Relationship between Age-Related Cognitive Impairment and Anatomical Changes in Dendritic Bundles and Neuronal Microcolumns in the Prefrontal Cortex

2021 ◽  
Author(s):  
Frank Jones
Keyword(s):  
Cognitive Impairment ◽  
Prefrontal Cortex ◽  
Anatomical Changes ◽  
Age Related ◽  
Dendritic Bundles

Age differences in ventromedial prefrontal cortex functional connectivity during socioemotional content processing

2020 ◽  
Vol 48 (7) ◽  
pp. 1-19
Author(s):  
Ryan T. Daley ◽  
Holly J. Bowen ◽  
Eric C. Fields ◽  
Angela Gutchess ◽  
Elizabeth A. Kensinger
Keyword(s):  
Prefrontal Cortex ◽  
Functional Connectivity ◽  
Inferior Frontal Gyrus ◽  
Age Groups ◽  
Emotional Content ◽  
Ventromedial Prefrontal Cortex ◽  
Anterior Cingulate ◽  
Supramarginal Gyrus ◽  
Age Related ◽  
Content Processing

Self-relevance effects are often confounded by the presence of emotional content, rendering it difficult to determine how brain networks functionally connected to the ventromedial prefrontal cortex (vmPFC) are affected by the independent contributions of self-relevance and emotion. This difficulty is complicated by age-related changes in functional connectivity between the vmPFC and other default mode network regions, and regions typically associated with externally oriented networks. We asked groups of younger and older adults to imagine placing emotional and neutral objects in their home or a stranger's home. An age-invariant vmPFC cluster showed increased activation for self-relevant and emotional content processing. Functional connectivity analyses revealed age × self-relevance interactions in vmPFC connectivity with the anterior cingulate cortex. There were also age × emotion interactions in vmPFC functional connectivity with the anterior insula, orbitofrontal gyrus, inferior frontal gyrus, and supramarginal gyrus. Interactions occurred in regions with the greatest differences between the age groups, as revealed by conjunction analyses. Implications of the findings are discussed.

Elevated Inflammatory Markers and Arterial Stiffening Exacerbate Tau but Not Amyloid Pathology in Older Adults with Mild Cognitive Impairment

2021 ◽  
pp. 1-13
Author(s):  
Alexandra L. Clark ◽  
Alexandra J. Weigand ◽  
Kelsey R. Thomas ◽  
Seraphina K. Solders ◽  
Lisa Delano-Wood ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Inflammatory Markers ◽  
Memory Performance ◽  
Cognitive Testing ◽  
Interactive Effects ◽  
Protein Biomarkers ◽  
Age Related ◽  
T Tau

Background: Age-related cerebrovascular and neuroinflammatory processes have been independently identified as key mechanisms of Alzheimer’s disease (AD), although their interactive effects have yet to be fully examined. Objective: The current study examined 1) the influence of pulse pressure (PP) and inflammatory markers on AD protein levels and 2) links between protein biomarkers and cognitive function in older adults with and without mild cognitive impairment (MCI). Methods: This study included 218 ADNI (81 cognitively normal [CN], 137 MCI) participants who underwent lumbar punctures, apolipoprotein E (APOE) genotyping, and cognitive testing. Cerebrospinal (CSF) levels of eight pro-inflammatory markers were used to create an inflammation composite, and amyloid-beta 1–42 (Aβ 42), phosphorylated tau (p-tau), and total tau (t-tau) were quantified. Results: Multiple regression analyses controlling for age, education, and APOE ɛ4 genotype revealed significant PP x inflammation interactions for t-tau (B = 0.88, p = 0.01) and p-tau (B = 0.84, p = 0.02); higher inflammation was associated with higher levels of tau within the MCI group. However, within the CN group, analyses revealed a significant PP x inflammation interaction for Aβ 42 (B = –1.01, p = 0.02); greater inflammation was associated with higher levels of Aβ 42 (indicative of lower cerebral amyloid burden) in those with lower PP. Finally, higher levels of tau were associated with poorer memory performance within the MCI group only (p s <  0.05). Conclusion: PP and inflammation exert differential effects on AD CSF proteins and provide evidence that vascular risk is associated with greater AD pathology across our sample of CN and MCI older adults.

scholarly journals A Preliminary Analysis of Hearing Loss and Its Association With Mild Cognitive Impairment

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 451-452
Author(s):  
Mary Caroline Yuk ◽  
Rebecca Allen ◽  
Marcia Hay-McCutcheon ◽  
Dana Carroll ◽  
Anne Halli-Tierney
Keyword(s):  
Hearing Loss ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Emotional Health ◽  
Medical Center ◽  
Pearson Correlation ◽  
Well Being ◽  
Hearing Screening ◽  
Community Dwelling ◽  
Age Related

Abstract Age related hearing loss, or presbycusis, is a global condition that is increasing in its prevalence. Despite being one of the most common chronic conditions among the older population, there is much more to understand about its association with other aspects of physical and emotional health and well-being. Current research is suggesting that hearing loss is more prevalent in those with cognitive impairment compared to those without cognitive impairment. This study analyzed the incidence of hearing loss and its linkage to mild cognitive impairment in a community-dwelling geriatric population. With the increasing prevalence of this condition in both rural and urban communities of Alabama, it becomes a more pressing matter to understand comorbidities and risk factors for future decline in functioning. This study was conducted in an interdisciplinary geriatrics primary care outpatient clinic in a Family, Internal, and Rural Medicine department affiliated with a university medical center in the Deep South. Ninety-one participants completed the Montreal Cognitive Assessment (MoCA) and a hearing screening. Hearing screenings were conducted in quiet rooms in the medical center using Phonak hearing screening cards. Detection of 500, 1000, 2000, and 4000 Hz tones was assessed. Pearson correlation analyses demonstrated an association between hearing loss mild cognitive impairment. Poorer hearing was significantly associated with lower scores on the MoCA. Conducting behavioral health screenings like this in other primary geriatrics clinics and community settings could improve care and identification of patient needs by integrating important data regarding comorbidities and independent living.

scholarly journals Pharmacological rescue of cognitive function in a mouse model of chemobrain

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Lien D. Nguyen ◽  
Tom T. Fischer ◽  
Barbara E. Ehrlich
Keyword(s):  
Cognitive Impairment ◽  
Prefrontal Cortex ◽  
Calcium Oscillations ◽  
Neuronal Morphology ◽  
Post Injection ◽  
Object Recognition Test ◽  
Cognitive Changes ◽  
Memory Acquisition ◽  
Underlying Mechanisms ◽  
Trisphosphate Receptor

Abstract Background After chemotherapy, many cancer survivors suffer from long-lasting cognitive impairment, colloquially known as “chemobrain.” However, the trajectories of cognitive changes and the underlying mechanisms remain unclear. We previously established paclitaxel-induced inositol trisphosphate receptor (InsP3R)-dependent calcium oscillations as a mechanism for peripheral neuropathy, which was prevented by lithium pretreatment. Here, we investigated if a similar mechanism also underlay paclitaxel-induced chemobrain. Method Mice were injected with 4 doses of 20 mg/kg paclitaxel every other day to induced cognitive impairment. Memory acquisition was assessed with the displaced object recognition test. The morphology of neurons in the prefrontal cortex and the hippocampus was analyzed using Golgi-Cox staining, followed by Sholl analyses. Changes in protein expression were measured by Western blot. Results Mice receiving paclitaxel showed impaired short-term spatial memory acquisition both acutely 5 days post injection and chronically 23 days post injection. Dendritic length and complexity were reduced in the hippocampus and the prefrontal cortex after paclitaxel injection. Concurrently, the expression of protein kinase C α (PKCα), an effector in the InsP3R pathway, was increased. Treatment with lithium before or shortly after paclitaxel injection rescued the behavioral, cellular, and molecular deficits observed. Similarly, memory and morphological deficits could be rescued by pretreatment with chelerythrine, a PKC inhibitor. Conclusion We establish the InsP3R calcium pathway and impaired neuronal morphology as mechanisms for paclitaxel-induced cognitive impairment. Our findings suggest lithium and PKC inhibitors as candidate agents for preventing chemotherapy-induced cognitive impairment.

scholarly journals Formaldehyde and De/Methylation in Age-Related Cognitive Impairment

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 913
Author(s):  
Ting Li ◽  
Yan Wei ◽  
Meihua Qu ◽  
Lixian Mou ◽  
Junye Miao ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cell Proliferation ◽  
Cognitive Impairment ◽  
Metabolic Pathways ◽  
Memory Formation ◽  
Epigenetic Alterations ◽  
Diagnostic Biomarker ◽  
Reactive Substance ◽  
Age Related ◽  
Novel Therapeutic

Formaldehyde (FA) is a highly reactive substance that is ubiquitous in the environment and is usually considered as a pollutant. In the human body, FA is a product of various metabolic pathways and participates in one-carbon cycle, which provides carbon for the synthesis and modification of bio-compounds, such as DNA, RNA, and amino acids. Endogenous FA plays a role in epigenetic regulation, especially in the methylation and demethylation of DNA, histones, and RNA. Recently, epigenetic alterations associated with FA dysmetabolism have been considered as one of the important features in age-related cognitive impairment (ARCI), suggesting the potential of using FA as a diagnostic biomarker of ARCI. Notably, FA plays multifaceted roles, and, at certain concentrations, it promotes cell proliferation, enhances memory formation, and elongates life span, effects that could also be involved in the aetiology of ARCI. Further investigation of and the regulation of the epigenetics landscape may provide new insights about the aetiology of ARCI and provide novel therapeutic targets.

scholarly journals Paucity of Entorhinal Cortex Pathology of the Alzheimer’s Type in SuperAgers with Superior Memory Performance

2021 ◽  
Author(s):  
Tamar Gefen ◽  
Allegra Kawles ◽  
Beth Makowski-Woidan ◽  
Janessa Engelmeyer ◽  
Ivan Ayala ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Entorhinal Cortex ◽  
Memory Performance ◽  
Amyloid Plaques ◽  
Memory Capacity ◽  
Relative Magnitude ◽  
Age Related ◽  
Increased Risk ◽  
Superior Memory ◽  
Normal Controls

Abstract Advancing age is typically associated with declining memory capacity and increased risk of Alzheimer’s disease (AD). Markers of AD such as amyloid plaques (AP) and neurofibrillary tangles (NFTs) are commonly found in the brains of cognitively average elderly but in more limited distribution than in those at the mild cognitive impairment and dementia stages of AD. Cognitive SuperAgers are individuals over age 80 who show superior memory capacity, at a level consistent with individuals 20–30 years their junior. Using a stereological approach, the current study quantitated the presence of AD markers in the memory-associated entorhinal cortex (ERC) of seven SuperAgers compared with six age-matched cognitively average normal control individuals. Amyloid plaques and NFTs were visualized using Thioflavin-S histofluorescence, 6E10, and PHF-1 immunohistochemistry. Unbiased stereological analysis revealed significantly more NFTs in ERC in cognitively average normal controls compared with SuperAgers (P &lt; 0.05) by a difference of ~3-fold. There were no significant differences in plaque density. To highlight relative magnitude, cases with typical amnestic dementia of AD showed nearly 100 times more entorhinal NFTs than SuperAgers. The results suggest that resistance to age-related neurofibrillary degeneration in the ERC may be one factor contributing to preserved memory in SuperAgers.

scholarly journals Blood Pressure Profiles and Cognitive Function from Adulthood to Old Age: Chasing a Golden Middle Way?

2021 ◽  
Vol 10 (15) ◽  
pp. 3243
Author(s):  
Rita Del Pinto ◽  
Davide Grassi ◽  
Raffaella Bocale ◽  
Francesco Carubbi ◽  
Claudio Ferri ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Demographic Shift ◽  
Antihypertensive Medications ◽  
Microvascular Damage ◽  
Middle Way ◽  
Alzheimer Type Dementia ◽  
Age Related ◽  
Pressure Profiles

With the demographic shift toward advanced ages, it is imperative to understand the biological mechanisms behind common, disabling age-related diseases such as cognitive impairment in its mild form to overt dementia. Hypertension, a major cardiovascular risk factor, is epidemiologically linked to vascular and Alzheimer-type dementia, with possible mechanisms being atherosclerotic macro- and microvascular damage leading to neuronal cell death, as well as proinflammatory events responsible for neurodegeneration. Nevertheless, there is currently a knowledge gap as to which population to target, what the diagnostics test, and how to manage early pathogenic events in order to prevent such a dramatic and disabling condition. While clinical trials data support the benefit of active BP control with antihypertensive medications on the risk of future cognitive impairment, hypotension appears to be related to accelerated cognitive decline in both the fit and the cognitively frail elderly. Dedicated, technologically advanced studies assessing the relation of BP with dementia are needed to clarify the pathophysiological mechanisms in the association before a tailored preventive, diagnostic, and therapeutic approach to one of the most widespread modern medical challenges becomes a reality.

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