Diseases Commons^™

Estimating Dementia Risk In An African American Population Using The Dctclock, Marissa Ciesla, Jeff Pobst, Joyce Gomes-Osman, Melissa Lamar, Lisa L Barnes, Russell Banks, Ali Jannati, David Libon, Rodney Swenson, Sean Tobyne, David Bates, John Showalter, Alvaro Pascual-Leone

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

The prevalence of Alzheimer's disease (AD) and related dementias (ADRD) is increasing. African Americans are twice as likely to develop dementia than other ethnic populations. Traditional cognitive screening solutions lack the sensitivity to independently identify individuals at risk for cognitive decline. The DCTclock is a 3-min AI-enabled adaptation of the well-established clock drawing test. The DCTclock can estimate dementia risk for both general cognitive impairment and the presence of AD pathology. Here we performed a retrospective analysis to assess the performance of the DCTclock to estimate future conversion to ADRD in African American participants from the Rush Alzheimer's Disease Research …

Precision Medicine Approach To Alzheimer’S Disease: Rationale And Implications, Dale E. Bredesen, Kat Toups, Ann Hathaway, Deborha Gordon, Henrianna Chung, Cyrus Raji, Alan Boyd, Benjamin D. Hill, Sharon Hausman-Cohen, Mouna Attarha, Won Jong Chwa, Alexei Kurakin, Michael Jarrett

University Faculty and Staff Publications

The neurodegenerative disease field has enjoyed extremely limited success in the development of effective therapeutics. One potential reason is the lack of disease models that yield accurate predictions and optimal therapeutic targets. Standard clinical trials have pre-determined a single treatment modality, which may be unrelated to the primary drivers of neurodegeneration. Recent proof-of-concept clinical trials using a precision medicine approach suggest a new model of Alzheimer’s disease (AD) as a chronic innate encephalitis that creates a network insufficiency. Identifying and addressing the multiple potential contributors to cognitive decline for each patient may represent a more effective strategy. Here we review …

Sex Differences In The Association Between Cardiovascular Diseases And Dementia Subtypes: A Prospective Analysis Of 464,616 Uk Biobank Participants, Caiyun Dong, Chunmiao Zhou, Chunying Fu, Wenting Hao, Akihiko Ozaki, Nipun Shrestha, Salim S. Virani, Shiva Raj Mishra, Dongshan Zhu

Office of the Provost

Background: Whether the association of cardiovascular diseases (CVDs) with dementia differs by sex remains unclear, and the role of socioeconomic, lifestyle, genetic, and medical factors in their association is unknown.
Methods: We used data from the UK Biobank, a population-based cohort study of 502,649 individuals. We used Cox proportional hazards models to estimate sex-specific hazard ratios (HRs) and 95% confidence intervals (CI), and women-to-men ratio of HRs (RHR) for the association between CVD (coronary heart diseases (CHD), stroke, and heart failure) and incident dementia (all-cause dementia, Alzheimer's Disease (AD), and vascular dementia (VD)). The moderator roles of socioeconomic (education, income), …

Visual And Verbal Serial List Learning In Patients With Statistically-Determined Mild Cognitive Impairment., Victor Wasserman, Sheina Emrani, Emily F Matusz, David Miller, Kelly Davis Garrett, Katherine A Gifford, Timothy J Hohman, Angela L Jefferson, Rhoda Au, Rod Swenson, David J Libon, Consortium For Clinical And Epidemiological Neuropsychological Data Analysis (Cenda).

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Background and Objective: Prior research with patients with mild cognitive impairment (MCI) suggests that visual versus verbal episodic memory test performance may be more sensitive to emergent illness. However, little research has examined visual versus verbal episodic memory performance as related to MCI subtypes.

Research Design and Methods: Patients were diagnosed with non-MCI, amnestic MCI (aMCI), and combined mixed/dysexecutive MCI (mixed/dys MCI). Visual and verbal episodic memory were assessed with the Brief Visuospatial Memory Test-Revised (BVMT-R) and the 12-word Philadelphia (repeatable) Verbal Learning Test (P[r]VLT), respectively.

Results: BVMT-R and P(r)VLT scores yielded similar between-group patterns of performance. Non-MCI patients scored …

Astrocyte Activation And The Calcineurin/Nfat Pathway In Cerebrovascular Disease, Susan D. Kraner, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Calcineurin (CN) is a Ca²⁺/calmodulin-dependent protein phosphatase with high abundance in nervous tissue. Though enriched in neurons, CN can become strongly induced in subsets of activated astrocytes under different pathological conditions where it interacts extensively with the nuclear factor of activated T cells (NFATs). Recent work has shown that regions of small vessel damage are associated with the upregulation of a proteolized, highly active form of CN in nearby astrocytes, suggesting a link between the CN/NFAT pathway and chronic cerebrovascular disease. In this Mini Review article, we discuss CN/NFAT signaling properties in the context of vascular disease and …

In Vivo Brainstem Imaging In Alzheimer’S Disease: Potential For Biomarker Development, David J. Braun, Linda J. Van Eldik

Neuroscience Faculty Publications

The dearth of effective treatments for Alzheimer’s disease (AD) is one of the largest public health issues worldwide, costing hundreds of billions of dollars per year. From a therapeutic standpoint, research efforts to date have met with strikingly little clinical success. One major issue is that trials begin after substantial pathological change has occurred, and it is increasingly clear that the most effective treatment regimens will need to be administered earlier in the disease process. In order to identify individuals within the long preclinical phase of AD who are likely to progress to dementia, improvements are required in biomarker development. …

Ca2+, Astrocyte Activation And Calcineurin/Nfat Signaling In Age-Related Neurodegenerative Diseases, Pradoldej Sompol, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Mounting evidence supports a fundamental role for Ca²⁺ dysregulation in astrocyte activation. Though the activated astrocyte phenotype is complex, cell-type targeting approaches have revealed a number of detrimental roles of activated astrocytes involving neuroinflammation, release of synaptotoxic factors and loss of glutamate regulation. Work from our lab and others has suggested that the Ca²⁺/calmodulin dependent protein phosphatase, calcineurin (CN), provides a critical link between Ca²⁺ dysregulation and the activated astrocyte phenotype. A proteolyzed, hyperactivated form of CN appears at high levels in activated astrocytes in both human tissue and rodent tissue around regions of amyloid and …

Incidence Of Dementia In Elderly Latin Americans: Results Of The Maracaibo Aging Study, Gladys E. Maestre, Luis J. Mena, Jesus D. Melgarejo, Daniel C. Aguirre-Acevedo, Gloria Pino-Ramírez, Milady Urribarrí, Inara J. Chacon, Carlos A. Chavez, Luis Falque-Madrid, Ciro A. Gaona

School of Medicine Publications and Presentations

Introduction—There are few longitudinal studies of dementia in developing countries. We used longitudinal data from the Maracaibo Aging Study (MAS) to accurately determine the age- and sex-specific incidence of dementia in elderly Latin Americans.

Methods—The DSM IV-R was used to diagnose dementia, which was classified as Alzheimer’s disease (AD), vascular dementia (VaD), or other. Age- and sex-specific incidence was estimated as the number of new cases of dementia divided by person-years of follow-up (p-y).

Results—The incidence of all dementia diagnoses was 9.10 per 1000 p-y (95% CI 7.13–11.44; 8026 total p-y), 5.18 for AD (95% CI 3.72–7.03; …

Chlamydia Pneumoniae: An Etiologic Agent For Late-Onset Dementia, Brian J. Balin Phd, Christine Hammond, Christopher S. Little, Susan Hingley, Zein Al-Atrache, Denah Appelt, Judith A Whittum-Hudson, Alan P Hudson

PCOM Scholarly Papers

The disease known as late-onset Alzheimer's disease is a neurodegenerative condition recognized as the single most common form of senile dementia. The condition is sporadic and has been attributed to neuronal damage and loss, both of which have been linked to the accumulation of protein deposits in the brain. Significant progress has been made over the past two decades regarding our overall understanding of the apparently pathogenic entities that arise in the affected brain, both for early-onset disease, which constitutes approximately 5% of all cases, as well as late-onset disease, which constitutes the remainder of cases. Observable neuropathology includes: neurofibrillary …

Role Of Microglial Amylin Receptors In Mediating Beta Amyloid (Aβ)-Induced Inflammation, Wen Fu, Vlatka Vukojevic, Aarti Patel, Rania Soudy, David Mactavish, David Westaway, Kamaljit Kaur, Valeri Goncharuk, Jack Jhamandas

Pharmacy Faculty Articles and Research

Background: Neuroinflammation in the brain consequent to activation of microglia is viewed as an important component of Alzheimer’s disease (AD) pathology. Amyloid beta (Aβ) protein is known to activate microglia and unleash an inflammatory cascade that eventually results in neuronal dysfunction and death. In this study, we sought to identify the presence of amylin receptors on human fetal and murine microglia and determine whether Aβ activation of the inflammasome complex and subsequent release of cytokines is mediated through these receptors.

Methods: The presence of dimeric components of the amylin receptor (calcitonin receptor and receptor activity modifying protein 3) …

Cyclic Ac253, A Novel Amylin Receptor Antagonist, Improves Cognitive Deficits In A Mouse Model Of Alzheimer’S Disease, Rania Soudy, Aarti Patel, Wen Fu, Kamaljit Kaur, David Mactavish, David Westaway, Rachel Davey, Jeffrey Zajac, Jack Jhamandas

Pharmacy Faculty Articles and Research

Introduction: Amylin receptor serves as a portal for the expression of deleterious effects of amyloid b-protein (Ab), a key pathologic hallmark of Alzheimer’s disease. Previously, we showed that AC253, an amylin receptor antagonist, is neuroprotective against Ab toxicity in vitro and abrogates Ab-induced impairment of hippocampal long-term potentiation.

Methods: Amyloid precursor protein–overexpressing TgCRND8 mice received intracerebroventricularly AC253 for 5 months. New cyclized peptide cAC253 was synthesized and administered intraperitoneally three times a week for 10 weeks in the same mouse model. Cognitive functions were monitored, and pathologic changes were quantified biochemically and immunohistochemically.

Results: AC253, when administered …

Changes In The Plasma Proteome At Asymptomatic And Symptomatic Stages Of Autosomal Dominant Alzheimer's Disease, Julia Muenchhoff, Anne Poljak, Anbupalam Thalamuthu, Veer Gupta, Pratishtha Chatterjee, Mark Raftery, Colin Masters, John Morris, Randall Bateman, Anne Fagan, Ralph Martins, Perminder Sachdev

Research outputs 2014 to 2021

The autosomal dominant form of Alzheimer's disease (ADAD) is far less prevalent than late onset Alzheimer's disease (LOAD), but enables well-informed prospective studies, since symptom onset is near certain and age of onset is predictable. Our aim was to discover plasma proteins associated with early AD pathology by investigating plasma protein changes at the asymptomatic and symptomatic stages of ADAD. Eighty-one proteins were compared across asymptomatic mutation carriers (aMC, n = 15), symptomatic mutation carriers (sMC, n = 8) and related noncarriers (NC, n = 12). Proteins were also tested for associations with cognitive measures, brain amyloid deposition and glucose …

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. …