Pathological correlates of impaired self-awareness of memory function in Alzheimer’s disease

Abstract Introduction Impaired self-awareness of memory function, a.k.a. anosognosia, is a common symptom in Alzheimer’s disease (AD); however, its pathological correlates remain unclear. Here, we investigated the impact of amyloid and tau on memory self-awareness. Methods Two hundred thirty-six clinically normal (N) and 102 impaired (I) participants from the ADNI cohort were included. Amyloid (global) and tau burden (in entorhinal and inferior temporal cortices) were assessed using positron emission tomography (PET). Self-awareness of memory was assessed using discrepancy indexes of subjective participant-informant ratings, as well as participant-objective scores of memory performance. Subjective and objective values were derived from the Everyday Cognition memory questionnaire and Logical Memory (delayed recall). Results Lower awareness (both methods) of memory function was associated with higher levels of pathology in the I group as compared to N. There was a significant effect of tauopathy, but not amyloidosis, on individual complaint, such that higher levels of tau associated with lower awareness. Discussion Impaired self-awareness appears progressively in the evolution of the disease related to AD biomarkers. Discordant subjective and objective measures may be important for clinical consideration.

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Impact of Comorbid Depression on Serial Position Effects in Alzheimer’s Disease

GeroPsych ◽

10.1024/1662-9647/a000115 ◽

2014 ◽

Vol 27 (4) ◽

pp. 161-169 ◽

Cited By ~ 1

Author(s):

Nienke A. Hofrichter ◽

Sandra Dick ◽

Thomas G. Riemer ◽

Carsten Schleussner ◽

Monique Goerke ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Serial Position ◽

Episodic Memory ◽

Memory Performance ◽

Memory Function ◽

Word List ◽

Position Effects ◽

Serial Position Effects ◽

List Memory

Hippocampal dysfunction and deficits in episodic memory have been reported for both Alzheimer’s disease (AD) and major depressive disorder (MDD). Primacy performance has been associated with hippocampus-dependent episodic memory, while recency may reflect working memory performance. In this study, serial position profiles were examined in a total of 73 patients with MDD, AD, both AD and MDD, and healthy controls (HC) by means of CERAD-NP word list memory. Primacy performance was most impaired in AD with comorbid MDD, followed by AD, MDD, and HC. Recency performance, on the other hand, was comparable across groups. These findings indicate that primacy in AD is impaired in the presence of comorbid MDD, suggesting additive performance decrements in this specific episodic memory function.

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Effects of repetitive paired associative stimulation on brain plasticity and working memory in Alzheimer’s disease: a pilot randomized double-blind-controlled trial

International Psychogeriatrics ◽

10.1017/s1041610220003518 ◽

2020 ◽

pp. 1-13

Author(s):

Sanjeev Kumar ◽

Reza Zomorrodi ◽

Zaid Ghazala ◽

Michelle S. Goodman ◽

Daniel M. Blumberger ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Working Memory ◽

Brain Plasticity ◽

Controlled Trial ◽

Memory Performance ◽

Double Blind ◽

Paired Associative Stimulation ◽

Post Hoc ◽

The Impact

ABSTRACT Design: Pilot randomized double-blind-controlled trial of repetitive paired associative stimulation (rPAS), a paradigm that combines transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) with peripheral median nerve stimulation. Objectives: To study the impact of rPAS on DLPFC plasticity and working memory performance in Alzheimer’s disease (AD). Methods: Thirty-two patients with AD (females = 16), mean (SD) age = 76.4 (6.3) years were randomized 1:1 to receive a 2-week (5 days/week) course of active or control rPAS. DLPFC plasticity was assessed using single session PAS combined with electroencephalography (EEG) at baseline and on days 1, 7, and 14 post-rPAS. Working memory and theta–gamma coupling were assessed at the same time points using the N-back task and EEG. Results: There were no significant differences between the active and control rPAS groups on DLPFC plasticity or working memory performance after the rPAS intervention. There were significant main effects of time on DLPFC plasticity, working memory, and theta–gamma coupling, only for the active rPAS group. Further, on post hoc within-group analyses done to generate hypotheses for future research, as compared to baseline, only the rPAS group improved on post-rPAS day 1 on all three indices. Finally, there was a positive correlation between working memory performance and theta–gamma coupling. Conclusions: This study did not show a beneficial effect of rPAS for DLPFC plasticity or working memory in AD. However, post hoc analyses showed promising results favoring rPAS and supporting further research on this topic. (Clinicaltrials.gov-NCT01847586)

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Decreased Alpha Reactivity from Eyes-Closed to Eyes-Open in Non-Demented Older Adults with Alzheimer’s Disease: A Combined EEG and [18F]florbetaben PET Study

Journal of Alzheimer s Disease ◽

10.3233/jad-200442 ◽

2020 ◽

Vol 77 (4) ◽

pp. 1681-1692

Author(s):

Soohyun Chae ◽

Jinsick Park ◽

Min Soo Byun ◽

Dahyun Yi ◽

Jun Ho Lee ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Stage ◽

Memory Function ◽

Amyloid Β ◽

Clinical Predictors ◽

Eyes Closed ◽

Positron Emission ◽

Eyes Open ◽

Early Biomarker

Background: The degree of alpha attenuation from eyes-closed (EC) to eyes-open (EO) has been suggested as a neural marker of cognitive health, and its disruption has been reported in patients with clinically defined Alzheimer’s disease (AD) dementia. Objective: We tested if EC-to-EO alpha reactivity was related to cerebral amyloid-β (Aβ) deposition during the early stage of AD. Methods: Non-demented participants aged ≥55 years who visited the memory clinic between March 2018 and June 2019 (N = 143; 67.8% female; mean age±standard deviation, 74.0±7.6 years) were included in the analyses. Based on the [18F]florbetaben positron emission tomography assessment, the participants were divided into Aβ+ (N = 70) and Aβ- (N = 73) groups. EEG was recorded during the 7 min EC condition followed by a 3 min EO phase, and a Fourier transform spectral analysis was performed. Results: A significant three-way interaction was detected among Aβ positivity, eye condition, and the laterality factor on alpha-band power after adjusting for age, sex, educational years, global cognition, depression, medication use, and white matter hyperintensities on magnetic resonance imaging (F = 5.987, p = 0.016); EC-to-EO alpha reactivity in the left hemisphere was significantly reduced in Aβ+ subjects without dementia compared with the others (F = 3.984, p = 0.048). Conclusion: Among mild cognitive impairment subjects, alpha reactivity additively contributed to predict cerebral Aβ positivity beyond the clinical predictors, including vascular risks, impaired memory function, and apolipoprotein E ɛ4. These findings support that EC-to-EO alpha reactivity acts as an early biomarker of cerebral Aβ deposition and is a useful measurement for screening early-stage AD.

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

Scientific Reports ◽

10.1038/s41598-019-49731-8 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 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.

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The impact of age and Alzheimer’s disease risk factors on memory performance over time

Aging Health ◽

10.2217/ahe.12.77 ◽

2013 ◽

Vol 9 (1) ◽

pp. 115-124 ◽

Cited By ~ 1

Author(s):

Natalie C Kaiser ◽

Karen J Miller ◽

Prabha Siddarth ◽

Linda M Ercoli ◽

Gary W Small

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Disease Risk ◽

Memory Performance ◽

The Impact ◽

Over Time

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The Impact of Meditation on the Cognitive Functions of Patients with Alzheimer’s Disease

10.5327/1516-3180.231 ◽

2021 ◽

Author(s):

Maria Clara Lopes Rezende ◽

Mariana Vanon Moreira ◽

Bárbara Gomes Muffato ◽

Yves Henrique Faria Dias ◽

Ana Luíza Badini Tubenchlak ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Memory Function ◽

Brain Network ◽

Brain Structure And Function ◽

Improve Sleep Quality ◽

And Function ◽

The Impact ◽

The Brain ◽

Positive Effect

Introduction: Alzheimer’s disease (AD) is the most common form of dementia, which has no cure and, also, effective therapies to prevent or slow the progression of AD remain elusive. Thus, it is necessary to find another way to treat this disease Objective: Investigate the impact of meditation on the cognitive function of patients with AD. Methods: In April 2021, a systematic review was carried out on MEDLINE using the descriptors: “Meditation” and “Alzheimer Disease” and their variations. Studies published in the last 10 years and in English were included. Results: Of the 40 articles found, four are part of this review. It was showed that meditation generates improvements in memory as it increases cerebral blood flow, stabilizes synapses and elevates important neurotransmitters. Aligned, it can improve sleep quality and retrospective memory function. Furthermore, daily practices help in neuropsychological conditions and generate beneficial changes in brain structure and function. Finally, it provokes changes in the brain network, such as the increased power of the theta band, involved in memory processes. Conclusion: The results imply a positive effect of meditation on patients with AD. However, further research is needed to confirm the validity of the results.

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Evidence for a pervasive autobiographical memory impairment in Logopenic Progressive Aphasia: clinical and neural correlates

10.1101/2020.06.14.20131383 ◽

2020 ◽

Cited By ~ 1

Author(s):

Siddharth Ramanan ◽

David Foxe ◽

Hashim El-Omar ◽

Rebekah M. Ahmed ◽

John R. Hodges ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Autobiographical Memory ◽

Memory Impairment ◽

Language Disorder ◽

Memory Performance ◽

Memory Function ◽

Structured Interview ◽

Progressive Aphasia ◽

Memory Impairments

ABSTRACTLogopenic Progressive Aphasia is a rare language disorder characterised by repetition and naming difficulties, reflecting the progressive degeneration of left-lateralized peri-sylvian temporal and inferior parietal regions. Mounting evidence suggests that cognitive impairments in this syndrome extend beyond the language domain to include episodic encoding and retrieval disturbances. To date, it remains unknown whether autobiographical memories from across the lifespan are also subject to decline, yet this information is critical to arrive at a comprehensive understanding of the Logopenic syndrome. The objective of this study was to provide the first in depth examination of autobiographical memory function in Logopenic Progressive Aphasia using the Autobiographical Interview, a validated semi-structured interview which assesses recollection of the past under free and probed recall conditions. Autobiographical memory performance in 10 well-characterised Logopenic Progressive Aphasia patients was contrasted with that of 18 typical amnestic Alzheimer’s disease and 16 healthy Control participants. Relative to Controls, Logopenic Progressive Aphasia cases showed marked impairment in the free recall of episodic details, scoring comparably to disease-matched cases of Alzheimer’s disease. This impairment was evident across all time periods and persisted even when formal structured probing was provided. Importantly, controlling for overall level of language disruption failed to ameliorate the autobiographical memory impairment in the Logopenic Progressive Aphasia group, suggesting a genuine amnesia spanning recent and remote memories. Whole-brain voxel-based morphometry analyses revealed that total episodic information retrieved in Logopenic Progressive Aphasia was associated with decreased grey matter intensity predominantly in a bilateral posterior parietal network. Taken together, our findings reveal for the first time the presence of marked remote and recent autobiographical memory impairments in Logopenic Progressive Aphasia, that cannot be explained solely due to their language difficulties or disease staging. Our findings hold important clinical implications for the accurate characterization of Logopenic Progressive Aphasia, and suggest that episodic memory difficulties should be considered as one of the core clinical features of this syndrome.

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Abnormal Temporal Lobe Response in Alzheimer's Disease during Cognitive Processing as Measured by 11C-2-Deoxy-D-Glucose and PET

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1987.50 ◽

1987 ◽

Vol 7 (2) ◽

pp. 248-251 ◽

Cited By ~ 50

Author(s):

J. D. Miller ◽

M. J. de Leon ◽

S. H. Ferris ◽

A. Kluger ◽

A. E. George ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Processing ◽

Temporal Lobe ◽

Verbal Memory ◽

Right Hemisphere ◽

Memory Performance ◽

Memory Task ◽

Metabolic Rates ◽

Positron Emission

Elderly controls and probable Alzheimer's disease patients underwent serial positron emission tomography (PET) studies during a baseline condition and while performing a verbal memory task. for the temporal lobes, all 7 Alzheimer patients demonstrated a relative shift in glucose metabolic rates to the right hemisphere during the memory condition relative to baseline, and 5 of 7 controls showed a shift to the left hemisphere. Baseline absolute regional metabolic rates replicate previous findings and were somewhat less useful than the memory challenge in differentiating patients from controls. These results indicate that a temporal lobe abnormality in Alzheimer's disease is related to memory performance.

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Association between increased levels of amyloid-β oligomers in plasma and episodic memory loss in Alzheimer’s disease

Alzheimer s Research & Therapy ◽

10.1186/s13195-019-0535-7 ◽

2019 ◽

Vol 11 (1) ◽

Cited By ~ 3

Author(s):

Xue Meng ◽

Tao Li ◽

Xiao Wang ◽

Xiaozhen Lv ◽

Zhiyu Sun ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Episodic Memory ◽

Cognitive Performance ◽

Memory Performance ◽

Amyloid Β ◽

Disease Assessment ◽

Control Groups ◽

Delayed Recall ◽

And Control

Abstract Objective The objectives of this study were to investigate whether the plasma levels of oligomeric amyloid-β (OAβ) were affected in Alzheimer’s disease (AD) and to examine the associations (or possible correlations) between plasma OAβ levels and memory performance. Method Thirty subjects with AD and 28 cognitively normal controls were recruited in the study. The multimer detection system (MDS) was used to measure the levels of OAβ in the plasma. In addition to assessing the general cognitive function with the Mini-Mental State Examination (MMSE), Cognitive Abilities Screening Instrument (CASI), and Alzheimer’s Disease Assessment Scale–cognitive portion (ADAS-Cog), the common objects memory test (COMT) was used to examine the episodic memory performance. Pearson’s and partial correlation analyses were conducted to explore the associations between cognitive performance and OAβ levels in the plasma. A receiving operating curve (ROC) analysis was used to discriminate between the AD and control groups. Results The plasma OAβ levels in the AD group were significantly higher than those in the control group [1.88 (0.38) ng/ml vs 1.20 (0.40) ng/ml, p < 0.001]. The elevated levels of plasma OAβ showed a strong correlation with cognitive performance in patients with AD, including an inverse correlation with scores on the MMSE (r = − 0.43, p = 0.02), CASI (r = − 0.56, p < 0.01), and the immediate recall (r = − 0.45, p = 0.01), 5-min delayed recall (r = − 0.56, p < 0.01), and 30-min delayed recall (r = − 0.71, p < 0.001) tests of the COMT, and a positive correlation with the ADAS-Cog scores (r = 0.59, p < 0.001). The EDTA plasma Aβ oligomer optical density (OD) value measured using the MDS could discriminate between the AD and control groups with an area under the curve (AUC) of 0.89. The optimal sensitivity and specificity were 82.1% and 90.0%, respectively. Conclusion The elevated levels of OAβ in the plasma distinguished the AD and control groups and were associated with the severity of symptoms, especially memory performance, in patients with AD. Our results suggested that plasma OAβ could potentially be a simple and non-invasive blood-based biomarker for AD diagnosis. Furthermore, longitudinal studies are warranted to explore the application of plasma OAβ levels as a valid diagnostic biomarker in patients with AD.

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What’s the Cut-Point?: A Systematic Investigation of Tau PET Thresholding Methods

10.21203/rs.3.rs-962722/v1 ◽

2021 ◽

Author(s):

Alexandra June Weigand ◽

Anne Maass ◽

Graham Eglit ◽

Mark Bondi

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Memory Performance ◽

Operating Characteristics ◽

Cut Points ◽

Cut Point ◽

Pet Tracer ◽

Tau Pet ◽

Standard Deviations ◽

The Impact

Abstract Background: Tau positron emission tomography (PET) is increasing in popularity for biomarker characterization of Alzheimer’s disease (AD), and recent frameworks rely on tau PET cut-points to stage individuals along the AD continuum. Given the lack of standardization in tau PET thresholding methods, this study sought to systematically canvass and characterize existing studies that have derived tau PET cut-points and then directly assess different methods of tau PET thresholding in terms of their concurrent validity.Methods: First, a literature search was conducted in PubMed to identify studies of AD and related clinical phenotypes that used the Flortaucipir (AV-1451) tau PET tracer to derive a binary cut-point for tau positivity. Of 540 articles screened and 47 full-texts reviewed, 23 cohort studies met inclusion criteria with a total of 6,536 participants. In a 2x2x2 design that systematically varied region (temporal meta-ROI and entorhinal cortex), analytic method (receiver-operating characteristics and 2 standard deviations above comparison group), and criterion/comparison variable (amyloid-beta positivity or cognitive diagnosis), a sample from the Alzheimer’s Disease Neuroimaging Initiative yielded eight different tau PET cut-points. Results: For the systematic review, notable variability in sample characteristics, preprocessing methods, region of interest, and analytic approach were observed, which were accompanied by discrepancy in proposed tau PET cut points. The empirical follow-up indicated the cut-point derived based on 2 standard deviations above a cognitively unimpaired group in the temporal meta-ROI best differentiated tau positive and negative groups on cerebrospinal fluid phosphorylated tau, Mini-Mental State Examination score, and delayed memory performance. Conclusions: Given the impact of discrepant thresholds on tau positivity rates, biomarker staging, and eligibility for future clinical treatment trials, recommendations are offered to standardize cut-point derivations as additional tau PET tracers are developed and implemented in AD studies.

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