Memory and thinking in later life, and their decline.
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526 to 550 of 1,152Cheng ST (2017)reviewMEDLINE-indexed journal, not yet read by usCurrent psychiatry reports359 citations Dementia Caregiver Burden: a Research Update and Critical Analysis.
Purpose of review: This article provides an updated review of the determinants of caregiver burden and depression, with a focus on care demands and especially the differential effects of various neuropsychiatric symptoms or symptom clusters. Moreover, studies on caregivers for frontotemporal and Lewy body dementias were referred to in order to identify differences and similarities with the mainstream literature based largely on Alzheimer caregivers.
Recent findings: As a group, neuropsychiatric symptoms are most predictive of caregiver burden and depression regardless of dementia diagnosis, but the effects appear to be driven primarily by disruptive behaviors (e.g., agitation, aggression, disinhibition), followed by delusions and mood disturbance. Disruptive behaviors are more disturbing partly because of the adverse impact on the emotional connection between the caregiver and the care-r…
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Consistency of dementia caregiver intervention classification: an evidence-based synthesis.
Background: There are many systematic reviews and meta-analyses (SRs) of interventions for family caregivers of persons with Alzheimer's disease or a related dementia. A challenge when synthesizing the efficacy of dementia caregiver interventions is the potential discrepancy in how they are categorized. The objective of this study was to systematically examine inconsistencies in how dementia caregiver interventions are classified.
Methods: We searched Ovid Medline®, Ovid PsycINFO®, Ovid Embase®, and the Cochrane Library to identify previous SRs published and indexed in bibliographic databases through January 2015. Following a graphical network analysis, open-coding of classification definitions was conducted. A descriptive analysis was then completed to examine classification consistency of individual interventions across SR grouping labels.
Results: Twenty-three SRs were identified. A g…
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'Old and ill': death anxiety and coping strategies influencing health professionals' well-being and dementia care.
Objectives: This paper examined the psychological factors that influence the well-being of health professionals who work with people with dementia and the types of care (person-centred or task-oriented) provided to these patients.
Methods: The literature was reviewed to identify the factors influencing the well-being of, and types of care provided by, health professionals working with people experiencing dementia.
Results: Based on our review of the literature, we propose that approaches to care and the well-being of health professionals working with dementia patients are influenced by the characterisation of dementia as a terminal illness that typically occurs in older people. Drawing upon terror management theory, we argue that exposure to dementia patients is likely to promote awareness of one's own mortality and death-related anxiety. A theoretical model is presented which posits tha…
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Alzheimer's disease and gut microbiota.
Alzheimer's disease (AD) is a most common neurodegenerative disorder, which associates with impaired cognition. Gut microbiota can modulate host brain function and behavior via microbiota-gut-brain axis, including cognitive behavior. Germ-free animals, antibiotics, probiotics intervention and diet can induce alterations of gut microbiota and gut physiology and also host cognitive behavior, increasing or decreasing risks of AD. The increased permeability of intestine and blood-brain barrier induced by gut microbiota disturbance will increase the incidence of neurodegeneration disorders. Gut microbial metabolites and their effects on host neurochemical changes may increase or decrease the risk of AD. Pathogenic microbes infection will also increase the risk of AD, and meanwhile, the onset of AD support the "hygiene hypothesis". All the results suggest that AD may begin in the gut, and is c…
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The Gut-Brain Axis, Including the Microbiome, Leaky Gut and Bacterial Translocation: Mechanisms and Pathophysiological Role in Alzheimer's Disease.
Alzheimer's disease (AD), the most common form of dementia, is a progressive disorder manifested by gradual memory loss and subsequent impairment in mental and behavioral functions. Though the primary risk factor for AD is advancing age, other factors such as diabetes mellitus, hyperlipidemia, obesity, vascular factors and depression play a role in its pathogenesis. The human gastrointestinal tract has a diverse commensal microbial population, which has bidirectional interactions with the human host that are symbiotic in health, and in addition to nutrition, digestion, plays major roles in inflammation and immunity. The most prevalent hypothesis for AD is the amyloid hypothesis, which states that changes in the proteolytic processing of the amyloid precursor protein leads to the accumulation of the amyloid beta (Aβ) peptide. Aβ then triggers an immune response that drives neuroinflammati…
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Benzodiazepine Use in Older Adults: Dangers, Management, and Alternative Therapies.
Several major medical and psychiatric organizations, including the American Geriatrics Society, advise against using benzodiazepines or nonbenzodiazepine hypnotics in older adults. Despite these recommendations, benzodiazepines continue to be massively prescribed to a group with the highest risk of serious adverse effects from these medications. This article summarizes legitimate reasons for prescribing benzodiazepines in the elderly, serious associated risks of prescribing them, particularly when not indicated, barriers physicians encounter in changing their prescription patterns, and evidence-based strategies on how to discontinue benzodiazepines in older patients. Although more research is needed, we propose several alternatives for treating insomnia and anxiety in older adults in primary care settings. These include nonpharmacological approaches such as sleep restriction-sleep compre…
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Therapies for Prevention and Treatment of Alzheimer's Disease.
Alzheimer's disease (AD) is the most common cause of dementia associated with a progressive neurodegenerative disorder, with a prevalence of 44 million people throughout the world in 2015, and this figure is estimated to double by 2050. This disease is characterized by blood-brain barrier disruption, oxidative stress, mitochondrial impairment, neuroinflammation, and hypometabolism; it is related to amyloid-β peptide accumulation and tau hyperphosphorylation as well as a decrease in acetylcholine levels and a reduction of cerebral blood flow. Obesity is a major risk factor for AD, because it induces adipokine dysregulation, which consists of the release of the proinflammatory adipokines and decreased anti-inflammatory adipokines, among other processes. The pharmacological treatments for AD can be divided into two categories: symptomatic treatments such as acetylcholinesterase inhibitors a…
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The role of omega-3 polyunsaturated fatty acids eicosapentaenoic and docosahexaenoic acids in the treatment of major depression and Alzheimer's disease: Acting separately or synergistically?
Omega-3 polyunsaturated fatty acids (n-3-PUFAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may improve or prevent some psychiatric and neurodegenerative diseases in both experimental and clinical studies. As important membrane components, these PUFAs benefit brain health by modulating neuroimmune and apoptotic pathways, changing membrane function and/or competing with n-6 PUFAs, the precursors of inflammatory mediators. However, the exact role of each fatty acid in neuroimmune modulation and neurogenesis, the interaction between EPA and DHA, and the best EPA:DHA ratios for improving brain disorders, remain unclear. It is also unknown whether EPA, as a DHA precursor, acts directly or via DHA. Here, we discuss recent evidence of EPA and DHA effects in the treatment of major depression and Alzheimer's disease, as well as their potential synergistic action on anti-in…
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Can anxiety damage the brain?
Purpose of review: Stress exacerbates mental illnesses such as depression but also appears to increase risk of dementia, suggesting a common mechanism for development of stress-induced affective and cognitive impairment. The purpose of this review is to address the question of whether anxiety 'damages' the brain, and to identify potential mechanisms for the link between stress and neuropsychiatric illness.
Recent findings: Anxiety disorders are associated with alterations in fear neurocircuitry such that 'bottom-up' processes in the amygdala which respond to threat are exaggerated, and regulation of these processes by the prefrontal cortex (PFC) and hippocampus is impaired. Chronic stress exposure similarly alters fear neurocircuitry by enhancing amygdalar functioning while causing structural degeneration in the PFC and hippocampus thereby inhibiting PFC/hippocampus control over the stre…
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Sahakian BJ, Bruhl AB, Cook J, Killikelly C, Savulich G, Piercy T, Hafizi S, Perez J, Fernandez-Egea E, Suckling J, Jones PB (2015)reviewMEDLINE-indexed journal, not yet read by usPhilosophical transactions of the Royal Society of London. Series B, Biological sciences63 citations The impact of neuroscience on society: cognitive enhancement in neuropsychiatric disorders and in healthy people.
In addition to causing distress and disability to the individual, neuropsychiatric disorders are also extremely expensive to society and governments. These disorders are both common and debilitating and impact on cognition, functionality and wellbeing. Cognitive enhancing drugs, such as cholinesterase inhibitors and methylphenidate, are used to treat cognitive dysfunction in Alzheimer's disease and attention deficit hyperactivity disorder, respectively. Other cognitive enhancers include specific computerized cognitive training and devices. An example of a novel form of cognitive enhancement using the technological advancement of a game on an iPad that also acts to increase motivation is presented. Cognitive enhancing drugs, such as methylphenidate and modafinil, which were developed as treatments, are increasingly being used by healthy people. Modafinil not only affects 'cold' cognition,…
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South Asian older adults with memory impairment: improving assessment and access to dementia care.
Objective: With increasing international migration, mental health care of migrants and ethnic minorities is a public health priority. South Asian older adults experience difficulties in accessing services for memory impairment, dementia and mental illness. This review examines barriers and facilitators in the pathway to culturally appropriate mental health care.
Methods: Web of Knowledge, Pubmed and Ovid databases were searched for literature on South Asian older adults or their family carers, their understandings of mental illness and dementia and their pattern of service use. Dates were from 1984 to 2012. Abstracts were assessed for relevance, followed by detailed reading of salient papers. Three researchers rated the quality of each included study. A narrative synthesis was undertaken of extracted and charted data.
Results: Eighteen studies met the eligibility criteria for the review.…
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Solovyev ND (2015)reviewMEDLINE-indexed journal, not yet read by usJournal of inorganic biochemistry183 citations Importance of selenium and selenoprotein for brain function: From antioxidant protection to neuronal signalling.
Multiple biological functions of selenium manifest themselves mainly via 25 selenoproteins that have selenocysteine at their active centre. Selenium is vital for the brain and seems to participate in the pathology of disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and epilepsy. Since selenium was shown to be involved in diverse functions of the central nervous system, such as motor performance, coordination, memory and cognition, a possible role of selenium and selenoproteins in brain signalling pathways may be assumed. The aim of the present review is to analyse possible relations between selenium and neurotransmission. Selenoproteins seem to be of special importance in the development and functioning of GABAergic (GABA, γ-aminobutyric acid) parvalbumin positive interneurons of the cerebral cortex and hippocampus. Dopamine pathway might be also …
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Telomere length variations in aging and age-related diseases.
Telomeres are gene sequences present at chromosomal ends and are responsible for maintaining genome integrity. Telomere length is maximum at birth and decreases progressively with advancing age and thus is considered as a biomarker of chronological aging. This age associated decrease in the length of telomere is linked to various ageing associated diseases like diabetes, hypertension, Alzheimer's disease, cancer etc. and their associated complications. Telomere length is a result of combined effect of oxidative stress, inflammation and repeated cell replication on it, and thus forming an association between telomere length and chronological aging and related diseases. Thus, decrease in telomere length was found to be important in determining both, the variations in longevity and age-related diseases in an individual. Ongoing and progressive research in the field of telomere length dynami…
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Starkstein SE (2014)reviewMEDLINE-indexed journal, not yet read by usCortex; a journal devoted to the study of the nervous system and behavior159 citations Anosognosia in Alzheimer's disease: diagnosis, frequency, mechanism and clinical correlates.
Anosognosia is present in a large proportion of patients with mild Alzheimer's disease (AD), and its frequency increases with the progression of the illness. Several instruments have been validated to assess anosognosia in AD, but there is no consensus regarding the best diagnostic strategy. Anosognosia in AD is a significant predictor of apathy and is significantly related to lower depression and anxiety scores, more severe caregiver burden and dangerous behaviours. Studies using different imaging modalities have demonstrated an association between anosognosia and dysfunction in frontal, temporomedial and temporoparietal regions. The mechanism of anosognosia remains unknown, but it has been explained as a consequence of deficits of encoding and updating biographical memory, and dysfunction of comparator, executive and metacognitive systems.
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Maternal immune activation and abnormal brain development across CNS disorders.
Epidemiological studies have shown a clear association between maternal infection and schizophrenia or autism in the progeny. Animal models have revealed maternal immune activation (mIA) to be a profound risk factor for neurochemical and behavioural abnormalities in the offspring. Microglial priming has been proposed as a major consequence of mIA, and represents a critical link in a causal chain that leads to the wide spectrum of neuronal dysfunctions and behavioural phenotypes observed in the juvenile, adult or aged offspring. Such diversity of phenotypic outcomes in the mIA model are mirrored by recent clinical evidence suggesting that infectious exposure during pregnancy is also associated with epilepsy and, to a lesser extent, cerebral palsy in children. Preclinical research also suggests that mIA might precipitate the development of Alzheimer and Parkinson diseases. Here, we summari…
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Anderson ND, Damianakis T, Kröger E, Wagner LM, Dawson DR, Binns MA, Bernstein S, Caspi E, Cook SL, BRAVO Team (2014)reviewMEDLINE-indexed journal, not yet read by usPsychological bulletin208 citations The benefits associated with volunteering among seniors: a critical review and recommendations for future research.
There is an urgent need to identify lifestyle activities that reduce functional decline and dementia associated with population aging. The goals of this article are to review critically the evidence on the benefits associated with formal volunteering among older adults, propose a theoretical model of how volunteering may reduce functional limitations and dementia risk, and offer recommendations for future research. Database searches identified 113 papers on volunteering benefits in older adults, of which 73 were included. Data from descriptive, cross-sectional, and prospective cohort studies, along with 1 randomized controlled trial, most consistently reveal that volunteering is associated with reduced symptoms of depression, better self-reported health, fewer functional limitations, and lower mortality. The extant evidence provides the basis for a model proposing that volunteering incre…
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HDL and cognition in neurodegenerative disorders.
High-density lipoproteins (HDLs) are a heterogeneous group of lipoproteins composed of various lipids and proteins. HDL is formed both in the systemic circulation and in the brain. In addition to being a crucial player in the reverse cholesterol transport pathway, HDL possesses a wide range of other functions including anti-oxidation, anti-inflammation, pro-endothelial function, anti-thrombosis, and modulation of immune function. It has been firmly established that high plasma levels of HDL protect against cardiovascular disease. Accumulating evidence indicates that the beneficial role of HDL extends to many other systems including the central nervous system. Cognition is a complex brain function that includes all aspects of perception, thought, and memory. Cognitive function often declines during aging and this decline manifests as cognitive impairment/dementia in age-related and progre…
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Late-life depression in the primary care setting: challenges, collaborative care, and prevention.
Late-life depression is highly prevalent worldwide. In addition to being a debilitating illness, it is a risk factor for excess morbidity and mortality. Older adults with depression are at risk for dementia, coronary heart disease, stroke, cancer and suicide. Individuals with late-life depression often have significant medical comorbidity and, poor treatment adherence. Furthermore, psychosocial considerations such as gender, ethnicity, stigma and bereavement are necessary to understand the full context of late-life depression. The fact that most older adults seek treatment for depression in primary care settings led to the development of collaborative care interventions for depression. These interventions have consistently demonstrated clinically meaningful effectiveness in the treatment of late-life depression. We describe three pivotal studies detailing the management of depression in …
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Vagus nerve stimulation…25 years later! What do we know about the effects on cognition?
VNS therapy was delivered to patients for the first time in 1988. After 25 years, insight in the antiepileptic and antidepressant mechanism of action of VNS has grown steadily. The effects on cognition and especially memory remain controversial. This review provides an elaborate overview of studies addressing cognition and describes potential underlying mechanisms for the reported effects. Short-term VNS has an effect on verbal memory recognition when administered at the correct timing and dosage. Chronic VNS resulted into a positive effect on the cognitive status in an Alzheimer population. Positive effect of chronic VNS in epilepsy or depression patients on global cognitive functioning are less convincing. Neither do the results reveal a negative effect which has major implications for chronic treatment of neurology patients. A cascade of neurochemical processes put in motion by change…
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Neuroprotective effects of lithium: implications for the treatment of Alzheimer's disease and related neurodegenerative disorders.
Lithium is a well-established therapeutic option for the acute and long-term management of bipolar disorder and major depression. More recently, based on findings from translational research, lithium has also been regarded as a neuroprotective agent and a candidate drug for disease-modification in certain neurodegenerative disorders, namely, Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and, more recently, Parkinson's disease (PD). The putative neuroprotective effects of lithium rely on the fact that it modulates several homeostatic mechanisms involved in neurotrophic response, autophagy, oxidative stress, inflammation, and mitochondrial function. Such a wide range of intracellular responses may be secondary to two key effects, that is, the inhibition of glycogen synthase kinase-3 beta (GSK-3β) and inositol monophosphatase (IMP) by lithium. In the present review, we revi…
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What is normal in normal aging? Effects of aging, amyloid and Alzheimer's disease on the cerebral cortex and the hippocampus.
What can be expected in normal aging, and where does normal aging stop and pathological neurodegeneration begin? With the slow progression of age-related dementias such as Alzheimer's disease (AD), it is difficult to distinguish age-related changes from effects of undetected disease. We review recent research on changes of the cerebral cortex and the hippocampus in aging and the borders between normal aging and AD. We argue that prominent cortical reductions are evident in fronto-temporal regions in elderly even with low probability of AD, including regions overlapping the default mode network. Importantly, these regions show high levels of amyloid deposition in AD, and are both structurally and functionally vulnerable early in the disease. This normalcy-pathology homology is critical to understand, since aging itself is the major risk factor for sporadic AD. Thus, rather than necessaril…
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How does brain insulin resistance develop in Alzheimer's disease?
Compelling preclinical and clinical evidence supports a pathophysiological connection between Alzheimer's disease (AD) and diabetes. Altered metabolism, inflammation, and insulin resistance are key pathological features of both diseases. For many years, it was generally considered that the brain was insensitive to insulin, but it is now accepted that this hormone has central neuromodulatory functions, including roles in learning and memory, that are impaired in AD. However, until recently, the molecular mechanisms accounting for brain insulin resistance in AD have remained elusive. Here, we review recent evidence that sheds light on how brain insulin dysfunction is initiated at a molecular level and why abnormal insulin signaling culminates in synaptic failure and memory decline. We also discuss the cellular basis underlying the beneficial effects of stimulation of brain insulin signalin…
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Physiological and functional consequences of caregiving for relatives with dementia.
Background: Chronic stress negatively affects health and well-being. A growing population of informal dementia caregivers experience chronic stress associated with extraordinary demands of caring for a relative with dementia. This review summarizes physiological and functional changes due to chronic dementia caregiver stress.
Methods: A literature search for papers assessing effects of dementia caregiving was conducted focusing on publications evaluating differences between caregivers and non-caregivers in objective measures of health and cognition.
Results: The review identified 37 studies describing data from 4,145 participants including 749 dementia caregivers and 3,396 non-caregiver peers. Objective outcome measures affected in dementia caregivers included markers of dyscoagulation, inflammation, and cell aging as well as measures of immune function, sleep, and cognition. Though dive…
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Emotional and behavioral symptoms in neurodegenerative disease: a model for studying the neural bases of psychopathology.
Disruptions in emotional, cognitive, and social behavior are common in neurodegenerative disease and in many forms of psychopathology. Because neurodegenerative diseases have patterns of brain atrophy that are much clearer than those of psychiatric disorders, they may provide a window into the neural bases of common emotional and behavioral symptoms. We discuss five common symptoms that occur in both neurodegenerative disease and psychopathology (i.e., anxiety, dysphoric mood, apathy, disinhibition, and euphoric mood) and their associated neural circuitry. We focus on two neurodegenerative diseases (i.e., Alzheimer's disease and frontotemporal dementia) that are common and well characterized in terms of emotion, cognition, and social behavior and in patterns of associated atrophy. Neurodegenerative diseases provide a powerful model system for studying the neural correlates of psychopatho…
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Neuropathology of stress.
Environmental challenges are part of daily life for any individual. In fact, stress appears to be increasingly present in our modern, and demanding, industrialized society. Virtually every aspect of our body and brain can be influenced by stress and although its effects are partly mediated by powerful corticosteroid hormones that target the nervous system, relatively little is known about when, and how, the effects of stress shift from being beneficial and protective to becoming deleterious. Decades of stress research have provided valuable insights into whether stress can directly induce dysfunction and/or pathological alterations, which elements of stress exposure are responsible, and which structural substrates are involved. Using a broad definition of pathology, we here review the "neuropathology of stress" and focus on structural consequences of stress exposure for different regions…
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