scholarly journals Cognitive Training Modulates Brain Hypersynchrony in a Population at Risk for Alzheimer’s Disease

2021 ◽  
Author(s):  
Isabel Suárez-Méndez ◽  
Ricardo Bruña ◽  
David López-Sanz ◽  
Pedro Montejo Carrasco ◽  
Mercedes Montenegro-Peña ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Training ◽  
Phase Locking ◽  
Cognitive Status ◽  
Subjective Cognitive Decline ◽  
Post Intervention ◽  
Preclinical Ad ◽  
Increased Risk ◽  
Before And After

Abstract BackgroundRecent neuroimaging studies in humans and animal models of Alzheimer’s disease (AD) demonstrated brain hyper-synchrony under amyloid burden, which is being identified as a proxy for conversion to dementia. The potential of non-pharmacological interventions to reverse this neurophysiological phenomenon in the early stages of the disease is still an open question. MethodBrain synchrony modulation by cognitive training (CogTr) was examined in a cohort of healthy controls (HC, n = 41, 22 trained) and individuals with subjective cognitive decline (SCD, n = 49, 24 trained). Magnetoencephalographic (MEG) activity and comprehensive neuropsychological scores were acquired before and after completion of a ten-week CogTr program aimed at improving cognitive function and daily living performance. Functional connectivity (FC) analyses were carried out using the phase-locking value. A mixed-effects ANOVA with factors stage (pre-intervention or post-intervention), CogTr (trained or non-trained), and cognitive status (HC or SCD) was used to estimate significant FC changes across MEG recordings.ResultsAlpha-band FC increases were observed for the whole sample (both trained and non-trained), but the effect was different in each group. For the trained group (both HC and SCD), we report a reduction in the FC increase within temporo-parietal and temporo-occipital connections. This effect was particularly manifest in trained participants with SCD, for whom the reduction in the FC increase also correlated with enhanced cognitive performance in different neuropsychological domains (memory, language, and executive function).ConclusionsCogTr programs could mitigate the increase in FC observed in preclinical AD, promoting brain synchrony normalization in groups at increased risk for developing the disease.

scholarly journals Association between methylation of BIN1 promoter in peripheral blood and preclinical Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hao Hu ◽  
Lan Tan ◽  
Yan-Lin Bi ◽  
Wei Xu ◽  
Lin Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Peripheral Blood ◽  
Late Onset ◽  
Early Stage ◽  
Susceptibility Gene ◽  
Subjective Cognitive Decline ◽  
Preclinical Ad ◽  
T Tau ◽  
New Evidence

AbstractThe bridging integrator 1 (BIN1) gene is the second most important susceptibility gene for late-onset Alzheimer’s disease (LOAD) after apolipoprotein E (APOE) gene. To explore whether the BIN1 methylation in peripheral blood changed in the early stage of LOAD, we included 814 participants (484 cognitively normal participants [CN] and 330 participants with subjective cognitive decline [SCD]) from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database. Then we tested associations of methylation of BIN1 promoter in peripheral blood with the susceptibility for preclinical AD or early changes of cerebrospinal fluid (CSF) AD-related biomarkers. Results showed that SCD participants with significant AD biological characteristics had lower methylation levels of BIN1 promoter, even after correcting for covariates. Hypomethylation of BIN1 promoter were associated with decreased CSF Aβ42 (p = 0.0008), as well as increased p-tau/Aβ42 (p = 0.0001) and t-tau/Aβ42 (p < 0.0001) in total participants. Subgroup analysis showed that the above associations only remained in the SCD subgroup. In addition, hypomethylation of BIN1 promoter was also accompanied by increased CSF p-tau (p = 0.0028) and t-tau (p = 0.0130) in the SCD subgroup, which was independent of CSF Aβ42. Finally, above associations were still significant after correcting single nucleotide polymorphic sites (SNPs) and interaction of APOE ɛ4 status. Our study is the first to find a robust association between hypomethylation of BIN1 promoter in peripheral blood and preclinical AD. This provides new evidence for the involvement of BIN1 in AD, and may contribute to the discovery of new therapeutic targets for AD.

scholarly journals Developing an Exergame Intervention to Prevent Alzheimer’s Disease

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 849-849
Author(s):  
Fang Yu ◽  
Dereck Salisbury ◽  
Tom Plocher
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Cognitive Training ◽  
Exercise Prescription ◽  
Subjective Cognitive Decline ◽  
Grocery Shopping ◽  
Cognitive Effect ◽  
Ad Prevention ◽  
The U.S

Abstract Delaying the onset of Alzheimer’s Disease by five years could save the U.S. ~$89 billion by 2030. Aerobic exercise and cognitive training are two promising interventions for AD prevention and the two together may have a synergistic cognitive effect than either alone. The purposes of this study were to develop an integrated virtual-reality cognitive training (VRCT) and cycling intervention known as exergame and test its feasibility in older adults with subjective cognitive decline (SCD). The VRCT included grocery shopping from a list, flower shopping from a list, dinnerware sorting, book sorting, and postage estimation. Twelve participants enrolled in the 1-month program (12 sessions) achieved 81.2% session adherence and 81.4% adherence to the exercise prescription. The exergame was well accepted by 75% of the participants and 100% were satisfied with the exergame quality and delivery. To conclude, exergame is a flexible intervention that is feasible for older adults with SCD.

scholarly journals RESTING HEART RATE MODERATES THE RELATIONSHIP BETWEEN NEUROPSYCHIATRIC SYMPTOMS, MCI, AND ALZHEIMER’S DISEASE

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S641-S641
Author(s):  
Shanna L Burke
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Heart Rate ◽  
Relative Risk ◽  
Neuropsychiatric Symptoms ◽  
Cognitive Status ◽  
Resting Heart Rate ◽  
Data Set ◽  
Increased Risk ◽  
The Relationship

Abstract Little is known about how resting heart rate moderates the relationship between neuropsychiatric symptoms and cognitive status. This study examined the relative risk of NPS on increasingly severe cognitive statuses and examined the extent to which resting heart rate moderates this relationship. A secondary analysis of the National Alzheimer’s Coordinating Center Uniform Data Set was undertaken, using observations from participants with normal cognition at baseline (13,470). The relative risk of diagnosis with a more severe cognitive status at a future visit was examined using log-binomial regression for each neuropsychiatric symptom. The moderating effect of resting heart rate among those who are later diagnosed with mild cognitive impairment (MCI) or Alzheimer’s disease (AD) was assessed. Delusions, hallucinations, agitation, depression, anxiety, elation, apathy, disinhibition, irritability, motor disturbance, nighttime behaviors, and appetite disturbance were all significantly associated (p&lt;.001) with an increased risk of AD, and a reduced risk of MCI. Resting heart rate increased the risk of AD but reduced the relative risk of MCI. Depression significantly interacted with resting heart rate to increase the relative risk of MCI (RR: 1.07 (95% CI: 1.00-1.01), p&lt;.001), but not AD. Neuropsychiatric symptoms increase the relative risk of AD but not MCI, which may mean that the deleterious effect of NPS is delayed until later and more severe stages of the disease course. Resting heart rate increases the relative risk of MCI among those with depression. Practitioners considering early intervention in neuropsychiatric symptomology may consider the downstream benefits of treatment considering the long-term effects of NPS.

scholarly journals Subjective cognitive decline: The first clinical manifestation of Alzheimer's disease?

2016 ◽  
Vol 10 (3) ◽  
pp. 170-177 ◽  
Author(s):  
Adalberto Studart Neto ◽  
Ricardo Nitrini
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Clinical Manifestation ◽  
Neurodegenerative Disorder ◽  
Subjective Cognitive Decline ◽  
Subjective Memory ◽  
Increased Risk

ABSTRACT Background: Mild cognitive impairment is considered as the first clinical manifestation of Alzheimer's disease (AD), when the individual exhibits below performance on standardized neuropsychological tests. However, some subjects before having a lower performance on cognitive assessments already have a subjective memory complaint. Objective: A review about subjective cognitive decline, the association with AD biomarkers and risk of conversion to dementia. Methods: We performed a comprehensive non-systematic review on PubMed. The keywords used in the search were terms related to subjective cognitive decline. Results: Subjective cognitive decline is characterized by self-experience of deterioration in cognitive performance not detected objectively through formal neuropsychological testing. However, various terms and definitions have been used in the literature and the lack of a widely accepted concept hampers comparison of studies. Epidemiological data have shown that individuals with subjective cognitive decline are at increased risk of progression to AD dementia. In addition, there is evidence that this group has a higher prevalence of positive biomarkers for amyloidosis and neurodegeneration. However, Alzheimer's disease is not the only cause of subjective cognitive decline and various other conditions can be associated with subjective memory complaints, such as psychiatric disorders or normal aging. The features suggestive of a neurodegenerative disorder are: onset of decline within the last five years, age at onset above 60 years, associated concerns about decline and confirmation by an informant. Conclusion: These findings support the idea that subjective cognitive complaints may be an early clinical marker that precedes mild cognitive impairment due to Alzheimer's disease.

scholarly journals Neuroinflammation characterizes the earliest changes in Alzheimer’s disease pathology and associated subjective cognitive impairment in adult hydrocephalus biopsies

2020 ◽  
Author(s):  
Wenrui Huang ◽  
Anne Marie Bartosch ◽  
Harrison Xiao ◽  
Xena Flowers ◽  
Sandra Leskinen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Status ◽  
Subjective Cognitive Decline ◽  
Cognitive Symptoms ◽  
Microglial Phenotype ◽  
Neuronal Genes ◽  
Early Alzheimer’S Disease ◽  
Disease Associated Genes ◽  
Microglial Response

AbstractIn an effort to better characterize the transcriptomic changes that accompany early Alzheimer’s disease (AD) pathology in living patients and correlate with contemporaneous cognitive data, we performed RNA-seq on 106 cortical biopsies that were taken during shunt placement for adult onset hydrocephalus with varying degrees of comorbid AD pathology. A restricted set of genes correlate with AD pathology in these biopsies, and co-expression network analysis demonstrates an evolution from microglial homeostasis to a disease-associated microglial phenotype in conjunction with increasing AD pathologic burden, along with a subset of additional astrocytic and neuronal genes that accompany these changes. Further analysis demonstrates that these correlations are driven by patients that report mild cognitive symptoms, despite similar levels of β-amyloid and tau pathology in comparison to patients who report no cognitive symptoms. Interestingly, downregulation of homeostatic genes and upregulation of disease-associated genes also correlate with microglial plaque invasion and an activated microglial morphology, and this change is not sensitive to cognitive status, suggesting that an initial microglial response to AD pathology is eventually maladaptive. Taken together, these findings highlight a restricted set of microglial and non-microglial genes and suggest that early AD pathology is largely characterized by a loss of homeostatic genes and an activated microglial phenotype that continues to evolve in conjunction with accumulating AD pathology in the setting of subjective cognitive decline.

scholarly journals Research on Design Strategies of Cognitive Training System Based on SCD Elderly Behavioral and Psychological Characteristics

2020 ◽  
Vol 179 ◽  
pp. 02048
Author(s):  
Yanmin XUE ◽  
Rui LIN ◽  
Chang GE
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
System Design ◽  
Cognitive Training ◽  
Computer Aided Design ◽  
Training System ◽  
Psychological Characteristics ◽  
Design System ◽  
Subjective Cognitive Decline ◽  
Design Strategies

Alzheimer’s disease (hereinafter referred to as AD) has become a major global health problem for the elderly. Combining with the current computer-aided design system design for prevention and training of Alzheimer’s disease is one of the important ways to solve this problem. This study aims at the early subjective cognitive decline of Alzheimer’s disease (hereinafter referred to as SCD) . Through investigation and research, the behavior and psychological characteristics of SCD elderly are sorted out, and the main functions of cognitive training system are located. The main functions, interactions, colors and layout of the current cognitive system are summarized by analyzing the existing cognitive training system, and compared with the research results, a more reasonable system function, interaction mode, interface color and layout are determined. Therefore, the cognitive training system design strategy based on the behavioral and psychological characteristics of SCD elderly is summarized.

Biomarkers and Tools for Predicting Alzheimer’s Disease at the Preclinical Stage

2021 ◽  
Vol 19 ◽  
Author(s):  
Tao-Ran Li ◽  
Qin Yang ◽  
Xiaochen Hu ◽  
Ying Han
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Communication ◽  
High Sensitivity ◽  
Screening Tools ◽  
Therapeutic Window ◽  
Subjective Cognitive Decline ◽  
Preclinical Stage ◽  
Functional Changes ◽  
Preclinical Ad

: Alzheimer’s disease (AD) is the only leading cause of death for which no disease-modifying therapy is currently available. Over the past decade, a string of disappointing clinical trial results has forced us to shift our focus to the preclinical stage of AD, which represents the most promising therapeutic window. However, the accurate diagnosis of preclinical AD requires the presence of brain β-amyloid deposition determined by cerebrospinal fluid or amyloid-positron emission tomography, significantly limiting routine screening and diagnosis in non-tertiary hospital settings. Thus, an easily accessible marker or tool with high sensitivity and specificity is highly needed. Recently, it has been discovered that individuals in the late stage of preclinical AD may not be truly “asymptomatic” in that they may have already developed subtle or subjective cognitive decline. In addition, advances in blood-derived biomarker studies have also allowed detection of pathologic changes in preclinical AD. Exosomes, as cell-to-cell communication messengers, can reflect the functional changes of their source cell. Methodological advances have made it possible to extract brain-derived exosomes from peripheral blood, making exosomes an emerging biomarker carrier and liquid biopsy tool for preclinical AD. The eye and its associated structures have rich sensory-motor innervation. In this regard, studies have indicated that they may also provide reliable markers. Here, our report covers the current state of knowledge of neuropsychological and eye tests as screening tools for preclinical AD and assesses the value of blood and brain-derived exosomes as carriers of biomarkers in conjunction with the current diagnostic paradigm.

scholarly journals Adaptive working memory strategy training in early Alzheimer's disease: Randomised controlled trial

2017 ◽  
Vol 210 (1) ◽  
pp. 61-66 ◽  
Author(s):  
J. D. Huntley ◽  
A. Hampshire ◽  
D. Bor ◽  
A. Owen ◽  
R. J. Howard
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Working Memory ◽  
Cognitive Function ◽  
Cognitive Training ◽  
Controlled Trial ◽  
Verbal Working Memory ◽  
Strategy Training ◽  
Post Intervention ◽  
Early Alzheimer’S Disease

BackgroundInterventions that improve cognitive function in Alzheimer's disease are urgently required.AimsTo assess whether a novel cognitive training paradigm based on ‘chunking’ improves working memory and general cognitive function, and is associated with reorganisation of functional activity in prefrontal and parietal cortices (trial registration: ISRCTN43007027).MethodThirty patients with mild Alzheimer's disease were randomly allocated to receive 18 sessions of 30 min of either adaptive chunking training or an active control intervention over approximately 8 weeks. Pre- and post-intervention functional magnetic resonance imaging (fMRI) scans were also conducted.ResultsAdaptive chunking training led to significant improvements in verbal working memory and untrained clinical measures of general cognitive function. Further, fMRI revealed a bilateral reduction in task-related lateral prefrontal and parietal cortex activation in the training group compared with controls.ConclusionsChunking-based cognitive training is a simple and potentially scalable intervention to improve cognitive function in early Alzheimer's disease.

Blink rate study in patients with Alzheimer's disease, Mild Cognitive Impairment and Subjective Cognitive Decline

2021 ◽  
Vol 19 ◽  
Author(s):  
Fabrizia D’Antonio ◽  
Maria Ilenia De Bartolo ◽  
Gina Ferrazzano ◽  
Micaela Sepe Monti ◽  
Letizia Imbriano ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Cognitive Status ◽  
Subjective Cognitive Decline ◽  
Blink Rate ◽  
Compensatory Mechanisms ◽  
Rate Study

Background: Blink rate (BR) is considered a marker of dopaminergic activity in humans. BR is increased in patients with Mild Cognitive Impairment (MCI), but no study has yet investigated whether BR changes with the progression of cognitive decline from MCI to Alzheimer’s disease (AD) and whether BR abnormalities are present in subjects with Subjective Cognitive Decline (SCD). Objective: The aim of our study was to assess BR in patients with AD, MCI, and SCD and to correlate BR with demographic and clinical features of cognitive decline. Methods: We enrolled 22 subjects with SCD, 23 with MCI, and 18 with AD and a group of 20 age-matched healthy controls (HCs). Cognitive function was assessed by testing global cognitive status and frontal, attentional, memory, verbal, and visuospatial functions. BR was measured by counting the number of blinks per minute. Results: MCI subjects had an increased BR (p<0.001), whereas AD subjects had a lower BR than HCs (p<0.05). Conversely, SCD subjects had a BR similar to HCs. No significant correlations emerged between neuropsychological scores and BR in SCD, MCI, and AD subjects. Conclusion: Increased BR in MCI likely reflects early compensatory mechanisms occurring before AD, whereas decreased BR in AD suggests dopaminergic system involvement in this condition.

scholarly journals Evidence for Reduced Autobiographical Memory Episodic Specificity in Cognitively Normal Middle-Aged and Older Individuals at Increased Risk for Alzheimer’s Disease Dementia

2018 ◽  
Vol 24 (10) ◽  
pp. 1073-1083 ◽  
Author(s):  
Matthew D. Grilli ◽  
Aubrey A. Wank ◽  
John J. Bercel ◽  
Lee Ryan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Older Individuals ◽  
Autobiographical Memories ◽  
Middle Aged ◽  
Cognitively Normal ◽  
Preclinical Ad ◽  
Increased Risk ◽  
And Gender

AbstractObjectives: Alzheimer’s disease (AD) typically eludes clinical detection for years, if not decades. The identification of subtle cognitive decline associated with preclinical AD would not only advance understanding of the disease, but also provide clinical targets to assess preventative and early intervention treatments. Disrupted retrieval of detailed episodic autobiographical memories may be a sensitive indicator of subtle cognitive decline, because this type of memory taxes a core neural network affected by preclinical AD neuropathology. Methods: To begin to address this idea, we assessed the episodic specificity of autobiographical memories retrieved by cognitively normal middle-aged and older individuals who are carriers of the apolipoprotein E ε4 allele – a population at increased risk for subtle cognitive decline related to neuropathological risk factors for AD. We compared the ε4 carriers to non-carriers of ε4 similar in age, education, and gender. Results: The ε4 carriers did not perform worse than the non-carriers on a comprehensive battery of neuropsychological tests. In contrast, as a group, the ε4 carriers generated autobiographical memories that were reduced in “internal” or episodic details relative to non-carriers. Conclusions: These findings support the notion that reduced autobiographical episodic detail generation may be a marker of subtle cognitive decline associated with AD. (JINS, 2018, 24, 1073–1183)

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