Research Abstracts
The Alzheimer Day Virtual Research Showcase was created to provide you with the opportunity to learn more about the outstanding cognitive aging, dementia, and neuroscience research at Northwestern University.
Click on the topics below to view research in these areas or scroll down to view all research abstracts.
- Cell & Molecular Biology
- Clinical Best Practices
- Clinicopathologic Studies
- Community Engagement
- Health Services
- Neuroanatomy
- Neuroscience
- Pharmacology
- Physiology
- Recruitment Science
- Social & Behavioral Sciences
If you are interested in learning more, you can also download a PDF copy of this year's abstract book.
Cell & Molecular Biology
TLR4 Antagonists as A Potential Therapeutic for Alzheimer’s Disease-Associated Neuroinflammation
First author: Deebika Balu
Increased inflammation in the brain is one of the early events in Alzheimer’s disease (AD) progression in humans. Thus, targeting inflammation may decrease AD symptoms. However, anti-inflammatory drugs so far have not been successful, partly due to complexity of AD. People with the E4 variant of APOE gene have increased odds of AD risk compared to E3 variant carriers. Also, women have increased AD risk compared to men. To target early inflammation in the brain in the context of AD, we used a novel drug that inhibits a protein that modulates inflammation in the brain. We tested this drug in a mouse model that has the human variants of APOE3 and APOE4 and shows progressive increase in AD pathology with age, mimicking the progression of AD in humans. In this study, the novel drug improved cognition, decreased brain inflammation and decreased AD pathology in female mice that have human APOE4. Thus, the drug may be a potential alternative or a combination medication for the high-risk population, females with APOE4 gene.
Anti-CD49d Antibody Treatment Improves Survival and Attenuates Neurocognitive Deficits after Traumatic Brain Injury in Aged Mice
First Author: Zhangying Jennie Chen
Traumatic brain injury (TBI) occurs as a result of a severe physical injury or car accident and is a major cause of death and disability, with the highest incidence occurring in older adults. However, there have not been many studies investigating post-TBI treatments in older patients. In this study, we utilize an FDA-approved antibody to prevent T-cells from entering the injured mouse brains and investigate whether blocking T-cells can have improved TBI outcomes in specifically older mice.
Targeting TDP-43 loss-of-function induced mis-splicing in ALS-FTD
First Author: Wanhao Chi
TDP-43 dysfunction has been found in several neurodegenerative disorders, including amyotrophic Lateral Sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer’s Disease (AD). TDP-43 dysfunction leads to mis-splicing several dozen genes, compromising their physiological functions. This study aims to develop an innovative approach to suppress mis-splicing collectively. We first establish a cellular system to study TDP-43 dysfunction-induced mis-splicing using human induced pluripotent stem cells (hiPSCs)-derived motor neurons. We then design antisense oligonucleotides (ASOs) targeting two mis-spliced genes and screen ASOs using the cellular system. Lastly, we multiplex ASOs from each gene using spherical nucleic acids (SNAs) and deliver multiplexed SNAs to hiPSC-derived motor neurons to restore genes’ function. Together, this study establishes a proof-of-concept experiment of collectively targeting TDP-43 dysfunction-induced mis-splicing.
Bone morphogenetic protein signaling is exacerbated in Alzheimer's Disease
First Author: Sara Rose Dunlop
Bone morphogenic protein (BMP) is one pathway increased by the aging process. Increased BMP signaling leads to impaired memory in mice. These results show an increase in BMP signaling in the Alzheimer’s disease brain and suggests that levels of BMP proteins are related to severity of cognitive decline. This suggests that BMP could be a potential target for AD disease modifying therapies.
DISE Contributes to Neurotoxicity in Alzheimer's Disease
First Author: Bidur Paudel
Alzheimer's disease (AD) is characterized by progressive neurodegeneration, but the specific events that cause cell death remain poorly understood. We recently discovered a powerful mechanism of cell death called Death Induced by Survival gene Elimination (DISE) (2) where toxic short (s)RNAs/miRNAs that are rich in G-rich seeds enter the RNA induced silencing complex (RISC) and kills cells by targeting genes essential for cell survival (1). The RISC of most cells is occupied by miRNAs with nontoxic seeds, which may protect them from DISE by blocking loading of toxic sRNAs. However, during aging miRNA expression decreases and toxic sRNAs may enter the RISC more readily leaving cells primed for DISE. We analyzed RISC bound sRNAs (R-sRNAs) of in vitro, in vivo AD mouse models, aged mice, and AD patients and showed that in mouse models that show neurodegeneration and during aging R-sRNAs shift to more toxic seeds. In contrast, in cells that survived in post-mortem brains of AD patients and "SuperAgers", R-sRNAs shift to more nontoxic seeds, supporting a protective function of miRNAs. We provide evidence that DISE contributes to neuronal loss seen in AD and increasing the levels of protective miRNAs in the brain could lead to a novel way of treating the disease.
Single cell transcriptomics reveals cerebrospinal fluid immune dysregulation during healthy brain aging and cognitive impairment
First Author: Natalie Piehl
Cerebrospinal fluid (CSF) contains a tightly regulated immune system. Yet, little is known about how CSF immunity is altered with aging or neurodegenerative disease. Here, we performed single cell RNA sequencing on CSF from 45 cognitively normal subjects ranging from 54-82 years old. We reveal upregulation of lipid transport genes in monocytes with age. We then compared this cohort to 14 cognitively impaired subjects. In cognitively impaired subjects, downregulation of lipid transport genes in monocytes occurred concomitantly with altered cytokine signaling to CD8 T cells. Clonal CD8 T effector memory cells upregulated C-X-C Motif Chemokine Receptor 6 (CXCR6) in cognitively impaired subjects. The CXCR6 ligand, C-X-C Motif Chemokine Ligand 16 (CXCL16), was elevated in CSF of cognitively impaired subjects, suggesting CXCL16-CXCR6 signaling as a mechanism for antigen-specific T cell entry into the brain. Cumulatively, these results reveal cerebrospinal fluid immune dysregulation during healthy brain aging and cognitive impairment.
Peripheral immunomodulatory effects of Apolipoprotein E4 in Alzheimer's disease
First Author: Abhirami Ramakrishnan
Apolipoprotein E (APOE) is a fat transport molecule with several forms (including E3 and E4) known to influence Alzheimer's disease (AD) risk. In particular, the APOE E4 is the largest genetic risk factor for late-onset sporadic AD. Our recent findings uncovered activated immune cells and altered levels of the gene encoding APOE in AD cerebrospinal fluid (CSF). Yet, whether different forms of APOE affect blood immune systems in AD remains unknown. In this study, we analyzed immune cells in the blood using DNA and RNA profiling of 55 age-matched healthy control (HC) and AD patients with an equal distribution of APOE E3 and E4 carriers. We reveal parallel changes in DNA and RNA of immune cell types known as monocytes and activated central memory T cells in AD patients distinct to those carrying APOE E4. These findings reveal that different forms of APOE may affect AD risk via changes in blood immunity.
Annexin A6 in membrane resealing in Alzheimer's disease
First Author: Katherine Sadleir
Traumatic brain injury (TBI) occurs as a result of a severe physical injury or car accident and is a major cause of death and disability, with the highest incidence occurring in older adults. However, there have not been many studies investigating post-TBI treatments in older patients. In this study, we utilize an FDA-approved antibody to prevent T-cells from entering the injured mouse brains and investigate whether blocking T-cells can have improved TBI outcomes in specifically older mice.
Increased production of Reactive Oxygen Species by Human Microglia in SuperAgers in Response to Soluble Oligomeric and Fibrillar Amyloid-β Peptide
First Author: Erfan Taefi
Microglia are specialized immune cells of the brain and play an important role in responding to foreign substances and misfolded proteins, such as the amyloid beta (Aβ) peptide, that can lead to Alzheimer's disease. When these misfolded proteins accumulate, an immune response is initiated and activated microglia release reactive oxygen species (ROS), which are damaging to cells, in an attempt to combat invaders. In this experiment, we measured the levels of ROS production by microglia in SuperAgers and normal controls in the presence of increasing concentrations of Aβ and found that there is an increased response in SuperAgers. This may indicate a superior protective response to foreign materials by SuperAgers compared to normal individuals.
Clinical Best Practices
Evaluation of the 10-item Communicative Participation Item Bank for Persons with Primary Progressive Aphasia and their Communication Partners
First Author: Ollie Fegter
Primary progressive aphasia (PPA) is a dementia syndrome that impairs language functions such as speaking and understanding. It is important to measure how much PPA interferes with people’s ability to participate in communication activities, such as communicating in a small group of people, asking a question, or having a long conversation about a book or movie. The 10-item Communicative Participation Item Bank (CPIB) is a survey commonly used by speech-language pathologists to measure how much a condition interferes with communication activities but has not yet been evaluated rigorously in persons with PPA. In this study we are interviewing people with PPA and their communication partners as they complete the CPIB, to gather their impressions regarding its clarity, relevance to their experiences with PPA, and if important communication experiences are captured by this survey. This research will help us develop a better questionnaire for individuals living with PPA and their families.
Suitability of Goal Attainment Scaling in Older Adult Populations with Neurodegenerative Disease Experiencing Dementia or Cognitive Impairment: A Systematic Review
First Author: Ollie Fegter
This project looks at a measurement tool used in speech-language, occupational, and cognitive therapy called Goal Attainment Scaling (GAS). GAS allows people to set specific goals and then measures their progress towards those goals while they are receiving treatment. This project specifically looks at how well GAS measures change in people with neurodegenerative disease who are experiencing cognitive difficulties. We searched 8 databases and found over 500 relevant articles. We searched these articles to make sure they focus on people with cognitive difficulties, include GAS scores, and include people receiving treatment focused on cognition, communication, or quality of life. Ten articles fit these criteria. We analyzed GAS scores from before and after treatment for each of these articles. Our results showed that GAS is an effective way to measure change in this population. As such, it is likely a useful tool in speech-language, occupational, and cognitive therapies.
Clinicopathologic Studies
Trajectories of Neurocognitive Decline in Aphasic versus Behavioral Dementia Syndromes due to Pick Disease
First Author: Allegra Kawles
Two types of atypical dementia syndromes are 1) primary progressive aphasia (PPA), characterized by progressive impairment of language, and 2) the behavioral variant of frontotemporal dementia (bvFTD), characterized by progressive dysfunction in personality. Interestingly, both PPA and bvFTD can be caused by the same pathology known as Pick’s disease (PiD). In this study, we investigated rates of decline in cognition and quantified densities of PiD pathology in regions important for language and/or behavior in those with bvFTD or PPA. Our findings suggest that the “defining” deficits at initial stages of bvFTD and PPA are also the ones that decline the fastest, such that bvFTD patients declined fastest in areas related to planning and attention and PPA patients showed fastest decline in language. We also found that bvFTD patients became too impaired to complete neuropsychological testing (“untestable”) significantly sooner than PPA patients. When we quantified PiD pathology, we found that bvFTD patients had significantly greater densities of PiD pathology in their overall neocortex. These results suggest that cognitive decline in PiD may be linked to relative abundance of pathology in the neocortex.
Amygdala pathology in early neuropsychiatric phenotypes due to 3R-Pick disease
First Author: Rachel Keszycki
Primary progressive aphasia (PPA) is a language-based dementia, whereas behavioral variant frontotemporal dementia (bvFTD) is characterized by personality changes. PPA and bvFTD are caused by different brain pathologies, which are discovered at autopsy. Many patients develop PPA or bvFTD when tau protein aggregates and spreads throughout the brain, damaging cells. These processes are associated with inflammation in the brain.
For this study, participants with PPA or bvFTD due to “Pick disease,” a form of tau pathology, committed to brain donation. We examined tau and inflammation in participants’ amygdala, which is a brain region involved in controlling emotions and behavior. We found that levels of tau pathology were similar between PPA and bvFTD. However, inflammation tended to be higher in bvFTD and was associated with more behavioral changes, such as apathy.
Our findings suggest that disease processes beyond brain pathology, such as inflammation, may impact patients’ symptoms, representing an additional treatment target.
Spatial extent and intensity of Alzheimer associated tau PET burden is greater in agrammatic than logopenic primary progressive aphasia
First Author: Adam Martersteck
This study investigated differences in the amount and location of abnormal tau protein in the language-related syndrome called primary progressive aphasia (PPA) using PET imaging. The study found that one subtype of PPA, which has difficulty with grammar (agrammatic PPA), had higher levels of tau protein than the other subtype, which has difficulty with finding words (logopenic PPA). The differences were observed across the parietal and occipital lobe. This suggests that agrammatic PPA caused by Alzheimer’s disease may have more severe tau protein build-up in the brain, which could impact how the disease progresses. Further PET studies and participants are needed to validate the results.
Epicenters of cortical atrophy in primary progressive aphasia differ by underlying neuropathology
First Author: Adam Martersteck
This study is about primary progressive aphasia (PPA), a clinical syndrome which affects the language network of the brain. The researchers used brain scans to study the differences between PPA caused by two different diseases: frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). They found that the areas of the brain affected by the diseases were different, with FTLD mainly affecting the front part of the brain and AD mainly affecting an area further back. This helps us to better understand the differences between these two diseases that cause PPA.
Stereological densities of corticobasal degeneration neuropathology are anatomically distinct in PPA vs bvFTD
First Author: Grace Minogue
Primary progressive aphasia (PPA) is a dementia syndrome characterized by progressive impairment of language and primary atrophy of left-sided brain regions. Behavioral variant frontotemporal dementia (bvFTD) is a dementia syndrome characterized by progressive dysfunction in personality, and atrophy in frontal brain regions. Interestingly, both PPA and bvFTD are associated with an underlying neurodegenerative disease found at autopsy known as frontotemporal lobar degeneration caused by the protein tau (FTLD-tau). More specifically, both PPA and bvFTD can be associated with a subtype of FTLD-tau called corticobasal degeneration (CBD). This study investigated the distribution of CBD pathology in various brain regions in bvFTD and PPA to establish important relationships between clinical symptoms demonstrated during life and location of disease at death.
Burden of pathology in hippocampal subregions can distinguish amnestic dementia with comorbid Alzheimer’s and TDP-43 pathology from pure Alzheimer’s and FTLD-TDP
First Author: Grace Minogue
Recently, it has been discovered that memory-related (amnestic) dementia is often caused by more than one disease in the postmortem brain. This study aimed to investigate two proteins that appear together in almost 80% of individuals with amnestic dementia: 1) Alzheimer’s disease characterized by amyloid plaques and tau-tangles and; 2) an abnormal inclusion in brain cells known as TAR DNA-binding protein 43 (TDP-43). The goal was distinguishing the role each disease plays in amnestic dementia. We focused our analysis on three regions of the memory-center of the brain, the hippocampus. We found important and significant differences between the amount and location of tau vs TDP-43 in regions of the hippocampus, which help us to distinguish and better understand these two diseases as separate entities.
Spatial transcriptomics reveals long-term neuropathological effects of amyloid-β immunization
First Author: Lynn van Olst
New Alzheimer's disease (AD) therapeutics include immunization against a protein called amyloid-β (Aβ), which is associated with the disease. In the first active Aβ vaccination trial, AN1792, AD patients showed evidence of Aβ clearance 15 years after the treatment, but still developed severe dementia before death. To investigate the long-term effects of this treatment, we used a new technique to analyze brain tissue from patients who had been immunized against Aβ. We found genetic signatures in areas of the brain where Aβ had been cleared that suggested nerve cells were being repaired and inflammation was reduced. Immune cells and blood vessels in the protective barrier around the brain of immunized AD patients expressed specific genes that help to clear the Aβ protein from the brain. However, we also found that some of the genes that help maintain the protective barrier were decreased. Overall, these findings show that active immunization against Aβ has long-term effects on the brain in AD patients.
Alzheimer’s Disease Neuroimaging Initiative 4 (ADNI4)
First Author: Jelena Pejic
The overall goal of the Alzheimer’s Disease Neuroimaging Initiative 4 (ADNI4) Study is to determine the relationships among the clinical, cognitive, imaging, genetic and biochemical biomarker characteristics for early detection of Alzheimer's disease (AD). ADNI4 seeks to understand the entire spectrum of AD, as the pathology evolves from normal aging through very mild symptoms, to mild cognitive impairment (MCI), to dementia.
Longitudinal Early-onset Alzheimer’s Disease Study (LEADS)
First Author: Ali Raja
While the risk of Alzheimer's disease (AD) increases with advancing age, approximately 5% of AD patients develop symptoms before age 65 (~280,000 Americans). Patients with early-onset Alzheimer’s disease (EOAD), occurring before the age of 65, are an understudied segment of the patient population with AD. To develop more effective AD treatments, scientists need to understand the genetic, biological and clinical processes involved in EOAD. The Longitudinal Early-onset Alzheimer's Disease (LEADS) study will develop a public resource that will enable future planning and implementation of EOAD clinical trials.
Inhibition of ACAT as a Therapeutic Target for Alzheimer’s Disease is Independent of ApoE4-lipidation
First Author: Ana C. Valencia-Olvera
Alzheimer’s disease (AD) is characterized by brain accumulation of fats and aggregated proteins that lead to cognitive decline. The greatest intrinsic risk factor for AD is inheritance of the APOE4 gene. To identify therapeutic leads, targets, and strategies for the treatment of AD we generated the mouse model called E4FAD. The E4FAD mice contain the human APOE4 gene and develop cognitive decline linked to the accumulation of fats and aggregated proteins.
In this study we reduced the amount of accumulated fats in the E4FAD brain by using a commercially available drug originally designed to reduce the buildup of fats in cardiovascular tissue. Blocking the buildup of fats in E4FAD brain led to a better cognitive performance and lower accumulation of proteins. The efficacy and potential for disease modification observed in this study with human APOE4 supports further testing of therapies that block brain accumulation of fats for AD treatments.
Anatomic Selectivity of Neuronal and Glial Tau in Primary Progressive Aphasia with 4R FTLD-tauopathies
First Author: Antonia Zouridakis
Our lab studies the relationship between clinical symptoms of dementia during life and the underlying pathologic disease in the brain found at death. Interestingly, one clinical syndrome can be caused by multiple diseases, so there is no direct correlation between pathology and clinical disorder. To better characterize these complex relationships, we examine the amount and location of specific misfolded proteins in various diseases to see how location of pathology may correlate to clinical presentation.
In this project, we analyzed the brains of people with Primary Progressive Aphasia (PPA), a language-based dementia, that also showed a disease known as Progressive Supranuclear Palsy (PSP), which is characterized by abnormalities in the protein "tau." We examined the distribution of PSP disease markers in several brain regions to distinguish PSP from other diseases that can also present with PPA and found several features unique to those with PPA due to PSP. Further study of this clinicopathologic relationship will lead to earlier and more accurate diagnoses as well as better treatment outcomes.
Neuroanatomy
Shades of Grey in Human White Matter
First Author: Antonia Zouridakis
Brain tissue is traditionally separated into two categories: gray matter, which contains the neurons (the cells that send and receive messages between the brain and rest of the body), and white matter, which is found deeper in the brain and made up of other non-neuronal cells and nerve fibers. It was discovered in 1867 that some neurons exist in the white matter in humans; however, their characteristics and functional role in the nervous system have not yet been extensively studied. In this project, we studied white matter neurons (WMNs) in the brains of cognitively normal people as well as people with Alzheimer’s disease (AD), a dementia characterized by progressive memory loss. We analyzed features of these WMNs, such as size and distribution, in several brain regions to characterize them in the healthy versus disease state. Additionally, we visually explored the relationship with these neurons and neighboring blood vessels, as it is believed that WMNs modulate blood flow in the brain in some way, potentially impacting cortical circuitry and signaling. Further study of the functional role of these neurons will help us understand their impact on cognition and thus potential role in disease pathogenesis.
White matter tract disruption predicts cognitive disfunction in patients with glioma
First Author: Mia Andreoli
White matter tracts are pathways that connect different regions of the brain and transmit essential information for various cognitive processes. A number of neurological diseases may disrupt these functional networks, including brain tumors. It is important to gain a better understanding of the functions of different white matter tract in patients with brain tumors in order to maximize cognitive preservation throughout treatment. Our findings demonstrate that specific white matter pathways predict memory, motor dexterity, attention, visuospatial ability, processing speed, speech fluency, and abstract reasoning. Additionally, large white matter tracts are associated with multiple functions. These findings highlight important white matter tracts to aim to preserve during surgery. They also may help physicians counsel patients regarding the anticipated cognitive impairments associated with the location of their tumor.
Community Engagement
Mesulam Center Brain Scholars Program: Empowering Diverse Next Generation of Neurologist and Neuroscientists
First Author: Paige Barenthin
The Brain Scholars Program is a new initiative of the Mesulam Center for Cognitive Neurology and Alzheimer’s Disease (Mesulam Center) committed to providing meaningful, positive scientific and professional experiences in the health sciences for students from underrepresented groups at all levels, with a focus on brain health. So far over 60 students have participated in activities offered by the Brain Scholars Program through visits to the Mesulam Center. Continuing and expanding its efforts, the Brain Scholars Program hopes to empower increasing numbers of students from underrepresented groups at all levels, from middle school to university, to pursue education and professional careers in the health sciences, including clinical and research efforts related to brain aging and dementia.
Race-Based Corrections in Cognitive Function Scores May Obscure Disparities: The Disparities in Sleep and Cognitive Outcomes (DISCO) study
First Author: Thanh- Huyen T. Vu
Older adults who self-identify as Black or Hispanic/Latino ethnicity are reported to have worse scores on cognitive function tests at a similar age as White or non-Hispanic adults. However, these differences are often hidden when scores from cognitive function include race (e.g., race-corrected). Our goal was to describe the actual differences in scores by race and ethnicity to highlight the higher burden of cognitive decline in Black and Latino older adults.
It's a Family Affair: Addressing the Needs of Black Caregivers Through a Community Based Dementia Caregiver Program
First Author: Dianne Oladejo
Our research aims to address the unique challenges faced by Black families caring for loved ones with dementia. We collaborated with community-based organizations to create a culturally tailored, family-centered dementia caregiving program for Black individuals on Chicago's Far South Side. We conducted interviews with Black caregivers of family members with dementia and found that they faced high levels of stress and burden, needed education on dementia progression and cultural beliefs, and required respite and access to local resources. By understanding the experiences of Black caregivers, we hope to build capacity in routine caregiving and reduce caregiver stress, ultimately improving the lives of both caregivers and those with dementia.
The Mesulam Center Underrepresented Groups (URG) Recruitment and Retention Taskforce: connecting with, recruiting, and retaining diverse research participants through community engagement
First Author: Phyllis Timpo
The URG Recruitment and Retention Taskforce team is committed to diversifying our research cohorts through community engagement strategies. As we continue to grow our CER strategies, we will continue to develop new partnerships and strengthen our existing partnerships, develop programming and dissemination strategies to retain existing diverse participants, create culturally tailored study materials and begin to understand the feasibility of developing a participant advisory board.
Using Community-University Partnership to Increase Brain Health Awareness in Community-Dwelling Black Older Adults on the South Side of Chicago
First Author: Janie Urbanic
The South Loop Village and Northwestern Mesulam Center is a community-university partnership to build trust in communities that are traditionally underrepresented in research by meeting communities where they are to address health disparities and promote health equity in ADRD disease prevention and research. Next steps include continued program development and data collection on specific outcomes, such as participant health behaviors, brain health knowledge, social interactions, and emotional wellbeing.
Introducing the MidCog Study: a prospective, observational cohort study investigating modifiable risk factors to cognitive decline in middle-aged adults
First Author: Pauline Zheng
The world is rapidly aging, with increasing number of older adults living with Alzheimer’s disease and related dementia. Recent evidence suggests clinically meaningful declines in cognition might present as early as middle age. Studying cognitive changes in mid-life adulthood could elucidate modifiable factors to Alzheimer’s disease pathology, yet few cognitive aging studies include this age group. The purpose of the MidCog study is to begin investigations of less-studied, potentially modifiable, midlife determinants of later life cognitive outcomes. The MidCog study is actively recruiting participants who are 1) ages 35-64; 2) English-speaking, 3) a patient receiving primary care at Access Community Health Network or Northwestern Medicine internal medicine practices, and 4) without severe, uncorrectable vision, hearing, or cognitive impairments. Participants are compensated up to $125.
Health Services
Primary Care Detection of Cognitive Impairment Leveraging Health & Consumer Technologies in Underserved Communities: The MyCog Strategy
First Author: Morgan Bonham
Cognitive deficits and impairment, including Alzheimer’s disease and related dementias (ADRD), are highly prevalent among older adults - with higher rates among Black and Hispanic/Latino individuals - and have devastating consequences to families and entire communities. Responding to increasing calls for early detection of cognitive impairment in everyday clinical settings, the MyCog Trial is testing a promising, and highly scalable way to identify older adults with a possible cognitive impairment, or even dementia, in busy, resource-constrained primary care settings serving communities of color who are experiencing higher rates of undetected or delayed diagnoses of Alzheimer’s disease.
Length of stay relates to inpatient antipsychotic use in Alzheimer's type dementia at a large US-based tertiary care hospital
First Author: Joshua Cahan
Behavioral issues like agitation are a frequent problem in older adults with Alzheimer's disease when admitted to the hospital, often necessitating antipsychotic medications. Antipsychotics carry an FDA black box warning for increased risk of death in the elderly and are important to monitor as a result. Looking at 4,603 admissions of patients with Alzheimer's disease to Northwestern Memorial Hospital, we explored the relationship between the length of stay and antipsychotic use. Our study shows that the length of stay was longer in patients who received an inpatient antipsychotic, but not for patients that had a home antipsychotic prescription prior to admission. This data suggests that longer hospitalizations may increase antipsychotic use in patients with Alzheimer's disease and does not suggest that antipsychotics prolong hospital length of stay.
Lorenzo’s House, an international nonprofit empowers families living with younger-onset dementia through our holistic model.
First Author: Diana Cose
Lorenzo’s House, an international nonprofit empowers families living with younger-onset dementia through our holistic model.
Communication Bridge: A person-centered Internet-based intervention for individuals with Primary Progressive Aphasia
First Author: Eunbi Kwon
The Communication Bridge program is focused on developing interventions that maximize communication participation, quality of life, and access to care while also minimizing burden for persons with PPA and their communication partner(s). This poster describes the history and projected next steps of this research program.
Neuroscience
Primary Progressive Aphasia Research Program at the Mesulam Center for Cognitive Neurology and Alzheimer Disease
First Author: Lauren Ables-Torres
Primary progressive aphasia (PPA) is a neurodegenerative dementia syndrome characterized by a progressive loss of language function. The Mesulam Center seeks to advance PPA research through a collaborative program aimed at studying, educating, and improving treatment for individuals living with PPA and their families. Participants in the observational PPA program visit Chicago every 1-2 years to complete neuropsychological assessments that measure language, memory, and cognition, along with undergoing multiple brain imaging examinations with MRI and PET scanners. Researchers combine neuropsychological testing with neuroimaging to better understand the underlying mechanisms of language decline in the PPA brain. At the same time, participants can take part in the web-based speech therapy program Communication Bridge, support groups, or other research programs that are designed to improve access and quality of specialized care for individuals with PPA and their families.
Cognitive SuperAgers are Protected from Phosphorylated Tau Accumulation in Basal Forebrain Cholinergic Neurons
First Author: Ivan Ayala
This study provides confirmation of the resistance displayed by SuperAger brains to accumulation of proteins and axonal abnormalities. This resistance is observed in the basal forebrain cholinergic system of the brain which is involved in the cognitive processing of memory. Understanding factors that contribute to superior memory in SuperAgers will assist in devising treatments for Alzheimer’s disease in which memory decline is the primary abnormality, and to help cognitively normal elderly preserve memory capacity.
Detection of MAP2K3 Immunoreactivity in the Human Cerebral Cortex and Primary Human Microglia, and Loss in Frontotemporal Lobar Degeneration with TDP-43 Proteinopathy
First Author: Atousa Bahrami
MAP2K3 is a signaling protein that is activated by different forms of stressful stimuli and inflammatory signals in the brain and resides in a pathway linked to memory. For the first time, we were able to detect this protein in cultured human brain immune cells (microglia), stem cell derived human cortical neurons and brain samples of cognitively normal controls and participants with frontotemporal lobar degeneration (FTLD) with TDP-43 pathology. Consistent with its role in inflammation, MAP2K3 was found in high levels in microglia when compared with neurons, its levels were reduced in neurons in FTLD, but appeared to be increased in neurons. Thus, MAP2K3 can be detected in human brain cells and its relationship with cognitive abnormalities tracked.
Neural basis of word and sentence comprehension in PPA: a deficit- based neuroimaging approach.
First Author: Elena Barbieri
Primary Progressive Aphasia (PPA) is a dementia syndrome caused by neurodegenerative brain disease in which language deficits slowly progress over time initially before other cognitive and behavioral difficulties arise. The study of language disorders can inform our knowledge regarding the regions of the brain that support language in a healthy brain, a step that is crucial to better understand the mechanisms underlying language deficits in PPA and to develop treatment approaches (e.g., speech therapy, noninvasive brain stimulation) for this disease. In this study, we attempt to uncover the role that different regions of the brain play in comprehending words and sentences. This is important since some individuals can understand sentences better than single words and vice versa.
Neuropathology-specific neural pathways underlying agrammatism in PPA
First Author: Elena Barbieri
Primary Progressive Aphasia is a dementia syndrome caused by neurodegenerative brain disease. In PPA, language deficits slowly progress over time, especially in the initial stages of illness, and other cognitive changes become apparent with a few years. This study shows that two different disease proteins collect in different brain regions but yet cause the same kind of language difficulty. This fact challenges what we have learned about aphasia from studying individuals with stroke and supports the need for novel intervention techniques in PPA."
Regional Relationship between Brain Hypometabolism and Atrophy in Semantic Primary Progressive Aphasia
First Author: Jordan Behn
This study looked at the brains of individuals with semantic primary progressive aphasia (PPA-S), a subtype of PPA with a difficulty naming and understanding single words. In this study, we found a region of the brain that may play a particularly important role in these symptoms, the left anterior temporal lobe (ATL). This region is affected both by atrophy (a decrease in brain volume) and hypometabolism (a decrease in brain cell activity). We also found further regions that were only affected by one of the two abnormalities. This suggests a more complex relationship between structural and metabolic changes in PPA-S, with both contributing to its symptoms. By understanding these differences, researchers can develop more targeted therapies to help individuals with PPA-S.
Chronic Levetiracetam Treatment Alters Synaptic Protein Turnover in Alzheimer’s Mouse Model and Reduces Production of Aβ42
First Author: Olivia DeGulis
Alzheimer’s disease (AD) is defined as dementia with the presence of tau tangles and amyloid beta plaques. Toxic Aβ42 protein pieces, that are the foundation for these plaques, are produced because of sequential processing of the amyloid precursor protein (APP). These cut up protein fragment are highly likely to clump together and form the plaques, or aggregations. These proteins accumulate throughout the brain and lead to cognitive decline.
Levetiracetam (Lev) is an anti-epileptic drug. It has been prescribed for a decade for epilepsy treatment. But the mechanism of action of Lev has not yet been discovered.
We set out to investigate if Lev treatment in Alzheimer's mouse models can induce Aβ clearance to prevent the spread of these toxic peptides, or even prevent the production of them in the first place. We found a trend of lowered newly made Aβ in the Lev-treated animals, suggesting that this drug is lowering production of these toxic peptides seen in AD. Overall, Lev provides a potential mechanism for therapeutic target that could minimize AD pathology.
Functional Connectivity within Two Large-Scale Memory Systems in SuperAgers
First Author: Bram Diamond
Complaints of memory decline in late life are common but not universal. SuperAgers are adults 80-years or older with exceptional memory abilities. In fact, SuperAgers have memory performance at least as good as adults in their 50’s and 60’s. The Northwestern SuperAging Study is exploring what factors contribute to SuperAgers’ superior memory performance. The secret to SuperAgers’ memory may involve a small region of their brain called the hippocampus. The front and back of the hippocampus communicate with different parts of the brain and the back-half is more involved in remembering. We investigated if communication from the back-half of the hippocampus to other regions of the brain was stronger for SuperAgers than normal agers but did not find a significant difference. SuperAgers’ exceptional memory abilities may instead be supported by multiple regions communicating throughout the brain. This works helps inform future analyses investigating unique brain features of successful cognitive aging.
Molecular mechanisms of apathy and affective symptoms in Alzheimer’s disease
First Author: Jeffrey Dunn
Although great research effort has focused on discovering the mechanisms of memory deficits and cognitive decline in Alzheimer’s disease (AD), relatively little is known about the specific causes of the neuropsychiatric symptoms that are also experienced by millions of individuals with AD. Apathy and affective (i.e., anxiety and depression) symptoms are the two most common neuropsychiatric symptoms in AD. To improve understanding of these symptoms, we have analyzed the expression levels and unique relationships between genes in a region of the brain known as the anterior cingulate cortex. Our results indicate that apathy and affective symptoms are related to changes in different aspects of the brain’s immune response. These findings have the potential to help advance the development of more effective medications for the AD population by identifying new targets for the treatment of apathy and affective symptoms in AD.
Validation of the NIH Toolbox Odor Identification Test across Normal Cognition, Amnestic Mild Cognitive Impairment, and Dementia due to Alzheimer’s Disease
First Author: Shiloh Echevarria-Cooper
Olfactory (sense of smell) impairments are known to be common in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease dementia (ADd), and may occur earlier in the disease progression than more serious cognitive symptoms. This study evaluates scores on the NIH Toolbox Odor Identification Test across healthy controls, participants with aMCI, and participants with ADd. We found that scores on this test can reliably distinguish healthy controls from participants with aMCI or ADd. We suggest that this quick and cost-effective test may be included in annual senior wellness exams, and that (in the absence of other rhinological explanations) those with low scores should be referred for further neuropsychological testing.
Not All Tauopathies are Created Equal
First Author: Donte Garcia
Cortical Basal Degeneration (CBD) is a neurodegenerative disease that results in cognitive deficits and progressive loss of verbal communication ability and motor capabilities. In Alzheimer’s Disease (AD), the basal forebrain cholinergic neurons (BFCNs) are a primary target for tau protein inclusions which lead to cell death. To contribute to understanding CBD development, we investigated whether BFCNs in CBD are also vulnerable to tau protein induced cell death. This was done by staining and quantifying BFCNs and tau protein inclusions in human CBD postmortem brain tissue. We found that BFCNs in CBD displayed tau protein inclusions, but these protein inclusions did not seem to lead to degeneration as seen in AD. This is important as it implies a difference in underlying biology and that cholinergic based therapies used for treating AD is likely to be ineffective in treating CBD.
Using AAV-mediated overexpression of Nrf2 to prevent Alzheimer's neuropathology
First Author: Karen Gomez
A common feature of neurodegenerative diseases is oxidative stress leading to the dysfunction of neuronal cells. Oxidative stress has been observed in degenerative conditions and normal aging, leading to damaged proteins, nucleic acids, and lipids. Nrf2 (Nuclear factor erythroid 2-related factor 2) is a key regulator in redox balance and signaling, controlling the expression of many antioxidant and detoxification genes. We are interested in exploring the connection between Nrf2 expression and Alzheimer’s disease. In this study, we overexpressed Nrf2 in a mouse model of Alzheimer's disease, hoping to demonstrate neuroprotective effects.
Noradrenergic dysregulation, sleep and cognition in older adults with insomnia
First Author: Daniela Grimaldi
Insomnia disorder is prevalent among older adults with detrimental consequences on health, including increased risk of cognitive decline and Alzheimer’s disease-related dementias (ADRD). Yet, the mechanisms underlying these associations remain poorly understood. The noradrenergic (NA) system plays a fundamental role in the regulation of sleep and cognition, and its function significantly declines with aging. However, the potential mechanistic relevance of NA system’s dysregulation in insomnia and insomnia-related cognitive impairment has never been investigated, particularly in older adults. In this study, we showed novel evidence of reduced 24-h NA activity in older adults with insomnia compared to good sleeper controls of similar age, which was associated with poorer sleep quality and cognitive function. These results will help understand novel mechanisms of insomnia pathophysiology and risk for ADRD, and help the development of novel therapeutic targets for older adults with insomnia who are at higher risk for cognitive decline and ADRD.
Structural brain network degeneration associated with agitation in dementia
First Author: Lisanne Jenkins
Agitation is a behavioral syndrome involving increased motor activity, restlessness, aggressiveness and emotional distress. It is associated with negative outcomes, including reduced quality of life, caregiver distress, and mortality. Using a new method to study structural brain imaging, we found that agitation was associated with reduced integration and specialization of different brain networks important for cognition. This information could provide insights into new treatment methods for agitation.
Amyloid beta oligomers, inflammatory astrogliosis, and the therapeutic action of NU-9 in the 5xFAD model
First Author: Dan Kranz
We are working toward developing a treatment for Alzheimer's Disease (AD) that targets neurotoxic molecules that accumulate in the brains of AD patients (called amyloid beta oligomers; AβOs). The role of AβOs in AD was first proposed by our laboratory and has become well established as a key component in initiating the disease. Recently, AβOs have emerged as targets for experimental AD drugs in ongoing clinical trials. The current study of a drug recently developed at Northwestern provides great optimism for the drug's potential as a new type of Alzheimer's disease therapeutic.
Northwestern Alzheimer's Disease Research Center (NADRC) Clinical Core
First Author: Kathryn LaFroscia
The Clinical Core is a longitudinal study that collects information on research participants yearly, following their neuropsychological testing scores throughout their participation. Our data includes participants across the cognitive aging spectrum to study memory and aging. Information collected from this study is shared across different collaborators associated with the National Alzheimer Coordinating Center. Participants are also able to donate their brain for research as the culminating aspect of their dedication to Clinical Core.
Neural Mechanisms Underlying Confrontation and Generative Naming in behavioral variant Frontotemporal Dementia
First Author: Grace Lee
Behavioral frontotemporal dementia (bvFTD) is a neurological condition that presents with deficits in behavior, executive functions, and language. Individuals with bvFTD can have difficulties in naming such deficits in naming objects and fluency. The neural mechanisms for the correlation between generative naming and bvFTD are not well characterized. Our findings will help in the understanding of the connections between bvFTD and decline in grey matter volume correlated with deficits in naming.
Evaluating the Causal Association Between Genetically Proxied Psychiatric Disorders and SuperAging
First Author: Malik Nassan
We found that genetically predicted schizophrenia and bipolar disorder are associated with increased risk for neurodegeneration and less chance of cognitive resilience.
Proteome fidelity during aging
First Author: Nalini Rao
Unraveling the complex mechanisms underlying aging would have profound implications for both age-related diseases and, importantly, the quality of healthcare. We set out to investigate how protein turnover in the brain changes during aging. Taken together, our findings extend our current understanding of healthy aging and suggest that protein turnover is a dynamic process that undergoes differential fluctuations that may be caused by reduced proteasome fidelity.
The SuperAging Research Initiative: A multisite consortium focused on identifying factors promoting extraordinary cognitive aging
First Author: Emily Rogalski
The Northwestern SuperAging Research Program was designed to approach aging and Alzheimer’s disease differently. Instead of studying the negative consequences of aging and disease, the program is identifying and factors that allow for a unique aging trajectory where individuals maintain youthful memory function. In 2021 Northwestern received an award from the National Institute on Aging (NIA) and the McKnight Brain Research Foundation to expand and establish an international multi-center study, which aims to amplify efforts to isolate factors that promote highly preserved cognitive aging. The resulting SuperAging Research Initiative is now enrolling participants at five research sites across the United States and Canada.
Investigating the role of rare genetic variants in Angiotensin-1- Converting Enzyme in Alzheimer’s Disease pathogenesis
First Author: Miranda Salvo
Alzheimer’s disease (AD) is the most prevalent form of dementia. AD causes neurons in the brain to die because of a buildup of sticky protein aggregates called amyloid plaques and tau tangles. Apart from these aggregates in the brain, some people with AD have shared comorbidities – or co-existing conditions – like high blood pressure. This research focuses on studying a protein, ACE1, that controls blood pressure and how it could be involved in the progression of AD. Importantly, our work may inform on how current blood pressure medications can be an effective treatment for AD.
Alterations in Basal Ganglia Connectivity in Individuals with Primary Progressive Aphasia due to Alzheimer’s Disease and Frontotemporal Degeneration
First Author: Daniel Seog
Primary progressive aphasia (PPA) is a language disorder caused by neurodegenerative disease. There are several different underlying diseases that can cause PPA. In this study we compared the brain connectivity of patients based on which disease was causing their PPA, either corticobasal degeneration/progressive supranuclear palsy (CBD/PSP) or Alzheimer’s disease (AD). We found that both groups of people with PPA had reduced brain connections in a specific area called the basal ganglia. This region is located deep in the center of the brain and plays an important role in many of the brain’s functions including movement, thinking, and emotion. However, there was no difference between the two groups in this area, suggesting that CBD/PSP and AD may similarly affect the functionality of this important brain region.
Northwestern Alzheimer’s Disease Research Center Neuroimaging Biomarker Core
First Author: Ulises Sosa Alatorre
Imaging Biomarker Core at the Mesulam Center aims to enhance research activities on aging and dementia. Multimodal neuroimaging data are available to enhance diagnostic characterization of the participants and to enrich projects of our collaborators.
High Levels of the Dendritic Spine Protein Spinophilin in Cognitive SuperAgers
First Author: Regina Taefi
Synapses are points of contact between nerve cells that allow neural communication. The goal of this experiment was to determine whether there are differences in the levels of synaptic proteins in aged individuals with superior memory capacity, known as SuperAgers, when compared with cognitively normal elderly. It is known that synapses are lost in patients with Alzheimer's Disease. The initial results of this study suggest that SuperAgers may have higher levels of a protein found at sites of synapses than their cognitively average peers. These findings suggest that integrity of synapses is an important factor in preservation of cognitive abilities in old age.
Elevated Carotid Pulse Wave Velocity is associated with Cognitive Impairment and Cerebral Amyloid Deposition: A Phase-Contrast MRI Study
First Author: Jianing Tang
Increasing evidence suggests that vascular compliance could offer valuable insights into the pathology of Alzheimer’s disease. Recently, carotid pulse wave velocity (cPWV) between the internal carotid artery and common carotid artery has been successfully measured by a fast single-slice oblique-sagittalPC-MRI technique. In this study, we evaluated the role of cPWV in brain amyloid deposition and cognitive decline in an aged cohort. The results showed greater cPWV was associated with cognitive decline and amyloid pathology. Our findings suggest elevated cPWV may affect amyloid clearance in brain, leading to cognitive impairment. cPWV could be a potential sensitive imaging marker of AD.
Strain-Dependent Disease Progression in a Conditional Wild-Type Human TDP-43 Transgenic Mouse Model
First Author: Yekaterina Taylor
Frontotemporal dementia (FTD) is characterized by accumulation of abnormal proteins in the brain, including tar DNA binding protein (TDP-43). Here we describe a transgenic mouse model overexpressing human TDP-43 in the brain that recapitulates many of the abnormalities seen in FTD, including accumulation of TDP-43, neuronal loss, loss of neuronal connections, and behavioral abnormalities. We also demonstrate that the strain of mice used has great influence on the speed of disease progression and severity. Our findings demonstrate that the mouse line described is appropriate for mechanistic studies of FTD with TDP-43 pathology and for testing potential therapeutic targets, and suggest that attention needs to be directed to the strain of mice used in transgenic models of neurodegenerative disease.
Quantitative Proteomics Based Identification of Novel AD Therapeutic Targets
First Author: Arun Upadhyay
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder affecting more than five million people in the United States. AD progresses at a slow rate and causes a gradual decline in cognitive abilities leading to dementia. An increased resurgence in the amyloid cascade hypothesis has been observed, following the approval of Aducanumab and the promising effects shown by Lecanemab, two antibodies targeting Aβ peptides and other higher-order structures, including fibrils. Now, the focus has again shifted to reinvestigate the Aβ modifiers and amyloid partners that may affect Aβ42 aggregation and amyloid formation in AD patients’ brains. Targeting these new proteins may provide novel candidates to develop future AD therapeutics.
Alterations in Auditory and Language Network Connectivity in Primary Progressive Aphasia
First Author: Kate Vidano
This study looked at how the brain connects the parts that process sound and the parts that process language in people with two different types of primary progressive aphasia (PPA), a neurological disorder that affects language. We used brain scans to compare the connections in people with semantic PPA (PPA-S) and logopenic PPA (PPA-L). We found that PPA-L had weaker connections between some parts of the brain responsible for storing language information, which could explain why people with this type have trouble repeating words and make word substitutions while speaking. PPA-S had weaker connections between parts of the brain responsible for language processing, which could explain why people with this type have trouble finding and understanding words. By understanding these differences, researchers can develop more targeted therapies to help individuals based on which type of PPA they have.
Proteomic Characterization of a Novel Antibody for FTLD-TDP Pathologic TDP-43
First Author: Anika Wilen
Frontotemporal lobar dementia (FTLD) is the third most prevalent degenerative cause of dementia. One of its many subtypes, FTLD-TDP, is characterized by brain aggregates positive for transactive response DNA binding protein with Mr 43 kD (TDP-43). A novel antibody (MAb#9) was produced that targets TDP-43 and seems to be strongly reactive to pathological TDP-43 aggregates with minimal reactivity to normal TDP-43. The aim of this study is to validate MAb#9 using the blood, plasma, and cerebrospinal fluid (CSF) of patients with various forms of dementia including Alzheimer’s Disease and FTLD-TDP. As it stands, it is very difficult, invasive, and time-consuming to diagnose different dementias. Potentially, MAb#9 can be used to create a test to differentiate between FTLD-TDP and other dementias to revolutionize the diagnosis and treatment process. Patients would be diagnosed faster and in a more cost-effective way.
Pharmacology
The VIVA-MIND Study
First Author: Kailey Basham
The VIVA-MIND Study is a Phase II multi-center, placebo-controlled study that will evaluate whether an oral investigational drug is safe and effective at slowing or halting Alzheimer’s Disease (AD) progression. The investigational drug is aimed to reduce an abnormal form of a protein called "amyloid", which accumulates in the brains of people with AD.
The AHEAD Study
First Author: Loreece Haddad
An abnormal form of a protein called “amyloid” builds up in the brains of people with Alzheimer’s disease (AD), but not every person with amyloid build up will develop memory problems or AD dementia. The AHEAD 3-45 Study is a Phase III multi-center, placebo-controlled study that will evaluate whether an investigational drug reduces the risk of developing AD dementia.
Physiology
Study design and concepts for heart-brain MRI evaluation in aging and hypertension
First Author: Kelly Jarvis
Studies have linked cardiovascular risk factors, such as hypertension and physical inactivity, with dementia. However, the underlying details of how this can occur remain unclear. Imaging tools can be very helpful for studying these relationships. In this study we plan to use an advanced imaging technique called 4D flow MRI to measure blood flow in the chest and head. We have designed a 1-hour imaging session for capturing 4D flow MRI along with neuroimaging measures of brain structure. Our goal is to gain a better understanding of relationships between the heart and brain in individuals with hypertension and healthy cognitive aging.
Recruitment Sciences
Using Community Engaged Research Strategies to Promote Sense of Community in Diverse SuperAging Research Initiative Participants
First Author: Phyllis Timpo
Studies demonstrate that community engaged research (CER) supports minority recruitment into Alzheimer’s Disease research. In contrast, few studies have explored whether CER can engage diverse ‘SuperAgers,’ adults age 80+ with superior episodic memory. The SuperAging Research Initiative, a multi-site research program across the U.S. and Canada, seeks to recruit 40% Black adults over 80 years of age, using principles of recruitment and retention science and CER. The unique cultural historical background and socio-political conditions of Black Americans in this age cohort pose unique challenges and present an opportunity to implement novel approaches to recruitment and retention. Here we share the Northwestern SuperAging Research Initiative’s CER efforts, which includes fostering community. Sense of community has been identified as an important factor in the lives black Americans (Coffman and Belue, 2009). Psychological Sense of Community is a feeling that members have belonging, matter to one another and to the group, and share faith that needs will be met through their commitment (McMillan, 1976). The four central tenets of psychological sense of community are: membership, influence, integration and fulfillment of needs and shared emotional connections.
Social & Behavioral Sciences
Psychosocial Pathway Seminar Series Training
First Author: Lauren Dowden
The Psychosocial Pathway [PsP] identifies psychosocial concerns that may cause barriers to research participation or issues of safety and well-being for research participants and their study partners. To enhance training for research participant-facing staff [RPFS] with identifying these concerns, a Psychosocial Pathway Seminar Series Training [PPPSST] was designed offering didactic presentations, applied improvisation skill building and panel discussions to develop competency with the PsP referral process, communication strategies for navigating challenging conversations and situations, cultural humility with diverse populations and discussing brain donation. PPSST appears to be a feasible training model for RPFS to address research participant safety, well-being and retention concerns.
Reducing Fear and avoidance of memory loss (REFRAME) study: A pilot randomized control trial to reduce fear and avoidance and improve well- being in older adults
First Author: Francesca Farina
Our findings suggest that psychological interventions can alleviate fear of Alzheimer's disease and other dementias in vulnerable older adults, and that the therapeutic benefits may extend to broader health-related outcomes, like depression, social engagement, and well-being. Addressing dementia-related fears has important implications for healthy aging, as individuals may be more likely to engage in activities that are protective against dementia, but were previously avoided because of fear.
A randomized controlled trial of a positive affect skills intervention to reduce stress in family caregivers of individuals with Alzheimer’s disease: Protocol and design for the LEAF 2.0 study
First Author: Veronika Grote
LEAF 2.0 (Life Enhancing Activities for Family Caregivers) is a research study to examine the effects of a positive emotion regulation intervention for family caregivers. LEAF 2.0 is testing whether delivery of the intervention by (1) by trained facilitators via Zoom or (2) via an online, self-guided version can improve psychological well being in caregivers.
Construct Validity Indicators for the Tablet Computer-Based NIH Toolbox Cognition Battery (NIHTB-CB) from the ARMADA STUDY
First Author: Emily Ho
The purpose of this investigation is to determine the extent to which different sets of measures can potentially be harmonized, or meaningfully compared, so that previously unconnected datasets can be used to further accelerate scientific discovery. The Advancing Reliable Measurement in Alzheimer’s Disease and Cognitive Aging (ARMADA) study’s primary goal is to describe the extent of many health outcomes in a cognitively impaired population, compared to those that do not present such symptoms. This study examines how well one set of standardized measures, the NIH Toolbox Assessment of Neurological and Behavioral Function Cognition Battery, compares with tests from a national neuropsychological battery administered across many research centers focusing on Alzheimer's Disease participants. We find that measures of cognitive flexibility and episodic memory exhibited the highest correlations, followed by measures of general knowledge. This helps support construct validity, or the ability of similar measures to assess similar underlying relevant themes.
Differences in Intra-individual Variability on the NIH Toolbox in Older Adults with Normal Cognition, Mild Cognitive Impairment, and Dementia of the Alzheimer Type
First Author: Tatiana Karpouzian-Rogers
Variability in how quickly an individual responds to different cognitive tasks can differentiate older adults with normal cognition, mild cognitive impairment (MCI), or dementia of the Alzheimer type (DAT). The purpose of this study was to look in intra-individual variability (IIV), or how variable someone responds across trials on the same test, on the NIH Toolbox. The NIH Toolbox is a computerized suite of tests measuring cognition, and has been recently validated in older adults across the cognitive aging spectrum. Our study showed large differences in IIV when comparing individuals with DAT to individuals with NC or MCI. There were smaller, but meaningful, differences between the NC and MCI groups. These results indicate that IIV is an important cognitive measure, and future plans include investigating which measure of IIV is the most useful, and how it may change over time.
Health-related quality of life in patients with Primary Progressive Aphasia
First Author: Eunbi Kwon
Primary progressive aphasia (PPA) is a type of neurodegenerative dementia characterized by a gradual loss of language function. The worsening of language impairment over time often negatively impacts the quality of life in individuals with PPA. Yet, current research evaluating quality of life in a large sample of PPA patients is lacking. The Health Utilities Index (HUI) is a reliable and valid rating scale used to measure health-related quality of life (HRQoL) by providing the overall utility scores as well as single utility scores in each health domain such as vision, hearing, speech, etc. This study aims to provide a summary of health-related quality of life in a large sample of PPA patients and examine whether health-related quality of life is associated with disease severity.
Longitudinal Performance on the NIH Toolbox Cognition Module in a Cognitive Aging Sample
First Author: Molly Mather
Early detection of cognitive changes that occur due to Alzheimer’s disease (AD) is crucial, as this allows for timely implementation of behavioral interventions and disease-modifying treatments. Historically, diagnosis of early AD dementia has required many hours of cognitive testing, which is time- and resource-intensive and not readily accessible for many people. Efficient tests of memory and other thinking abilities are needed to be able to catch AD dementia at the earliest stages across diverse populations. One example is the NIH Toolbox Cognition, which includes a number of different tests of thinking abilities and is easily administered on an iPad. The current study focuses on how scores on the NIH Toolbox Cognition change over time in persons without cognitive difficulties and those with early AD dementia. Ultimately, this may allow for a better understanding of how NIH Toolbox Cognition can pick up on subtle signs of cognitive decline in older adults.
Boosting Positive Emotion in Caregivers: Moderators of a Positive Psychological Intervention
First Author: Taylor Maynard
There are numerous negative health effects associated with dementia caregiving, including increased stress and depression. Interventions aiming to increase positive emotion could improve health and psychological outcomes for dementia caregivers. The Life Enhancing Activities for Family Caregivers (LEAF) intervention is an online-facilitated, 6-week, evidence-based intervention designed to increase positive emotion in caregivers. We examined data collected from the LEAF trial to identify which caregiver characteristics (e.g., age, gender, caregivers’ relationship to the person with dementia, and length of time caregiving) affected LEAF outcomes over time. Our results suggest that gender and length of time providing care play an important role in the extent to which a caregiver benefits from a positive emotion skills intervention. This study will assist in identifying caregivers for whom positive skills interventions work best, suggest ways that the intervention should be tailored to match caregiver characteristics, and target outcomes most impacted according to caregivers’ individual differences.
PPA Tele-Savvy: Results of an Online Pilot Intervention with Caregivers of Persons with Primary Progressive Aphasia
First Author: Darby Morhardt
Primary Progressive Aphasia (PPA) results from a neurodegenerative disease such as frontotemporal lobar degeneration or Alzheimer’s disease and is characterized by a progressive loss of specific language functions eventually progressing to widespread cognitive decline consistent with generalized dementia. Most interventions available to dementia caregivers do not match PPA caregiving families' needs for tailored psychosocial support. This pilot study is an adaptation of Tele-Savvy, an evidence-based online psychoeducation caregiver program. Goals: (1) address communication and other cognitive and behavioral challenges facing informal caregivers of those living with PPA throughout disease progression, and (2) help caregivers achieve competence in their role. Nine spousal caregivers were recruited to a pilot mixed methods study, which included seven 90-minute weekly videoconference sessions, mindfulness exercises and homework assignments. Participants provided feedback throughout the intervention. Pre-post effects were assessed on PPA knowledge, mood, caregiver burden, perceived stress, competence, quality of life and dyadic relationship. A focus group was held 4 weeks post-intervention. Pre-post results revealed a post-intervention trend toward decreased depression and reported relationship strain. Thematic analysis of recorded videos and transcribed weekly sessions, in addition to an evaluation focus group revealed four themes: a) Increasing knowledge of PPA; b) Learning communication and connection strategies; c) Initiating care planning; d) Integrating intellectual and emotional aspects of PPA caregiving. Participants were provided findings for their feedback. This study demonstrated the feasibility of offering an adaptation of the Tele-Savvy intervention for caregivers of persons with PPA. An informed second pilot study will be held in Spring 2023.
Managing Medications across the Alzheimer’s disease spectrum from a Patient-Caregiver Perspective
First Author: Rachel O'Conor
Many individuals with Alzheimer’s disease and related dementias (ADRD) are managing other health conditions and multiple medications. Taking medications is a critical component of health management but can be difficult with multi-drug regimens. We talked with people living with ADRD and their care partners to better understand how individuals were managing their medications. We found that individuals with early stage ADRD prefer to maintain independence in managing their medications, while those with later stage ADRD delegate responsibilities to care partners. Care partners became more involved with medications after observing individuals were having greater difficulty with medicines.
The Alzheimer’s Drug, Lecanemab: Patient and Family’s Understanding, Perceptions and Experience with Drug Consultation
First Author: Kate O'Neil
Lecanemab is a treatment for Alzheimer’s Disease that was recently granted accelerated approval from the FDA. Through clinical trials, this treatment was reported to show a 27% reduction in decline from Alzheimer’s Disease while also being associated with some serious side effects. The primary aim of this study is to hear directly from patients and families how interested they are in this treatment, what their concerns are and measure their understanding of the risks and benefits.
Longitudinal Performance on Three Words Three Shapes in Primary Progressive Aphasia
First Author: Janelli Rodriguez
Primary progressive aphasia (PPA) is a dementia syndrome caused by neurodegenerative brain disease. In PPA, difficulties in language abilities (speaking, understanding, reading, writing) are the earliest signs of illness because the disease starts in the language parts of the brain. Memory, or the ability to recall recent events and other information, is spared early in early PPA; however, as the disease worsens, it is hard to test memory not only because memory declines as the brain disease spreads to memory centers but also because, as language worsens, it is hard to communicate what one remembers. 3W3S is a test that allows us to show the true state of memory ability in individuals with PPA and to measure that state over time.
Teleconference Group Singing Programs for Well-being of Healthy Older Adults and Persons with Neurocognitive Disorders During the COVID-19 Pandemic
First Author: Rhiana Schafer
This research looks at different types of online singing programs during the COVID-19 pandemic, and how programs like these may improve the well-being of older adults. One type of program was a virtual choir, where they learned and performed new songs, and the other was a sing-along to familiar songs. Groups were split into cognitively healthy and cognitively impaired older adults. People who participated in the choir reported via online survey that it helped to improve their well-being. The survey asked specifically about anxiety, social connections, and physical well-being, and also gave space to discuss "other" areas of well-being (emotional, social, and intellectual well-being were mentioned the most. This research is important because it shows that these programs can improve well-being, and can be administered effectively online, providing stability and connection amidst a time of disruption and isolation.
Let’s talk: Preliminary results of a conversation-based hearing aid trial for adults with cognitive impairment
First Author: Pamela Souza
When adults with mild cognitive impairment or dementia also have age-related hearing loss, the combined demands of hearing and cognition may make communication very difficult. Hearing aids can be helpful but are often not used, due in part to questions about how much benefit they provide when memory or thinking skills are affected. In this clinical trial, we measure benefit of hearing aids for adults with combined hearing loss and cognitive impairment. The study includes tests of how well participants and those they communicate with often (such as spouse or caregiver) can converse without hearing aids versus with hearing aids, and with different types of hearing aid sound processing. Our data suggest that hearing aid benefit depends on the listener’s hearing and cognitive abilities and on the way the hearing aid processes sound.
Combined Music Enrichment and Verbal Stimulation for Individuals with Neurocognitive Disorders: Preliminary Feasibility Results
First Author: Clara Takarabe
The social world of persons with neurocognitive disorder (dementia) and their care partners contracts as their condition progresses. However, the need for social and intellectual stimulation and interaction persists. Creating safe environments and social interventions which respect the cognitive capacities of the person with neurocognitive disorder are a means by which to support the social, emotional, and intellectual lives of the person with neurocognitive disorder and their care partners. In this study, we show the feasibility of clinically-informed social-musical programs for persons with neurocognitive disorder and their care partners.
Developing a Method for Memory Improvement Overnight in the Home
First Author: Erika Yamazaki
The goal of this new line of research is to improve quality-of-life in individuals in the early stages of a neurological disorder of memory. We are developing an innovative and easy-to-use methodology for this purpose. Based on our prior research, we are hypothesizing that this method, when used overnight repeatedly, can boost recall abilities for a small set of important memories. This memory facilitation will be achieved using scalable technology by softly presenting sounds during sleep in a way that avoids any sleep disruption. The sounds we use are designed to focus on specific information that is difficult to consistently recollect in each person’s daily life.
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