Neurosciences Commons^™

Engagement Of Understudied Populations As Community Change: The South Texas Adrc Model, Gladys E. Maestre, Neela K. Patel, Rosa V. Pirela, Robin C. Hilsabeck, Kendra Stine, Neyra García, Roberto Reyes, Omar Oropeza, Cristian Maestre, Jesus D. Melgarejo, Sarah Williams-Blangero, Ney Alliey Rodriguez

School of Medicine Publications

Many populations experiencing the highest burdens of Alzheimer's disease and related dementias remain understudied, in part because traditional recruitment and retention models are insufficient to support sustained engagement. The Outreach, Recruitment, and Engagement Core (OREC) of the South Texas Alzheimer's Disease Research Center reconceptualized participant recruitment as a long-term system change in a Hispanic-majority, urban–rural region. OREC institutionalizes shared power through community advisory governance, aligns research protocols with local lived realities (through patient navigators, community health workers/promotores, and decentralized access points), and employs a data-driven feedback loop for continuous improvement. In 1 year, 46 outreach events touched 10,134 individuals (71% …

Predicting Accumulation And Age At Onset Of Amyloid-Β From Genetic Risk And Resilience For Alzheimer's Disease, Eleanor K. O'Brien, Timothy Cox, Shane Fernandez, Pierrick Bourgeat, Tenielle Porter, Ben Goudey, James D. Doecke, Colin L. Masters, Jurgen Fripp, Kwangsik Nho, Victor L. Villemagne, Carlos Cruchaga, Christopher C. Rowe, Andrew J. Saykin, Vincent Doré, Simon M. Laws

Research outputs 2022 to 2026

Background: Accumulation of brain amyloid beta (Aβ), a key pathological hallmark of Alzheimer's disease (AD), begins decades before cognitive symptoms. Being able to predict the risk of Aβ accumulation, or the age at which Aβ exceeds a critical threshold, may enable intervention to delay or prevent onset of AD. Methods: Using published genome-wide association studies (GWASs), we developed polygenic scores (PGS) for AD risk (PGSrisk) and resilience (PGSresilience), and tested whether these predicted (i) if an individual is an Aβ accumulator (‘Accumulator Status’), and (ii) in accumulators, the age at which brain Aβ exceeds a 20 centiloid (CL) threshold (‘Age …

Decentralizing Dementia Research To The Us–Mexico Border: The Rio Grande Valley Ad-Rcmar As A Model For Translational Equity, Gladys E. Maestre, John Blangero, Eron Manusov, Gabriel A. De Erausquin, Francisco Fernandez, Silvia Mejia-Arango, Vincent P. Diego, Juan C. Lopez-Alvarenga, Claudia Alaniz, Neyra García, Rosa V. Pirela, Andrew Tsin, Michael Mahaney

School of Medicine Publications

Translational equity means ensuring that diagnostics, treatments, care models, and prevention strategies are developed and implemented so they work for populations with the greatest burden and least access to care. In Alzheimer's disease and related dementias (ADRD), where most evidence derives from highly educated, non-Hispanic White participants at large academic centers, translational equity is critical to prevent misclassification, limited access, and widening disparities and to ensure that underrepresented communities shape how new knowledge moves into practice. Hispanic and other populations in the United States are disproportionately affected by ADRD yet remain underrepresented in research, with gaps especially pronounced in high-poverty …

Mitigating Disparities In Diagnosis Of Dementia, Lycia Tramujas Vasconcellos Neumann, Simin Mahinrad, Erin L. Abner, Soo Borson, Goldie S. Byrd, Maria Carrillo, Lindsay Clark, Anthony N. Correro Ii, Kacie D. Deters, Gladys E. Maestre

School of Medicine Publications

The field of Alzheimer's disease and related dementias (AD/ADRD) is undergoing a transformative shift with a better understanding of disease biology, biomarker-based diagnostics, and disease-modifying therapies. Yet, these advancements risk exacerbating existing disparities in diagnosis and care. The 2024 Alzheimer's Association International Conference (AAIC) Advancements: Exploring Equity in Diagnosis convened interdisciplinary experts to address these inequities and chart a path toward population-generalizable research and practice. This article synthesizes key insights from the conference, highlighting considerations for inclusive and representative research design, ethical approaches in diagnostic disclosure, as well as challenges and solutions at individual, community, and systemic levels to advance …

Age-Related Increase In Plasma P-Tau217 In Amyloid-Beta–Negative Cognitively Unimpaired Individuals Affects Diagnostic Interpretation, Anna E. Mammel, Fernando Gonzalez-Ortiz, Ali Mousavi, Kelsey Hallett, Mary Encarnacion, Don Biehl, Pradip Gill, Sazan Ismael, Christopher Fowler, James D. Doecke, Larry Ward, Hans Frykman

Research outputs 2022 to 2026

Introduction: The extent to which non-pathological aging influences plasma biomarkers remains unclear. Here, we investigate factors influencing plasma p-tau217 levels in cognitively unimpaired (CU), amyloid-beta–negative (Aβ-) individuals. Methods: Plasma p-tau217 was measured in CU Aβ- positron emission tomography–negative (PET-) participants using two immunoassays (ALZpath n = 360 and LUMIPULSE G1200 n = 73). Associations between p-tau217 and age groups (60–69, 70–79, and 80+ years), apolipoprotein E (APOE) genotype, and gender were evaluated. Results: ALZpath plasma p-tau217 showed a non-pathological age-related increase (p < 0.001), and increased percentage within the intermediate zone with age. Lumipulse p-tau217 showed an increase in the percentage of subjects with positive results with age, however, this trend was not significant (p > 0.05). Men had higher levels of p-tau217 only with the ALZpath assay (p = 0.02; Lumipulse: p = …

Neuroinflammation At The Crossroads Of Neurodegeneration: The Roles Of Microglia And Astrocytes In Parkinson's Disease, Alzheimer's Disease, And Multiple Sclerosis, Mohannad A. Almikhlafi

Neurosciences

Neuroinflammation plays a critical role in the pathogenesis of neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis. This review explores the underlying mechanisms of neuroinflammation, with a focus on the roles of microglia, astrocytes, peripheral immune cell infiltration, and cytokine release. The complex interplay between oxidative stress and chronic inflammation accelerates neurodegeneration, contributing to disease progression. Microglial activation, initially protective, becomes harmful when sustained over time, driving chronic inflammation. Similarly, astrocytes once considered passive are now recognized for their active involvement in both inflammatory and neuroprotective responses, depending on their activation state. Prolonged activation of microglia and …

Feeding The Mind: Dietary Consumption And Neural Aging, Bhavani Tuppale

Senior Theses

Neural aging is the process of physiological decline in the brain and increased vulnerability to neurodegenerative diseases. Neurodegenerative diseases such as Alzheimer’s disease are associated with aging and the interaction of genetics and lifestyle choices. Previous research studies have connected Alzheimer’s disease with dysfunction in the metabolic system. To combat age-associated dysfunctions in the metabolic system, research studies propose using the ketogenic diet, which utilizes ketone bodies as an energy source instead of glucose. The thesis analyzes literature on the effect of neural aging on various model organisms, how a ketogenic diet affects aging model organisms, and how aging and …

3-Deoxyanthocyanidins Inhibit Β-Amyloid Aggregation, Toxicity, And Mitochondrial Dysfunction: Evidence From Mc-65 Cells And Molecular Dynamics Simulations, Rasheed A. Abdulraheem, Ammar U. Danazumi, Philipp Nitschke, Luke Gray Whiley, Abdulrahman Ibrahim Tudu, Ranil Coorey, Zhoyu Li, Prashant Bharadwaj, Vijay Jayasena, Stuart K. Johnson, Ralph N. Martins, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Accumulation of amyloid-beta (Aβ42) senile plaques in the brain is a hallmark of Alzheimer's disease (AD). Although some drug have been approvaled recently, none has demonstrated robust disease-modifying outcome. The 3-deoxyanthocyanidins (3-DXA) and their derivatives represent a more stable class of polyphenols, present at uniquely high concentrations in sorghum grains. Although 3-DXA exhibit strong potential to modulate protein aggregation processes, their effects on AD pathology remain unexplored. In this study, we investigated the inhibitory effects of three 3-DXA derivatives, apigeninidin chloride (AC), luteolinidin chloride (LC), and 7-methoxy apigeninidin (7-MAC), on Aβ42 aggregation and associated neurotoxicity. Thioflavin T fluorescence assay was …

Impact Of Plasma Ptau181 Levels On Clinician Diagnostic Confidence And Management In Memory And Cognition Clinics: A Multi-Site Before-And-After Study, Johannes C. Michaelian, Azadeh Feizpour, James C. Vickers, Jane E. Alty, Jessica M. Collins, Vincent Doré, Catriona Ireland, Anna E. King, Ralph N. Martins, Michael Woodward, Sharon L. Naismith, Christopher C. Rowe

Research outputs 2022 to 2026

Introduction: Recent advances allow blood tests to detect key proteins linked to Alzheimer's disease (AD). Methods: In this before-and-after study across three Australian memory and cognition clinics, we evaluated the impact on clinicians' diagnostic confidence and management following disclosure of routine patients' AD probability, using predefined plasma phosphorylated tau 181 (pTau181) thresholds set at 90% sensitivity and 90% specificity for amyloid-beta (Aβ) positron emission tomography (PET) positivity. Results: One hundred thirteen participants (mean age: 71.2 ± 8.4; mean Mini-Mental State Examination score: 27.7 ± 2.5) with dementia (n = 17, 15.0%), mild cognitive impairment (n = 48, 42.5%), and subjective …

Investigating Tau Pathology In The Retina And Anterior Segment Structures Of The Eye In A 3-Nitropropionic Acid–Induced Tauopathy Mouse Model, Mohamed Sayed Ahmed Abdel-Kader Qasem

Theses and Dissertations

Background and Objectives: Alzheimer's disease, the most prevalent neurodegenerative disorder in older adults, is characterized by accumulation of hyperphosphorylated tau and amyloid-beta (Aβ) plaques in the central nervous system. Given the retina's shared embryological origin with the brain, its direct neural connectivity via the optic nerve, and similarities in vasculature and age-related degeneration patterns, retinal pathology may serve as an early, non-invasive biomarker for Alzheimer's disease. This study employed 3-nitropropionic acid (3NP) as a pathway-specific tauopathy model driven by mitochondrial dysfunction. The study particularly aimed to investigate whether retinal and corneal tau pathology reflects underlying tau-related neurodegeneration triggered by …

Regulation Of Autophagy-Mediated Pathways By Diet, Physical Activity, And Sleep In Alzheimer's Disease, Ajish Ariyath, Zoe Mputhia, Christopher Dougherty, Bushra Kaleelur Rahuman, W. M.A.D.Binosha Fernando, Belinda Brown, Samantha L. Gardener, Stephanie R. Rainey-Smith, Ralph Martins, Prashant Bharadwaj

Research outputs 2022 to 2026

Alzheimer's disease (AD) is a progressive, age-related, neurodegenerative disorder marked by cognitive decline, memory loss, and accumulation of amyloid beta (Aβ) plaques and tau tangles. A key feature of AD is impaired protein homeostasis, often driven by autophagy dysfunction. Autophagy, a cellular degradation and recycling process, plays a vital role in maintaining neuronal health and is increasingly recognized as a therapeutic target in AD. Lifestyle factors such as diet, physical activity, and sleep can positively influence autophagy and support cognitive function. Intermittent fasting (IF) and calorie restriction (CR) activate autophagy and promote longevity; physical activity enhances cerebral blood flow and …

Task-Optimized Brain Parcellations Reveal Latent Functional Organization For Enhanced Connectivity-Based Neuroimaging Classification, Andrew Hannum, Mario A. Lopez

Computer Science: Faculty Scholarship

Brain parcellation schemes are fundamental to neuroimaging, yet general-purpose atlases may obscure the specific functional architecture relevant to a given cognitive task or clinical condition. This reflects a growing consensus that the “optimal” brain map is context-dependent. Here, we introduce a novel framework that validates this principle by generating task-optimized human brain parcellation maps directly from supervised learning objectives. Our method defines functional parcels by grouping brain regions based on the similarity of their contributions to a classifier's decision boundary for a specific goal (e.g., cognitive state decoding or clinical group separation). This approach prioritizes a region's discriminative role over …

Prevalence Of Dementia In Selected Middle East And North Africa (Mena) Countries: A Systematic Review And Meta-Analysis, Mohsen Sedighi, Mohammad Hasan Shahabi, Alireza Amanollahi, Khurshid Alam, Soudabeh Shemehsavar, Zahra Shirzadi, Serena Sabatini, Ahmad R. Khatoonabadi, Matthew Prina, Akram A. Hosseini, Claire V. Burley, Jennifer Dunne, Simin Mahinrad, Iman Dajani, Ralph N. Martins, Blossom C.M. Stephan, Ali Chaari, Hamid R. Sohrabi

Research outputs 2022 to 2026

Data on dementia epidemiology in the Middle East and North Africa (MENA) region is limited. This systematic review and meta-analysis examined dementia prevalence across MENA. Databases were searched up to October 2024. Analyses were stratified by country and sex. Pooled prevalence was estimated using a random-effects model with a 95% confidence interval (CI). Fifty-two studies on the selected countries met inclusion criteria, covering 87,219 individuals with dementia from a total population of 1,045,908. The pooled prevalence was 12.16% (95% CI: 9.61–14.96) for the region and the Israel had the highest prevalence (17.00%), followed by Iran (13.20%), Turkey (11.40%), Saudi Arabia …

When Does Alzheimer's Disease Start? Plasma Aβ42/40 Assays Show Steep Changes At Aβ-Pet Centiloid 15, Mean Age Of 66 Years, Rodrigo Cánovas, Timothy Cox, Vincent Doré, Pierrick Bourgeat, Jurgen Fripp, Azadeh Feizpour, Rosita Shishegar, Christopher J. Fowler, Simon M. Laws, Tenielle Porter, Stephanie Rainey-Smith, Leslie M. Shaw, Randall J. Bateman, Yan Li, Ovod Vitaliy, Michael W. Weiner, John C. Morris, Tammie L.S. Benzinger, Suzanne E. Schindler, Akinori Nakamura, Takeshi Iwatsubo, Takeshi Ikeuchi, Takashi Kato, Paul Maruff, Hamid R. Sohrabi, Christopher C. Rowe, Ralph Martins, Colin L. Masters, James Doecke

Research outputs 2022 to 2026

Objective: Sporadic late-onset Alzheimer's disease (AD) is characterized by a long pre-clinical phase where amyloid-beta (Aβ) and tau begin to accumulate in the brain. The primary objective was to determine the age at which AD starts by finding the average population age when both positron emission tomography (PET) Aβ (Aβ-PET) and plasma Aβ42/40 become abnormal. Methods: Two high performance immunoprecipitation-mass spectrometry (IP-MS) assays (WashU/C2N and Shimadzu) were tested on samples from 1,450 participants who were diagnosed as cognitively unimpaired (CU), mild cognitive impairment (MCI), or AD-dementia across 4 international cohorts. Natural history modeling and trajectory analyses of the combined Aβ-PET …

Restoration Of Sfrp3 Preserves The Neural Stem Cell Pool And Spatial Discrimination Ability In A Mouse Model Of Alzheimer's Disease, Chia-Hsuan Fu, Jin Park, Umberto Tosi, Francisco A Blanco, Manuel Silva-Pérez, Kavitha Muralidharan, Jason C You, Minjung Lee, Gabriel S Stephens, Xiaohong Zhang, Yi Zheng, Helen Scharfman, Kimberley F Tolias, Jeannie Chin

Faculty, Staff and Students Publications

Individuals with Alzheimer's disease (AD) have an increased incidence of seizures, which worsen cognitive decline. Using a transgenic mouse model of AD neuropathology that exhibits spontaneous seizures, we previously found that seizure activity stimulates and accelerates depletion of the hippocampal neural stem cell (NSC) pool, which was associated with deficits in neurogenesis-dependent spatial discrimination. However, the precise molecular mechanisms that drive seizure-induced activation and depletion of NSCs are unclear. Here, using mice of both sexes, we performed RNA-sequencing on the hippocampal dentate gyrus and identified differentially expressed regulators of neurogenesis in the Wnt signaling pathway that regulates many aspects of …

A Transdiagnostic, Multi-Modal Approach To Understanding Apathy: Methodological And Analytical Framework, Yunglin Gazes, Hideo Suzuki, Lee-Anne Morris, Seonjoo Lee, Zekai Jin, Edward D Huey, Bryan B Chen, Campbell Le Heron, Sarah R Heibronner, Nora Vanegas-Arroyave

Faculty, Staff and Students Publications

Apathy is characterized by loss of motivation and manifests as a reduction of goal-directed behavior. Apathy is highly prevalent across neurodegenerative diseases, including Alzheimer's Disease (AD) and Parkinson's Disease (PD), and is an important contributor to the disability and reduce quality of life in these conditions. The treatment of apathy remains challenging due to a lack of specific therapies, largely attributed to an incomplete understanding of its cognitive and neuroanatomical underpinnings, crucial for developing targeted interventions. Apathy can be mechanistically studied through effort-based decision-making (EBDM) paradigms, where individuals choose between low- and high-effort tasks for varying reward magnitudes. Anatomically, apathy …

A Molecular Renaissance In Alzheimer's Disease Research: The Rise Of Systems Biology And Spatial Omics, Lucia M. Perez-Navarro, Juan Lopez-Alvarenga

School of Medicine Publications

Recent advances in multi-omics and spatial proteomics are reshaping our understanding of Alzheimer's disease. Guo et al.1 applied integrative multi-omics to stratify mild cognitive impairment into biologically distinct subtypes with divergent progression trajectories: one metabolically impaired and slow-progressing, the other immune-activated and rapidly declining. Current techniques such as STC-DESI, LCM-MS, and machine learning enhance regional proteomic resolution, supporting biomarker discovery and spatially targeted interventions. This work exemplifies a broader shift toward precision medicine and a systems-level molecular framework in neurodegenerative disease research.

Cognitive Reserve Predicts Baseline Tau Burden In The Us Pointer Trial Imaging Cohort, Valory N Pavlik, Chris J Weber, Joseph C Masdeu, Laura D Baker, Melissa M Yu, Michele York, Rachel A Whitmer, Susan M Landau, Theresa M Harrison, Tomas M Holland, Laura Lovato

Faculty, Staff and Students Publications

Introduction: Higher cognitive reserve (CR) is associated with reduced dementia risk. We hypothesized that higher CR is associated with less baseline Alzheimer's disease (AD) pathology in the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) cohort.

Methods: A subsample of participants underwent amyloid beta and tau positron emission tomography imaging. Regression analysis was used to model the association between educational attainment (EA) as a CR proxy measure, amyloid positivity, and entorhinal cortex (ERC) and meta-temporal region of interest (meta-ROI) tau standardized uptake value ratio (SUVR).

Results: In 911 participants with complete imaging data, higher …

Empowering Community Health Workers In Dementia Care In South Texas, Stephanie Santiago-Mejias, Shanae L. Rhodes, Fayron R. Epps, Robin C. Hilsabeck, Noe Garza, Sudha Seshadri, Neela K. Patel

School of Medicine Publications

Alzheimer's disease and related dementias disproportionately affect minority racial and ethnic communities. Community health workers are essential in addressing these disparities. We evaluated the impact of an educational workshop focusing on improving knowledge and preparedness in dementia care. Sixty-one CHWs attended in-person sessions in Texas and completed surveys to measure confidence and plans to apply the knowledge gained. Results revealed a significant increase in confidence in providing dementia care post-training (p < 0.001). Qualitative analysis identified five primary roles of CHWs. These findings demonstrate the potential of training interventions to improve knowledge gaps and empower CHWs to address dementia in underserved communities.

Addressing Language Challenges In Bilingual Neuropsychological Assessments At The South Texas Alzheimer's Disease Research Center (Adrc), Stephanie Santiago-Mejias, Gabrielle Hromas, Ashley Laroche, David A. Gonzalez, Robin C. Hilsabeck, Katya Rascovsky, Silvia Mejia-Arango, Amy Werry-Mcfarlin, Claudia Satizabal, Hector Trevino

School of Medicine Publications

Introduction: Neuropsychological assessment of bilingual (English/Spanish) individuals presents challenges that can impact test validity. Language proficiency influences cognitive performance, yet clear guidelines for determining the appropriate test language are lacking. We describe our experiences at the South Texas Alzheimer's Disease Research Center (STAC) in addressing these challenges within the context of National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) assessments and broader Alzheimer's Disease Research Center (ADRC) protocols. We outline steps toward a structured language assessment approach.

Methods: We implemented a process to assess language proficiency, integrating self-reported and objective measures, including the language dominance index (LDI). Case examples …

A Large-Scale Multi-Centre Study Characterising Atrophy Heterogeneity In Alzheimer's Disease, Vikram Venkatraghavan, Damiano Archetti, Pierrick Bourgeat, Chenyang Jiang, Mara Ten Kate, Anna C. Van Loenhoud, Rik Ossenkoppele, Charlotte E. Teunissen, Elsmarieke Van De Giessen, Yolande A.L. Pijnenburg, Giovanni B. Frisoni, Béla Weiss, Zoltán Vidnyánszky, Tibor Auer, Stanley Durrleman, Alberto Redolfi, Simon M. Laws, Paul Maruff, Neil P. Oxtoby, Andre Altmann, Daniel C. Alexander, Wiesje M. Van Der Flier, Frederik Barkhof, Betty M. Tijms

Research outputs 2022 to 2026

Previous studies identified atrophy-based Alzheimer's disease(AD) subtypes linked to distinct clinical symptoms, but their consistency across subtyping approaches remains unclear. This large-scale study evaluates subtype concordance using two data-driven approaches. In this work, we analyzed data from n=10,011 patients across 10 AD cohorts spanning Europe, the US, and Australia, extracting regional volumes using Freesurfer. To characterize atrophy heterogeneity in the AD continuum, we developed a two-step approach, Snowphlake (Staging NeurOdegeneration With PHenotype informed progression timeLine of biomarKErs), to identify subtypes and atrophy-event sequences within each subtype. Results were compared with SuStaIn (Subtype and Stage Inference), which jointly estimates subtypes and …

Moderate Coffee And Tea Consumption Is Associated With Slower Cognitive Decline, Stephanie R. Rainey-Smith, Kelsey R. Sewell, Belinda M. Brown, Hamid R. Sohrabi, Ralph N. Martins, Samantha L. Gardener

Research outputs 2022 to 2026

Background: Globally, coffee and tea are consumed extensively, potentially providing neuroprotection through anti-inflammatory and antioxidative stress effects. Objective: This study aimed to investigate associations between coffee and tea intake and cognitive function. Methods: In a longitudinal prospective cohort study, dementia-free (n = 8715; age range 60.0–85.2 years) older adults from the UK Biobank self-reported coffee and tea intake over the previous year; ‘never’, ‘moderate’ (1–3 cups/day), or ‘high’ (≥4 cups/day). Participants completed cognitive assessments at ≥2 timepoints (mean of 9.11 years). Results: Those ‘never’ consuming coffee and ‘moderate’ coffee consumers (β = 0.06, p = 0.005; β = 0.07, p <  0.001, respectively), as well as ‘moderate’ tea consumers and ‘high’ tea consumers (β = 0.06, p = 0.009; β = 0.06, p = 0.003, respectively) had slower fluid intelligence decline. Additionally, those ‘never’ consuming coffee and ‘moderate’ coffee consumers had a slower increase in pairs matching errors (β = −0.05, p = 0.022; β = 0.05, p = 0.013) compared to ‘high’ consumers. Conclusions: ‘Moderate’ coffee, and ‘moderate’ and ‘high’ tea intake may be a protective factor against cognitive decline. Randomized controlled trials are required to establish causal relationships leading to evidence-based recommendations regarding benefits of coffee and tea intake.

Blood Biomarkers Of Alzheimer's Disease In Australians Habitually Consuming Various Plant-Based Diets, Shaun Eslick, Grace Austin, Jessica J.A. Ferguson, Manohar L. Garg, Christopher Oldmeadow, Ralph N. Martins

Research outputs 2022 to 2026

Background: Evidence suggests that plant-based diets (PBDs) may be protective against neurodegenerative diseases such as Alzheimer's disease (AD). Objective: This study examined associations between blood-based AD biomarkers in individuals 30–75 years without current or diagnosed cardiovascular disease following different PBDs versus regular meat-eating diets (RMEs). Methods: This secondary analysis of the Plant-based Diets study measured Aβ1–42/Aβ1–40, p-tau181, NFL, and GFAP in 237 plasma samples using SIMOA from individuals following vegan, pesco-vegetarian (PVs), lacto-ovo vegetarian (LOVs), semi-vegetarian (SVs), or RME diets. Multivariable regression adjusted for age and sex. Results: Following adjustments for age and sex, plasma Aβ1–42/Aβ1–40ratio was significantly higher in …

Ocular Changes As Potential Biomarkers For Early Diagnosis Of Alzheimer's Disease, Purna Chandra Poudel, Shaun M. Frost, Shaun Eslick, Hamid R. Sohrabi, Kevin Taddei, Eugene Hone, Ralph N. Martins

Research outputs 2022 to 2026

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. AD diagnosis often involves a thorough assessment, including clinical evaluation, cognitive testing, medical history examination, genetic testing, and biomarker analysis. Currently, the invasive nature and high costs of biomarker testing, such as cerebrospinal fluid analysis and neuroimaging, have limited the early detection and intervention of the disease. Therefore, researchers have explored cheaper and less invasive options, such as ocular imaging. This review discusses the close relationship between the eye and the central nervous system and ocular changes as a potential non-invasive AD biomarker. Ocular changes …

The Role Of Diet In Moderating The Relationship Between Symptoms Of Depression And Brain Amyloid Load, Hilal Salim Said J. Al Shamsi, Samantha L. Gardener, Stephanie R. Rainey-Smith, Hamid R. Sohrabi, Kevin C.M. Taddei, Colin L. Masters, Vincent M. Doré, Christopher L. Rowe, W. M.A.D.Binosha Fernando, Ralph N. Martins

Research outputs 2022 to 2026

Background: Healthy lifestyle factors, including diet, may affect brain amyloid beta (Aβ) load. This study examines dietary patterns as moderators of the relationships among symptoms of depression, anxiety, and brain Aβ load. Method: A cross-sectional study of cognitively unimpaired older adults (n = 524) from the Australian Imaging, Biomarkers, and Lifestyle study assessed dietary patterns, depressive and anxiety symptoms, and brain Aβ load. Moderation and simple slope analyses were conducted. Results: The Dietary Approaches to Stop Hypertension (DASH) diet moderated the relationship between depressive and anxiety symptoms and brain Aβ load. Higher symptoms were associated with greater Aβ load in …

Amyloid Accumulation, Brain Atrophy, And Cognitive Decline In Emergent Alzheimer's Disease, Ying Xia, Pierrick Bourgeat, Vincent Doré, Jurgen Fripp, Yen Ying Lim, Simon M. Laws, Christopher Fowler, Christopher C. Rowe, Colin L. Masters, Elizabeth J. Coulson, Paul Maruff

Research outputs 2022 to 2026

Introduction : Emergent Alzheimer's disease (AD) represents a transitional stage where cognitively unimpaired (CU) individuals exhibit subthreshold but increasing amyloid-β (Aβ) levels. The impact of Aβ accumulation on brain volume loss and cognition during this early stage remains unclear. Methods: This retrospective cohort study analyzed data from 408 CU participants who were initially Aβ− (< 15 Centiloids) and followed for up to 15 years. Changes in basal forebrain and hippocampal volume, along with domain-specific cognitive performance, were compared between those who progressed to Aβ+ (≥20 Centiloids) and those who remained Aβ−. Results: Sixty-five CU participants progressed to Aβ+, indicating emergent AD, and showed faster Aβ accumulation and subtle memory decline. However, no significant differences in rate of BF and hippocampal atrophy were observed between groups. Discussion: The results suggest that during this emergent phase of AD, Aβ accumulation is associated with episodic memory loss, in the absence of detectable accelerated brain atrophy. Highlights: Identified cognitively unimpaired individuals in the emergent stage of Alzheimer's disease (AD). Emergent AD exhibits a greater rate of amyloid-β (Aβ) accumulation. No accelerated volume loss detected in the basal forebrain or hippocampus. Emergent AD is also associated with a subtle decline in memory. Early Aβ accumulation may impair cognitive function before structural atrophy.

Baseline Characteristics Of The Us Study To Protect Brain Health Through Lifestyle Intervention To Reduce Risk (Us Pointer): Successful Enrollment Of A Diverse Clinical Trial Cohort At Risk For Cognitive Decline, Rachel A Whitmer, Laura D Baker, Maria C Carrillo, Heather M Snyder, Maryjo L Cleveland, Darren R Gitelman, Miia Kivipelto, Xiaoyan I Leng, Laura Lovato, Kathryn V Papp, Valory N Pavlik, Stephen P Salloway, Christy C Tangney, Sarah Tomaszewski Farias, Jeff D Williamson, Sharon Wilmoth, Nancy Woolard, Melissa Yu, Mark Andrew Espeland, U.S. Pointer Study Group

Faculty, Staff and Students Publications

Introduction: The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is a 2-year randomized controlled trial of two lifestyle interventions in 2111 older adults at increased risk for cognitive decline.

Methods: Sociodemographic and clinical characteristics and rates of ancillary study participation were described with means and frequencies.

Results: U.S. POINTER successfully enrolled a cohort, ages 60-79 years, which was ethno-racially inclusive (>30% individuals from groups often under-represented in clinical trials with cognitive outcomes) and 18% residing in neighborhoods with moderate or high levels of socioeconomic deprivation. Enrollees were cognitively intact but at increased …

Baseline Habitual Dietary Nitrate Intake And Alzheimer's Disease Related Neuroimaging Biomarkers In The Australian Imaging, Biomarkers And Lifestyle Study Of Ageing, Anjana Rajendra, Nicola P. Bondonno, Kevin Murray, Liezhou Zhong, Stephanie R. Rainey-Smith, Samantha L. Gardener, Lauren C. Blekkenhorst, Vincent Doré, Victor L. Villemagne, Simon M. Laws, Belinda M. Brown, Kevin Taddei, Colin L. Masters, Christopher C. Rowe, Ralph N. Martins, Jonathan M. Hodgson, Catherine P. Bondonno

Research outputs 2022 to 2026

Background: Dietary nitrate, as a nitric oxide (NO) precursor, may support brain health and protect against dementia. Objective: Our primary aim was to investigate whether dietary nitrate is associated with neuroimaging markers of brain health linked with Alzheimer's disease (AD). Participants: Study participants were cognitively unimpaired individuals from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) who had β-amyloid positron emission tomography (PET) scans (n = 554) and magnetic resonance imaging (MRI) scans (n = 335) and had completed a Food Frequency Questionnaire at baseline. Methods: Source-specific nitrate intakes were estimated using comprehensive nitrate food composition databases. Rates …

Multi-Omics Delineate Growth Factor Network Underlying Exercise Effects In An Alzheimer’S Mouse Model, Xin Li, Chaozhong Liu, Wenbo Li, Guantong Qi, Yanwan Dai, Chaohao Gu, Yuxiang Sun, Wenjun Zhou, Veronica C Ciliberto, Jing Liang, Udhaya Kumar S, Dongyin Guan, Zhaoyong Hu, Hui Zheng, Zhandong Liu, Hu Chen, Ying-Wooi Wan, Zheng Sun

Duncan NRI Faculty and Staff Publications

Introduction: Physical exercise is a primary defense against age-related cognitive decline and Alzheimer's disease (AD).

Methods: We conducted single-nucleus transcriptomic and chromatin accessibility analyses (snRNA-seq and snATAC-seq) on the hippocampus of mice carrying mutations in the amyloid precursor protein gene (APPNL-G-F) following prolonged voluntary wheel-running exercise.

Results: Exercise mitigates amyloid-induced changes in transcriptome and chromatin accessibility through cell type-specific regulatory networks converging on growth factor signaling, particularly the epidermal growth factor receptor (EGFR) signaling. The beneficial effects of exercise on neurocognition can be blocked by pharmacological inhibition of EGFR and its downstream PI3K signaling. Exercise leads to elevated levels of …

Circulating Medium- And Long-Chain Acylcarnitines Are Associated With Plasma P-Tau181 In Cognitively Normal Older Adults, Tahmida Sharmin, Pratishtha Chatterjee, James D. Doecke, Nicholas J. Ashton, Kevin Huynh, Steve Pedrini, Hamid R. Sohrabi, Benjamin Heng, Shaun Eslick, Henrik Zetterberg, Kaj Blennow, Manohar Garg, Ralph N. Martins

Research outputs 2022 to 2026

Alzheimer's disease (AD) pathogenesis involves dysregulation in diverse biochemical processes. Nevertheless, plasma tau phosphorylated at threonine 181 (P-tau181), a recognised AD biomarker, has been described to reflect early-stage cortical amyloid-β (Aβ) deposition in cognitively normal (CN) adults. Therefore, identifying changes in plasma metabolites associated with plasma P-tau181 at the pre-clinical stage may provide insights into underlying biochemical mechanisms to better understand initial AD pathogenesis. In the current study, plasma P-tau181, quantified via single molecule array (Simoa) technology, and plasma metabolites, quantified via targeted-mass spectrometry, were investigated for associations in CN older adults and upon stratification by positron emission tomography (PET)-Aβ …