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 Neurogranin, a synaptic protein, is associated with memory independent of Alzheimer biomarkers

Neurology ◽  
2017 ◽  
Vol 89 (17) ◽  
pp. 1782-1788 ◽  
Author(s):  
Kaitlin B. Casaletto ◽  
Fanny M. Elahi ◽  
Brianne M. Bettcher ◽  
John Neuhaus ◽  
Barbara B. Bendlin ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Aging ◽  
Brain Aging ◽  
Memory Performance ◽  
Verbal Learning ◽  
Delayed Recall ◽  
Age Related ◽  
T Tau ◽  
The Relationship ◽  
With Memory

Objective:To determine the association between synaptic functioning as measured via neurogranin in CSF and cognition relative to established Alzheimer disease (AD) biomarkers in neurologically healthy older adults.Methods:We analyzed CSF concentrations of neurogranin, β-amyloid (Aβ42), phosphorylated tau (p-tau), and total tau (t-tau) among 132 neurologically normal older adults (mean 64.5, range 55–85), along with bilateral hippocampal volumes and a measure of episodic memory (Auditory Verbal Learning Test, delayed recall). Univariable analyses examined the relationship between neurogranin and the other AD-related biomarkers. Multivariable regression models examined the relationship between neurogranin and delayed recall, adjusting for age and sex, and interaction terms (neurogranin × AD biomarkers).Results:Higher neurogranin concentrations were associated with older age (ρ = 0.20, p = 0.02), lower levels of p-tau and t-tau, and smaller hippocampal volumes (p < 0.03), but not with CSF Aβ42 (p = 0.18). In addition, CSF neurogranin demonstrated a significant relationship with memory performance independent of the AD-related biomarkers; individuals with the lowest CSF neurogranin concentrations performed better on delayed recall than those with medium or high CSF neurogranin concentrations (p < 0.01). Notably, CSF p-tau, t-tau, and Aβ42 and hippocampal volumes were not significantly associated with delayed recall scores (p > 0.40), and did not interact with neurogranin to predict memory (p > 0.10).Conclusions:Synaptic dysfunction (assessed via neurogranin) may be an early pathologic process in age-related neurodegeneration, and a sensitive marker of age-related cognitive abilities, potentially preceding or even acting independently from AD pathogenesis. Synaptic functioning may be a useful early marker of cognitive aging and possibly a target for future brain aging interventions.

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 Cross-sectional associations of tau-PET signal with cognition in cognitively unimpaired adults

Neurology ◽  
2019 ◽  
Vol 93 (1) ◽  
pp. e29-e39 ◽  
Author(s):  
Val J. Lowe ◽  
Tyler J. Bruinsma ◽  
Heather J. Wiste ◽  
Hoon-Ki Min ◽  
Stephen D. Weigand ◽  
...  
Keyword(s):  
Entorhinal Cortex ◽  
Medial Temporal Lobe ◽  
Memory Performance ◽  
Standardized Uptake Value ◽  
Brain Regions ◽  
Population Based ◽  
Cognitive Test ◽  
Amyloid Pet ◽  
Cross Sectional ◽  
Tau Pet

ObjectiveTo assess cross-sectional associations of neurofibrillary tangles, measured by tau-PET, with cognitive performance in cognitively unimpaired (CU) adults.MethodsTau- and amyloid-PET were performed in 579 CU participants aged 50–98 from the population-based Mayo Clinic Study of Aging. Associations between tau-PET signal in 43 brain regions and cognitive test scores were assessed using penalized linear regression. In additional models, participants were classified by normal/abnormal global amyloid-PET (A+/A−) and normal/abnormal regional tau-PET (T+/T−). Regional tau-PET cutpoints were defined as standardized uptake value ratio (SUVR) greater than the 95th percentile of tau-PET SUVR in that region among 117 CU participants aged 30–49.ResultsHigher tau-PET signal was associated with poorer memory performance in all medial temporal lobe (MTL) regions and also in the middle temporal pole and frontal olfactory regions. The largest association with tau-PET and memory z scores was seen in the entorhinal cortex; this association was independent of tau-PET signal in other brain regions. Tau-PET in the entorhinal cortex was also associated with poorer global and language performance. In the entorhinal cortex, T+ was associated with lower memory performance among both A− and A+.ConclusionsTau deposition in MTL regions, as reflected by tau-PET signal, was associated with poorer performance on memory tests in CU participants. The association with entorhinal cortex tau-PET was independent of tau-PET signal in other brain regions. Longitudinal studies are needed to understand the fate of CU participants with elevated medial temporal tau-PET signal.

scholarly journals Olfactory testing does not predict β-amyloid, MRI measures of neurodegeneration or vascular pathology in the British 1946 birth cohort

2020 ◽  
Vol 267 (11) ◽  
pp. 3329-3336
Author(s):  
Sarah M. Buchanan ◽  
Thomas D. Parker ◽  
Christopher A. Lane ◽  
Ashvini Keshavan ◽  
Sarah E. Keuss ◽  
...  
Keyword(s):  
White Matter ◽  
Birth Cohort ◽  
Entorhinal Cortex ◽  
Cortical Thickness ◽  
White Matter Hyperintensity ◽  
Amyloid Pet ◽  
Brain Health ◽  
Cognitively Normal ◽  
Olfactory Identification ◽  
Β Amyloid

Abstract Objective To explore the value of olfactory identification deficits as a predictor of cerebral β-amyloid status and other markers of brain health in cognitively normal adults aged ~ 70 years. Methods Cross-sectional observational cohort study. 389 largely healthy and cognitively normal older adults were recruited from the MRC National Survey of Health and Development (1946 British Birth cohort) and investigated for olfactory identification deficits, as measured by the University of Pennsylvania Smell Identification Test. Outcome measures were imaging markers of brain health derived from 3 T MRI scanning (cortical thickness, entorhinal cortex thickness, white matter hyperintensity volumes); 18F florbetapir amyloid-PET scanning; and cognitive testing results. Participants were assessed at a single centre between March 2015 and January 2018. Results Mean (± SD) age was 70.6 (± 0.7) years, 50.8% were female. 64.5% had hyposmia and 2.6% anosmia. Olfaction showed no association with β-amyloid status, hippocampal volume, entorhinal cortex thickness, AD signature cortical thickness, white matter hyperintensity volume, or cognition. Conclusion and relevance In the early 70s, olfactory function is not a reliable predictor of a range of imaging and cognitive measures of preclinical AD. Olfactory identification deficits are not likely to be a useful means of identifying asymptomatic amyloidosis. Further studies are required to assess if change in olfaction may be a proximity marker for the development of cognitive impairment.

scholarly journals Plasmon-Activated Water Reduces Amyloid Burden and Improves Memory in Animals with Alzheimer’s Disease

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chia-Hsiung Cheng ◽  
Kun-Ju Lin ◽  
Chien-Tai Hong ◽  
Dean Wu ◽  
Hung-Ming Chang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Memory Performance ◽  
Memory Function ◽  
Amyloid Β ◽  
Amyloid Pet ◽  
Amyloid Burden ◽  
Daily Consumption ◽  
Innovative Strategy

Abstract With the great extension of the human lifespan in recent times, many aging diseases have inevitably followed. Dementia is one of the most-commom neurodegenerative aging diseases, in which inflammation-related Alzheimer’s disease (AD) is the most prevalent cause of dementia. Amyloid accumulation in the brain, which occurs before any clinical presentations, might be the first and key step in the development of AD. However, many clinical trials have attempted to remove amyloid from brains of AD patients, but none has so far been successful. Negatively charged plasmon-activated water (PAW) is created by resonantly illuminated gold (Au) nanoparticles (NPs), which reduce the hydrogen-bonded (HB) structure of water. PAW was found to possess anti-oxidative and anti-inflammatory effects. Herein, we report on an innovative strategy to retard the progression of AD by the daily consumption of PAW instead of normal deionized (DI) water. APPswe/PS1dE9 transgenic mice were treated with PAW or DI water from the age of 5 months for the next 9 months. Encouragingly, compared to DI water-treated mice, mice treated with PAW presented better memory performance on a test of novel object recognition and had a significantly lower amyloid burden according to 18F-florbetapir amyloid-PET and phosphorylated (p)-tau burden according to Western blotting and immunohistochemistry measurements. There were no obvious side effects in PAW-treated mice. Collectively, our findings support that PAW was able to reduce the amyloid and p-tau burden and improve memory in an AD mouse model. However, the protein levels of molecules involved in amyloid metabolism and oligomeric amyloid did not change. We propose that the effects of PAW of reducing the amyloid burden and improving memory function cannot be attributed to synthesis/degradation of amyloid-βprotein but probably in preventing aggregation of amyloid-β proteins or other mechanisms, including anti-inflammation. Further applications of PAW in clinical trials to prevent the progression of AD are being designed.

scholarly journals Health Conditions and Memory Performance: a study with older adult women

2017 ◽  
Vol 70 (3) ◽  
pp. 640-646 ◽  
Author(s):  
Alice Milani Nespollo ◽  
Samira Reschetti Marcon ◽  
Nathalie Vilma Pollo de Lima ◽  
Tatiane Lebre Dias ◽  
Mariano Martínez Espinosa
Keyword(s):  
Older Adult ◽  
Educational Level ◽  
Memory Performance ◽  
Verbal Learning ◽  
Depression Scale ◽  
Health Perception ◽  
Depression Symptoms ◽  
Adult Women ◽  
Delayed Recall ◽  
Immediate Memory

ABSTRACT Objective: to verify the correlation between health condition and memory performance of older adult women in the community. Method: Analytical cross-sectional study developed with 28 older adult women living in Cuiabá-MT. They answered the Mini-Mental State Examination (MMSE), and a shortened Geriatric Depression Scale (GDS-15) to screen for dementia and depression symptoms. Memory skills were assessed through Rey Auditory Verbal Learning Test (RAVLT). Results: The mean age was 66.36 years and 75% of the participants had educational level higher than 7 years. The MMSE mean score was 28.45. The correlations found were: educational level and immediate memory (r = 0.49; p = 0.008); delayed recall and immediate memory (r = 0.71; p < 0.001); memory recognition and immediate memory (r = 0.43; p = 0.021) and recognition memory with delayed recall (r = 0.47; p = 0.012). Conclusion: High scores in the MMSE and a satisfactory health perception among the participants were evident. There was no correlation between memory performance and health perception.

scholarly journals A Longitudinal Analysis of the Association Between Subclinical Hearing Loss and Cognition

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 895-896
Author(s):  
Alexandria Irace ◽  
Nicole Armstrong ◽  
Jennifer Deal ◽  
Alexander Chern ◽  
Luigi Ferrucci ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Standardized Test ◽  
Verbal Learning ◽  
Covariance Structure ◽  
California Verbal Learning Test ◽  
Cognitive Assessments ◽  
Delayed Recall ◽  
Age Related ◽  
Learning Test ◽  
Age Related Hearing Loss

Abstract Several studies have demonstrated that age-related hearing loss (defined as &gt;25 dB pure tone average [PTA]) is longitudinally associated with worse cognition. We aimed to investigate whether subclinical hearing loss (SCHL), or imperfect hearing traditionally categorized as normal (PTA ≤25 dB), may be similarly linked to cognitive decline. Subjects included cognitively normal adults ≥50 years old in the Baltimore Longitudinal Study of Aging with PTA ≤25 dB measured between January 1991 - September 1994 who had repeated cognitive assessments from January 1991 - November 2019 (n=263). The exposure was hearing based on the better ear PTA. The outcomes were standardized test scores in the following domains: learning/memory, mental status, executive function, visuospatial ability, and language. Multivariable linear-mixed effects models with random intercepts and slopes and unstructured variance-covariance structure were used to model the association between hearing and change in cognition over time, adjusting for baseline age, sex, years of education, and race. Mean age was 68.3 years (standard deviation [SD]=8.9) and follow-up ranged from 0-27.7 years (mean=12.5, SD=7.9). A 10-dB worsening in hearing was longitudinally associated with an annual decline of 0.016 SDs (95% confidence interval [CI]: 0.0002, 0.033) in California Verbal Learning Test (CVLT) short-delayed recall, 0.019 SDs (95% CI: 0.002, 0.036) in CVLT long-delayed recall, and 0.017 SDs (95% CI: 0.006, 0.028) in letter fluency after covariate adjustment. Poorer hearing among those with SCHL was associated with steeper declines in memory and verbal fluency scores. This relationship may begin at earlier levels of hearing loss than previously recognized.

Memory Performance as a Function of Age, Reattribution Training and Type of Mnemonic Strategy Training

1992 ◽  
Vol 36 (2) ◽  
pp. 141-145
Author(s):  
Marilyn L. Turner
Keyword(s):  
Memory Span ◽  
Memory Performance ◽  
Verbal Learning ◽  
Strategy Training ◽  
California Verbal Learning Test ◽  
Control Group ◽  
Verbal Skills ◽  
Mnemonic Strategy ◽  
Age Related ◽  
Method Of Loci

This experiment investigated whether mnemonic strategy training, occurring over a two-month period, would result in improved memory performance when combined with reattribution training. It was also hypothesized that the old and young may differ in their ability to perform nonverbal and verbal mnemonics. Therefore, age-related differences in memory performance were investigated as a function of whether the mnemonic was verbal (Alphabet Search Method) or non-verbal (Method of Loci), and whether or not reattribution training was combined with mnemonic training. Subjects were 34 old (Mean age = 69.5) and 34 young (Mean age = 22.8) adults. Memory performance was measured on the California Verbal Learning Test, the Nelson-Denny Vocabulary Test, the Beck Depression Inventory and four memory span tasks, prior and following a two-month period of weekly mnemonic strategy training sessions. A third of the subjects were trained with the Method of Loci, a third with Alphabet Search, and the remaining third served as the waitlist control group. In addition, half the young and old subjects from each mnemonic group did, and half did not, participate in a reattribution training workshop. Results clearly showed that mnemonic strategy training was useful for the old and young. However, the combination of reattribution and mnemonic strategy training only enhanced old, not young, memory scores when the type of strategy required verbal skills (Alphabet Search). The implication was that mnemonic strategy training may be more effective for the old if combined with reattribution training, and, if the mnemonic requires verbal rather than non-verbal skills.

Usefulness of Discriminability and Response Bias Indices for the Evaluation of Recognition Memory in Mild Cognitive Impairment and Alzheimer Disease

2016 ◽  
Vol 43 (1-2) ◽  
pp. 1-14 ◽  
Author(s):  
María Julieta Russo ◽  
Gabriela Cohen ◽  
Jorge Campos ◽  
Maria Eugenia Martin ◽  
María Florencia Clarens ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Alzheimer Disease ◽  
Recognition Memory ◽  
Response Bias ◽  
Memory Performance ◽  
Verbal Learning ◽  
False Alarms ◽  
Significant Group ◽  
Delayed Recall

Background: Most studies examining episodic memory in Alzheimer disease (AD) have focused on patients' impaired ability to remember information. This approach provides only a partial picture of memory deficits since other factors involved are not considered. Objective: To evaluate the recognition memory performance by using a yes/no procedure to examine the effect of discriminability and response bias measures in amnestic mild cognitive impairment (a-MCI), AD dementia, and normal-aging subjects. Methods: We included 43 controls and 45 a-MCI and 51 mild AD dementia patients. Based on the proportions of correct responses (hits) and false alarms from the Rey Auditory Verbal Learning Test (RAVLT), discriminability (d′) and response bias (C) indices from signal detection theory (SDT) were calculated. Results: Results showed significant group differences for d′ (F (2) = 83.26, p < 0.001), and C (F (2) = 6.05, p = 0.00). The best predictors of group membership were delayed recall and d′ scores. The d′ measure correctly classified subjects with 82.98% sensitivity and 91.11% specificity. Conclusions: a-MCI and AD dementia subjects exhibit less discrimination accuracy and more liberal response bias than controls. Furthermore, combined indices of delayed recall and discriminability from the RAVLT are effective in defining early AD. SDT may help enhance diagnostic specificity.

scholarly journals Integrity of white matter structure is related to episodic memory performance in the low-educated elderly

2017 ◽  
Vol 75 (11) ◽  
pp. 778-784 ◽  
Author(s):  
Elisa de Paula França Resende ◽  
Fernanda Freire Tovar-Moll ◽  
Fernanda Meireles Ferreira ◽  
Ivanei Bramati ◽  
Leonardo Cruz de Souza ◽  
...  
Keyword(s):  
White Matter ◽  
Episodic Memory ◽  
Diffusion Tensor ◽  
Memory Performance ◽  
Verbal Learning ◽  
Cognitive Screening ◽  
Delayed Recall ◽  
Learning Test ◽  
Low Educated ◽  
The Right

ABSTRACT The low-educated elderly are a vulnerable population in whom studying the role of white matter integrity on memory may provide insights for understanding how memory declines with aging and disease. Methods: Thirty-one participants (22 women), 23 cognitively healthy and eight with cognitive impairment-no dementia, aged 80.4 ± 3.8 years, with 2.2 ± 1.9 years of education, underwent an MRI scan with diffusion tensor imaging (DTI) acquisition. We verified if there were correlations between the performance on the Brief Cognitive Screening Battery (BCSB) and the Rey Auditory Verbal Learning Test (RAVLT) with DTI parameters. Results: The BCSB delayed recall task correlated with frontotemporoparietal connection bundles, with the hippocampal part of the cingulum bilaterally and with the right superior longitudinal fasciculus. The RAVLT learning and delayed recall scores also correlated with the hippocampal part of the cingulum bilaterally. Conclusions: Although preliminary, our study suggests that the integrity of white matter frontotemporoparietal fasciculi seems to play a role in episodic memory performance in the low-educated elderly. This finding opens opportunities to study potential targets for memory decline prevention in vulnerable populations.

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