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 < 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.

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.

Vztah mezi presbyakuzí a poruchou kognitivních funkcí ve stáří PDF uzamčeno English info

2021 ◽  
Vol 70 (4) ◽  
pp. 223-233
Author(s):  
Jakub Fuksa ◽  
Milan Profant ◽  
Martin Chovanec ◽  
Josef Syka
Keyword(s):  
Hearing Loss ◽  
Cognitive Impairment ◽  
Hearing Aids ◽  
Cognitive Functions ◽  
Auditory Information ◽  
Ageing Population ◽  
Published Evidence ◽  
Age Related ◽  
Keywords Dementia ◽  
Increased Risk

Age-related hearing loss, presbycusis, is one of the most frequent sensory impairments in the ageing population. It is associated with pathologies of both inner ear and the central parts of the auditory system. Intact cognitive functions are necessary for the proper processing of complex auditory information. Since the beginning of the 80s, there is an increasing amount of evidence linking presbycusis to cognitive impairment and increased risk of dementia. The exact cause, which connects these two pathologies, is still unknown, although there are several hypotheses with various levels of evidence available. This review aims to describe the role of cognitive functions in the auditory processing, to summarize published evidence for a relationship between the hearing loss and cognitive impairment with a possible mechanism, which would explain this link. In addition, we discuss specific features of cognitive assessment in a person with hearing loss and describe the effect of hearing loss treatment, e. g. with hearing aids, cochlear implant and cognitive-hearing training on cognitive functions. Keywords: dementia – hearing loss – presbycusis – cognitive decline

scholarly journals Memory-Related Frontal Brainwaves Predict Transition to Mild Cognitive Impairment in Healthy Older Individuals Five Years Before Diagnosis

2020 ◽  
pp. 1-11
Author(s):  
Yang Jiang ◽  
Juan Li ◽  
Frederick A. Schmitt ◽  
Gregory A. Jicha ◽  
Nancy B. Munro ◽  
...  
Keyword(s):  
Older Adults ◽  
Working Memory ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Memory Performance ◽  
Memory Task ◽  
Cognitive Status ◽  
Older Individuals ◽  
Increased Risk ◽  
Differentiation Pattern

Background: Early prognosis of high-risk older adults for amnestic mild cognitive impairment (aMCI), using noninvasive and sensitive neuromarkers, is key for early prevention of Alzheimer’s disease. We have developed individualized measures in electrophysiological brain signals during working memory that distinguish patients with aMCI from age-matched cognitively intact older individuals. Objective: Here we test longitudinally the prognosis of the baseline neuromarkers for aMCI risk. We hypothesized that the older individuals diagnosed with incident aMCI already have aMCI-like brain signatures years before diagnosis. Methods: Electroencephalogram (EEG) and memory performance were recorded during a working memory task at baseline. The individualized baseline neuromarkers, annual cognitive status, and longitudinal changes in memory recall scores up to 10 years were analyzed. Results: Seven of the 19 cognitively normal older adults were diagnosed with incident aMCI for a median 5.2 years later. The seven converters’ frontal brainwaves were statistically identical to those patients with diagnosed aMCI (n = 14) at baseline. Importantly, the converters’ baseline memory-related brainwaves (reduced mean frontal responses to memory targets) were significantly different from those who remained normal. Furthermore, differentiation pattern of left frontal memory-related responses (targets versus nontargets) was associated with an increased risk hazard of aMCI (HR = 1.47, 95% CI 1.03, 2.08). Conclusion: The memory-related neuromarkers detect MCI-like brain signatures about five years before diagnosis. The individualized frontal neuromarkers index increased MCI risk at baseline. These noninvasive neuromarkers during our Bluegrass memory task have great potential to be used repeatedly for individualized prognosis of MCI risk and progression before clinical diagnosis.

Memory in individuals with mild cognitive impairment in relation to APOE and CSF Aβ42

2010 ◽  
Vol 22 (4) ◽  
pp. 598-606 ◽  
Author(s):  
Valgeir Thorvaldsson ◽  
Arto Nordlund ◽  
Ivar Reinvang ◽  
Kaj Blennow ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Memory Performance ◽  
Interactive Effect ◽  
Amyloid Β ◽  
Total Sample ◽  
Increased Risk ◽  
Latent Curve ◽  
Latent Curve Models ◽  
Ε4 Allele

ABSTRACTBackground: The ε4 allele of the apolipoprotein E (APOE) gene and low levels of cerebrospinal fluid (CSF) amyloid β-proteins 42 (Aβ) have previously been associated with increased risk of cognitive decline in old age. In this study we examine the interaction of these markers with episodic memory in a sample identified as having mild cognitive impairment (MCI).Methods: The sample (N = 149) was drawn from the Gothenburg MCI study and measured according to three free recall tests on three occasions spanning over four years. Second-order Latent Curve Models (LCM) were fitted to the data.Results: Analyses accounting for age, gender, education, APOE, Aβ42, and interaction between APOE and Aβ42 revealed that the ε4 allele was significantly associated with level of memory performance in the presence of low Aβ42 values (≤452 ng/L). Associations between memory performance and Aβ42 were significant among the ε4 carriers but not among the non-carriers. The Aβ42 marker was, however, significantly associated with changes in memory over the study time period in the total sample.Conclusion: The findings support the hypothesis of an interactive effect of APOE and Aβ42 for memory decline in MCI patients.

scholarly journals Entorhinal cortex tau, amyloid-β, cortical thickness and memory performance in non-demented subjects

Brain ◽  
2019 ◽  
Vol 142 (4) ◽  
pp. 1148-1160 ◽  
Author(s):  
David S Knopman ◽  
Emily S Lundt ◽  
Terry M Therneau ◽  
Prashanthi Vemuri ◽  
Val J Lowe ◽  
...  
Keyword(s):  
Entorhinal Cortex ◽  
Cortical Thickness ◽  
Memory Performance ◽  
Verbal Learning ◽  
Amyloid Β ◽  
Gradient Boosting ◽  
Amyloid Pet ◽  
Delayed Recall ◽  
Age Related ◽  
Z Scores

AbstractAs more biomarkers for Alzheimer’s disease and age-related brain conditions become available, more sophisticated analytic approaches are needed to take full advantage of the information they convey. Most work has been done using categorical approaches but the joint relationships of tau PET, amyloid PET and cortical thickness in their continuous distributions to cognition have been under-explored. We evaluated non-demented subjects over age 50 years in the Mayo Clinic Study of Aging, 2037 of whom had undergone 3 T MRI scan, 985 amyloid PET scan with 11C-Pittsburgh compound B (PIB) and MRI, and 577 PIB-PET, 18F-AV1451 flortaucipir PET and MRI. Participants received a nine-test cognitive battery. Three test scores (logical memory delayed recall, visual reproduction delayed recall and auditory verbal learning test delayed recall) were used to generate a memory composite z-score. We used Gradient Boosting Machine models to analyse the relationship between regional cortical thickness, flortaucipir PET signal, PIB-PET signal and memory z-scores. Age, education, sex and number of test exposures were included in the model as covariates. In this population-based study of non-demented subjects, most of the associations between biomarkers and memory z-scores accrued after 70 years of age. Entorhinal cortex exhibited the strongest associations between biomarkers and memory z-scores. Other temporal regions showed similar but attenuated associations, and non-temporal regions had negligible associations between memory z-scores and biomarkers. Entorhinal flortaucipir PET signal, PIB-PET signal and entorhinal cortical thickness were independently and additively associated with declining memory z-scores. In contrast to global PIB-PET signal where only very high amyloid-β levels were associated low memory z-scores, entorhinal flortaucipir PET signal just above background levels was associated with low memory z-scores. The lowest memory z-scores occurred with the confluence of elevated entorhinal flortaucipir PET signal and lower entorhinal cortical thickness.

scholarly journals Sensorial frailty: age-related hearing loss and the risk of cognitive impairment and dementia in later life

2018 ◽  
Vol 10 ◽  
pp. 204062231881100 ◽  
Author(s):  
Francesco Panza ◽  
Madia Lozupone ◽  
Rodolfo Sardone ◽  
Petronilla Battista ◽  
Marco Piccininni ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Clinical Condition ◽  
Oldest Old ◽  
Population Based ◽  
Older Age ◽  
Age Related ◽  
Increased Risk ◽  
Age Related Hearing Loss

The peripheral hearing alterations and central auditory processing disorder (CAPD) associated with age-related hearing loss (ARHL), may impact cognitive disorders in older age. In older age, ARHL is also a significant marker for frailty, another age-related multidimensional clinical condition with a nonspecific state of vulnerability, reduced multisystem physiological reserve, and decreased resistance to different stressors (i.e. sensorial impairments, psychosocial stress, diseases, injuries). The multidimensional nature of frailty required an approach based on different pathogeneses because this clinical condition may include sensorial, physical, social, nutritional, cognitive, and psychological phenotypes. In the present narrative review, the cumulative epidemiological evidence coming from several longitudinal population-based studies, suggested convincing links between peripheral ARHL and incident cognitive decline and dementia. Moreover, a few longitudinal case-control and population-based studies also suggested that age-related CAPD in ARHL, may be central in determining an increased risk of incident cognitive decline, dementia, and Alzheimer’s disease (AD). Cumulative meta-analytic evidence confirmed cross-sectional and longitudinal association of both peripheral ARHL and age-related CAPD with different domains of cognitive functions, mild cognitive impairment, and dementia, while the association with dementia subtypes such as AD and vascular dementia remained unclear. However, ARHL may represent a modifiable condition and a possible target for secondary prevention of cognitive impairment in older age, social isolation, late-life depression, and frailty. Further research is required to determine whether broader hearing rehabilitative interventions including coordinated counseling and environmental accommodations could delay or halt cognitive and global decline in the oldest old with both ARHL and dementia.

scholarly journals Circulating Inflamma-miRs as Potential Biomarkers of Cognitive Impairment in Patients Affected by Alzheimer’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Angelica Giuliani ◽  
Simona Gaetani ◽  
Giulia Sorgentoni ◽  
Silvia Agarbati ◽  
Maristella Laggetta ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Minimally Invasive ◽  
Circulating Biomarkers ◽  
Inflammatory Status ◽  
Age Related ◽  
Increased Risk ◽  
Healthy Control ◽  
State Examination

Alzheimer’s disease (AD), the most prevalent neurodegenerative disease in the growing population of elderly people, is still lacking minimally-invasive circulating biomarkers that could facilitate the diagnosis and the monitoring of disease progression. MicroRNAs (miRNAs) are emerging as tissue-specific and/or circulating biomarkers of several age-related diseases, but evidence on AD is still not conclusive. Since a systemic pro-inflammatory status was associated with an increased risk of AD development and progression, we focused our investigation on a subset of miRNAs modulating the inflammatory process, namely inflamma-miRNAs. The expression of inflamma-miR-17-5p, -21-5p, -126-3p, and -146a-5p was analyzed in plasma samples from 116 patients with AD compared with 41 age-matched healthy control (HC) subjects. MiR-17-5p, miR-21-5p, and miR-126-3p plasma levels were significantly increased in AD patients compared to HC. Importantly, a strong inverse relationship was observed between miR-21-5p and miR-126-3p, and the cognitive impairment, assessed by Mini-Mental State Examination (MMSE). Notably, miR-126-3p was able to discriminate between mild and severe cognitive impairment. Overall, our results reinforce the hypothesis that circulating inflamma-miRNAs could be assessed as minimally invasive tools associated with the development and progression of cognitive impairment in AD.

scholarly journals Nitride oxide synthase 3 and klotho gene polymorphisms in the pathogenesis of chronic kidney disease and age-related cognitive impairment: a systematic review and meta-analysis

F1000Research ◽  
2021 ◽  
Vol 9 ◽  
pp. 252
Author(s):  
Atma Gunawan ◽  
Jonny Karunia Fajar ◽  
Fredo Tamara ◽  
Aditya Indra Mahendra ◽  
Muhammad Ilmawan ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Cognitive Impairment ◽  
Kidney Disease ◽  
Meta Analysis ◽  
Initial Assessment ◽  
Age Related ◽  
Increased Risk ◽  
Nitride Oxide ◽  
Oxide Synthase ◽  
Increased Susceptibility

Background: While it has been known that the development of chronic kidney disease (CKD) and age-related cognitive impairment involves several mediators, the evidence in clinical practice only reveals nitride oxide synthase (NOS) and klotho. However, the evidence for this topic is conflicted. The aim of this study was to assess the role of NOS and klotho single nucleotide polymorphisms (SNPs) in the pathogenesis of CKD and age-related cognitive impairment. Methods: We performed a meta-analysis during October to December 2019. Paper collection was performed in major scientific websites, and we extracted information of interest from each paper. Data were analyzed using a Z-test with either random or fixed effect model. Results: Our initial assessment identified NOS3 G894T, NOS3 T786C, NOS3 4b/4a, klotho (KL) G395A, and KL C1818T as the gene candidate for our meta-analysis. Our pooled calculation revealed that NOS3 G894T was associated with the risk of both age-related cognitive impairment and CKD. Increased susceptibility to age-related cognitive impairment was observed in the GG genotype, and increased risk of CKD was found in patients with a single T allele and TT genotype for NOS3 nucleotide 894. For NOS3 4b/4a, increased risk of CKD was only found in 4a4a genotype. For NOS3 T786C, we failed to show the association with both CKD and age-related cognitive impairment. Subsequently, for KL G395A, A allele and GA genotype were found to correlate with increased susceptibility to CKD, while its correlation to age-related cognitive impairment was failed to clarify. For KL C1818T, our analysis failed to find the correlation with the risk of CKD. Conclusions: Our results reveal that the NOS3 G894T gene polymorphism has a crucial role in the pathogenesis of both CKD and age-related cognitive impairment.

scholarly journals Superior Memory and Higher Cortical Volumes in Unusually Successful Cognitive Aging

2012 ◽  
Vol 18 (6) ◽  
pp. 1081-1085 ◽  
Author(s):  
Theresa M. Harrison ◽  
Sandra Weintraub ◽  
M.-Marsel Mesulam ◽  
Emily Rogalski
Keyword(s):  
Cognitive Aging ◽  
Successful Aging ◽  
Memory Impairment ◽  
Memory Performance ◽  
Anterior Cingulate ◽  
Normative Values ◽  
Cognitively Normal ◽  
Age Related ◽  
Cortical Morphometry ◽  
Superior Memory

AbstractIt is “normal” for old age to be associated with gradual decline in memory and brain mass. However, there are anecdotal reports of individuals who seem immune to age-related memory impairment, but these individuals have not been studied systematically. This study sought to establish that such cognitive SuperAgers exist and to determine if they were also resistant to age-related loss of cortical brain volume. SuperAgers were defined as individuals over age 80 with episodic memory performance at least as good as normative values for 50- to 65-year-olds. Cortical morphometry of the SuperAgers was compared to two cognitively normal cohorts: age-matched elderly and 50- to 65-year-olds. The SuperAgers’ cerebral cortex was significantly thicker than their healthy age-matched peers and displayed no atrophy compared to the 50- to 65-year-old healthy group. Unexpectedly, a region of left anterior cingulate cortex was significantly thicker in the SuperAgers than in both elderly and middle-aged controls. Our findings identify cognitive and neuroanatomical features of a cohort that appears to resist average age-related changes of memory capacity and cortical volume. A better understanding of the underlying factors promoting this potential trajectory of unusually successful aging may provide insight for preventing age-related cognitive impairments or the more severe changes associated with Alzheimer's disease. (JINS, 2012, 18, 1–5)

scholarly journals Prevalence and Characterization of Mild Cognitive Impairment in Retired National Football League Players

2013 ◽  
Vol 19 (8) ◽  
pp. 873-880 ◽  
Author(s):  
Christopher Randolph ◽  
Stella Karantzoulis ◽  
Kevin Guskiewicz
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
National Football League ◽  
Neurodegenerative Disorder ◽  
Chronic Traumatic Encephalopathy ◽  
Clinical Sample ◽  
Late Life ◽  
Age Related ◽  
Increased Risk ◽  
Neurocognitive Profiles

AbstractIt has been hypothesized that exposure to repetitive head trauma from contact sports over a long-playing career may eventuate in an increased risk of late-life cognitive impairment. There are currently two competing hypotheses about the possible mechanism underlying such impairment. One is the presence of a unique neurodegenerative disorder known as “chronic traumatic encephalopathy” (CTE). The other is diminished cerebral reserve leading to the earlier clinical expression of age-related neurodegenerative diseases such as mild cognitive impairment (MCI) and Alzheimer's disease (AD). The present study examined informant AD8 inventory data in a sample of 513 retired National Football League (NFL) players. These data were indicative of possible cognitive impairment in 35.1% of this relatively young sample. A comparison of neurocognitive profiles in a subsample of this group to a clinical sample of patients with a diagnosis of MCI due to AD revealed a highly similar profile of impairments. Overall, the data suggest that there may be an increased prevalence of late-life cognitive impairment in retired NFL players, which may reflect diminished cerebral reserve. The findings are considered preliminary, but emphasize the need for larger, controlled studies on this issue. (JINS, 2013,19, 1–8)

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