Memory and thinking in later life, and their decline.
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451 to 475 of 1,152A Armstrong R (2019)reviewMEDLINE-indexed journal, not yet read by usFolia neuropathologica364 citations Risk factors for Alzheimer's disease.
Early reviews identified over 20 risk factors associated with Alzheimer's disease (AD) including age, familial inheritance, exposure to aluminium, traumatic brain injury (TBI), and associated co-morbidities such as vascular disease and infection. In the light of recent evidence, this review reconsiders these risk factors, identifies those currently regarded as important, and discusses various hypotheses to explain how they may cause AD. Rare forms of early-onset familial AD (EO-FAD) are strongly linked to causal gene mutations, viz. mutations in amyloid precursor protein (APP) and presenilin (PSEN1/2) genes. By contrast, late-onset sporadic AD (LO-SAD) is a multifactorial disorder in which age-related changes, genetic risk factors, such as allelic variation in apolipoprotein E (Apo E) and many other genes, vascular disease, TBI and risk factors associated with diet, the immune system, mi…
matched on Alzheimer Disease (mesh), Amyloid beta-Peptides (mesh)
The Role of Amyloid-β Oligomers in Toxicity, Propagation, and Immunotherapy.
The incidence of Alzheimer's disease (AD) is growing every day and finding an effective treatment is becoming more vital. Amyloid-β (Aβ) has been the focus of research for several decades. The recent shift in the Aβ cascade hypothesis from all Aβ to small soluble oligomeric intermediates is directing the search for therapeutics towards the toxic mediators of the disease. Targeting the most toxic oligomers may prove to be an effective treatment by preventing their spread. Specific targeting of oligomers has been shown to protect cognition in rodent models. Additionally, the heterogeneity of research on Aβ oligomers may seem contradictory until size and conformation are taken into account. In this review, we will discuss Aβ oligomers and their toxicity in relation to size and conformation as well as their influence on inflammation and the potential of Aβ oligomer immunotherapy.
matched on Alzheimer Disease (mesh), Amyloid beta-Peptides (mesh)
The Role of Oxidative Stress-Induced Epigenetic Alterations in Amyloid-β Production in Alzheimer's Disease.
An increasing number of studies have proposed a strong correlation between reactive oxygen species (ROS)-induced oxidative stress (OS) and the pathogenesis of Alzheimer's disease (AD). With over five million people diagnosed in the United States alone, AD is the most common type of dementia worldwide. AD includes progressive neurodegeneration, followed by memory loss and reduced cognitive ability. Characterized by the formation of amyloid-beta (Aβ) plaques as a hallmark, the connection between ROS and AD is compelling. Analyzing the ROS response of essential proteins in the amyloidogenic pathway, such as amyloid-beta precursor protein (APP) and beta-secretase (BACE1), along with influential signaling programs of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and c-Jun N-terminal kinase (JNK), has helped visualize the path between OS and Aβ overproduction. In this …
matched on Alzheimer Disease (mesh), Amyloid beta-Peptides (mesh)
Alkaloids as a source of potential anticholinesterase inhibitors for the treatment of Alzheimer's disease.
Objectives: The inhibition of acetylcholinesterase (AChE), the key enzyme in the breakdown of acetylcholine, is currently the main pharmacological strategy available for Alzheimer's disease (AD). In this sense, many alkaloids isolated from natural sources, such as physostigmine, have been long recognized as acetyl- and butyrylcholinesterase (BChE) inhibitors. Since the approval of galantamine for the treatment of AD patients, the search for new anticholinesterase alkaloids has escalated, leading to promising candidates such as huperzine A. This review aims to summarize recent advances in current knowledge on alkaloids as AChE and BChE inhibitors, highlighting structure-activity relationship (SAR) and docking studies.
Key findings: Natural alkaloids belonging to the steroidal/triterpenoidal, quinolizidine, isoquinoline and indole classes, mainly distributed within Buxaceae, Amaryllidaceae…
matched on Alzheimer Disease (mesh), Amyloid beta-Peptides (mesh)
Melatonin in Alzheimer's disease.
Alzheimer's disease (AD), an age-related neurodegenerative disorder with progressive cognition deficit, is characterized by extracellular senile plaques (SP) of aggregated β-amyloid (Aβ) and intracellular neurofibrillary tangles, mainly containing the hyperphosphorylated microtubule-associated protein tau. Multiple factors contribute to the etiology of AD in terms of initiation and progression. Melatonin is an endogenously produced hormone in the brain and decreases during aging and in patients with AD. Data from clinical trials indicate that melatonin supplementation improves sleep, ameliorates sundowning and slows down the progression of cognitive impairment in AD patients. Melatonin efficiently protects neuronal cells from Aβ-mediated toxicity via antioxidant and anti-amyloid properties. It not only inhibits Aβ generation, but also arrests the formation of amyloid fibrils by a structu…
matched on Alzheimer Disease (mesh), Amyloid beta-Peptides (mesh)
Telomere shortening and Alzheimer's disease.
Telomeres, at the ends of chromosomes and strands of genetic material, become shorter as cells divide in the process of aging. Telomere length has been considered as a biological marker of age. Telomere length shortening has also been evidenced as the causable role in age-related neurodegenerative diseases, including Alzheimer's disease (AD). It has been demonstrated that telomere shortening has been associated with cognitive impairment, amyloid pathology and hyper-phosphorylation of tau in AD and plays an important role in the pathogenesis of AD via the mechanism of oxidative stress and inflammation. However, it seems that there is no relationship between telomere shortening and AD. Therefore, it is essential for further clarification of telomere-related pathogenesis in AD.
matched on Alzheimer Disease (mesh), Amyloid beta-Peptides (mesh)
Epigenetics, oxidative stress, and Alzheimer disease.
Alzheimer disease (AD) is a progressive neurodegenerative disorder whose clinical manifestations appear in old age. The sporadic nature of 90% of AD cases, the differential susceptibility to and course of the illness, as well as the late age onset of the disease suggest that epigenetic and environmental components play a role in the etiology of late-onset AD. Animal exposure studies demonstrated that AD may begin early in life and may involve an interplay between the environment, epigenetics, and oxidative stress. Early life exposure of rodents and primates to the xenobiotic metal lead (Pb) enhanced the expression of genes associated with AD, repressed the expression of others, and increased the burden of oxidative DNA damage in the aged brain. Epigenetic mechanisms that control gene expression and promote the accumulation of oxidative DNA damage are mediated through alterations in the m…
matched on Alzheimer Disease (mesh), Amyloid beta-Peptides (mesh)
Anesthesiology and cognitive impairment: a narrative review of current clinical literature.
Background: The impact of general anesthesia on cognitive impairment is controversial and complex. A large body of evidence supports the association between exposure to surgery under general anesthesia and development of delayed neurocognitive recovery in a subset of patients. Existing literature continues to debate whether these short-term effects on cognition can be attributed to anesthetic agents themselves, or whether other variables are causative of the observed changes in cognition. Furthermore, there is conflicting data on the relationship between anesthesia exposure and the development of long-term neurocognitive disorders, or development of incident dementia in the patient population with normal preoperative cognitive function. Patients with pre-existing cognitive impairment present a unique set of anesthetic considerations, including potential medication interactions, challenge…
matched on Cognitive Dysfunction (mesh), Dementia (keyword)
Contributions of loneliness to cognitive impairment and dementia in older adults are independent of other risk factors and Alzheimer's pathology: a narrative review.
Loneliness significantly contributes to cognitive impairment and dementia in older adults. Loneliness is a distressing feeling resulting from a perceived lack of social connection (i.e., a discrepancy between desired and actual social relationships), while social isolation is a related term that can be defined by number and type of social relationships. Importantly, loneliness is distinct from social isolation in that it is associated with a distressing self-perception. The primary focus of this narrative review is the impact of chronic loneliness on cognitive impairment and dementia among older adults. Loneliness has a significant association with many factors that are related to worse cognition, and therefore we include discussion on health, mental health, as well as the physiological effects of loneliness, neuropathology, and potential treatments. Loneliness has been shown to be relat…
matched on Dementia (keyword), cognitive decline (text), mild cognitive impairment (text)
The Gut Microbiota and Alzheimer's Disease.
The gut microbiota comprises a complex community of microorganism species that resides in our gastrointestinal ecosystem and whose alterations influence not only various gut disorders but also central nervous system disorders such as Alzheimer's disease (AD). AD, the most common form of dementia, is a neurodegenerative disorder associated with impaired cognition and cerebral accumulation of amyloid-β peptides (Aβ). Most notably, the microbiota-gut-brain axis is a bidirectional communication system that is not fully understood, but includes neural, immune, endocrine, and metabolic pathways. Studies in germ-free animals and in animals exposed to pathogenic microbial infections, antibiotics, probiotics, or fecal microbiota transplantation suggest a role for the gut microbiota in host cognition or AD-related pathogenesis. The increased permeability of the gut and blood-brain barrier induced …
matched on Alzheimer Disease (mesh), Amyloid beta-Peptides (keyword)
Caruso G, Torrisi SA, Mogavero MP, Currenti W, Castellano S, Godos J, Ferri R, Galvano F, Leggio GM, Grosso G, Caraci F (2022)reviewMEDLINE-indexed journal, not yet read by usPharmacology & therapeutics97 citations Polyphenols and neuroprotection: Therapeutic implications for cognitive decline.
Dietary polyphenols have been the focus of major interest for their potential benefits on human health. Several preclinical studies have been conducted to provide a rationale for their potential use as therapeutic agents in preventing or ameliorating cognitive decline. However, results from human studies are scarce and poorly documented. The aim of this review was to discuss the potential mechanisms involved in age-related cognitive decline or early stage cognitive impairment and current evidence from clinical human studies conducted on polyphenols and the aforementioned outcomes. The evidence published so far is encouraging but contrasting findings are to be taken into account. Most studies on anthocyanins showed a consistent positive effect on various cognitive aspects related to aging or early stages of cognitive impairment. Studies on cocoa flavanols, resveratrol, and isoflavones pro…
matched on Cognitive Dysfunction (mesh), cognitive decline (text)
An Integrative Framework to Guide Social Engagement Interventions and Technology Design for Persons With Mild Cognitive Impairment.
Social isolation and loneliness in older adults are associated with poor health outcomes and have been linked to an increased risk of cognitive impairment and incident dementia. Social engagement has been identified as a key factor in promoting positive health behaviors and quality of life and preventing social isolation and loneliness. Studies involving cognitively healthy older adults have shown the protective effects of both in-person and technology-based social engagement. However, the benefits of social engagement for people who are already at-risk of developing dementia, namely those with mild cognitive impairment (MCI), have yet to be elucidated. We present a narrative review of the literature, summarizing the research on social engagement in MCI. First, we identified social networks (quality, size, frequency, and closeness) and social activities (frequency, format, purpose, type,…
matched on Cognitive Dysfunction (mesh), mild cognitive impairment (text)
Sex differences in sleep and sleep loss-induced cognitive deficits: The influence of gonadal hormones.
Males and females can respond differentially to the same environmental stimuli and experimental conditions. Chronic sleep loss is a frequent and growing problem in many modern societies and has a broad variety of negative outcomes for health and well-being. While much has been done to explore the deleterious effects of sleep deprivation (SD) on cognition in both human and animal studies over the last few decades, very little attention has been paid to the part played by sex differences and gonadal steroids in respect of changes in cognitive functions caused by sleep loss. The effects of gonadal hormones on sleep regulation and cognitive performances are well established. Reduced gonadal function in menopausal women and elderly men is associated with sleep disturbances and cognitive decline as well as dementia, which suggests that sex steroids play a key role in modulating these condition…
matched on Cognitive Dysfunction (mesh), cognitive decline (text)
Mechanisms of radiotherapy-associated cognitive disability in patients with brain tumours.
Standard treatment of primary and metastatic brain tumours includes high-dose megavoltage-range radiation to the cranial vault. About half of patients survive >6 months, and many attain long-term control or cure. However, 50-90% of survivors exhibit disabling cognitive dysfunction. The radiation-associated cognitive syndrome is poorly understood and has no effective prevention or long-term treatment. Attention has primarily focused on mechanisms of disability that appear at 6 months to 1 year after radiotherapy. However, recent studies show that CNS alterations and dysfunction develop much earlier following radiation exposure. This finding has prompted the hypothesis that subtle early forms of radiation-induced CNS damage could drive chronic pathophysiological processes that lead to permanent cognitive decline. This Review presents evidence of acute radiation-triggered CNS inflammation, …
matched on Cognitive Dysfunction (mesh), cognitive decline (text)
Diet-Induced Cognitive Deficits: The Role of Fat and Sugar, Potential Mechanisms and Nutritional Interventions.
It is of vital importance to understand how the foods which are making us fat also act to impair cognition. In this review, we compare the effects of acute and chronic exposure to high-energy diets on cognition and examine the relative contributions of fat (saturated and polyunsaturated) and sugar to these deficits. Hippocampal-dependent memory appears to be particularly vulnerable to the effects of high-energy diets and these deficits can occur rapidly and prior to weight gain. More chronic diet exposure seems necessary however to impair other sorts of memory. Many potential mechanisms have been proposed to underlie diet-induced cognitive decline and we will focus on inflammation and the neurotrophic factor, brain-derived neurotrophic factor (BDNF). Finally, given supplementation of diets with omega-3 and curcumin has been shown to have positive effects on cognitive function in healthy …
matched on Memory Disorders (mesh), cognitive decline (text)
Liu P, Wu L, Peng G, Han Y, Tang R, Ge J, Zhang L, Jia L, Yue S, Zhou K, Li L, Luo B, Wang B (2019)MEDLINE-indexed journal, not yet read by usBrain, behavior, and immunity472 citations Altered microbiomes distinguish Alzheimer's disease from amnestic mild cognitive impairment and health in a Chinese cohort.
Objective: (Background): Alzheimer's disease (AD), clinically characterized by the progressive neurodegenerative condition and cognitive impairment, is one of the main causes of disability in elder people worldwide. Recently, several animal studies indicated that the 'gut-brain' axis might contribute to the amyloid deposition of AD. However, data about gut dysbiosis in human AD remains scarce in the literature, especially including the whole process of AD. In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC). Additionally, the potential association between IM and clinical characteristics of AD was evaluated.
Methods: A total of 97 subjects (33 AD, 32 aMCI, and 32 HC) were recruited in the study. The composit…
matched on Alzheimer Disease (mesh), Cognitive Dysfunction (mesh), mild cognitive impairment (text)
Gaggioni G, Ly JQM, Muto V, Chellappa SL, Jaspar M, Meyer C, Delfosse T, Vanvinckenroye A, Dumont R, Coppieters 't Wallant D, Berthomier C, Narbutas J, Van Egroo M, Luxen A, Salmon E, Collette F, Phillips C, Schmidt C, Vandewalle G (2019)MEDLINE-indexed journal, not yet read by usNeurobiology of aging37 citations Age-related decrease in cortical excitability circadian variations during sleep loss and its links with cognition.
Cortical excitability depends on sleep-wake regulation, is central to cognition, and has been implicated in age-related cognitive decline. The dynamics of cortical excitability during prolonged wakefulness in aging are unknown, however. Here, we repeatedly probed cortical excitability of the frontal cortex using transcranial magnetic stimulation and electroencephalography in 13 young and 12 older healthy participants during sleep deprivation. Although overall cortical excitability did not differ between age groups, the magnitude of cortical excitability variations during prolonged wakefulness was dampened in older individuals. This age-related dampening was associated with mitigated neurobehavioral consequences of sleep loss on executive functions. Furthermore, higher cortical excitability was potentially associated with better and lower executive performance, respectively, in older and …
matched on Cognitive Aging (mesh), Cognitive Dysfunction (mesh), cognitive decline (text)
Mito R, Raffelt D, Dhollander T, Vaughan DN, Tournier JD, Salvado O, Brodtmann A, Rowe CC, Villemagne VL, Connelly A (2018)MEDLINE-indexed journal, not yet read by usBrain : a journal of neurology243 citations Fibre-specific white matter reductions in Alzheimer's disease and mild cognitive impairment.
Alzheimer's disease is increasingly considered a large-scale network disconnection syndrome, associated with progressive aggregation of pathological proteins, cortical atrophy, and functional disconnections between brain regions. These pathological changes are posited to arise in a stereotypical spatiotemporal manner, targeting intrinsic networks in the brain, most notably the default mode network. While this network-specific disruption has been thoroughly studied with functional neuroimaging, changes to specific white matter fibre pathways within the brain's structural networks have not been closely investigated, largely due to the challenges of modelling complex white matter structure. Here, we applied a novel technique known as 'fixel-based analysis' to comprehensively investigate fibre tract-specific differences at a within-voxel level (called 'fixels') to assess potential axonal los…
matched on Alzheimer Disease (mesh), Cognitive Dysfunction (mesh), mild cognitive impairment (text)
Loneliness and Cognitive Function in Older Adults: Findings From the Chinese Longitudinal Healthy Longevity Survey.
Objectives: To examine the relationship between loneliness and cognitive function and to explore the mediating role of physical health on the loneliness-cognition relationship in Chinese older adults (OAs).
Method: Data came from a nationally representative sample of 14,199 Chinese OAs (aged 65+) from 2002, 2005, 2008, and 2011 waves of the Chinese Longitudinal Healthy Longevity Survey. A latent variable cross-lagged panel model combined with mediation analysis was used to determine the relationship between loneliness and cognitive function and the mediating effect of increase in the number of chronic conditions (ΔNCCs) on the ascertained loneliness-cognition relationship.
Results: Severe loneliness at prior assessment points was significantly associated with poorer cognitive function at subsequent assessments, and vice versa. The ΔNCCs partially mediated this prospective reciprocal rela…
matched on Cognitive Aging (mesh), Cognitive Dysfunction (mesh), cognitive decline (text)
Therapeutic potential of Bifidobacterium breve strain A1 for preventing cognitive impairment in Alzheimer's disease.
It has previously been shown that the consumption of probiotics may have beneficial effects not only on peripheral tissues but also on the central nervous system and behavior via the microbiota-gut-brain axis, raising the possibility that treatment with probiotics could be an effective therapeutic strategy for managing neurodegenerative disorders. In this study, we investigated the effects of oral administration of Bifidobacterium breve strain A1 (B. breve A1) on behavior and physiological processes in Alzheimer's disease (AD) model mice. We found that administration of B. breve A1 to AD mice reversed the impairment of alternation behavior in a Y maze test and the reduced latency time in a passive avoidance test, indicating that it prevented cognitive dysfunction. We also demonstrated that non-viable components of the bacterium or its metabolite acetate partially ameliorated the cognitiv…
matched on Alzheimer Disease (mesh), Cognitive Dysfunction (mesh), cognitive decline (text)
Xiao S, Lewis M, Mellor D, McCabe M, Byrne L, Wang T, Wang J, Zhu M, Cheng Y, Yang C, Dong S (2016)MEDLINE-indexed journal, not yet read by usJournal of mental health (Abingdon, England)41 citations The China longitudinal ageing study: overview of the demographic, psychosocial and cognitive data of the Shanghai sample.
Background: China's ageing population will lead to increased neurodegenerative illness and age-related mental health problems.
Aims: The Chinese Longitudinal Ageing Study has been developed to better understand the impact of ageing on cognition and mental health. An overview of the sample, major diagnoses and results of the first wave of data collection is presented.
Method: One thousand and sixty-eight elderly Chinese (42.2% male), mean age of 72.8 years (SD = 8.5) completed a comprehensive cognitive, psychosocial and mental health assessment.
Results: Mean MMSE score was 24.73 (SD = 6.17). Primary generalised anxiety was detected in 0.4% of the sample. Sub-clinical depression and depressive disorder were diagnosed in 1.7% and 2.4% of the sample, respectively. Most (84.5%) reported subjective memory decline, however 66.5% had no cognitive impairment. Mild Cognitive Impairment (MCI) was …
matched on Dementia (mesh), Cognitive Dysfunction (mesh), mild cognitive impairment (text)
Serum 25-hydroxyvitamin D level and the risk of mild cognitive impairment and dementia: the Korean Longitudinal Study on Health and Aging (KLoSHA).
Objective: The association of low vitamin D status with mild cognitive impairment (MCI), a preclinical condition that can lead to dementia, has not yet been fully explored. Our aim was to investigate the association between vitamin D status and the future risk of MCI and dementia in older adults.
Design, setting and participants: We conducted a population-based prospective study as a part of the Korean Longitudinal Study on Health and Aging. Four hundred and twelve elderly participants who completed evaluations of cognitive function and metabolic parameters in 2005-2006 and 2010-2011 were analysed.
Major outcome measure: The rate of development of MCI or dementia during the study period was compared according to baseline vitamin D status. Binary logistic regression analysis was performed to investigate any independent association between vitamin D status and the risks of MCI or dementia.…
matched on Dementia (mesh), Cognitive Dysfunction (mesh), mild cognitive impairment (text)
Motivational processes in mild cognitive impairment and Alzheimer's disease: results from the Motivational Reserve in Alzheimer's (MoReA) study.
Background: Brain reserve, i.e., the ability of the brain to tolerate age- and disease-related changes in a way that cognitive function is still maintained, is assumed to be based on the lifelong training of various abilities. The Motivational Reserve in Alzheimer's (MoReA) is a longitudinal study that aims to examine motivational processes as a protective factor in mild Alzheimer's dementia (AD) and mild cognitive impairment (MCI). This paper presents the results of motivational variables, frequency of diagnoses, and prediction of global cognition as well as depression in a one-year longitudinal study.
Methods: The sample consists of 64 subjects with MCI and 47 subjects with mild AD at baseline. At baseline, the physical/neurological examinations, standard clinical assessment, neuropsychological testing, and assessment of motivational variables were performed. At follow-up (FU) one year…
matched on Alzheimer Disease (mesh), Cognitive Dysfunction (mesh), mild cognitive impairment (text)
Disrupted functional brain connectome in individuals at risk for Alzheimer's disease.
Background: Alzheimer's disease disrupts the topological architecture of whole-brain connectivity (i.e., the connectome); however, whether this disruption is present in amnestic mild cognitive impairment (aMCI), the prodromal stage of Alzheimer's disease, remains largely unknown.
Methods: We employed resting-state functional magnetic resonance imaging and graph theory approaches to systematically investigate the topological organization of the functional connectome of 37 patients with aMCI and 47 healthy control subjects. Frequency-dependent brain networks were derived from wavelet-based correlations of both high- and low-resolution parcellation units.
Results: In the frequency interval .031-.063 Hz, the aMCI patients showed an overall decreased functional connectivity of their brain connectome compared with control subjects. Further graph theory analyses of this frequency band revealed …
matched on Alzheimer Disease (mesh), Cognitive Dysfunction (mesh), mild cognitive impairment (text)
Binnewijzend MA, Schoonheim MM, Sanz-Arigita E, Wink AM, van der Flier WM, Tolboom N, Adriaanse SM, Damoiseaux JS, Scheltens P, van Berckel BN, Barkhof F (2012)MEDLINE-indexed journal, not yet read by usNeurobiology of aging291 citations Resting-state fMRI changes in Alzheimer's disease and mild cognitive impairment.
Regional functional connectivity (FC) of 39 patients with Alzheimer's disease (AD), 23 patients with mild cognitive impairment (MCI), and 43 healthy elderly controls was studied using resting-state functional magnetic resonance imaging (rs-fMRI). After a mean follow-up of 2.8 ± 1.9 years, 7 MCI patients converted to AD, while 14 patients remained cognitively stable. Resting-state functional magnetic resonance imaging scans were analyzed using independent component analysis (ICA), followed by a "dual-regression" technique to create and compare subject-specific maps of each independent spatiotemporal component, correcting for age, sex, and gray matter atrophy. AD patients displayed lower FC within the default-mode network (DMN) in the precuneus and posterior cingulate cortex compared with controls, independent of cortical atrophy. Regional FC values of MCI patients were numerically in betw…
matched on Alzheimer Disease (mesh), Cognitive Dysfunction (mesh), mild cognitive impairment (text)