Medicine and Health Sciences Commons^™

Cholinergic Enhancement Of Brain Activation In Mild Cognitive Impairment During Episodic Memory Encoding, Shannon L. Risacher, Yang Wang, Heather A. Wishart, Laura A. Rabin, Laura A. Flashman, Brenna C. Mcdonald, John D. West, Robert B. Santulli, Andrew J. Saykin

Publications and Research

Objective: To determine the physiological impact of treatment with donepezil (Aricept) on neural circuitry supporting episodic memory encoding in patients with amnestic mild cognitive impairment (MCI) using functional magnetic resonance imaging (fMRI).

Methods: Eighteen patients with MCI and 20 age-matched healthy controls (HC) were scanned twice while performing an event-related verbal episodic encoding task. MCI participants were scanned before treatment and after approximately 3 months on donepezil; HCwere untreated but rescanned at the same interval.Voxel-level analyses assessed treatment effects on activation profiles in MCI patients relative to retest changes in non-treated HC. Changes in task-related connectivity in medial temporal circuitry …

Circulating Micrornas In Alzheimer's Disease: The Search For Novel Biomarkers, Véronique Dorval, Peter T. Nelson, Sébastien S. Hébert

Sanders-Brown Center on Aging Faculty Publications

Alzheimer's disease (AD) is the most common neurodegenerative disease in the elderly. While advancements have been made in understanding the genetic and molecular basis of AD, the clinical diagnosis of AD remains difficult, and post-mortem confirmation is often required. Furthermore, the onset of neurodegeneration precedes clinical symptoms by approximately a decade. Consequently, there is a crucial need for an early and accurate diagnosis of AD, which can potentially lead to strategies that can slow down or stop the progression of neurodegeneration and dementia. Recent advances in the non-coding RNA field have shown that microRNAs (miRNAs) can function as powerful biomarkers …

Amyloid-Β Probes: Review Of Structure-Activity And Brain-Kinetics Relationships, Todd J. Eckroat, Abdelrahman S. Mayhoub, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

The number of people suffering from Alzheimer's disease (AD) is expected to increase dramatically in the coming years, placing a huge burden on society. Current treatments for AD leave much to be desired, and numerous research efforts around the globe are focused on developing improved therapeutics. In addition, current diagnostic tools for AD rely largely on subjective cognitive assessment rather than on identification of pathophysiological changes associated with disease onset and progression. These facts have led to numerous efforts to develop chemical probes to detect pathophysiological hallmarks of AD, such as amyloid-β plaques, for diagnosis and monitoring of therapeutic efficacy. …

Memantine Protects Cholinergic And Glutamatergic Septal Neurons From Aβ1-40-Induced Toxicity, Luis V. Colom, María Teresa Castañeda Licón, D. Aleman, Ahmed Touhami

Health & Biomedical Sciences Faculty Publications and Presentations

The medial septal region (medial septum and diagonal band of Broca, MS/DB) controls hippocampal excitability and synaptic plasticity. MS/DB cholinergic neurons degenerate early in Alzheimer’s disease (AD). The presence of MS/DB glutamatergic neurons that project to the hippocampus and are vulnerable to Aβ suggests that excitotoxicity plays a role in AD septal degeneration and hippocampal dysfunction. To demonstrate the presence of excitotoxicity in Aβinduced septal damage, we compared rats injected with Aβ1–40 into the MS/DB with animals treated with memantine prior, during and after Aβ1–40 injections. Controls were injected with phosphate buffered saline (PBS). MS/DB cholinergic, glutamatergic and GABAergic neurons …

Aβ Alters The Dna Methylation Status Of Cell-Fate Genes In An Alzheimer’S Disease Model, Gary D. Isaacs, Noor Taher, Courtney Mckenzie, Rebecca Garrett, Matthew Baker, Nena Fox

Faculty Publications and Presentations

Alzheimer’s disease (AD) is characterized by neurofibrillary tangles and extracellular amyloid-β plaques (Aβ). Despite ongoing research, some ambiguity remains surrounding the role of Aβ in the pathogenesis of this neurodegenerative disease. While several studies have focused on the mutations associated with AD, our understanding of the epigenetic contributions to the disease remains less clear. To that end, we determined the changes in DNA methylation in differentiated human neurons with and without Aβ treatment. We isolated the DNA from neurons treated with Aβ or vehicle, and digested the two samples with either a methylation-sensitive (HpaII) or a methylation-insensitive (MspI) restriction endonuclease. …

A Blood-Based Predictor For Neocortical Aβ Burden In Alzheimer's Disease: Results From The Aibl Study, Samantha Burnham, Noel Faux, William Wilson, Simon Laws, David Ames, Justin Bedo, Ashley Bush, James Doecke, Kathryn Ellis, Richard Head, Gareth Jones, Harri Kiiveri, Ralph N. Martins, Alan Rembach, Christopher Rowe, Olivier Salvado, S Lance Macaulay, Colin Masters, Victor Villemagne

Research outputs 2013

Dementia is a global epidemic with Alzheimer’s disease (AD) being the leading cause. Early identification of patients at risk of developing AD is now becoming an international priority. Neocortical Aβ (extracellular β-amyloid) burden (NAB), as assessed by positron emission tomography (PET), represents one such marker for early identification. These scans are expensive and are not widely available, thus, there is a need for cheaper and more widely accessible alternatives. Addressing this need, a blood biomarker-based signature having efficacy for the prediction of NAB and which can be easily adapted for population screening is described. Blood data (176 analytes measured in …

Dietary Patterns Associated With Alzheimer's Disease And Related Chronic Disease Risk: A Review, Samantha L. Gardener, Stephanie R. Rainey-Smith, Jennifer Keogh, Suzanne Mathieson, Ralph N. Martins

Research outputs 2013

The world’s population is growing older due to improved healthcare and nutrition. As a result, Alzheimer’s disease (AD) prevalence is rapidly increasing. The focus of the current research climate is shifting from understanding AD pathology and diagnosis to primary prevention and intervention strategies. Diet represents one potential intervention strategy accessible to all. Accumulating evidence suggests diet plays a major role in risk and development of AD and AD-related chronic diseases of the periphery like cardiovascular disease (CVD) and diabetes. This paper reviews studies that have explored the relationship between “a priori” dietary patterns, AD and AD-related chronic disease risk. The …

Comparing Clinical Profiles In Alzheimer's Disease And Parkinson's Disease Dementia, Martin R. Farlow, Frederick A. Schmitt, Dag Aarsland, George T. Grossberg, Monique Somogyi, Xiangyi Meng

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Greater understanding of differences in baseline impairment and disease progression in patients with Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) may improve the interpretation of drug effects and the design of future studies.

METHODS: This was a retrospective analysis of three randomized, double-blind rivastigmine databases (one in PDD, two in AD). Impairment on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, 10-item Neuropsychiatric Inventory (NPI-10) and the ADCS-Clinical Global Impression of Change (CGIC) was compared [standardized difference (Cohen's d), similar if <0.1].

RESULTS: Patients with AD or PDD had similar levels …