Contextual embeddings, derived from deep language models (DLMs), provide a continuous vectorial representation of language. This embedding space differs fundamentally from the symbolic representations posited by traditional psycholinguistics. We hypothesize that language areas in the human brain, similar to DLMs, rely on a continuous embedding space to represent language. To test this hypothesis, we densely record the neural activity patterns in the inferior frontal gyrus (IFG) of three participants using dense intracranial arrays while they listened to a 30-minute podcast. From these fine-grained spatiotemporal neural recordings, we derive a continuous vectorial representation for each word (i.e., a brain embedding) in each patient. Using stringent zero-shot mapping we demonstrate that brain embeddings in the IFG and the DLM contextual embedding space have common geometric patterns. The common geometric patterns allow us to predict the brain embedding in IFG of a given left-out word based solely on its geometrical relationship to other non-overlapping words in the podcast. Furthermore, we show that contextual embeddings capture the geometry of IFG embeddings better than static word embeddings. The continuous brain embedding space exposes a vector-based neural code for natural language processing in the human brain.
PMCID:10980748
PMID: 38553456
ISSN: 2041-1723
CID: 5645352

Racial/Ethnic Differences in Long-COVID-Associated Symptoms among Pediatrics Population: Findings from Difference-in-differences Analyses in RECOVER Program

Chen, Yong; Zhang, Dazheng; Zhang, Bingyu; Wu, Qiong; Zhou, Ting; Tong, Jiayi; Lu, Yiwen; Chen, Jiajie; Wang, Huiyuan; Chisolm, Deena; Jhaveri, Ravi; Kenney, Rachel; Rothman, Russel; Rao, Suchitra; Williams, David; Hornig, Mady; Morris, Jeffrey; Forrest, Christopher
Racial/ethnic differences are associated with the potential symptoms and conditions of post-acute sequelae SARS-CoV-2 infection (PASC) in adults. These differences may exist among children and warrant further exploration. We conducted a retrospective cohort study for children and adolescents under the age of 21 from the thirteen institutions in the RECOVER Initiative. The cohort is 225,723 patients with SARS-CoV-2 infection or COVID-19 diagnosis and 677,448 patients without SARS-CoV-2 infection or COVID-19 diagnosis between March 2020 and October 2022. The study compared minor racial/ethnic groups to Non-Hispanic White (NHW) individuals, stratified by severity during the acute phase of COVID-19. Within the severe group, Asian American/Pacific Islanders (AAPI) had a higher prevalence of fever/chills and respiratory symptoms, Hispanic patients showed greater hair loss prevalence in severe COVID-19 cases, while Non-Hispanic Black (NHB) patients had fewer skin symptoms in comparison to NHW patients. Within the non-severe group, AAPI patients had increased POTS/dysautonomia and respiratory symptoms, and NHB patients showed more cognitive symptoms than NHW patients. In conclusion, racial/ethnic differences related to COVID-19 exist among specific PASC symptoms and conditions in pediatrics, and these differences are associated with the severity of illness during acute COVID-19.
PMCID:10996810
PMID: 38585924
ISSN: 2693-5015
CID: 5746052

In vivo mapping of hippocampal venous vasculature and oxygenation using susceptibility imaging at 7T

Li, Chenyang; Buch, Sagar; Sun, Zhe; Muccio, Marco; Jiang, Li; Chen, Yongsheng; Haacke, E Mark; Zhang, Jiangyang; Wisniewski, Thomas M; Ge, Yulin
Mapping the small venous vasculature of the hippocampus in vivo is crucial for understanding how functional changes of hippocampus evolve with age. Oxygen utilization in the hippocampus could serve as a sensitive biomarker for early degenerative changes, surpassing hippocampal tissue atrophy as the main source of information regarding tissue degeneration. Using an ultrahigh field (7T) susceptibility-weighted imaging (SWI) sequence, it is possible to capture oxygen-level dependent contrast of submillimeter-sized vessels. Moreover, the quantitative susceptibility mapping (QSM) results derived from SWI data allow for the simultaneous estimation of venous oxygenation levels, thereby enhancing the understanding of hippocampal function. In this study, we proposed two potential imaging markers in a cohort of 19 healthy volunteers aged between 20 and 74 years. These markers were: 1) hippocampal venous density on SWI images and 2) venous susceptibility (Δχvein) in the hippocampus-associated draining veins (the inferior ventricular veins (IVV) and the basal veins of Rosenthal (BVR) using QSM images). They were chosen specifically to help characterize the oxygen utilization of the human hippocampus and medial temporal lobe (MTL). As part of the analysis, we demonstrated the feasibility of measuring hippocampal venous density and Δχvein in the IVV and BVR at 7T with high spatial resolution (0.25 × 0.25 × 1 mm3). Our results demonstrated the in vivo reconstruction of the hippocampal venous system, providing initial evidence regarding the presence of the venous arch structure within the hippocampus. Furthermore, we evaluated the age effect of the two quantitative estimates and observed a significant increase in Δχvein for the IVV with age (p = 0.006, r2 = 0.369). This may suggest the potential application of Δχvein in IVV as a marker for assessing changes in atrophy-related hippocampal oxygen utilization in normal aging and neurodegenerative diseases such as AD and dementia.
PMID: 38554779
ISSN: 1095-9572
CID: 5645402

Proteomics from compartment-specific APEX2 labeling in Mycobacterium tuberculosis reveals Type VII secretion substrates in the cell wall

Jaisinghani, Neetika; Previti, Mary L; Andrade, Joshua; Askenazi, Manor; Ueberheide, Beatrix; Seeliger, Jessica C
The cell wall of mycobacteria plays a key role in interactions with the environment. Its ability to act as a selective filter is crucial to bacterial survival. Proteins in the cell wall enable this function by mediating the import and export of diverse metabolites, from ions to lipids to proteins. Identifying cell wall proteins is an important step in assigning function, especially as many mycobacterial proteins lack functionally characterized homologues. Current methods for protein localization have inherent limitations that reduce accuracy. Here we showed that although chemical labeling of live cells did not exclusively label surface proteins, protein tagging by the engineered peroxidase APEX2 within live Mycobacterium tuberculosis accurately identified the cytosolic and cell wall proteomes. Our data indicate that substrates of the virulence-associated Type VII ESX secretion system are exposed to the periplasm, providing insight into the currently unknown mechanism by which these proteins cross the mycobacterial cell envelope.
PMID: 37967559
ISSN: 2451-9448
CID: 5644222

The neutrophil to lymphocyte ratio associates with markers of Alzheimer's disease pathology in cognitively unimpaired elderly people

Jacobs, Tovia; Jacobson, Sean R; Fortea, Juan; Berger, Jeffrey S; Vedvyas, Alok; Marsh, Karyn; He, Tianshe; Gutierrez-Jimenez, Eugenio; Fillmore, Nathanael R; Bubu, Omonigho M; Gonzalez, Moses; Figueredo, Luisa; Gaggi, Naomi L; Plaska, Chelsea Reichert; Pomara, Nunzio; Blessing, Esther; Betensky, Rebecca; Rusinek, Henry; Zetterberg, Henrik; Blennow, Kaj; Glodzik, Lidia; Wisniewski, Thomas M; Leon, Mony J; Osorio, Ricardo S; Ramos-Cejudo, Jaime
BACKGROUND/UNASSIGNED:(p-tau), as well as the trajectories of these CSF measures obtained longitudinally. RESULTS/UNASSIGNED:A total of 111 ADNI and 190 NYU participants classified as CU with available NLR, CSF, and covariate data were included. Compared to NYU, ADNI participants were older (73.79 vs. 61.53, p < 0.001), had a higher proportion of males (49.5% vs. 36.8%, p = 0.042), higher BMIs (27.94 vs. 25.79, p < 0.001), higher prevalence of hypertensive history (47.7% vs. 16.3%, p < 0.001), and a greater percentage of Aβ-positivity (34.2% vs. 20.0%, p = 0.009). In the ADNI cohort, we found cross-sectional associations between the NLR and CSF Aβ42 (β=-12.193, p = 0.021), but not t-tau or p-tau. In the NYU cohort, we found cross-sectional associations between the NLR and CSF t-tau (β = 26.812, p = 0.019) and p-tau (β = 3.441, p = 0.015), but not Aβ42. In the NYU cohort alone, subjects classified as Aβ+ (n = 38) displayed a stronger association between the NLR and t-tau (β = 100.476, p = 0.037) compared to Aβ- subjects or the non-stratified cohort. In both cohorts, the same associations observed in the cross-sectional analyses were observed after incorporating longitudinal CSF data. CONCLUSIONS/UNASSIGNED:in the younger NYU cohort. Associations persisted after adjusting for comorbidities, suggesting a direct link between the NLR and AD. However, changes in associations between the NLR and specific AD biomarkers may occur as part of immunosenescence.
PMID: 38559231
ISSN: 2693-5015
CID: 5728992