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An Ewas Of Dementia Biomarkers And Their Associations With Age, African Ancestry, And Ptsd, Mark W. Miller, Erika J. Wolf, Xiang Zhao, Mark W. Logue, Sage E. Hawn

Psychology Faculty Publications

Background

Large-scale cohort and epidemiological studies suggest that PTSD confers risk for dementia in later life but the biological mechanisms underlying this association remain unknown. This study examined this question by assessing the influences of PTSD, APOE ε4 genotypes, DNA methylation, and other variables on the age- and dementia-associated biomarkers Aβ40, Aβ42, GFAP, NfL, and pTau-181 measured in plasma. Our primary hypothesis was that PTSD would be associated with elevated levels of these markers.

Methods

Analyses were based on data from a PTSD-enriched cohort of 849 individuals. We began by performing factor analyses of the biomarkers, the results of which …

Basal Forebrain Volume Reliably Predicts The Cortical Spread Of Alzheimer's Degeneration, Sara Fernández-Cabello, Martin Kronbichler, Koene R.A. Van Dijk, James A. Goodman, R. Nathan Spreng, Taylor W. Schmitz

Brain and Mind Institute Researchers' Publications

© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. Alzheimer's disease neurodegeneration is thought to spread across anatomically and functionally connected brain regions. However, the precise sequence of spread remains ambiguous. The prevailing model used to guide in vivo human neuroimaging and non-human animal research assumes that Alzheimer's degeneration starts in the entorhinal cortices, before spreading to the temporoparietal cortex. Challenging this model, we previously provided evidence that in vivo markers of neurodegeneration within the nucleus basalis of Meynert (NbM), a subregion of the basal forebrain heavily populated by cortically projecting cholinergic neurons, …

Longitudinal Alzheimer's Degeneration Reflects The Spatial Topography Of Cholinergic Basal Forebrain Projections, Taylor W. Schmitz, Marieke Mur, Meghmik Aghourian, Marc Andre Bedard, R. Nathan Spreng

Brain and Mind Institute Researchers' Publications

© 2018 The Author(s) The cholinergic neurons of the basal forebrain (BF) provide virtually all of the brain's cortical and amygdalar cholinergic input. They are particularly vulnerable to neuropathology in early Alzheimer's disease (AD) and may trigger the emergence of neuropathology in their cortico-amygdalar projection system through cholinergic denervation and trans-synaptic spreading of misfolded proteins. We examined whether longitudinal degeneration within the BF can explain longitudinal cortico-amygdalar degeneration in older human adults with abnormal cerebrospinal fluid biomarkers of AD neuropathology. We focused on two BF subregions, which are known to innervate cortico-amygdalar regions via two distinct macroscopic cholinergic projections. To …

Alzheimer's Disease Treatment Interventions And The Soul: Moral And Ethical Considerations, Bruce Vermeer

Faculty Work Comprehensive List

No abstract provided.

Five-Year Longitudinal Brain Volume Change In Healthy Elders At Genetic Risk For Alzheimer's Disease, Katherine Reiter, Kristy A. Nielson, Sally Durgerian, John L. Woodard, J. Carson Smith, Michael Seidenberg, Dana A. Kelly, Stephen M. Rao

Psychology Faculty Research and Publications

No abstract provided.

Diffusion Tensor Imaging Predictors Of Episodic Memory Decline In Healthy Elders At Genetic Risk For Alzheimer’S Disease, Melissa A. Lancaster, Michael Seidenberg, J. Carson Smith, Kristy A. Nielson, John L. Woodard, Sally Durgerian, Stephen M. Rao

Psychology Faculty Research and Publications

Objectives: White matter (WM) integrity within the mesial temporal lobe (MTL) is important for episodic memory (EM) functioning. The current study investigated the ability of diffusion tensor imaging (DTI) in MTL WM tracts to predict 3-year changes in EM performance in healthy elders at disproportionately higher genetic risk for Alzheimer’s disease (AD). Methods: Fifty-one cognitively intact elders (52% with family history (FH) of dementia and 33% possessing an Apolipoprotein E ε4 allelle) were administered the Rey Auditory Verbal Learning Test (RAVLT) at study entry and at 3-year follow-up. DTI scanning, conducted at study entry, examined fractional anisotropy and mean, radial …

Interactive Effects Of Physical Activity And Apoe-Ε4 On White Matter Tract Diffusivity In Healthy Elders, J. Carson Smith, Melissa A. Lancaster, Kristy A. Nielson, John L. Woodard, Michael Seidenberg, Sally Durgerian, Ken Sakaie, Stephen M. Rao

Psychology Faculty Research and Publications

Older adult apolipoprotein-E epsilon 4 (APOE-ε4) allele carriers vary considerably in the expression of clinical symptoms of Alzheimer's disease (AD), suggesting that lifestyle or other factors may offer protection from AD-related neurodegeneration. We recently reported that physically active APOE-ε4 allele carriers exhibit a stable cognitive trajectory and protection from hippocampal atrophy over 18 months compared to sedentary ε4 allele carriers. The aim of this study was to examine the interactions between genetic risk for AD and physical activity (PA) on white matter (WM) tract integrity, using diffusion tensor imaging (DTI) MRI, in this cohort of healthy older adults (ages …

Exercise Training And Functional Connectivity Changes In Mild Cognitive Impairment And Healthy Elders, Theresa J. Chirles, Katherine Reiter, Lauren R. Weiss, Alfonso J. Alfini, Kristy A. Nielson, J. Smith Carson

Psychology Faculty Research and Publications

Background: Effective interventions are needed to improve brain function in mild cognitive impairment (MCI), an early stage of Alzheimer’s disease (AD). The posterior cingulate cortex (PCC)/precuneus is a hub of the default mode network (DMN) and is preferentially vulnerable to disruption of functional connectivity in MCI and AD. Objective: We investigated whether 12 weeks of aerobic exercise could enhance functional connectivity of the PCC/precuneus in MCI and healthy elders. Methods: Sixteen MCI and 16 healthy elders (age range = 60–88) engaged in a supervised 12-week walking exercise intervention. Functional MRI was acquired at rest; the PCC/precuneus was used as a …

Improved Cardiorespiratory Fitness Is Associated With Increased Cortical Thickness In Mild Cognitive Impairment, Katherine Reiter, Kristy A. Nielson, Theresa J. Smith, Lauren R. Weiss, Alfonso J. Alfini, J. C. Smith

Psychology Faculty Research and Publications

Cortical atrophy is a biomarker of Alzheimer’s disease (AD) that correlates with clinical symptoms. This study examined changes in cortical thickness from before to after an exercise intervention in mild cognitive impairment (MCI) and healthy elders. Thirty physically inactive older adults (14 MCI, 16 healthy controls) underwent MRI before and after participating in a 12-week moderate intensity walking intervention. Participants were between the ages of 61 and 88. Change in cardiorespiratory fitness was assessed using residualized scores of the peak rate of oxygen consumption (V̇O_2peak) from pre- to post-intervention. Structural magnetic resonance images were processed using FreeSurfer v5.1.0. …

Genetic Risk For Alzheimer's Disease Alters The Five-Year Trajectory Of Semantic Memory Activation In Cognitively Intact Elders, Stephen M. Rao, Aaron Bonner-Jackson, Kristy A. Nielson, Michael Seidenberg, J. Carson Smith, John L. Woodard, Sally Durgerian

Psychology Faculty Research and Publications

Healthy aging is associated with cognitive declines typically accompanied by increased task-related brain activity in comparison to younger counterparts. The Scaffolding Theory of Aging and Cognition (STAC) (Park and Reuter-Lorenz, 2009; Reuter-Lorenz and Park, 2014) posits that compensatory brain processes are responsible for maintaining normal cognitive performance in older adults, despite accumulation of aging-related neural damage. Cross-sectional studies indicate that cognitively intact elders at genetic risk for Alzheimer's disease (AD) demonstrate patterns of increased brain activity compared to low risk elders, suggesting that compensation represents an early response to AD-associated pathology. Whether this compensatory response persists or declines with the …

Modulatory Effects Of Gaba(B) Receptor Facilitation In A Model Of Chronic Inflammation, Michael A. Langhardt, Jefferson Kinney

McNair Poster Presentations

Inflammation within the brain (neuroinflammation) has been associated with a number of neurodegenerative diseases, including Alzheimerʼs disease (AD) (Solito et al., 2012). Within the brain, inflammation is defined broadly as prolonged activation of the brainʼs immune cells, known as glial cells. Excessive activation of glial cells within the brains of AD patients is a hallmark of the disease, however the mechanism by which this contributes to disease pathology is relatively unclear (Jo et al., 2014). Recently, studies have shown that glial cells, known as astrocytes, are able to synthesize and release the inhibitory neurotransmitter GABA (Charles et al., 2003). Further, …

Increased Cnv-Region Deletions In Mild Cognitive Impairment (Mci) And Alzheimer's Disease (Ad) Subjects In The Adni Sample, Guia Guffanti, Federica Torri, Jerod Rasmussen, Andrew P. Clark, Anita Lakatos, Jessica Turner, James H. Fallon, Andew Saykin, Michael Weiner, Marquis P. Vawter, James A. Knowles, Steven G. Potkin, Fabio Macciardi

Psychology Faculty Publications

We investigated the genome-wide distribution of CNVs in the Alzheimer's disease (AD) Neuroimaging Initia- tive (ADNI) sample (146 with AD, 313 with Mild Cognitive Impairment (MCI), and 181 controls). Comparison of single CNVs between cases (MCI and AD) and controls shows overrepresentation of large hetero- zygous deletions in cases (p-value b 0.0001). The analysis of CNV-Regions identifies 44 copy number variable loci of heterozygous deletions, with more CNV-Regions among affected than controls (p = 0.005). Seven of the 44 CNV-Regions are nominally significant for association with cognitive impairment. We validated and con- firmed our main findings with genome re-sequencing of …

Untangling Cultural Differences In Behavioral, Physiological, And Psychological Symptoms Of Dementia And Alzheimer’S Disease, John S. Avant

Calvert Undergraduate Research Awards

According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR; 4^th ed. Revised; American Psychiatric Association) and (BPSD) there are many behavioral, physiological, and psychological issues that have been correlated with the progression of the Alzheimer’s disease and other dementias. Examples of these issues include; emotional regulation problems, variations in eating behavior, and an advancing decline in memory. Though certain symptoms of the disease seem to be widely universal, current literature shows that a number of disparities do exist. There are several differences between and within populations suffering from Alzheimer’s disease and dementia that are influenced by various …

Semantic Memory Functional Mri And Cognitive Function After Exercise Intervention In Mild Cognitive Impairment, J Carson Smith, Kristy A. Nielson, Piero Antuono, Jeri-Annette Lyons, Ryan J. Hanson, Alissa Butts, Nathan Hantke, Matthew D. Verber

Psychology Faculty Research and Publications

Mild cognitive impairment (MCI) is associated with early memory loss, Alzheimer's disease (AD) neuropathology, inefficient or ineffective neural processing, and increased risk for AD. Unfortunately, treatments aimed at improving clinical symptoms or markers of brain function generally have been of limited value. Physical exercise is often recommended for people diagnosed with MCI, primarily because of its widely reported cognitive benefits in healthy older adults. However, it is unknown if exercise actually benefits brain function during memory retrieval in MCI. Here, we examined the effects of exercise training on semantic memory activation during functional magnetic resonance imaging (fMRI). Seventeen MCI participants …

Galantamine-Induced Tremulous Jaw Movements In Rats: Reversal With Adenosine A2a Antagonists, Chelsea Elizabeth Leser

Honors Scholar Theses

Alzheimer's disease is the most common neurdegenerative disorder, affecting millions of people worldwide. The underlying etiology of Alzheimer's disease, however, is such that treatment is difficult.

Researchers have linked a decrease in the transmission of the neurotransmitter acetylcholine to the cognitive deficits seen in Alzheimer's disease. Recent drug therapies have focused on using drugs that block the action of the enzyme, acetylcholinesterase, that breaks down acetylcholine. However, these drugs, known as acetylcholinesterase inhibitors, have been found to produce side effects that have the same characteristics as Parkinson's disease, the second most common neurodegenerative disorder. In this study, the acetylcholinesterase inhibitor, …

Structural Mri Discriminates Individuals With Mild Cognitive Impairment From Age-Matched Controls: A Combined Neuropsychological And Voxel Based Morphometry Study, Mehul A. Trivedi, Allison K. Wichmann, Britta M. Torgerson, Michael A. Ward, Taylor W. Schmitz, Michele L. Ries, Rebecca L. Koscik, Sanjay Asthana, Sterling C. Johnson

Brain and Mind Institute Researchers' Publications

Background: Several previous studies have reported that amnestic mild cognitive impairment (aMCI), a significant risk factor for Alzheimer's disease (AD), is associated with greater atrophy in the medial temporal lobe (MTL) and posterior cingulate gyrus (PCG). Method: In the present study, we examined the cross-sectional accuracy (i.e., the sensitivity and specificity) of voxel-based morphometry (VBM) in discriminating individuals with MCI (n = 15) from healthy age-matched controls (n = 15). In addition, we also sought to determine whether baseline GM volume predicted aMCI patients that converted to AD from those that did not approximately 2 years after the baseline visit. …

Pet And P300 Relationships In Early Alzheimer's Disease, James T. Marsh, Glena Andrews, Warren S. Brown, Walter Riege, Robert Strandburg, Deborah Dorsey, Adrianne Maltese, David Kuhl

Faculty Publications - Doctor of Psychology (PsyD) Program

The P300 (P3) wave of the auditory brain event-related potential was investigated in patients with probable Alzheimer's disease to determine whether P300 latency discriminated these patients from controls and whether prolonged P300 latency correlated with rates of brain glucose metabolism as measured by Positron Emission Tomography. P300 latency was prolonged by more than 1.5 standard deviations from age expectancy in 14 of 18 patients, but none of 17 controls. In these subjects P300 latency was shown to be inversely correlated with relative metabolic rates of parietal and, to a lesser extent, temporal and frontal association areas, but not with subcortical …