Browsing by Author "Apostolova, Liana"
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Item Accelerating diversity in Alzheimer's disease research by partnering with a community advisory board(Wiley, 2023-05-28) Pena-Garcia, Alex; Richards, Ralph; Richards, Mollie; Campbell, Christopher; Mosley, Hank; Asper, Joseph; Eliacin, Johanne; Polsinelli, Angelina; Apostolova, Liana; Hendrie, Hugh; Tackett, Andrew; Elliott, Caprice; Van Heiden, Sarah; Gao, Sujuan; Saykin, Andrew; Wang, Sophia; Medicine, School of MedicineIntroduction: Community advisory boards (CABs) and researcher partnerships present a promising opportunity to accelerate enrollment of underrepresented groups (URGs). We outline the framework for how the CAB and researchers at the Indiana Alzheimer's Disease Research Center (IADRC) partnered to accelerate URG participation in AD neuroimaging research. Methods: CAB and the IADRC researchers partnered to increase the CAB's impact on URG study enrollment through community and research interactions. Community interactions included the CAB collaboratively building a network of URG focused community organizations and collaborating with those URG-focused organizations to host IADRC outreach and recruitment events. Research interactions included direct impact (CAB members referring themselves or close contacts as participants) and strategic impact, mainly by the CAB working with researchers to develop and refine URG focused outreach and recruitment strategies for IADRC and affiliated studies to increase URG representation. We created a database infrastructure to measure how these interactions impacted URG study enrollment. Results: Out of the 354 URG research referrals made to the IADRC between October 2019 and December 2022, 267 referrals were directly referred by the CAB (N = 36) or from community events in which CAB members organized and/or volunteered at (N = 231). Out of these 267 referrals, 34 were enrolled in IADRC and 2 were enrolled in Indiana University Longitudinal Early Onset AD Study (IU LEADS). Of note, both studies require the prospective participants to be willing to do MRI and PET scans. As of December 2022, 30 out of the 34 enrolled participants have received a consensus diagnosis; the majority were cognitively normal (64.7%), with the remainder having mild cognitive impairment (17.6%) or early-stage AD (2.9%). Discussion: The IADRC CAB-researcher partnership had a measurable impact on the enrollment of African American/Black adults in AD neuroimaging studies. Future studies will need to test whether this conceptual model works for other sites and for other URGs.Item Alzheimer’s disease research progress in the Mediterranean region: the Alzheimer’s Association International Conference Satellite Symposium(Wiley, 2022) Sexton, Claire; Solis, Michele; Aharon-Peretz, Judith; Alexopoulos, Panagiotis; Apostolova, Liana; Bayen, Eléonore; Birkenhager, Betty; Cappa, Stefano; Constantinidou, Fofi; Fortea, Juan; Gerritsen, Debby L.; Hassanin, Hany I.; Ibanez, Agustin; Ioannidis, Panagiotis; Karageorgiou, Elissaios; Korczyn, Amos; Leroi, Iracema; Lichtwarck, Bjorn; Logroscino, Giancarlo; Lynch, Chris; Mecocci, Patrizia; Molinuevo, Jose Luis; Papatriantafyllou, John; Papegeorgiou, Sokratis; Politis, Antonis; Raman, Rema; Ritchie, Karen; Sanchez-Juan, Pascual; Sano, Mary; Scarmeas, Nikolas; Spiru, Luiza; Stathi, Afroditi; Tsolaki, Magda; Yener, Görsev; Zaganas, Ioannis; Zygouris, Stelios; Carrillo, Maria; Neurology, School of MedicineAs research and services in the Mediterranean region continue to increase, so do opportunities for global collaboration. To support such collaborations, the Alzheimer's Association was due to hold its seventh Alzheimer's Association International Conference Satellite Symposium in Athens, Greece in 2021. Due to the COVID-19 pandemic, the meeting was held virtually, which enabled attendees from around the world to hear about research efforts in Greece and the surrounding Mediterranean countries. Research updates spanned understanding the biology of, treatments for, and care of people with Alzheimer's disease (AD_ and other dementias. Researchers in the Mediterranean region have outlined the local epidemiology of AD and dementia, and have identified regional populations that may expedite genetic studies. Development of biomarkers is expected to aid early and accurate diagnosis. Numerous efforts have been made to develop culturally specific interventions to both reduce risk of dementia, and to improve quality of life for people living with dementia.Item Author Correction: Report from a multidisciplinary meeting on anxiety as a non-motor manifestation of Parkinson’s disease(Nature, 2020-06-02) Pontone, Gregory M.; Dissanayaka, Nadeeka; Apostolova, Liana; Brown, Richard G.; Dobkin, Roseanne; Dujardin, Kathy; Friedman, Joseph H.; Leentjens, Albert F. G.; Lenze, Eric J.; Marsh, Laura; Mari, Lynda; Monchi, Oury; Richard, Irene H.; Schrag, Anette; Strafella, Antonio P.; Vernaleo, Beth; Weintraub, Daniel; Mari, Zoltan; Neurology, School of MedicineItem Clinical criteria for limbic-predominant age-related TDP-43 encephalopathy(Wiley, 2025) Wolk, David A.; Nelson, Peter T.; Apostolova, Liana; Arfanakis, Konstantinos; Boyle, Patricia A.; Carlsson, Cynthia M.; Corriveau-Lecavalier, Nick; Dacks, Penny; Dickerson, Bradford C.; Domoto-Reilly, Kimiko; Dugger, Brittany N.; Edelmayer, Rebecca; Fardo, David W.; Grothe, Michel J.; Hohman, Timothy J.; Irwin, David J.; Jicha, Gregory A.; Jones, David T.; Kawas, Claudia H.; Lee, Edward B.; Lincoln, Karen; Maestre, Gladys E.; Mormino, Elizabeth C.; Onyike, Chiadi U.; Petersen, Ronald C.; Rabinovici, Gil D.; Rademakers, Rosa; Raman, Rema; Rascovsky, Katya; Rissman, Robert A.; Rogalski, Emily; Scheltens, Philip; Sperling, Reisa A.; Yang, Hyun-Sik; Yu, Lei; Zetterberg, Henrik; Schneider, Julie A.; Neurology, School of MedicineLimbic predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is highly prevalent in late life and a common co-pathology with Alzheimer's disease neuropathologic change (ADNC). LATE-NC is a slowly progressive, amnestic clinical syndrome. Alternatively, when present with ADNC, LATE-NC is associated with a more rapid course. With the emergence of anti-amyloid therapeutics, discrimination of LATE-NC from ADNC is critical and will lead to greater clinical recognition of amnestic patients without ADNC. Furthermore, co-pathology with LATE-NC may influence outcomes of these therapeutics. Thus there is a need to identify patients during life with likely LATE-NC. We propose criteria for clinical diagnosis of LATE as an initial framework for further validation. In the context of progressive memory loss and substantial hippocampal atrophy, criteria are laid out for probable (amyloid negative) or possible LATE (amyloid biomarkers are unavailable or when amyloid is present, but hippocampal neurodegeneration is out of proportion to expected pure ADNC). HIGHLIGHTS: Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a highly prevalent driver of neuropathologic memory loss in late life. LATE neuropathologic change (LATE-NC) is a common co-pathology with Alzheimer's disease neuropathologic change (ADNC) and may influence outcomes with emerging disease-modifying medicines. We provide initial clinical criteria for diagnosing LATE during life either when LATE-NC is the likely primary driver of symptoms or when observed in conjunction with AD. Definitions of possible and probable LATE are provided.Item Demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy: an international cohort study and individual participant data meta-analysis(Elsevier, 2024) Chapleau, Marianne; La Joie, Renaud; Yong, Keir; Agosta, Federica; Allen, Isabel Elaine; Apostolova, Liana; Best, John; Boon, Baayla D. C.; Crutch, Sebastian; Filippi, Massimo; Fumagalli, Giorgio Giulio; Galimberti, Daniela; Graff-Radford, Jonathan; Grinberg, Lea T.; Irwin, David J.; Josephs, Keith A.; Mendez, Mario F.; Mendez, Patricio Chrem; Migliaccio, Raffaella; Miller, Zachary A.; Montembeault, Maxime; Murray, Melissa E.; Nemes, Sára; Pelak, Victoria; Perani, Daniela; Phillips, Jeffrey; Pijnenburg, Yolande; Rogalski, Emily; Schott, Jonathan M.; Seeley, William; Sullivan, A. Campbell; Spina, Salvatore; Tanner, Jeremy; Walker, Jamie; Whitwell, Jennifer L.; Wolk, David A.; Ossenkoppele, Rik; Rabinovici, Gil D.; PCA International Work Group; Neurology, School of MedicineBackground: Posterior cortical atrophy is a rare syndrome characterised by early, prominent, and progressive impairment in visuoperceptual and visuospatial processing. The disorder has been associated with underlying neuropathological features of Alzheimer's disease, but large-scale biomarker and neuropathological studies are scarce. We aimed to describe demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy in a large international cohort. Methods: We searched PubMed between database inception and Aug 1, 2021, for all published research studies on posterior cortical atrophy and related terms. We identified research centres from these studies and requested deidentified, individual participant data (published and unpublished) that had been obtained at the first diagnostic visit from the corresponding authors of the studies or heads of the research centres. Inclusion criteria were a clinical diagnosis of posterior cortical atrophy as defined by the local centre and availability of Alzheimer's disease biomarkers (PET or CSF), or a diagnosis made at autopsy. Not all individuals with posterior cortical atrophy fulfilled consensus criteria, being diagnosed using centre-specific procedures or before development of consensus criteria. We obtained demographic, clinical, biofluid, neuroimaging, and neuropathological data. Mean values for continuous variables were combined using the inverse variance meta-analysis method; only research centres with more than one participant for a variable were included. Pooled proportions were calculated for binary variables using a restricted maximum likelihood model. Heterogeneity was quantified using I2. Findings: We identified 55 research centres from 1353 papers, with 29 centres responding to our request. An additional seven centres were recruited by advertising via the Alzheimer's Association. We obtained data for 1092 individuals who were evaluated at 36 research centres in 16 countries, the other sites having not responded to our initial invitation to participate to the study. Mean age at symptom onset was 59·4 years (95% CI 58·9-59·8; I2=77%), 60% (56-64; I2=35%) were women, and 80% (72-89; I2=98%) presented with posterior cortical atrophy pure syndrome. Amyloid β in CSF (536 participants from 28 centres) was positive in 81% (95% CI 75-87; I2=78%), whereas phosphorylated tau in CSF (503 participants from 29 centres) was positive in 65% (56-75; I2=87%). Amyloid-PET (299 participants from 24 centres) was positive in 94% (95% CI 90-97; I2=15%), whereas tau-PET (170 participants from 13 centres) was positive in 97% (93-100; I2=12%). At autopsy (145 participants from 13 centres), the most frequent neuropathological diagnosis was Alzheimer's disease (94%, 95% CI 90-97; I2=0%), with common co-pathologies of cerebral amyloid angiopathy (71%, 54-88; I2=89%), Lewy body disease (44%, 25-62; I2=77%), and cerebrovascular injury (42%, 24-60; I2=88%). Interpretation: These data indicate that posterior cortical atrophy typically presents as a pure, young-onset dementia syndrome that is highly specific for underlying Alzheimer's disease pathology. Further work is needed to understand what drives cognitive vulnerability and progression rates by investigating the contribution of sex, genetics, premorbid cognitive strengths and weaknesses, and brain network integrity.Item Designing the next-generation clinical care pathway for Alzheimer’s disease(Springer Nature, 2022) Hampel, Harald; Au, Rhoda; Mattke, Soeren; van der Flier, Wiesje M.; Aisen, Paul; Apostolova, Liana; Chen, Christopher; Cho, Min; De Santi, Susan; Gao, Peng; Iwata, Atsushi; Kurzman, Ricky; Saykin, Andrew J.; Teipel, Stefan; Vellas, Bruno; Vergallo, Andrea; Wang, Huali; Cummings, Jeffrey; Neurology, School of MedicineThe reconceptualization of Alzheimer's disease (AD) as a clinical and biological construct has facilitated the development of biomarker-guided, pathway-based targeted therapies, many of which have reached late-stage development with the near-term potential to enter global clinical practice. These medical advances mark an unprecedented paradigm shift and requires an optimized global framework for clinical care pathways for AD. In this Perspective, we describe the blueprint for transitioning from the current, clinical symptom-focused and inherently late-stage diagnosis and management of AD to the next-generation pathway that incorporates biomarker-guided and digitally facilitated decision-making algorithms for risk stratification, early detection, timely diagnosis, and preventative or therapeutic interventions. We address critical and high-priority challenges, propose evidence-based strategic solutions, and emphasize that the perspectives of affected individuals and care partners need to be considered and integrated.Item Developments in understanding early onset Alzheimer’s disease(Wiley, 2023) Griffin, Percy; Apostolova, Liana; Dickerson, Bradford C.; Rabinovici, Gil; Salloway, Stephen; Raghuram, Srilath; Brandt, Katie; Hall, Stephen; Masdeu, Joseph; Carrillo, Maria C.; Hammers, Dustin; Neurology, School of MedicineOn September 25 and 26, 2021, the Alzheimer's Association hosted the first meeting focused on people with early-onset Alzheimer's disease (EOAD)-sometimes referred to as younger onset Alzheimer's disease (AD). Though a diagnosis of AD can be devastating at any age, those with a younger onset-defined as symptoms developing prior to 65 years of age-face unique challenges. EOAD occurs when people are in the prime of their lives, often with multiple responsibilities including careers, community activities, and raising children and caring for older family members. These challenges warrant special consideration and study, yet people with EOAD are often excluded from AD research because of their atypical age of onset. To help fill this gap, we designed and launched the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) to enroll and follow 500 people with EOAD from > 15 sites in the United States, which the National Institute on Aging funded in 2018. The September 2021 meeting was designed to inform people with EOAD and their family members and caregivers about the latest research on the biology of EOAD, treatments in the pipeline, practical considerations about legal and financial arrangements for families, and the support networks available to them. More than 217 registrants attended.Item Feasibility of Recruiting People With Mild Cognitive Impairment in the Context of Heart Failure(Oxford University Press, 2024-12-31) Jung, Miyeon; Pressler, Susan; Hammers, Dustin; Apostolova, Liana; School of NursingRecruiting people with mild cognitive impairment (MCI) with another chronic condition such as heart failure (HF) can be arduous. Our investigative group will discuss the challenges encountered while recruiting older adults with both MCI and HF using data from a pilot study testing the efficacy of cognitive interventions to improve cognitive function and the strategies to overcome them. Initially, eligibility criteria included age ≥65 years, HF confirmed by echocardiography, and MCI defined using a 2-step process: (1) Montreal Cognitive Assessment (MoCA) ≤23; and (2) diagnostic consensus of MCI based on the presence of cognitive impairment in the absence of functional decline. Enrollment began on 4/3/2023 by screening Cardiology and Neurology clinics patients. Only 12 participants were enrolled over the next 7 months (rate=1.5 participants/month) due to high screen failure rates (59%) owing to MoCA performances above the eligibility threshold and low recruitment rate (5%). To meet recruitment goals (8 participants/month), eligibility criteria were modified by lowering the age cutoff from 65 to 55 years and removing the MoCA screen and the MCI requirements, while adding the requirement of subjective cognitive concern allowing both those with normal cognition and MCI but not dementia. Phone recruitment was added by screening electronic health records of people who diagnosed with HF. 7 months after implementing the modifications, additional 58 participants were consented exceeding our recruitment goals (69% of those consented=MCI, 26%=normal cognition, 5%=dementia/excluded from the study). In conclusion, feasibility of our original strategies recruiting older adults with both MCI and HF was not supported.Item Genetic variants for Alzheimer’s disease and comorbid conditions(Sage, 2024) Pan, Minmin; Lai, Dongbing; Unverzagt, Frederick; Apostolova, Liana; Hendrie, Hugh C.; Saykin, Andrew; Foroud, Tatiana; Gao, Sujuan; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthBackground: Alzheimer's disease and related dementias (ADRD) frequently co-occur with comorbidities such as diabetes and cardiovascular diseases in elderly populations. Objective: Utilize a life-course approach to identify genetic variants that are associated with the co-occurrence of ADRD and another comorbid condition. Methods: Research data from African American participants of the Indianapolis-Ibadan Dementia Project (IIDP) linked with electronic medical record (EMR) data and genome-wide association study (GWAS) data were utilized. The age of onset for ADRD was obtained from longitudinal follow-up of the IIDP study. Age of onset for comorbid conditions was obtained from EMR. The analysis included 1177 African Americans, among whom 174 were diagnosed with ADRD. A semi-parametric marginal bivariate survival model was used to examine the influence of single nucleotide polymorphisms (SNPs) on dual time-to-event outcomes while adjusting for sex, years of education, and the first principal component of GWAS data. Results: Targeted analysis of 20 SNPs that were reported to be associated with ADRD revealed that six were significantly associated with dual-disease outcomes, specifically congestive heart failure and cancer. In addition, eight novel SNPs were identified for associations with both ADRD and a comorbid condition. Conclusions: Using a bivariate survival model approach, we identified genetic variants associated not only with ADRD, but also with comorbid conditions. Our utilization of dual-disease models represents a novel analytic strategy for uncovering shared genetic variants for multiple disease phenotypes.Item Neurological Correlates of Social Bonding and Bridging(Oxford University Press, 2022-12-20) Manchella, Mohit; Logan, Paige; Perry, Brea; Peng, Siyun; Hamilton, Lucas; Risacher, Shannon; Saykin, Andrew; Apostolova, Liana; Neurology, School of MedicineSocial connectedness has been linked to decreased rates of cognitive decline in later life. However, recent work suggests that particular social network characteristics (i.e., bonding and bridging) may buffer against age-related degeneration. The present study analyzes social network and structural MRI data of 176 older adults from the Social Networks and Alzheimer’s Disease (SNAD) study. Results indicate that increased social bridging is associated with greater grey matter (GM) volume in several limbic structures. Increased social bonding is associated with greater GM volumes in several cerebral cortex structures as well as greater volumes in some components of the limbic system. Most notably, the effects of bridging are primarily lateralized in the left hemisphere while the effects of bonding are observed mostly in the right hemisphere. These results suggest that the neurocognitive benefits of social connectedness depend on the preponderance of bridging and/or bonding ties in older adults’ social networks.