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Learn more about cognitive aging, dementia, and neuroscience research at Northwestern University.
Although we cannot be in person, we hope you enjoy reading about the important cognitive aging, dementia and neuroscience research happening at Northwestern University.
Presenting the Marie and Carl Duncan Prize in Memory Disorders Research
A little history: Professor Carl Duncan is widely regarded as the first to demonstrate the existence of memory consolidation, showing the vulnerability of recently stored memories. His landmark work is cited more than half a century later. Upon his passing in 1999, his wife, Dr. Marie Duncan, who received her medical degree from Northwestern, set up the Duncan Fund to encourage research and discussion on issues related to memory. In addition to an annual lecture on fundamental research on memory in the name of Professor Duncan, the Duncan Fund inaugurated in 2006 the Marie and Carl Duncan Prize in Memory Disorders Research to award accomplishments in clinically relevant arenas of inquiry.
Erfan Taefi is the 2021 Duncan Award Winner
His project "Cultured Microglia from Cognitive SuperAgers Show High Rates of Proliferation" focused on better understanding the role of microglia — the cells of the immune system in the brain — in maintaining cognitive abilities in old age.
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Research Abstracts
Click on the topics below to view research in these areas or scroll down to view all research abstracts.
- Clinicopathologic Studies
- Clinical Best Practices
- Health Services
- Neuroanatomy
- Neuroscience
- Social and Behavioral Sciences
Clinicopathologic Studies
Putative Pathologic Correlates of Neurodegeneration in an Autopsy Series of FTLD-TDP Type C
Frontotemporal lobar degeneration caused by protein TDP-43 (FTLD-TDP) is a neurodegenerative disease where thefrontal and temporal lobes are atrophied due to an abnormal accumulation of the TDP-43 protein. There are several subtypes of FTLD-TDP: A, B, C, D, and E. Our project aimed to thoroughly classify the C subtype of FTLD-TDP. We found that areas that had a lot of atrophy, or shrinkage, tended to show less accumulation of TDP-43, and vice versa. This observation leads us to believe that when neurons die due to the toxic effects of TDP-43 build-up, the process that cleans up the dead neurons also clears out the TDP within the neuron. This discovery gives us a glimpse into the chain of events TDP-43-related diseases and can help guide treatments.
First author: Allegra Kawles
Integrity of Neuronal Size in the Entorhinal Cortex across the Cognitive Aging Spectrum
In older age, “normal” decline in memory can be associated with the development of abnormal proteins that build-up in brain cells, known as Alzheimer’s disease (AD), characterized by tau-tangles and amyloid plaques. These markers typically first emerge in a brain area responsible for memory known as the entorhinal cortex (ERC). However, there is a rare group of individuals over age 80 known as “Cognitive SuperAgers” who show exceptional memory at a level comparable to individuals 20-30 years their junior and appear to be immune to some of the disadvantageous effects of aging. The goal of this study was to determine whether the size of brain cells (i.e, shrinkage) in the ERC is one contributing factor. This study suggests that neuronal shrinkage is more closely associated with abnormal memory performance that is probably the result of tau-tangle build-up. More research on larger number of postmortem brains will be needed to determine the impact of neuronal size in memory-related brain regions in SuperAgers.
First author: Caren Nassif
Clinicoanatomic Distribution of the 3R tauopathy of Pick’s disease in behavioral variant Frontotemporal Dementia (bvFTD)
Behavioral variant frontotemporal dementia (bvFTD) is a neurodegenerative disease that affects one’s personality and behavior. While we diagnose bvFTD during life based on symptoms, we must diagnose its biological cause after death. We diagnose this by looking for abnormal clusters of proteins, or pathology, in the brain. While we expect that pathology is most abundant in areas related to symptoms, we wanted to methodically observe whether this correlation was true in those diagnosed with bvFTD and a pathology called Pick’s disease. Our results show it is true: the majority of these patient’s symptoms involved behavior, and pathology was most abundant in areas involved in behavior. However, regions implicated in memory also showed a lot of pathology, despite the patients’ lack of memory problems during life. This discovery begs the question whether memory regions of the brain are more vulnerable to pathology than other regions, and if so, why? This is an important question to address to understand how and why certain brain regions are so vulnerable to neurodegenerative diseases, including Alzheimer’s disease.
First author: Allegra Kawles
Distinct cognitive and neuropsychiatric features of amnestic dementia with comorbid Alzheimer and TDP-43 proteinopathies
My project looks at similarities and differences in clinical, neuropsychological, and psychiatric features between two groups with amnestic dementia: those individuals with only markers of Alzheimer's Disease ("AD") at brain autopsy, and those with both AD and a disease found at brain autopsy known as "TDP-43" ("TDP/AD"). Our group analyzed performances from different cognitive and behavioral domains including memory, attention, language, executive functioning, visuoconstruction, and mood/neuropsychiatric symptoms. We specifically compared visual memory and verbal memory between groups. Our findings suggest that there are different cognitive and neuropsychiatric profiles at disease onset in the AD group compared to the TDP/AD group. Interestingly, amnestic dementia with TDP/AD presented with more neuropsychiatric symptoms, like depression, and better visual memory recall abilities compared to verbal memory recall than the cases with only AD. These findings are important to help guide future studies and proper diagnosis of amnestic dementia.
First author: Makayla Kochheiser
Clinical features of limbic and subcortical Pick body distribution in behavioral variant Frontotemporal Dementia (bvFTD)
Patients with behavioral variant frontotemporal dementia (bvFTD) show marked changes in behavior and personality, and their brain scans usually reveal shrinking of the frontal cortex. Different brain pathologies may cause bvFTD. One of these is known as “Pick’s pathology,” which is found in the brain at autopsy and is visible under a microscope. This study examined behavioral symptoms in six participants diagnosed with bvFTD and Pick’s pathology. Participants donated their brains after death, and we quantified the level of Pick’s pathology in different brain regions within and below the cortex. Behavioral symptoms increased substantially as participants’ dementia worsened. Pick’s pathology was greatest in brain areas below the cortex, and this was related to prognosis. While shrinkage of the frontal cortex is characteristic of bvFTD on brain imaging, microscopic analysis after death suggests that the level of pathology in regions below the cortex also contributes significantly to this dementia.
First author: Rachel Keszycki
Phospho-tau comparisons in synaptosomal fractions from human brain tissue in Alzheimer’s disease progression
Intracellular inclusions of tau proteins correlate with, and precede, cognitive deficits in neurodegenerative disorders, including Alzheimer’s disease (AD). Tau can become phosphorylated in neurodegenerative diseased brains. In this study, we specifically looked at the presence and amount of phospho-tau in neuronal synapses. Phospho-tau shows differences across pre- and post-synaptic fractions when stratified by Braak neurofibrillary tangle stage.
First author: Jacyln Lilek
Analysis of soluble proteins implicated in Alzheimer’s Disease from formalin fixed paraffin embedded human brain tissue
The Mesulam Center houses the Neuropathology Core Brain Bank, with over 900 human brains. Most of the stored tissue is fixed in paraformaldehyde to preserve it for long-term storage. In this project, we have optimized a protocol for extracting proteins from the fixed tissue to increase its utilization in studies that reveal the presence or changes in different proteins that are associated with Alzheimer’s Disease and other dementias. In this study, we specifically targeted amyloid beta, tau, and Tar DNA-binding protein 43, all of which are key players in dementia research.
First author: Jaclyn Lilek
Clinical Best Practices
Communication Bridge: A person-centered Internet-based intervention for individuals with Primary Progressive Aphasia
The diagnosis of primary progressive aphasia (PPA) is made when a relatively isolated progressive impairment of language occurs as a result of neurodegenerative disease. Although there are no pharmacological treatments for PPA, speech-language therapy (SLT) is an intervention that can offer individuals with PPA a means to compensate for their communication difficulties. Unfortunately, individuals with PPA are under-referred for SLT treatment. Other barriers individuals with PPA may face in receiving care include limited availability of speech-language pathologists (SLPs) who specialize in PPA, and limited insurance coverage of SLT. In hopes of circumventing these barriers, the Communication Bridge study provides web-based SLT to individuals with PPA and their care partners residing both nationally and internationally. The study aims to understand SLT effects on communication abilities in people living with PPA and to determine optimal intervention strategies for this population.
First author: Marissa Esparza
Achieving Diversity in Research: The URG Recruitment Taskforce
The Underrepresented Group (URG) Recruitment Taskforce was created in June 2020 and is co-chaired by Brittanie Muse and Darby Morhardt. The mission of the URG Recruitment Taskforce is to achieve increased diversity of ADRD research cohorts at the Mesulam Center that is reflective of the affected population and community by promoting the identification, engagement, recruitment, and retention of individuals from underrepresented groups.
First author: Brittanie Muse
Adapting Programs and Supports during the COVID-19 Pandemic
The COVID-19 pandemic has profoundly affected older adults, people living with MCI or dementia, caregivers, people living in nursing homes and long-term care facilities as well as their families and care partners. In response, we adapted existing programs and created new programs to meet the needs of people living with MCI or dementia and their families. We developed online procedures for the Miller Family Quality of Life Enhancement Programs. We provided people living with MCI or dementia and their families with reliable information about caregiving and opportunities for social engagement during the COVID-19 pandemic through the creation of a Caregiving Resource Guide and timely updates about COVID-19 vaccination. The Northwestern Mesulam Center successfully adapted its programs and supports to address the evolving needs of persons living with MCI or dementia and their families during the COVID-19 pandemic.
First author: Deborah Dyslin
Health Services
Landscape assessment of culturally tailored brain health and Alzheimer’s disease and related dementias (ADRD) education messages and resources targeting Latinos
Culture is known to be a critical aspect of life and health behaviors and is an important consideration for the dissemination and uptake of information. We assessed and reviewed peer-reviewed articles and online public platforms and resources. Our search focused on culturally relevant messaging, brain-healthy behaviors, and health education related to cognitive impairment and ADRD, and the overlap between cognitive impairment and ADRD and COVID-19 targeting Latino consumers, caregivers, and Latino-serving providers. The review identified multiple gaps regarding brain health messaging to the Latino community. Further gaps were identified in the online resources related to dementia, COVID-19 health, and vaccine education. There is a need to tailor brain health education and community programming targeting Latino consumers and caregivers, and Latino-serving providers to promote brain health-protective behaviors in this high-risk population.
First author: Michelle Jaldin
Neuroanatomy
Mapping the Connectivity and Microstructure of the Human Lateral Olfactory Tracts with Diffusion MRI
The sense of smell, called “olfaction”, is the most commonly affected sense in aging. Olfactory dysfunction is seen in nearly 90% of patients with Alzheimer’s disease, and usually appears several years before signs of cognitive impairment. Olfactory loss has been suggested as a potential predictor for later cognitive decline. Whether olfactory decline in old age is due to degeneration in the olfactory nerve (also called the lateral olfactory tracts) is not known. In this study, we have optimized a novel MRI scanning method for characterizing tissue microstructure of the human lateral olfactory tracts. This method will allow us to track signs of olfactory nerve degeneration in elderly adults with early stage Alzheimer’s disease, and in elderly healthy controls.
First author: Shiloh Echevarria-Cooper
Neuroscience
The Implementation of a Freezerworks Data Management System into an Extensive Human Brain Bank and Biospecimen Repository
Banking human tissue is very important for conducting research on neruodegenerative diseases. Keeping track of all of the samples can be a difficult task, but we implemented a data management inventorying system into our lab to better manage the samples. This system has allowed for a standardized procedure when searching samples suitable for individual research studies when requested by researchers, as well as keeps track of how much we have left of each sample.
First author: Callen Spencer
Primary Progressive Aphasia Research Programs at the Mesulam Center for Cognitive Neurology and Alzheimer Disease
The Primary Progressive Aphasia (PPA) Research Program studies individuals who are diagnosed with PPA. PPA is a form of dementia that progressively affects the language areas of the brain. Over the past decade, we have invited participants to participate in our studies, which assess their language, memory, and cognitive skills through a series of tests. Participants also undergo different brain imaging scans so that we can better understand the causes of PPA and how this impacts an individual’s language functions. Overall, these studies hope to improve the diagnosis and treatment of those living with PPA, as well as understanding the underlying mechanisms of language.
First author: Shreya Kanchan
Isolation of Exosomes from Frozen Postmortem Human / Mouse Brain and Primary Human Microglia Culture Media
My project is trying to look at a molecule called exosome, which are in the form of spheres and are much smaller than cells. They bud out of the cell membranes and travel to other cells carrying chemical signals from cell to cell. We believe that protein diseases can also be spread in this method, like mis-folded TDP43, which can cause dementia. I was able to isolate pure exosomes from human and mouse brain tissue, as well as liquid media from cell cultures. My findings also suggest that these exosomes originated from microglia cells. The next step is to detect the contents inside the exosomes which we believe could be TDP43. If we are successful it will provide support to the theory that exosomes are involved in the propagation of neural disease and could possibly be used for future treatments.
First author: Ivan Ayala
Brain Hypometabolism and Cortical Thinning in Primary Progressive Aphasia
Primary progressive aphasia is a syndrome of progressive language impairment caused by neurodegenerative disease. This worsening of symptoms coincides with both a decrease in brain activity as well as a thinning of brain gray matter, both of which occur in brain areas known to play a role in language. However, the exact relationship between brain volume decreases and brain metabolism decreases is not well understood. This research uses fluorodeoxy-glucose positron emission tomography (FDG-PET) to look at brain activity, and voxel-based morphometry (VBM) to look at brain volume in persons with PPA. Our results replicate previously observed patterns for both of these methods. and serve as an essential early step in comparing and deciphering the relationship between brain atrophy and function that occurs over the progression of PPA.
First author: Jordan Behn
Neuropsychiatric phenotypes in PPA and bvFTD due to Pick’s disease
Primary progressive aphasia (PPA) is a language-based dementia, whereas behavioral variant frontotemporal dementia (bvFTD) involves significant psychiatric symptoms and personality changes. Different brain pathologies may cause bvFTD. One of these is “Pick’s pathology,” which is discovered in the brain at autopsy and is visible under a microscope. This study examined psychiatric symptoms in participants diagnosed with PPA or bvFTD who had Pick’s pathology at autopsy. Initially, symptoms such as apathy, disinhibition, repetitive behaviors, and appetite changes were more common in bvFTD than in PPA. Psychiatric symptoms increased significantly in both groups from the early to late stages of disease, and the types of symptoms expressed became similar between groups. Findings suggest that early examination of psychiatric symptoms can help distinguish between PPA and bvFTD.
First author: Rachel Keszycki
Northwestern Alzheimer's Disease Center (NADC) Neuroimaging Biomarker Core
The purpose of the Imaging Core is to collect Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) scans on Clinical Core research participants. The scans collected by Imaging Core allows researchers a unique snapshot of the brain and how it’s functioning, while also providing detailed data that can be used across multiple research studies and sites. Imaging Core has collected 106 scans since 2018.
First author: Abbey Page
Cognitive SuperAging: A model to explore resilience and resistance to aging and Alzheimer's disease
Many individuals have come to expect that memory and thinking abilities will begin to deteriorate with advancing age. Though such decline is common, the SuperAging Project at the Northwestern University Mesulam Center for Cognitive Neurology and Alzheimer’s Disease has found that some individuals are able to maintain high levels of cognitive function despite older age. The study has wide ranging implications and may ultimately provide clues on how to slow or avoid age-related cognitive decline. Click to view an image
First author: Beth Makowski-Woidan
Cultured Microglia from Cognitive SuperAgers Show High Rates of Proliferation
The Mesulam Center has been studying a group of SuperAging individuals that are 80 years of age or older with memory performance equal or better than individuals 20-30 years their junior. This study is focused on better understanding the role of microglia, the cells of the immune system in the brain, in maintaining cognitive abilities in old age. The results of our experiments point to significant enhancement of the proliferative capacity of microglia in SuperAgers, which may be an indication of a role for microglia in superior cognitive abilities.
First author: Erfan Taefi
Tunneling nanotubes at the neuro-immune interface in chronic inflammation and Alzheimer’s disease
Cells in the body need to communicate to coordinate biological functions, and my research focuses on a recently discovered form of rapid, long-range communication between cells via tunneling nanotubes (TNTs). TNTs are long, thin extensions of the plasma membrane that directly connect two cells, like skybridges that connect two buildings. TNTs pass messages and the content of those messages depends on local environmental signals. During chronic inflammation and neurodegenerative disease, TNTs may be detrimental, facilitating the spread of abnormal proteins such as amyloid-β (Aβ), a key protein in Alzheimer’s disease (AD) progression. My research focuses on uncovering the role of TNTs in microglia, the immune sentinels of the brain, during neuroinflammation and AD. Our results revealed TNTs frequently emerging from microglia and forming dynamic connections with other microglia or contacting neuronal structures. Further, we showed in microglia monocultures that TNTs can support the rapid spread of different forms of Aβ between interconnected microglia. This research could reveal the microglial TNT-driven communication network as a major avenue for the spread of abnormal proteins underlying neurodegenerative diseases and identify a potential therapeutic target for early AD progression.
First author: Colleen Zaccard
Relative Burden of Alzheimer’s Disease vs TDP-43 Hippocampal Pathology in Amnestic Dementia
Our study investigated two proteins, tau and TDP-43, that commonly appear together in the brains of people who had Alzheimer’s disease. Previous findings showed that individuals with both tau and TDP-43 together demonstrated significantly worse long term recall abilities compared to individuals with only tau. We quantified these 2 proteins in the area of the brain associated with memory, the hippocampus. We found that tau was significantly more present compared to TDP-43 in both the left and right hippocampi, as well as a specific region of the hippocampus associated with memory consolidation called CA1. This finding suggests that tau is responsible for the overwhelming majority of the molecular burden in Alzheimer’s disease among individuals who have both tau and TDP in their brains.
First author: Grace Minogue
Epigenetic Regulation of Memory and Behavior in Aging and Alzheimer’s Disease Mouse Models
Alzheimer’s disease (AD) is an aging-dependent disorder, but the relationship of aging and AD remains unclear. This study addresses the issue at the epigenetic level. Epigenetics is a process that influences gene expression but not structure. Current behavior results indicate that the changes of memory and mood behaviors are differentially regulated in aged and APP/PS1 mice, suggesting that aging may aggravate executive memory and anxiety-like behaviors AD. Next, we will investigate epigenetic modulation of these behaviors to understand the interaction of epigenetic regulation in aging and AD-related processes.
First author: Bryan McClarty
Levetiracetam treatment normalizes levels of the presynaptic endocytosis machinery and restores non-amyloidogenic APP processing in App knock-in mice
Hyperactivity and neural-network disruptions, like seizures, have been observed during the early stages of Alzheimer’s disease (AD). Interestingly, in a study of AD patients with seizures, a comparison of the anti-epileptic levetiracetam versus typical epilepsy drugs demonstrated that while all drugs were equally effective in reducing seizures, only levetiracetam led to improved performance on cognitive tasks. Intriguingly, the mechanism(s) of action for levetiracetam and how it could mitigate AD pathology remains unknown. Here, we used chronic levetiracetam treatment in AD mouse models in combination with mass-spectrometry to investigate how the proteome is affected by this common anti-epileptic to identify a mechanism of action. We discovered that levetiracetam serves as a useful therapeutic by normalizing levels of presynaptic endocytic proteins and altering APP cleavage leading to a decrease in both Aβ42 levels and amyloid plaques. These novel findings provide pioneering evidence for the previously documented therapeutic value of levetiracetam in AD.
First author: Nalini Rao
Task-evoked pupillary response and word frequency in Primary Progressive Aphasia
In some individuals with Primary Progressive Aphasia (PPA), there is difficulty understanding the meaning of words. One of the ways we can measure subtle differences in how one processes words is by measuring changes in pupil size. Prior studies have shown that the pupil dilates at a greater rate in relation to more difficult (or less frequent) words. Our study examined how the pupil changes in response to varying levels of word difficulty in PPA. In one group of participants (non-semantic), who tend to have less problems with word recognition, we observed an expected increase in pupil dilation in response to more difficult words. This effect was weakened in another group of participants, who are typically characterized by inability to comprehend words. Since individuals with PPA have difficulty with word output, these findings suggest that other measures, like pupillometry, may be helpful for studying language processing.
First author: Tatiana Karpouzian-Rogers
Social and Behavioral Sciences
Northwestern Alzheimer's Disease Center Outreach, Recruitment, and Engagement (ORE) Core 2020-21
The Northwestern Alzheimer’s Disease Research Center’s Outreach, Recruitment and Engagement Core works with communities for the purposes of raising public awareness of brain health and dementia, treatment and care, in addition to recruiting and retaining participants in center research. We are committed to training scientists and clinicians, and providing targeted psychoeducational programs and support services for persons living with dementia and their families.
First Author: Darby Morhardt, PhD, LCSW
The Mobile Toolbox (MTB): A technology-based remote platform for Cognitive research
“Mobile Toolbox” (MTB) is a technology-based research platform that includes a library of assessments and allows researchers to deploy smartphone-based measures and remotely assess cognitive functioning across the adult lifespan in a safe and effective way. By utilizing the devices that are already ubiquitous in our lives (i.e., smartphones) and removing the necessity for in-person testing, researchers will be able to assess cognition more frequently in older adults, allowing for better monitoring and earlier detection of cognitive decline.
First author: Zahra Hosseinian
Northwestern Alzheimer's Disease Center (NADC) Clinical Core
The Mesulam Center's Clinical Core is entering its 26th year maintaining a registry of approximately 500 research participants who are cognitively healthy or who have different forms of cognitive impairment or dementia. This year, the Clinical Core has continued to collect demographic, health, and neuropsychological information from our participants, while adapting to remote research methods during the COVID-19 pandemic.
First author: Michaela Riley
Medical Characterization of Cognitive SuperAgers: Investigating the medication profile of SuperAgers
As people get older the number of medications they are on increases. Northwestern SuperAgers are a unique group of people 80 years and older who demonstrate the memory performance of someone in their 50's or 60's. By looking at the medication profiles of SuperAgers and their peers, we can see if medications have any effect on memory performance.
First author: Janessa Engelmeyer
Intensity of walking training impacts cognition among assisted living residents with frailty
Research shows that exercise is good for brain health, and this pilot study explored the relationship between exercise and thinking to see if the intensity of exercise made any difference. Thirty-three people living in Assisted Living Facilities who have frailty or pre-frailty participated in an exercise program. While most people did not have a dementia diagnosis, they had low scores on thinking tests before they began the study. Some people exercised at a high intensity, while others exercised at a moderate intensity. They all completed thinking tests after the program, and we compared how much they improved or got worse. On one type of test, people who exercised moderately improved more, but on a different test the people who exercised vigorously improved more. We will continue studying how exercise intensity impacts thinking with a larger group so that people who want to improve their thinking can maximize their efforts.
First author: Christie Norrick
PPA Tele-Savvy: Developing an Online Intervention for Caregivers of Persons with Primary Progressive Aphasia
Primary Progressive Aphasia is a language based dementia. There are no caregiver interventions specifically designed for caregivers of persons living with PPA. This study is the adaptation and pilot testing of a well known and successful caregiver intervention (Tele-Savvy) for care partners of persons living with PPA.
First author: Darby Morhardt, PhD, LCSW
The Northwestern Buddy Program: Understanding the Factors that Affect Level of Connectedness Between First-Year Medical Students and Persons Living with Dementia
The Northwestern Buddy Program is a program that connects 1st-year medical students with persons living with dementia through the Northwestern Neurobehavior and Memory Clinic. My project aims to study the "connectedness" between students and their paired buddies. Connection - defined as compassion, care, respect, and an understanding and awareness of the person behind the diagnosis - is an essential component of good quality care and is strongly linked to positive health outcomes. My project looks at how students' baseline levels of empathy, knowledge, and attitudes towards dementia, as well as their previous personal and professional experiences with persons living with dementia, affect their level of connectedness with their buddy, as measured by number of hours spent together, student journal entries, and post-program focus groups among the persons with dementia.
First author: Nila Suresh
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