Neurology Commons^™

Dementia Incidence In Patients With Prurigo Nodularis: An Observational Retrospective Cohort Study, Madison P. Olexson, Ana Ormaza Vera, Chunghwan Ro, Clinton W. Enos

Department Dermatology Faculty Publications

[Introduction] Prurigo nodularis (PN) is a chronic neuroinflammatory dermatosis of unknown etiology characterized by severely pruritic, symmetrically-distributed nodules with a negative impact on quality of life [1]. While some consider PN a primary idiopathic disorder, it often arises as a secondary manifestation of underlying conditions, including atopic dermatitis (AD), chronic kidney disease (CKD), human-immunodeficiency-virus (HIV), and thyroid disorders [2]. Although patients with PN are at higher risk for psychiatric comorbidities including depression, anxiety, and suicidal ideation [3] research which investigates associations between PN and neurodegenerative disorders is limited [4]. Moreover, emerging evidence implicating sustained systemic inflammation, characteristic of psoriasis and …

Predicting Dementia Risk: Progress, Pitfalls, And Priorities, Patricia Nistor, Osvaldo Espin-Garcia, Zul Merali, Shehzad Ali

Brain and Mind Institute

As populations age, identifying individuals at high risk for dementia has become a cornerstone of prevention-oriented public health policy. Accurate and scalable risk stratification could enable early intervention and resource targeting. However, existing models face methodological limitations, including constraints in available data and follow-up duration, challenges in dementia ascertainment, heterogeneity in modelling approaches, and limited external validation. This commentary discusses these challenges and identifies methodological priorities for developing dementia risk algorithms that are robust and suitable for real-world implementation.

Cultural Adaptation Of An Innovative Reproductive Health Assessment Tool For Dementia Research In Africa: Insights From The Fember-Africa Study, Alice Moraa Ondieki, Anne Njogu, Cynthia I Sabel Smith, Edna Bosire, Karen Blackmon, Harrison Kaleli, Jasmit Shah, Rachel Maina, Sheila Waa, Chinedu Momoh

Brain and Mind Institute

Background: Dementia research accounts for only 0.1% of all research in Africa,making it the lowest among all low- and middle-income country (LMIC) regions. Thedevelopment and adaptation of biological and psychosocial measures in ethnicallyand culturally diverse populations remain limited but are essential for culturallyinformed research. This is particularly critical for examining sex- and gender-basedvulnerabilities to Alzheimer’s disease and related dementias (ADRD), including factorssuch as reproductive health and fertility.

Method: We conducted a thorough review of our clinical and health questionnaires forcultural relevance and sensitivity through a series (n = 3) of focus groups discussions.These focus groups included a diverse range of …

Living With Dementia In Kenya: Pathways To Care, Diagnosis And Management, Edna Bosire

Institute for Human Development, East Africa

Background: Sub-Saharan Africa (SSA) is experiencing a sharp rise in the size of theolder population; consequently, the incidence and prevalence of Alzheimer’s DiseaseRelated Dementias (AD/ADRD) is also expected to rise. There is limited research onAD/ADRD lived experiences have been conducted in SSA including Kenya. Our projectaimed to explore patient’s and caregivers lived experiences with Alzheimer’s disease inKenya.

Methods: This ethnographic study was conducted at the Aga Khan University hospital(AKUH), involving in-depth interviews with 21 health care providers, 26 patientswith mild cognitive impairment and 36 caregivers. We also conducted 10 homevisits and observations. Data were transcribed verbatim and thematically analysed.In what …

Blood-Based Clinical Markers For Early Dementia Detection: Insights From Ad-Detect-Cohort, Benard Aliwa, Jasmit Shah, Olivera Nesic Taylor,, Samuel Nguku, Juzar Hooker, Dilraj Sokhi, Sylvia Mbugua, Litha Musili, Rachel Maina, Harrison Kaleli, Levi Muyela, Anne Njoki Gitere, Anne Nyambura, Zul Merali, Karen Blackmon, Chinedu Momoh

Brain and Mind Institute

Background: Over 55 million people worldwide live with dementia, with more than60% residing in low- and middle-income countries. Alzheimer’s disease, the mostcommon form of dementia, accounts for 60–70% of cases. Early and accurate diagnosisremains a global challenge, necessitating novel approaches to mitigate the diseaseburden. Biomarkers hold significant promise in improving diagnostic accuracy andpredicting disease progression. Validated biomarkers for the preclinical stages ofdementia are crucial for advancing diagnosis and therapeutic strategies. We aimedto identify potential clinical markers for early dementia detection and assess theirpredictive accuracy in identifying high-risk individuals.

Method: We analyzed blood samples from dementia cases (n = 30) and …

Associations Of Estrogen With Modifiable And Non-Modifiable Risk Factors For Dementia: A Narrative Review, Sarah Gregory, Katie Bridgeman, Hannah Darwin, Mariapaola Barbato, Laura Booi, Anna Serrat, Antonella Chadha, Francesca Farina, Natalie Jenkins, Beverly Cheserem

Brain and Mind Institute

Female sex is associated with higher incidence and risk of dementia. Estrogen may rep-resent one important mechanism contributing to the increase in incidence rates. In thisreview, we synthesize narratively the evidence for associations between estrogen—across the life course from menarche to menopause, estrogen-containing hormonalcontraception and hormone replacement therapies, and pregnancy—with potentialmodifiable risk factors for dementia. These include education, hearing loss, traumaticbrain injury, hypertension, alcohol use, obesity, smoking, depression, physical inactiv-ity, diabetes, low-density lipoprotein (LDL) cholesterol, social isolation, air pollution,and untreated visual loss, as well as apolipoprotein E ε4. In addition, evidence is sum-marized for associations with sleep, diet, and stress. …

Evaluating The Impact Of Alcohol On Dementia: Evidence From 13 Developing Countries, Cyprian Mostert

Brain and Mind Institute

Background: The 2024 Lancet Commission on Dementia Prevention identified alcoholconsumption as a risk factor contributing to a global increase in dementia cases by onepercent.

Method: We used a panel VAR model to analyze the impact of alcohol consumption ondementia prevalence in 13 developing countries with different alcohol tax systems.

Result: In countries with progressive alcohol tax systems, an increase in taxes onbeer and spirits leads to a 10 percent reduction in per capita alcohol consumption.This decline corresponds to a 4 percent reduction in dementia prevalence within fouryears. In countries with hybrid alcohol tax systems, a combination of alcohol bansand tax …

Broadening Dementia Risk Models: Building On The 2024 Lancet Commission Report For A More Inclusive Global Framework, Cyprian Mostert, Chinedu Momoh, Andrea Winkler, Connor Mclaughlin, Harris Eyre, Mohamed Salama, Levi Muyela, Karen Blackmon, Zul Merali, Kirti Ranchod

Brain and Mind Institute

No abstract provided.

Recommended Best Practices For Construct-Centered Adaptation Of The Harmonized Cognitive Assessment Protocol, Emily Briceño, Darina Bassil, Pranali Khobragade, Anthony Ngugi, Martine Bejjani, Eric Ochieng, Silvia Mejia-Arango, Salima Douhou, Kazione Kulisewa, Miguel Rentería

Population Health, East Africa

Objectives The Harmonized Cognitive Assessment Protocol (HCAP) neuropsychological assessment approach aims to support the collection of harmonizable data on cognitive function for cross-national cognitive aging and dementia research. As the measurement of cognition is sensitive to differences in contextual, cultural, educational, linguistic, social, and other factors that may influence cognitive test performance, HCAP requires adaptation to be appropriate for the contexts in which it is administered. We aim to provide methodological recommendations for the adaptation and implementation of the HCAP and other cognitive data collection tools in novel settings.

Methods We drew from existing guidelines on cross-cultural psychological test adaptation …

Risk Of Major Depression In Partners Of People With Alzheimer's Disease: A National Cohort Study, Casey Crump, Jingkai Wei, Barbara G Vickrey, Alexis C Edwards, Paul E Schulz, Weiva Sieh, Jan Sundquist, Kristina Sundquist

Faculty, Staff and Student Publications

Background: Alzheimer's disease (AD) may cause significant psychosocial distress not only in the patient but also their partner. However, long-term risks of major depression in partners of AD patients are largely unknown.

Methods: A national cohort study was conducted of all 145 289 partners of people diagnosed with all-cause dementia, including 57 113 partners of people diagnosed with AD, in Sweden during 1998-2017, and 1 300 561 population-based controls. Cox regression was used to compute hazard ratios (HRs) for subsequent risk of major depression identified from nationwide outpatient and inpatient diagnoses through 2018, adjusting for sociodemographic factors and prior mental …

A Protective Role Of Src-1 Against Aging Associated Cognitive Decline, Hesong Liu, Yongjie Yang, Jonathan C Bean, Yang He, Hailan Liu, Rambabu Majji, Chen Liang, Nan Zhang, Meng Yu, Longlong Tu, Qingzhuo Liu, Yue Deng, Kristine M Conde, Na Yin, Mengjie Wang, Yongxiang Li, Junying Han, Sanika Vattakuzhiyil Jossy, Megan Elyse Burt, Hari Krishna Yalamanchili, Chunmei Wang

Duncan NRI Faculty and Staff Publications

Introduction: Research indicates a strong correlation between obesity and the risk of dementia, both are linked to steroid receptor coactivator-1 (SRC-1), a transcriptional coactivator.

Methods: We used RNA sequencing analysis (RNA-Seq) to investigate the transcriptome of SRC-1-KO mice, and identified S100 calcium-binding protein A6 (S100A6), an AD associated gene, as one target of SRC-1. We tested cognitive behaviors in SRC-1-KO mice and mice with a humanized SRC-1 mutation (SRC-1L1376P), and performed promoter luciferase assays on S100A6.

Results: Loss of SRC-1 caused alterations in gene signatures that are commonly associated with neurodegenerative diseases, including AD, and diminished the neural plasticity of …

Prevalence And Risk Factors Of Cerebral Microhemorrhages And Superficial Siderosis In Cognitively Unimpaired Older Adults: Analysis From The Chariot-Pro Substudy, Sujin Kang, Dimitra Kafetsouli, Jamie Ford, Janice Wong, Luc Bracoud, Joyce Suhy, Parthenia Giannakopoulou, Chinedu Momoh, Tom Russ, Craig Ritchie

Brain and Mind Institute

Introduction: Cerebral microhemorrhages (CMHs) and superficial siderosis (SS) are relatively common side effects of anti-amyloid immunotherapies, termed amyloid-related imaging abnormalities (ARIA-H). They are also observed in treatment-naïve older adults. This study explored relationships with modifiable and non-modifiable risk factors.

Methods: This cross-sectional study included 1414 cognitively unimpaired, treatment-naïve individuals aged 60 to 85 years from the Cognitive Health in Ageing Register: Investigational, Observational and Trial Studies in Dementia Research (CHARIOT): Prospective Readiness cOhort (PRO) SubStudy. Relationships between CMHs/SS and cardiovascular risk factors, amyloid beta (Aβ) load, apolipoprotein E (APOE) ε4 status, educational attainment, and white matter hyperintensities were …

Contextualization Of Harmonized Cognitive Assessment Protocol (Hcap) In An Aging Population In Rural Low-Resource Settings In Africa: Experiences And Strategies Adopted To Optimize Effective Adaption Of Cognitive Tests In Kenya, Roselyter Riang’A, Eunice Muthoni, Niranjani Nagarajan, Felix Agoi, Patrick Mwangala, Alden Gross, Jean Ikanga, Kenneth Langa, Edward Miguel, Anthony Ngugi

Population Health, East Africa

Cross-cultural adaptation of cognitive assessments is crucial for detecting Alzheimer's disease (AD) and related dementias (ADRD) in aging populations. This study documents the adaptation of the Harmonized Cognitive Assessment Protocol (HCAP) for a pilot study on the Longitudinal Study of Health and Aging in Kenya (LOSHAK) in rural Kilifi County, Kenya, highlighting challenges and strategies for optimizing outcomes. As part of the LOSHAK feasibility phase, cognitive tests including: the Swahili Mental State Examination, 10-word recall, animal naming, story recall, clock drawing, and making change, were administered to 202 participants (≥45 years) from the Kaloleni/Rabai Health and Demographic Surveillance System (KRHDSS). …

Mechanisms Of Interventions Targeting Modifiable Factors For Dementia Risk Reduction, Anna Matton, Ruth Stephen, Makrina Daniilidou, Mariagnese Barbera, Vilma Alanko, Marcel Ballin, Jamie Ford, Katri Hemiö, Jenni Lehtisalo, Chinedu Momoh

Brain and Mind Institute

The global prevalence of dementia is increasing. With no widely available and accessible treatments to halt or reverse the progression of dementia, exploring preventative strategies is critical. Lifestyle-based interventions show promise in preventing or delaying dementia onset. However, understanding the complex and multifactorial mechanisms underlying dementia, and how interventions target these pathways, is essential for developing personalized and effective strategies. In this review, we examined the current evidence of the mediating pathways in dementia risk reduction. We focused on mechanisms investigated in single-domain interventions on physical exercise, cognitive training, diet, metabolic/cardiovascular or psycho-social risk factors in line with those combined …

Dabigatran Reduced Acute Microgliosis In A Mouse Model With Tbi, Nicholas R. Eltman, Rashmeena Abbasi, Mary C. Kosciuk, Syed Ahmed, Jose L. Pascual, Randel L. Swanson, Nimish K. Acharya

Rowan-Virtua Research Day

Objective:

The study objective was to investigate the acute anti-inflammatory effects of dabigatran in a preclinical mouse controlled cortical impact (CCI) model of severe traumatic brain injury (TBI).

Design

Mice were separated into three groups: controlled cortical impact (CCI) with dabigatran (drug treatment, n=5), CCI with saline (positive control, n=5), and sham CCI without saline or dabigatran (negative control, n=3). Dabigatran (80mg/kg) or saline was administered orally at 2, 10, 18, 26, 34, and 42 hours following experimental CCI in the drug treatment or positive control groups, respectively. Animals in the negative control group received sham CCI only. 48h following …

Incident Hearing Loss And Subsequent Risk Of Dementia: The Health And Retirement Study 2010-2018, Jingkai Wei, Youngran Kim, Yike Li, Donglan Zhang, Casey Crump

Faculty, Staff and Student Publications

Background and Objectives

Research Design and Methods

Incidence Of Myocardial Infarction And Neurodegenerative Disease Co-Occurrence In The Rio Grande Valley: A Five-Year Retrospective Analysis, Sowmya Duddu, Maria Sophia Malbas, Allison Mcadams, Julia Paz, Miguel Quintanilla, Karina Zamora, Hansapani Rodrigo, Kelsey Baker

Research Symposium

Introduction: Neurodegenerative Diseases (NDDs) are a group of disorders leading to the degeneration of neurons causing varying degrees of functional loss. NDDs lead to a loss of independence for the patients and an emotional burden for the patients’ families or caretakers. Previous studies have shown that the prevalence of neurodegenerative diseases such as Alzheimer’s Disease or Vascular Dementia is high in the Rio Grande Valley. Due to the severity of these diseases, research is currently being done to determine the factors that correlate with the development of neurodegenerative diseases and whether there is a causative effect. The purpose of …

The Associations Of Sensory Impairment With 10-Year Risk Of Dementia And Alzheimer's Disease: The Health And Retirement Study, 2010-2020, Kun Li, Rahul Ghosal, Donglan Zhang, Yike Li, Matthew C Lohman, Monique J Brown, Anwar T Merchant, Chih-Hsiang Yang, Jean Neils-Strunjas, Daniela B Friedman, Jingkai Wei

Faculty, Staff and Student Publications

Background: Studies have examined the association between dual sensory impairment and late-life cognitive outcomes in the U.S with inconsistent findings.

Objective: To examine the associations between sensory impairment and 10-year risk of dementia or Alzheimer's disease among U.S. adults aged ≥ 50.

Methods: A prospective cohort study based on the Health and Retirement Study from 2010 to 2020. Individuals aged ≥ 50 years without self-reported dementia and Alzheimer's disease in 2010 were included in the analysis. Self-reported visual and hearing impairments were measures in 2010. Main failure events included self-reported incident dementia and Alzheimer's disease over a 10-year follow-up period. …

Dementia In A Resource-Constrained Sub-Saharan African Setting: A Comprehensive Retrospective Analysis Of Prevalence, Risk Factors, And Management At The Only Neuropsychiatric Facility In Northeastern Nigeria, Ibrahim Abdu Wakawa, Umar Baba Musami, Suleiman Hamidu Kwairanga, Placidus Nwankuba Ogualili, Mohammed Yusuf Mahmood, Muhammad Abba Fugu, Mohammed Mala Gimba, Muktar Mohammed Allamin, Zaharadeen Umar Abbas, Chinedu Momoh

Brain and Mind Institute

INTRODUCTION: Dementia prevalence is increasing in sub-Saharan Africa, poten-tially due to population growth and aging. Resource-constrained settings such asNortheastern Nigeria face challenges in dementia management.

METHODS: We assessed dementia burden and management at the Federal Neuropsy-chiatric Hospital Maiduguri, the only neuropsychiatric facility in Northeastern Nigeria.This retrospective analysis included patient records from 1999 to 2023 for individuals60 year of age and older with a dementia diagnosis.

RESULTS: Of the 1216 cases reported, Alzheimer’s disease (60.5%) was the mostcommon subtype, followed by vascular dementia (24.5%). Hypertension (41.6%) wasthe most frequent comorbidity. Memory loss was present in all cases, whereasbehavioral …

Ethical Considerations Of Percutaneous Endoscopic Gastrostomy Tube Placement In A Patient With Creutzfeldt-Jakob Disease And Advanced Dementia, Toni Habib, Niamh Siobhán Mulrooney, Yisroel Grabie, Mohammad Maruf, Sophia Kasapira

HCA Healthcare Journal of Medicine

Background

Creutzfeldt-Jakob disease (CJD) is a rapidly progressive neurodegenerative condition that is not easily diagnosed and has no curative treatments available, essentially requiring palliative measures, including tube feeding. Nonetheless, data shows that the endoscope used for percutaneous endoscopic gastrostomy (PEG) tube insertion can be a vector for CJD transmission.

Case Presentation

We discuss the case of an elderly patient diagnosed with CJD, requiring tube feeding. Multiple specialists were consulted, and they were unable to reach an agreement on the best approach. Eventually, the hospital ethics committee intervened, and the family agreed to comfort measures only. This case report sheds light …

Detection Of Elder Abuse Through Emergency Care Technicians Screening Tool Revision For Home-Based Primary Care (Detect-Rpc): A Cluster Randomised Controlled Trial Study Protocol, Brad Cannell, Nicholas Sevey, Melvin D Livingston, Jason Burnett, Kristin Lees Haggerty, Carolyn Pickering

Faculty, Staff and Student Publications

Introduction: The annual prevalence of elder mistreatment (EM) in cognitively intact older adults is estimated to be 11%, yet the annual prevalence in older adults with Alzheimer's disease and related dementias (AD/ADRD) is estimated to be as high as 75%. Associated with a decrease in quality of life and increase in risk of mortality, EM represents a significant public health burden. Home-based primary care (HBPC) providers are uniquely positioned to address the critical need for robust EM screening and reporting, especially among individuals with AD/ADRD. This protocol seeks to adapt the Detection of Elder mistreatment Through Emergency Care Technicians (DETECT) …

Systemic Therapy Targeting Psoriatic Inflammation Is Associated With Decreased Incidence Of Dementia: An Observational Retrospective Cohort Study, Madison P. Olexson, Ana Ormaza Vera, Chunghwan Ro, Clinton W. Enos

Department Dermatology Faculty Publications

[Introduction] To the Editor: Psoriasis, an immune-mediated chronic inflammatory skin disorder, has been implicated in cognitive impairment and dementia.1, 2, 3 Emerging evidence suggests that systemic inflammation contributes to neuroinflammation and resultant cytokine-driven neurodegeneration, although findings remain inconclusive.1, 2, 3 While systemic therapies such as biologics and conventional disease-modifying antirheumatic drugs are routinely used in psoriasis management, their role in modulating dementia in this population remains underexplored, with research yielding mixed results.1, 2, 3 We conducted a large-scale, retrospective cohort study to investigate the relationship between psoriasis and dementia and whether systemic treatments for psoriasis impact this association.

Multimodal Wearable Intelligence For Dementia Care In Healthcare 4.0: A Survey, Po Yang, Gaoshan Bi, Jun Qi, Xulong Wang, Yun Yang, Li Da Xu

Information Technology & Decision Sciences Faculty Publications

As a new revolution of Ubiquitous Computing and Internet of Things, multimodal wearable intelligence technique is rapidly becoming a new research topic in both academic and industrial fields. Owning to the rapid spread of wearable and mobile devices, this technique is evolving healthcare from traditional hub-based systems to more personalised healthcare systems. This trend is well-aligned with recent "Healthcare 4.0" which is a continuous process of transforming the entire healthcare value chain to be preventive, precise, predictive and personalised, with significant benefits to elder care. But empowering the utility of multimodal wearable intelligence technique for elderly care like people with …

Biological Validation Of Peak-Width Of Skeletonized Mean Diffusivity As A Vcid Biomarker: The Markvcid Consortium, Alison M Luckey, Saptaparni Ghosh, Chen-Pin Wang, Alexa Beiser, Rebecca Bernal, Zhiguang Li, Djass Mbangdadji, Elyas Fadaee, Haykel Snoussi, Angel Gabriel Velarde Dediós, Hector A Trevino, Monica Goss, Laura J Hillmer, Christopher E Bauer, Adam M Staffaroni, Lara Stables, Marilyn Albert, Jayandra J Himali, Thomas H Mosley, Lars Forsberg, Vilmundur Guðnason, Baljeet Singh, Herpreet Singh, Kristin Schwab, Joel H Kramer, Gary A Rosenberg, Karl G Helmer, Steven M Greenberg, Mohamad Habes, Danny J J Wang, Brian T Gold, Hanzhang Lu, Arvind Caprihan, Myriam Fornage, Lenore J Launer, Konstantinos Arfanakis, Sudha Seshadri, Charles Decarli, Pauline Maillard, Claudia L Satizabal

Faculty, Staff and Student Publications

BACKGROUND: Peak-width of skeletonized mean diffusivity (PSMD), a neuroimaging marker of cerebral small vessel disease (SVD), has shown excellent instrumental properties. Here, we extend our work to perform a biological validation of PSMD.

METHODS: We included 396 participants from the Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID-1) Consortium and three replication samples (Cohorts for Heart and Aging Research in Genomic Epidemiology = 6172, Rush University Medical Center = 287, University of California Davis Alzheimer's Disease Research Center = 567). PSMD was derived from diffusion tensor imaging using an automated algorithm. We related PSMD to a composite measure …

Genetic Risk Factors Underlying White Matter Hyperintensities And Cortical Atrophy, Yash Patel, Jean Shin, Eeva Sliz, Ariana Tang, Aniket Mishra, Rui Xia, Edith Hofer, Hema Sekhar Reddy Rajula, Ruiqi Wang, Frauke Beyer, Katrin Horn, Max Riedl, Jing Yu, Henry Völzke, Robin Bülow, Uwe Völker, Stefan Frenzel, Katharina Wittfeld, Sandra Van Der Auwera, Thomas H Mosley, Vincent Bouteloup, Jean-Charles Lambert, Geneviève Chêne, Carole Dufouil, Christophe Tzourio, Jean-François Mangin, Rebecca F Gottesman, Myriam Fornage, Reinhold Schmidt, Qiong Yang, Veronica Witte, Markus Scholz, Markus Loeffler, Gennady V Roshchupkin, M Arfan Ikram, Hans J Grabe, Sudha Seshadri, Stephanie Debette, Tomas Paus, Zdenka Pausova

Faculty, Staff and Student Publications

White matter hyperintensities index structural abnormalities in the cerebral white matter, including axonal damage. The latter may promote atrophy of the cerebral cortex, a key feature of dementia. Here, we report a study of 51,065 individuals from 10 cohorts demonstrating that higher white matter hyperintensity volume associates with lower cortical thickness. The meta-GWAS of white matter hyperintensities-associated cortical 'atrophy' identifies 20 genome-wide significant loci, and enrichment in genes specific to vascular cell types, astrocytes, and oligodendrocytes. White matter hyperintensities-associated cortical 'atrophy' showed positive genetic correlations with vascular-risk traits and plasma biomarkers of neurodegeneration, and negative genetic correlations with cognitive functioning. …

Association Between Risk Of Alzheimer’S Disease And Related Dementias And Angiotensin Receptor Ⅱ Blockers Treatment For Individuals With Hypertension In High-Volume Claims Data, Sori Kim Lundin, Xinyue Hu, Jingna Feng, Karl Kristian Lundin, Lu Li, Yong Chen, Paul Ernest Schulz, Cui Tao

Faculty, Staff and Student Publications

Background: Findings regarding the protective effect of Angiotensin II receptor blockers (ARBs) against Alzheimer's disease and related dementias (AD/ADRD) and cognitive decline have been inconclusive.

Methods: Individuals with hypertension who do not have any prior ADRD diagnosis were included in this retrospective cohort study from Optum's de-identified Clinformatics® Data Mart. We identified antihypertensive medication (AHM) drug classes and subclassified ARBs by blood-brain barrier (BBB) permeability. We compared baseline characteristics and used the Kaplan-Meier (KM) survival curve and adjusted Cox proportional hazards (PH) model for survival analyses.

Findings: From 6,390,826 individuals with hypertension, there were 1,839,176 ARB users, 3,366,841 non-ARB AHM …

Characterizing The Progression From Mild Cognitive Impairment To Dementia: A Network Analysis Of Longitudinal Clinical Visits, Muskan Garg, Sara Hejazi, Sunyang Fu, Maria Vassilaki, Ronald C Petersen, Jennifer St Sauver, Sunghwan Sohn

Faculty, Staff and Student Publications

Background: With the recent surge in the utilization of electronic health records for cognitive decline, the research community has turned its attention to conducting fine-grained analyses of dementia onset using advanced techniques. Previous works have mostly focused on machine learning-based prediction of dementia, lacking the analysis of dementia progression and its associations with risk factors over time. The black box nature of machine learning models has also raised concerns regarding their uncertainty and safety in decision making, particularly in sensitive domains like healthcare.

Objective: We aimed to characterize the progression of health conditions, such as chronic diseases and neuropsychiatric symptoms, …

Cerebrovascular Disease Is Associated With Alzheimer's Plasma Biomarker Concentrations In Adults With Down Syndrome, Andreas Engvig, Karl Trygve Kalleberg, Lars T. Westlye, Esten Høyland Leonardsen, Alzheimer’S Disease Neuroimaging Initiative Consortium

Neurology Faculty Publications

DNA methylation age (MA), brain age (BA), and frailty index (FI) are putative aging biomarkers linked to dementia risk. We investigated their relationship and combined potential for prediction of cognitive impairment and future dementia risk using the ADNI database. Of several MA algorithms, DunedinPACE and GrimAge2, associated with memory, were combined in a composite MA alongside BA and a data-driven FI in predictive analyses. Pairwise correlations between age- and sex-adjusted measures for MA (aMA), aBA, and aFI were low. FI outperformed BA and MA in all diagnostic tasks. A model including age, sex, and aFI achieved an area under the …

Long-Term Dementia Risk In Parkinson Disease, Julia Gallagher, Caroline Gochanour, Chelsea Caspell-Garcia, Roseanne D Dobkin, Dag Aarsland, Roy N Alcalay, Matthew J Barrett, Lana Chahine, Alice S Chen-Plotkin, Christopher S Coffey, Nabila Dahodwala, Jamie L Eberling, Alberto J Espay, James B Leverenz, Irene Litvan, Eugenia Mamikonyan, James Morley, Irene H Richard, Liana Rosenthal, Andrew D Siderowf, Tatyana Simuni, Michele K York, Allison W Willis, Sharon X Xie, Daniel Weintraub, Parkinson's Progression Markers Initiative

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVES: It is widely cited that dementia occurs in up to 80% of patients with Parkinson disease (PD), but studies reporting such high rates were published over two decades ago, had relatively small samples, and had other limitations. We aimed to determine long-term dementia risk in PD using data from two large, ongoing, prospective, observational studies.

METHODS: Participants from the Parkinson's Progression Markers Initiative (PPMI), a multisite international study, and a long-standing PD research cohort at the University of Pennsylvania (Penn), a single site study at a tertiary movement disorders center, were recruited. PPMI enrolled de novo, untreated …

A Genome-Wide Association Meta-Analysis Of All-Cause And Vascular Dementia, Mega Vascular Cognitive Impairment And Dementia (Megavcid) Consortium

Faculty, Staff and Students Publications

INTRODUCTION: Dementia is a multifactorial disease with Alzheimer's disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD.

METHODS: We conducted a GWAS of all-cause dementia (ACD) and examined the genetic overlap with VaD. Our dataset includes 800,597 individuals, with 46,902 and 8702 cases of ACD and VaD, respectively. Known AD loci for ACD and VaD were replicated. Bioinformatic analyses prioritized genes that are likely functionally relevant and shared with closely related traits and risk factors.

RESULTS: For ACD, novel loci identified were associated with energy transport (SEMA4D), neuronal excitability …