Memory and thinking in later life, and their decline.
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476 to 500 of 1,152Tranah GJ, Blackwell T, Stone KL, Ancoli-Israel S, Paudel ML, Ensrud KE, Cauley JA, Redline S, Hillier TA, Cummings SR, Yaffe K, SOF Research Group (2011)MEDLINE-indexed journal, not yet read by usAnnals of neurology411 citations Circadian activity rhythms and risk of incident dementia and mild cognitive impairment in older women.
Objective: Previous cross-sectional studies have observed alterations in activity rhythms in dementia patients but the direction of causation is unclear. We determined whether circadian activity rhythms measured in community-dwelling older women are prospectively associated with incident dementia or mild cognitive impairment (MCI).
Methods: Activity rhythm data were collected from 1,282 healthy community-dwelling women from the Study of Osteoporotic Fractures (SOF) cohort (mean age 83 years) with wrist actigraphy for a minimum of three 24-hour periods. Each participant completed a neuropsychological test battery and had clinical cognitive status (dementia, MCI, normal) adjudicated by an expert panel approximately 5 years later. All analyses were adjusted for demographics, body mass index (BMI), functional status, depression, medications, alcohol, caffeine, smoking, health status, and com…
matched on Dementia (mesh), Cognitive Dysfunction (mesh), mild cognitive impairment (text)
The impact of dementia and mild memory impairment (MMI) on intimacy and sexuality in spousal relationships.
Background: Sexuality and intimacy in couples in which one partner is affected by dementia has been widely researched. Few studies have explored these issues in couples where one partner is affected by mild memory impairment (MMI) or mild cognitive impairment (MCI). The objectives of this study were to (1) identify and contrast issues of intimacy and sexuality that spousal caregivers of persons with MMI and dementia may experience, and (2) identify future lines of research in this population.
Methods: Fourteen dementia and nine MMI spousal caregivers participated in focus groups conducted between 2008 and 2009 at the Stanford/VA Alzheimer's Research Center. Content analyses were conducted to identify themes.
Results: Five themes emerged: communication, marital cohesion, affectional expression, caregiver burden, and ambiguity concerning the future of the relationship. Dementia caregivers …
matched on Dementia (mesh), Memory Disorders (mesh), mild cognitive impairment (text)
Concerted type I interferon signaling in microglia and neural cells promotes memory impairment associated with amyloid β plaques.
The principal signals that drive memory and cognitive impairment in Alzheimer's disease (AD) remain elusive. Here, we revealed brain-wide cellular reactions to type I interferon (IFN-I), an innate immune cytokine aberrantly elicited by amyloid β plaques, and examined their role in cognition and neuropathology relevant to AD in a murine amyloidosis model. Using a fate-mapping reporter system to track cellular responses to IFN-I, we detected robust, Aβ-pathology-dependent IFN-I activation in microglia and other cell types. Long-term blockade of IFN-I receptor (IFNAR) rescued both memory and synaptic deficits and resulted in reduced microgliosis, inflammation, and neuritic pathology. Microglia-specific Ifnar1 deletion attenuated the loss of post-synaptic terminals by selective engulfment, whereas neural Ifnar1 deletion restored pre-synaptic terminals and decreased plaque accumulation. Overa…
matched on Alzheimer Disease (mesh), Memory Disorders (mesh), Amyloid beta-Peptides (mesh)
Uruno A, Matsumaru D, Ryoke R, Saito R, Kadoguchi S, Saigusa D, Saito T, Saido TC, Kawashima R, Yamamoto M (2020)MEDLINE-indexed journal, not yet read by usMolecular and cellular biology141 citations Nrf2 Suppresses Oxidative Stress and Inflammation in App Knock-In Alzheimer's Disease Model Mice.
Nrf2 (NF-E2-related-factor 2) is a stress-responsive transcription factor that protects cells against oxidative stresses. To clarify whether Nrf2 prevents Alzheimer's disease (AD), AD model AppNL-G-F/NL-G-F knock-in (AppNLGF ) mice were studied in combination with genetic Nrf2 induction model Keap1FA/FA mice. While AppNLGF mice displayed shorter latency to escape than wild-type mice in the passive-avoidance task, the impairment was improved in AppNLGF ::Keap1FA/FA mice. Matrix-assisted laser desorption ionization-mass spectrometry imaging revealed that reduced glutathione levels were elevated by Nrf2 induction in AppNLGF ::Keap1FA/FA mouse brains compared to AppNLGF mouse brains. Genetic Nrf2 induction in AppNLGF mice markedly suppressed the elevation of the oxidative stress marker 8-OHdG and Iba1-positive microglial cell number. We also determined the plasmalogen-phosphatidylethanolamin…
matched on Alzheimer Disease (mesh), Cognitive Dysfunction (mesh), Amyloid beta-Peptides (mesh)
Recent advancement in understanding of Alzheimer's disease: Risk factors, subtypes, and drug targets and potential therapeutics.
Alzheimer's disease (AD) is a significant neocortical degenerative disorder characterized by the progressive loss of neurons and secondary alterations in white matter tracts. Understanding the risk factors and mechanisms underlying AD is crucial for developing effective treatments. The risk factors associated with AD encompass a wide range of variables, including gender differences, family history, and genetic predispositions. Additionally, environmental factors such as air pollution and lifestyle-related conditions like cardiovascular disease, gut pathogens, and liver pathology contribute substantially to the development and progression of AD and its subtypes. This review provides current update and deeper insights into the role of diverse risk factors, categorizing AD into its distinct subtypes and elucidating their specific pathophysiological mechanisms. Unlike previous studies that o…
matched on Alzheimer Disease (mesh)
Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies.
Alzheimer's disease (AD) stands as the predominant form of dementia, presenting significant and escalating global challenges. Its etiology is intricate and diverse, stemming from a combination of factors such as aging, genetics, and environment. Our current understanding of AD pathologies involves various hypotheses, such as the cholinergic, amyloid, tau protein, inflammatory, oxidative stress, metal ion, glutamate excitotoxicity, microbiota-gut-brain axis, and abnormal autophagy. Nonetheless, unraveling the interplay among these pathological aspects and pinpointing the primary initiators of AD require further elucidation and validation. In the past decades, most clinical drugs have been discontinued due to limited effectiveness or adverse effects. Presently, available drugs primarily offer symptomatic relief and often accompanied by undesirable side effects. However, recent approvals of…
matched on Alzheimer Disease (mesh)
The path to next-generation disease-modifying immunomodulatory combination therapies in Alzheimer's disease.
The cautious optimism following recent anti-amyloid therapeutic trials for Alzheimer's disease (AD) provides a glimmer of hope after years of disappointment. Although these encouraging results represent discernible progress, they also highlight the need to enhance further the still modest clinical efficacy of current disease-modifying immunotherapies. Here, we highlight crucial milestones essential for advancing precision medicine in AD. These include reevaluating the choice of therapeutic targets by considering the key role of both central neuroinflammation and peripheral immunity in disease pathogenesis, refining patient stratification by further defining the inflammatory component within the forthcoming ATN(I) (amyloid, tau and neurodegeneration (and inflammation)) classification of AD biomarkers and defining more accurate clinical outcomes and prognostic biomarkers that better reflec…
matched on Alzheimer Disease (mesh)
Ly M, Yu GZ, Mian A, Cramer A, Meysami S, Merrill DA, Samara A, Eisenstein SA, Hershey T, Babulal GM, Lenze EJ, Morris JC, Benzinger TLS, Raji CA (2023)reviewMEDLINE-indexed journal, not yet read by usThe American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry74 citations Neuroinflammation: A Modifiable Pathway Linking Obesity, Alzheimer's disease, and Depression.
Obesity, depression and Alzheimer's disease (AD) are three major interrelated modern health conditions with complex relationships. Early-life depression may serve as a risk factor for AD, while late-life depression may be a prodrome of AD. Depression affects approximately 23% of obese individuals, and depression itself raises the risk of obesity by 37%. Mid-life obesity independently increases AD risk, while late-life obesity, particularly metabolically healthy obesity, may offer protection against AD pathology. Chronic inflammation serves as a key mechanism linking obesity, AD, and depression, encompassing systemic inflammation from metabolic disturbances, immune dysregulation through the gut microbiome, and direct interactions with amyloid pathology and neuroinflammation. In this review, we explore the biological mechanisms of neuroinflammation in relation to obesity, AD, and depressio…
matched on Alzheimer Disease (mesh)
Sen A, Tai XY (2023)reviewMEDLINE-indexed journal, not yet read by usCurrent neurology and neuroscience reports47 citations Sleep Duration and Executive Function in Adults.
Purpose of review: To review the literature examining the relationship between sleep and cognition, specifically examining the sub-domain of executive function. We explore the impact of sleep deprivation and the important question of how much sleep is required for optimal cognitive performance. We consider how other sleep metrics, such as sleep quality, may be a more meaningful measure of sleep. We then discuss the putative mechanisms between sleep and cognition followed by their contribution to developing dementia.
Recent findings: Sleep duration and executive function display a quadratic relationship. This suggests an optimal amount of sleep is required for daily cognitive processes. Poor sleep efficiency and sleep fragmentation are linked with poorer executive function and increased risk of dementia during follow-up. Sleep quality may therefore be more important than absolute duration…
matched on Dementia (mesh)
Technology-Based Interventions to Address Social Isolation and Loneliness Among Informal Dementia Caregivers: A Scoping Review.
Objective: Social isolation and loneliness are major public health concerns. Informal dementia caregivers are particularly vulnerable, as many are older adults themselves and at elevated risk of adverse mental and physical health outcomes. Technology-based interventions could offer accessible, affordable, and convenient solutions. A previous review included Internet-based supportive interventions for informal dementia caregivers published up to 2013; however, new publications, technological advances, and targeted outcomes justify conducting this scoping review. Here, we identified and synthesized recent technology-based interventions that addressed social isolation and loneliness among informal dementia caregivers.
Design: Scoping review.
Setting and participants: Informal dementia caregivers in the community.
Methods: Following Arksey and O'Malley's scoping review framework, we conducte…
matched on Dementia (mesh)
The Role of Diet as a Modulator of the Inflammatory Process in the Neurological Diseases.
Neurological diseases are recognized as major causes of disability and mortality worldwide. Due to the dynamic progress of diseases such as Alzheimer's disease (AD), Parkinson's Disease (PD), Schizophrenia, Depression, and Multiple Sclerosis (MD), scientists are mobilized to look for new and more effective methods of interventions. A growing body of evidence suggests that inflammatory processes and an imbalance in the composition and function of the gut microbiome, which play a critical role in the pathogenesis of various neurological diseases and dietary interventions, such as the Mediterranean diet the DASH diet, or the ketogenic diet can have beneficial effects on their course. The aim of this review was to take a closer look at the role of diet and its ingredients in modulating inflammation associated with the development and/or progression of central nervous system diseases. Present…
matched on Alzheimer Disease (mesh)
Kluger BM, Hudson P, Hanson LC, Bužgovà R, Creutzfeldt CJ, Gursahani R, Sumrall M, White C, Oliver DJ, Pantilat SZ, Miyasaki J (2023)reviewMEDLINE-indexed journal, not yet read by usThe Lancet. Neurology67 citations Palliative care to support the needs of adults with neurological disease.
Neurological diseases cause physical, psychosocial, and spiritual or existential suffering from the time of their diagnosis. Palliative care focuses on improving quality of life for people with serious illness and their families by addressing this multidimensional suffering. Evidence from clinical trials supports the ability of palliative care to improve patient and caregiver outcomes by the use of outpatient or home-based palliative care interventions for people with motor neuron disease, multiple sclerosis, or Parkinson's disease; inpatient palliative care consultations for people with advanced dementia; telephone-based case management for people with dementia in the community; and nurse-led discussions with decision aids for people with advanced dementia in long-term care. Unfortunately, most people with neurological diseases do not get the support that they need for their palliative …
matched on Dementia (mesh)
The Role of Obesity and Diabetes in Dementia.
Chronic conditions such as obesity, diabetes, and dementia are increasing in the United States (US) population. Knowledge of these chronic conditions, preventative measures, and proper management tactics is important and critical to preventing disease. The overlap between obesity, diabetes, and dementia is becoming further elucidated. These conditions share a similar origin through the components of increasing age, gender, genetic and epigenetic predispositions, depression, and a high-fat Western diet (WD) that all contribute to the inflammatory state associated with the development of obesity, diabetes, and dementia. This inflammatory state leads to the dysregulation of food intake and insulin resistance. Obesity is often the cornerstone that leads to the development of diabetes and, subsequently, in the case of type 2 diabetes mellitus (T2DM), progression to "type 3 diabetes mellitus (…
matched on Dementia (mesh)
Me, myself, and nature: living with dementia and connecting with the natural world - more than a breath of fresh air? A literature review.
Objective: Despite growing awareness of the importance of engagement with the natural world for people living with dementia, little is known about the impact specifically for people living independently in their own home. This review identifies, analyses and synthesises existing research, incorporating first-person narrative accounts of the benefits and potential challenges experienced in forging meaningful connections with the natural world.
Methods: Six databases were searched from February 2000 to February 2021. Relevant organisations and authors were contacted, and a hand search of included study reference lists was conducted. The findings of included studies were synthesised using a thematic analysis approach.
Findings: Sixteen studies were included: 13 qualitative and three mixed methods. Eight themes and three sub-themes were identified, revealing how contact with the natural worl…
matched on Dementia (mesh)
Gene-environment interactions in Alzheimer disease: the emerging role of epigenetics.
With the exception of a few monogenic forms, Alzheimer disease (AD) has a complex aetiology that is likely to involve multiple susceptibility genes and environmental factors. The role of environmental factors is difficult to determine and, until a few years ago, the molecular mechanisms underlying gene-environment (G × E) interactions in AD were largely unknown. Here, we review evidence that has emerged over the past two decades to explain how environmental factors, such as diet, lifestyle, alcohol, smoking and pollutants, might interact with the human genome. In particular, we discuss how various environmental AD risk factors can induce epigenetic modifications of key AD-related genes and pathways and consider how epigenetic mechanisms could contribute to the effects of oxidative stress on AD onset. Studies on early-life exposures are helping to uncover critical time windows of sensitiv…
matched on Alzheimer Disease (mesh)
Mou Y, Du Y, Zhou L, Yue J, Hu X, Liu Y, Chen S, Lin X, Zhang G, Xiao H, Dong B (2022)reviewMEDLINE-indexed journal, not yet read by usFrontiers in immunology330 citations Gut Microbiota Interact With the Brain Through Systemic Chronic Inflammation: Implications on Neuroinflammation, Neurodegeneration, and Aging.
It has been noticed in recent years that the unfavorable effects of the gut microbiota could exhaust host vigor and life, yet knowledge and theory are just beginning to be established. Increasing documentation suggests that the microbiota-gut-brain axis not only impacts brain cognition and psychiatric symptoms but also precipitates neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). How the blood-brain barrier (BBB), a machinery protecting the central nervous system (CNS) from the systemic circulation, allows the risky factors derived from the gut to be translocated into the brain seems paradoxical. For the unique anatomical, histological, and immunological properties underpinning its permeable dynamics, the BBB has been regarded as a biomarker associated with neural pathogenesis. The BBB permeability of mice and rats cause…
matched on Alzheimer Disease (mesh)
Interventions to reduce loneliness in caregivers: An integrative review of the literature.
Older adults are at an increased risk of loneliness. Many also serve as informal caregivers for persons with dementia and other disabling conditions, further predisposing them to loneliness. The primary objective was to assess current loneliness interventions for caregivers to inform development of effective therapies to improve their quality of life. An integrative review of the literature was conducted using five electronic databases and 12 studies were included for further analysis. Data were extracted regarding the type of intervention implemented, caregiver characteristics, and intervention effects. Five main intervention types emerged: mindful meditation, computer applications, music therapy, peer support, and community programs. Most care recipients had dementia, and most caregivers were spouses. Peer support was the most frequently utilized intervention, and common intervention s…
matched on Dementia (mesh)
Reimagining cholinergic therapy for Alzheimer's disease.
Currently, enhancement of cholinergic neurotransmission via cholinesterase inhibitors represents the main available approach to treat cognitive and behavioural symptoms of the early as well as late stages of Alzheimer's disease. Restoring the cholinergic system has been a primary means of improving cognition in Alzheimer's disease, as four of the six approved therapies are acetylcholinesterase inhibitors. Memantine is an N-methyl-d-aspartate antagonist with a well-documented clinical effect on behavioural symptoms, which is often added to cholinesterase inhibitors to potentiate their effect and aducanumab, targeting the amyloid pathology, has recently been approved. The early, progressive and selective degeneration of the cholinergic system together and its close relation to cognitive deficits supports the use of cholinergic therapy for Alzheimer's disease. This review provides an update…
matched on Alzheimer Disease (mesh)
Impaired insulin signalling and allostatic load in Alzheimer disease.
The discovery of insulin in 1921 revolutionized the treatment of diabetes and paved the way for numerous studies on hormone signalling networks and actions in peripheral tissues and in the central nervous system. Impaired insulin signalling, a hallmark of diabetes, is now established as a key component of Alzheimer disease (AD) pathology. Here, we review evidence showing that brain inflammation and activation of cellular stress response mechanisms comprise molecular underpinnings of impaired brain insulin signalling in AD and integrate impaired insulin signalling with AD pathology. Further, we highlight that insulin resistance is an important component of allostatic load and that allostatic overload can trigger insulin resistance. This bidirectional association between impaired insulin signalling and allostatic overload favours medical conditions that increase the risk of AD, including d…
matched on Alzheimer Disease (mesh)
Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer's disease.
Gut microbiota represents a diverse and dynamic population of microorganisms harboring the gastrointestinal tract, which influences the host health and disease. Gut microbiota communicates with the brain and vice versa through complex bidirectional communication systems - the gut-brain axis, which integrates the peripheral intestinal function with emotional and cognitive brain centers via neuro-immuno-endocrine mediators. Aging alters the gut microbial population, which not only leads to gastrointestinal disturbances but also causes central nervous system (CNS) disorders such as dementia. Alzheimer's disease (AD) is the most common form of dementia affecting the older person, characterized by beta-amyloid (Aβ) plaques and neurofibrillary tangles leading to the cognitive deficit and memory impairment. Multiple experimental and clinical studies revealed the role of gut microbiota in host c…
matched on Alzheimer Disease (mesh)
Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders.
Emerging evidence indicates that gut microbiota is important in the regulation of brain activity and cognitive functions. Microbes mediate communication among the metabolic, peripheral immune, and central nervous systems via the microbiota-gut-brain axis. However, it is not well understood how the gut microbiome and neurons in the brain mutually interact or how these interactions affect normal brain functioning and cognition. We summarize the mechanisms whereby the gut microbiota regulate the production, transportation, and functioning of neurotransmitters. We also discuss how microbiome dysbiosis affects cognitive function, especially in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.
matched on Alzheimer Disease (mesh)
Nutritional Support of Neurodevelopment and Cognitive Function in Infants and Young Children-An Update and Novel Insights.
Proper nutrition is crucial for normal brain and neurocognitive development. Failure to optimize neurodevelopment early in life can have profound long-term implications for both mental health and quality of life. Although the first 1000 days of life represent the most critical period of neurodevelopment, the central and peripheral nervous systems continue to develop and change throughout life. All this time, development and functioning depend on many factors, including adequate nutrition. In this review, we outline the role of nutrients in cognitive, emotional, and neural development in infants and young children with special attention to the emerging roles of polar lipids and high quality (available) protein. Furthermore, we discuss the dynamic nature of the gut-brain axis and the importance of microbial diversity in relation to a variety of outcomes, including brain maturation/function…
matched on Cognitive Aging (mesh)
The impact of the microbiota-gut-brain axis on Alzheimer's disease pathophysiology.
The gut microbiota is a complex ecosystem that comprises of more than 100 trillion symbiotic microbial cells. The microbiota, the gut, and the brain form an association, 'the microbiota-gut-brain axis,' and synchronize the gut with the central nervous system and modify the behavior and brain immune homeostasis. The bidirectional communication between gut and brain occurs via the immune system, the vagus nerve, the enteric nervous system, and microbial metabolites, including short-chain fatty acids (SCFAs), proteins, and tryptophan metabolites. Recent studies have implicated the gut microbiota in many neurodegenerative diseases, including Alzheimer's disease (AD). In this review, we present an overview of gut microbiota, including Firmicutes, Bacteroidetes, SCFA, tryptophan, bacterial composition, besides age-related changes in gut microbiota composition, the microbiota-gut-brain axis pat…
matched on Alzheimer Disease (mesh)
The Impact of Systemic Inflammation on Alzheimer's Disease Pathology.
Alzheimer's disease (AD) is a devastating age-related neurodegenerative disorder with an alarming increasing prevalence. Except for the recently FDA-approved Aducanumab of which the therapeutic effect is not yet conclusively proven, only symptomatic medication that is effective for some AD patients is available. In order to be able to design more rational and effective treatments, our understanding of the mechanisms behind the pathogenesis and progression of AD urgently needs to be improved. Over the last years, it became increasingly clear that peripheral inflammation is one of the detrimental factors that can contribute to the disease. Here, we discuss the current understanding of how systemic and intestinal (referred to as the gut-brain axis) inflammatory processes may affect brain pathology, with a specific focus on AD. Moreover, we give a comprehensive overview of the different prec…
matched on Alzheimer Disease (mesh)
Barriers and facilitators to the implementation of social robots for older adults and people with dementia: a scoping review.
Background: Psychosocial issues, such as social isolation and loneliness among older adults and people with dementia, continue to pose challenges with a rapidly aging population worldwide. Social robots are a rapidly emerging field of technology, developed to help address the psychosocial needs of this population. Although studies have reported positive findings regarding their psychosocial benefits, their implementation in real-world practice remains a challenge. Nevertheless, little is known about the factors affecting their implementation. The purpose of this review is to provide a systematic overview of the barriers and facilitators affecting the implementation of social robots for older adults and people with dementia.
Method: The Arksey and O'Malley approach with methodological enhancement by Levac et al. was used to guide the conduct of this review. Seven electronic databases were…
matched on Dementia (mesh)