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Alzheimer's & Dementia : the Journal of... Jan 2013Vascular disease was once considered the principal cause of aging-related dementia. More recently, however, research emphasis has shifted to studies of progressive... (Review)
Review
Vascular disease was once considered the principal cause of aging-related dementia. More recently, however, research emphasis has shifted to studies of progressive neurodegenerative disease processes, such as those giving rise to neuritic plaques, neurofibrillary tangles, and Lewy bodies. Although these studies have led to critical insights and potential therapeutic strategies, interest in the role of systemic and cerebrovascular disease mechanisms waned and has received relatively less attention and research support. Recent studies suggest that vascular disease mechanisms play an important role in the risk for aging-related cognitive decline and disorders. Vascular disease frequently coexists with cognitive decline in aging individuals, shares many risk factors with dementias considered to be of the "Alzheimer type," and is observed more frequently than expected in postmortem material from individuals manifesting "specific" disease stigmata, such as abundant plaques and tangles. Considerable difficulties have emerged in attempting to classify dementias as being related to vascular versus neurodegenerative causes, and several systems of criteria have been used. Despite multiple attempts, a lack of consensus remains regarding the optimal means of incorporating vascular disease into clinical diagnostic, neurocognitive, or neuropathologic classification schemes for dementias. We propose here an integrative, rather than a strictly taxonomic, approach to the study and elucidation of how vascular disease mechanisms contribute to the development of dementias. We argue that, instead of discriminating between, for example, "Alzheimer's disease," "vascular dementia," and other diseases, there is a greater need to focus clinical and research efforts on elucidating specific pathophysiologic mechanisms that contribute to dementia phenotypes and neuropathologic outcomes. We outline a multitiered strategy, beginning with clinical and public health interventions that can be implemented immediately, enhancements to ongoing longitudinal studies to increase their informative value, and new initiatives to capitalize on recent advances in systems biology and network medicine. This strategy will require funding from multiple public and private sources to support collaborative and interdisciplinary research efforts to take full advantage of these opportunities and realize their societal benefits.
Topics: Cerebrovascular Disorders; Dementia; Humans
PubMed: 23183137
DOI: 10.1016/j.jalz.2012.02.007 -
Cortex; a Journal Devoted To the Study... Oct 2020Disinhibition, mainly caused by damage in frontotemporal brain regions, is one of the major causes of caregiver distress in neurodegenerative dementias. Behavioural... (Review)
Review
Disinhibition, mainly caused by damage in frontotemporal brain regions, is one of the major causes of caregiver distress in neurodegenerative dementias. Behavioural inhibition deficits are usually described as a loss of social conduct and impulsivity, whereas cognitive inhibition deficits refer to impairments in the suppression of prepotent verbal responses and resistance to distractor interference. In this review, we aim to discuss inhibition deficits in neurodegenerative dementias through behavioural, cognitive, neuroanatomical and neurophysiological exploration. We also discuss impulsivity and compulsivity behaviours as related to disinhibition. We will therefore describe different tests available to assess both behavioural and cognitive disinhibition and summarise different manifestations of disinhibition across several neurodegenerative diseases (behavioural variant of frontotemporal dementia, Alzheimer's disease, Parkinson's disease, progressive supranuclear palsy, Huntington's disease). Finally, we will present the latest findings about structural, metabolic, functional, neurophysiological and also neuropathological correlates of inhibition impairments. We will briefly conclude by mentioning some of the latest pharmacological and non pharmacological treatment options available for disinhibition. Within this framework, we aim to highlight i) the current interests and limits of tests and questionnaires available to assess behavioural and cognitive inhibition in clinical practice and in clinical research; ii) the interpretation of impulsivity and compulsivity within the spectrum of inhibition deficits; and iii) the brain regions and networks involved in such behaviours.
Topics: Alzheimer Disease; Cognition; Frontotemporal Dementia; Humans; Inhibition, Psychological; Neuropsychological Tests; Supranuclear Palsy, Progressive
PubMed: 32919754
DOI: 10.1016/j.cortex.2020.08.001 -
Journal of Cerebral Blood Flow and... Jul 2015Alzheimer's disease (AD) is the most common form of age-related dementias. In addition to genetics, environment, and lifestyle, growing evidence supports vascular... (Review)
Review
Alzheimer's disease (AD) is the most common form of age-related dementias. In addition to genetics, environment, and lifestyle, growing evidence supports vascular contributions to dementias including dementia because of AD. Alzheimer's disease affects multiple cell types within the neurovascular unit (NVU), including brain vascular cells (endothelial cells, pericytes, and vascular smooth muscle cells), glial cells (astrocytes and microglia), and neurons. Thus, identifying and integrating biomarkers of the NVU cell-specific responses and injury with established AD biomarkers, amyloid-β (Aβ) and tau, has a potential to contribute to better understanding of the disease process in dementias including AD. Here, we discuss the existing literature on cerebrospinal fluid biomarkers of the NVU cell-specific responses during early stages of dementia and AD. We suggest that the clinical usefulness of established AD biomarkers, Aβ and tau, could be further improved by developing an algorithm that will incorporate biomarkers of the NVU cell-specific responses and injury. Such biomarker algorithm could aid in early detection and intervention as well as identify novel treatment targets to delay disease onset, slow progression, and/or prevent AD.
Topics: Alzheimer Disease; Animals; Astrocytes; Biomarkers; Brain; Dementia; Diet; Endothelial Cells; Exercise; Humans; Microglia; Pericytes; Stress, Physiological
PubMed: 25899298
DOI: 10.1038/jcbfm.2015.76 -
The Journal of Neuropsychiatry and... 2018Traumatic brain injury (TBI) is often considered to be a risk factor for the later development of neurodegenerative conditions, but some findings do not support a link.... (Review)
Review
Traumatic brain injury (TBI) is often considered to be a risk factor for the later development of neurodegenerative conditions, but some findings do not support a link. Differences in research methods, clinical samples, and limitations encountered when assessing and documenting TBI details likely contribute to the mixed reports in the literature. Despite some variability in findings, a review of the literature does provide support for the notion that TBI appears to be associated with earlier onset of some neurodegenerative disorders, although clearly not everyone with a TBI appears to be at an increased risk. Whereas a mechanistic link remains unknown, TBI has been found to initiate an accumulation of pathological processes related to several neurodegenerative disorders. The authors propose a hypothetical model that relates TBI to the development of pathological burden overlapping with some neurodegenerative conditions, in which onset of cognitive/behavioral impairments is hastened in some individuals, but pathological processes stabilize afterward, resulting in a similar course of decline to individuals with dementia who do not have a history of TBI.
Topics: Brain Injuries, Traumatic; Dementia; Humans; Neurodegenerative Diseases
PubMed: 29061090
DOI: 10.1176/appi.neuropsych.17070145 -
Clinical Interventions in Aging 2013There are an estimated 35 million people with dementia across the world, of whom 50% experience regular pain. Despite this, current assessment and treatment of pain in... (Review)
Review
There are an estimated 35 million people with dementia across the world, of whom 50% experience regular pain. Despite this, current assessment and treatment of pain in this patient group are inadequate. In addition to the discomfort and distress caused by pain, it is frequently the underlying cause of behavioral symptoms, which can lead to inappropriate treatment with antipsychotic medications. Pain also contributes to further complications in treatment and care. This review explores four key perspectives of pain management in dementia and makes recommendations for practice and research. The first perspective discussed is the considerable uncertainty within the literature on the impact of dementia neuropathology on pain perception and processing in Alzheimer's disease and other dementias, where white matter lesions and brain atrophy appear to influence the neurobiology of pain. The second perspective considers the assessment of pain in dementia. This is challenging, particularly because of the limited capacity of self-report by these individuals, which means that assessment relies in large part on observational methods. A number of tools are available but the psychometric quality and clinical utility of these are uncertain. The evidence for efficient treatment (the third perspective) with analgesics is also limited, with few statistically well-powered trials. The most promising evidence supports the use of stepped treatment approaches, and indicates the benefit of pain and behavioral interventions on both these important symptoms. The fourth perspective debates further difficulties in pain management due to the lack of sufficient training and education for health care professionals at all levels, where evidence-based guidance is urgently needed. To address the current inadequate management of pain in dementia, a comprehensive approach is needed. This would include an accurate, validated assessment tool that is sensitive to different types of pain and therapeutic effects, supported by better training and support for care staff across all settings.
Topics: Aged; Aged, 80 and over; Dementia; Humans; Pain Management
PubMed: 24204133
DOI: 10.2147/CIA.S36739 -
Psychogeriatrics : the Official Journal... Jun 2009There are two types of dementia with early onset: (i) presenile dementias; and (ii) senile dementias with early onset. Most patients who develop dementia before 65 years... (Review)
Review
There are two types of dementia with early onset: (i) presenile dementias; and (ii) senile dementias with early onset. Most patients who develop dementia before 65 years of age have Alzheimer's disease (AD). The remainder are likely to have vascular dementia (VaD), frontotemporal dementia, head injury, alcohol intoxication, or metabolic disorder. Presenile dementias, caused by frontotemporal lobar degeneration, progressive supranuclear palsy, and corticobasal degeneration, usually occur in patients of presenile and are rarely seen in patients of senile age. Although the factors responsible for the accelerated onset of the illness are not fully known, genetic abnormalities appear to be important in some types of presenile dementia, such as frontotemporal dementia with parkinsonism linked to chromosome 17. Conversely, senile dementias such as sporadic AD and VaD commonly occur in patients of senile age. These disorders may also occur in patients of presenile age, although less frequently. Alzheimer's disease was originally classified as a 'presenile dementia'. Since the 1980s, 'senile dementia of Alzheimer type' (SDAT) and 'Alzheimer's disease' have been considered to belong to the same pathological entity and both are now known as 'dementia of Alzheimer's type (DAT)' or merely 'Alzheimer's disease'. Rapid progression of cognitive impairment with neuropsychological syndromes and neurological symptoms has been considered a characteristic of early onset AD. However, recently, neurological symptoms such as spastic paraparesis, seizures, and myoclonic convulsions have been reported to occur infrequently in early onset AD, although language problems and visuospatial dysfunctions are common. There are at least three dominant genes that have been identified in cases of familial Alzheimer's disease with early onset, namely the amyloid precursor gene (APP), and the genes encoding presenilin 1 (PSEN1) and presenilin 2 (PSEN2). Therefore, genetic abnormalities are important factors contributing to the earlier onset of the illness. It is also important to investigate the pathophysiological mechanism in relation to genetic abnormalities, environmental factors, physical illnesses, and metabolic disturbances to understand the processes underlying the development of dementia with early onset.
Topics: Age of Onset; Alzheimer Disease; Dementia; Dementia, Vascular; Disease Progression; Humans; Middle Aged; Neurodegenerative Diseases
PubMed: 19604328
DOI: 10.1111/j.1479-8301.2009.00274.x -
Journal of Neurochemistry Nov 2019Dementias are prevalent brain disorders in the aged population. Dementias pose major socio-medical burden, but currently there is no cure available. Novel proteomics... (Review)
Review
Dementias are prevalent brain disorders in the aged population. Dementias pose major socio-medical burden, but currently there is no cure available. Novel proteomics approaches hold promise to identify alterations of the brain proteome that could provide clues on disease etiology, and identify candidate proteins to develop further as a biomarker. In this review, we focus on recent proteomics findings from brains affected with Alzheimer's Disease, Parkinson Disease Dementia, Frontotemporal Dementia, and Amyotrophic Lateral Sclerosis. These studies confirmed known cellular changes, and in addition identified novel proteins that may underlie distinct aspects of the diseases. This article is part of the special issue "Proteomics".
Topics: Alzheimer Disease; Amyotrophic Lateral Sclerosis; Biomarkers; Brain; Dementia; Disease Progression; Frontotemporal Dementia; Humans; Neurodegenerative Diseases; Parkinson Disease; Proteome; Proteomics
PubMed: 30289976
DOI: 10.1111/jnc.14603 -
Alzheimer's & Dementia : the Journal of... Oct 2022With population growth and aging, the number of people with dementia and related disorders will grow substantially in the years ahead, bringing with it significant...
With population growth and aging, the number of people with dementia and related disorders will grow substantially in the years ahead, bringing with it significant societal, health-care, and economic challenges. Here, we analyze dementia policies of seven major countries in Asia/Pacific, Europe, and North America to identify opportunities for early actions to mitigate disease burden. We find that most countries are addressing this need by including a specific focus on early action in their national dementia strategies (five of seven countries), implementing public health initiatives for risk reduction, prevention, and early detection and diagnosis (six of seven countries); supporting enabling research for early detection and risk reduction (six of seven countries); and enacting a system for early, regular brain health screening (one of seven). We discuss risks and opportunities for integrating early action policies and conducting additional systematic research to understand the potential benefits and impacts of these policies.
Topics: Humans; Delivery of Health Care; Cost of Illness; Public Health; Policy; Dementia
PubMed: 35293672
DOI: 10.1002/alz.12655 -
Neurodegenerative Disease Management Aug 2019Posterior cortical atrophy (PCA) is a progressive neurocognitive syndrome, most commonly associated with the loss of complex visuospatial functions. Diagnosis is... (Review)
Review
Posterior cortical atrophy (PCA) is a progressive neurocognitive syndrome, most commonly associated with the loss of complex visuospatial functions. Diagnosis is challenging, and international consensus classification and nomenclature for PCA subtypes have only recently been reached. Presently, no established treatments exist. Efforts to develop treatments are hampered by the lack of standardized methods to monitor illness progression. Although measures developed from work with Alzheimer's disease and other dementias provide a foundation for diagnosing and monitoring progression, PCA presents unique challenges for clinicians counseling patients and families on clinical status and prognosis, and experts designing clinical trials of interventions. Here, we review issues facing PCA clinical research and care, summarize our approach to diagnosis and monitoring of disease progression, and outline ideas for developing tools for these purposes.
Topics: Age of Onset; Aged; Alzheimer Disease; Atrophy; Cognition Disorders; Cognitive Dysfunction; Dementia; Diagnosis, Differential; Disease Management; Disease Progression; Executive Function; Female; Genetic Predisposition to Disease; Humans; Language Disorders; Male; Memory Disorders; Mental Status and Dementia Tests; Middle Aged; Neuroimaging; Occipital Lobe; Perceptual Disorders; Psychomotor Disorders; Severity of Illness Index; Vision Disorders; Visual Perception
PubMed: 31392920
DOI: 10.2217/nmt-2018-0052 -
International Psychogeriatrics Dec 2010Worldwide, lifespan is lengthening. Concomitantly, late-life dementias are increasingly common, challenging both personal and public health internationally. After age... (Review)
Review
Worldwide, lifespan is lengthening. Concomitantly, late-life dementias are increasingly common, challenging both personal and public health internationally. After age 65, rates of dementia tend to double every five years in developed countries and every seven in developing ones. The late-life dementias, particularly Alzheimer's disease, have profound effects on aging individuals and their caregivers. Multidisciplinary research has explored the potential for various approaches to prevent or delay the onset of late-life dementias. Outlining that research, including our team's Adult Changes in Thought and Kame studies, this review concludes that delaying the onset of these dementias appears feasible, although absolute prevention may not be. Today, the most promising methods appear to include controlling vascular risk factors like hypertension and engaging in physical exercise - and possibly mental exercise. If people can delay the onset of dementias, they can lead more fulfilling lives for longer, spending less time suffering from dementia and letting their families spend less time coping with the disease. It is possible that trends toward more knowledge-based societies, where cognitive health is so vital, may increasingly exert evolutionary pressure favoring larger and healthier brains - and a "compression of cognitive morbidity" - well into old age. Public health's great triumph, increased lifespan, should give more of the world's people the reward of many years of dementia-free life. Rather than the personal difficulties and public health burdens of many years of functional impairment, dependency, and suffering with dementia, some interventions may delay the onset of Alzheimer's disease and other dementias.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cognition; Dementia; Dementia, Vascular; Exercise; Global Health; Humans; Hypertension; International Cooperation; Longevity; Morbidity; Quality of Life; Risk Factors
PubMed: 20594386
DOI: 10.1017/S1041610210001080