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Neurology Dec 2017Goal 1 of the National Plan to Address Alzheimer's Disease is to prevent and effectively treat Alzheimer disease and Alzheimer disease-related dementias by 2025. To help... (Review)
Review
Goal 1 of the National Plan to Address Alzheimer's Disease is to prevent and effectively treat Alzheimer disease and Alzheimer disease-related dementias by 2025. To help inform the research agenda toward achieving this goal, the NIH hosts periodic summits that set and refine relevant research priorities for the subsequent 5 to 10 years. This proceedings article summarizes the 2016 Alzheimer's Disease-Related Dementias Summit, including discussion of scientific progress, challenges, and opportunities in major areas of dementia research, including mixed-etiology dementias, Lewy body dementia, frontotemporal degeneration, vascular contributions to cognitive impairment and dementia, dementia disparities, and dementia nomenclature.
Topics: Alzheimer Disease; Dementia; Goals; Humans; Research; United States
PubMed: 29117955
DOI: 10.1212/WNL.0000000000004717 -
Clinical Neurophysiology : Official... Jan 2016Lewy body dementias (LBD) include both dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD), and the differentiation of LBD from other... (Review)
Review
OBJECTIVE
Lewy body dementias (LBD) include both dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD), and the differentiation of LBD from other neurodegenerative dementias can be difficult. Currently, there are few biomarkers which might assist early diagnosis, map onto LBD symptom severity, and provide metrics of treatment response. Traditionally, biomarkers in LBD have focussed on neuroimaging modalities; however, as biomarkers need to be simple, inexpensive and non-invasive, neurophysiological approaches might also be useful as LBD biomarkers.
METHODS
In this review, we searched PubMED and PsycINFO databases in a semi-systematic manner in order to identify potential neurophysiological biomarkers in the LBDs.
RESULTS
We identified 1491 studies; of these, 37 studies specifically examined neurophysiological biomarkers in LBD patients. We found that there was substantial heterogeneity with respect to methodologies and patient cohorts.
CONCLUSION
Generally, many of the findings have yet to be replicated, although preliminary findings reinforce the potential utility of approaches such as quantitative electroencephalography and motor cortical stimulation paradigms.
SIGNIFICANCE
Various neurophysiological techniques have the potential to be useful biomarkers in the LBDs. We recommend that future studies focus on maximising the diagnostic specificity and sensitivity of the most promising neurophysiological biomarkers.
Topics: Electroencephalography; Humans; Lewy Body Disease; Magnetoencephalography; Neuropsychological Tests; Transcranial Magnetic Stimulation
PubMed: 26183755
DOI: 10.1016/j.clinph.2015.06.020 -
Journal of the American Medical... Jun 2016Poor gait performance predicts risk of developing dementia. No structured critical evaluation has been conducted to study this association yet. The aim of this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Poor gait performance predicts risk of developing dementia. No structured critical evaluation has been conducted to study this association yet. The aim of this meta-analysis was to systematically examine the association of poor gait performance with incidence of dementia.
METHODS
An English and French Medline search was conducted in June 2015, with no limit of date, using the medical subject headings terms "Gait" OR "Gait Disorders, Neurologic" OR "Gait Apraxia" OR "Gait Ataxia" AND "Dementia" OR "Frontotemporal Dementia" OR "Dementia, Multi-Infarct" OR "Dementia, Vascular" OR "Alzheimer Disease" OR "Lewy Body Disease" OR "Frontotemporal Dementia With Motor Neuron Disease" (Supplementary Concept). Poor gait performance was defined by standardized tests of walking, and dementia was diagnosed according to international consensus criteria. Four etiologies of dementia were identified: any dementia, Alzheimer disease (AD), vascular dementia (VaD), and non-AD (ie, pooling VaD, mixed dementias, and other dementias). Fixed effects meta-analyses were performed on the estimates in order to generate summary values.
RESULTS
Of the 796 identified abstracts, 12 (1.5%) were included in this systematic review and meta-analysis. Poor gait performance predicted dementia [pooled hazard ratio (HR) combined with relative risk and odds ratio = 1.53 with P < .001 for any dementia, pooled HR = 1.79 with P < .001 for VaD, HR = 1.89 with P value < .001 for non-AD]. Findings were weaker for predicting AD (HR = 1.03 with P value = .004).
CONCLUSIONS
This meta-analysis provides evidence that poor gait performance predicts dementia. This association depends on the type of dementia; poor gait performance is a stronger predictor of non-AD dementias than AD.
Topics: Aged; Aged, 80 and over; Dementia; Female; Gait; Humans; Male; Predictive Value of Tests; Psychomotor Performance
PubMed: 26852960
DOI: 10.1016/j.jamda.2015.12.092 -
The Medical Clinics of North America Jan 1993With so many conditions that can manifest in dementia, the question arises as to how extensive an evaluation need be done on the individual patient presenting with... (Review)
Review
With so many conditions that can manifest in dementia, the question arises as to how extensive an evaluation need be done on the individual patient presenting with dementia. Thorough physical, neurologic, and psychiatric examinations are the cornerstones of the work-up, with special attention paid to the history, use of medications, and mental status of the patient. Laboratory tests recommended by the National Institutes of Health Consensus Conference on Differential Diagnosis of Dementing Diseases include a complete blood count, electrolyte and metabolic screen, thyroid panel, vitamin B12 and folate levels, syphilis serology, urinalysis, chest radiograph and electrocardiogram, and head CT scan. These evaluations are sufficient to diagnose the majority of treatable dementias. Other evaluations including magnetic resonance imaging, electroencephalography, cerebrospinal fluid examination, cerebral blood flow and metabolism measures (rate of cerebral blood flow, single photon emission computed tomography, and positron-emission tomography), and brain biopsy all can be of additional assistance in diagnosing the cause of the dementia when justified by the clinical setting. When the appropriate diagnosis is made, therapy is directed at the primary disorder. Successful treatment of the primary condition may result in stabilization or partial or complete reversal of the cognitive disturbance. In some instances, judicious pharmacologic management of the accompanying behavioral disturbance may be required.
Topics: Avitaminosis; Cerebrovascular Circulation; Dementia; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Factitious Disorders; Humans; Psychotherapy; Tomography, X-Ray Computed
PubMed: 8419719
DOI: 10.1016/s0025-7125(16)30280-2 -
European Journal of Nuclear Medicine... Jul 2016The multifaceted nature of the pathology of dementia spectrum disorders has complicated their management and the development of effective treatments. This is despite the... (Review)
Review
The multifaceted nature of the pathology of dementia spectrum disorders has complicated their management and the development of effective treatments. This is despite the fact that they are far from uncommon, with Alzheimer's disease (AD) alone affecting 35 million people worldwide. The cholinergic system has been found to be crucially involved in cognitive function, with cholinergic dysfunction playing a pivotal role in the pathophysiology of dementia. The use of molecular imaging such as SPECT and PET for tagging targets within the cholinergic system has shown promise for elucidating key aspects of underlying pathology in dementia spectrum disorders, including AD or parkinsonian dementias. SPECT and PET studies using selective radioligands for cholinergic markers, such as [(11)C]MP4A and [(11)C]PMP PET for acetylcholinesterase (AChE), [(123)I]5IA SPECT for the α4β2 nicotinic acetylcholine receptor and [(123)I]IBVM SPECT for the vesicular acetylcholine transporter, have been developed in an attempt to clarify those aspects of the diseases that remain unclear. This has led to a variety of findings, such as cortical AChE being significantly reduced in Parkinson's disease (PD), PD with dementia (PDD) and AD, as well as correlating with certain aspects of cognitive function such as attention and working memory. Thalamic AChE is significantly reduced in progressive supranuclear palsy (PSP) and multiple system atrophy, whilst it is not affected in PD. Some of these findings have brought about suggestions for the improvement of clinical practice, such as the use of a thalamic/cortical AChE ratio to differentiate between PD and PSP, two diseases that could overlap in terms of initial clinical presentation. Here, we review the findings from molecular imaging studies that have investigated the role of the cholinergic system in dementia spectrum disorders.
Topics: Choline; Dementia; Diagnostic Imaging; Humans; Synapses
PubMed: 26984612
DOI: 10.1007/s00259-016-3349-x -
Health Services Research Aug 2019To estimate dementia's incremental cost to the traditional Medicare program.
OBJECTIVE
To estimate dementia's incremental cost to the traditional Medicare program.
DATA SOURCES
Health and Retirement Study (HRS) survey-linked Medicare part A and B claims from 1991 to 2012.
STUDY DESIGN
We compared Medicare expenditures for 60 months following a claims-based dementia diagnosis to those for a randomly selected, matched comparison group.
DATA COLLECTION/EXTRACTION METHODS
We used a cost estimator that accounts for differential survival between individuals with and without dementia and decomposes incremental costs into survival and cost intensity components.
PRINCIPAL FINDINGS
Dementia's five-year incremental cost to the traditional Medicare program is approximately $15 700 per patient, nearly half of which is incurred in the first year after diagnosis. Shorter survival with dementia mitigates the incremental cost by about $2650. Increased costs for individuals with dementia were driven by more intensive use of Medicare part A covered services. The incremental cost of dementia was about $7850 higher for females than for males because of sex-specific differential mortality associated with dementia.
CONCLUSIONS
Dementia's cost to the traditional Medicare program is significant. Interventions that target early identification of dementia and preventable inpatient and post-acute care services could produce substantial savings.
Topics: Age Factors; Aged; Aged, 80 and over; Alzheimer Disease; Comorbidity; Dementia; Female; Health Expenditures; Humans; Male; Medicare; Retrospective Studies; Sex Factors; Socioeconomic Factors; Time Factors; United States
PubMed: 30868557
DOI: 10.1111/1475-6773.13134 -
Seminars in Neurology Nov 2011Genetic factors are now recognized to play an important role in most age-related dementias. Although other factors, including aging itself, contribute to dementia, in... (Review)
Review
Genetic factors are now recognized to play an important role in most age-related dementias. Although other factors, including aging itself, contribute to dementia, in this review the authors focus on the role of specific disease-causing genes and genetic factors in the most common age-related dementias. They review each dementia within the context of a genes/environment continuum, with varying levels of genetic versus environmental influence. All major classes of dementia will be discussed but greatest attention will be given to the most common dementia, Alzheimer's disease, for which several new genetic factors were recently identified.
Topics: Alzheimer Disease; Apolipoproteins E; DNA Repeat Expansion; Dementia; Frontotemporal Lobar Degeneration; Genetic Predisposition to Disease; Humans; Huntington Disease; Lewy Body Disease; Mutation; Prion Diseases
PubMed: 22266883
DOI: 10.1055/s-0031-1299784 -
Journal of Extracellular Vesicles Dec 2023Dementia is a leading cause of death worldwide, with increasing prevalence as global life expectancy increases. The most common neurodegenerative disorders are...
Proteomic comparison between non-purified cerebrospinal fluid and cerebrospinal fluid-derived extracellular vesicles from patients with Alzheimer's, Parkinson's and Lewy body dementia.
Dementia is a leading cause of death worldwide, with increasing prevalence as global life expectancy increases. The most common neurodegenerative disorders are Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). With this study, we took an in-depth look at the proteome of the (non-purified) cerebrospinal fluid (CSF) and the CSF-derived extracellular vesicles (EVs) of AD, PD, PD-MCI (Parkinson's disease with mild cognitive impairment), PDD and DLB patients analysed by label-free mass spectrometry. This has led to the discovery of differentially expressed proteins that may be helpful for differential diagnosis. We observed a greater number of differentially expressed proteins in CSF-derived EV samples (N = 276) compared to non-purified CSF (N = 169), with minimal overlap between both datasets. This finding suggests that CSF-derived EV samples may be more suitable for the discovery phase of a biomarker study, due to the removal of more abundant proteins, resulting in a narrower dynamic range. As disease-specific markers, we selected a total of 39 biomarker candidates identified in non-purified CSF, and 37 biomarker candidates across the different diseases under investigation in the CSF-derived EV data. After further exploration and validation of these proteins, they can be used to further differentiate between the included dementias and may offer new avenues for research into more disease-specific pharmacological therapeutics.
Topics: Humans; Alzheimer Disease; Lewy Body Disease; Parkinson Disease; Dementia; Proteomics; Extracellular Vesicles; Biomarkers
PubMed: 38082559
DOI: 10.1002/jev2.12383 -
Acta Bio-medica : Atenei Parmensis Nov 2020Dementia is a disease associated with cognitive and/or behavioral changes that interfere with the ability to perform daily activities. Alzheimer's disease is the most... (Review)
Review
BACKGROUND AND AIM
Dementia is a disease associated with cognitive and/or behavioral changes that interfere with the ability to perform daily activities. Alzheimer's disease is the most common type of dementia. The aim of this mini-review is to summarize all the syndromes characterized by dementia and for which the associated gene is known.
METHODS
We searched those syndromes in PubMed and OMIM database.
RESULTS
Two forms of dementia exist: the multifactorial dementia results from the interaction of different genetic and environmental factors, the hereditary dementia associated with a single gene. Individuals with a family history of dementia and early onset of the disease are more likely to have a hereditary form of dementia. Dementias are mainly autosomal dominant, but they can also be autosomal recessive or X-linked.
CONCLUSIONS
Since dementia has high clinical and genetic heterogeneity, the use in diagnostics of a large panel of genes may greatly help to speed up the determination of the molecular diagnosis and/or establish a risk of recurrence in family members for the purpose of planning appropriate preventive and/or therapeutic measures.
Topics: Alzheimer Disease; Dementia; Humans
PubMed: 33170157
DOI: 10.23750/abm.v91i13-S.10602 -
Dialogues in Clinical Neuroscience Dec 2016Suffering related to dementia is multifaceted because cognitive and physical functioning slowly deteriorates. Advanced age and sex, two of the most prominent risk... (Review)
Review
Suffering related to dementia is multifaceted because cognitive and physical functioning slowly deteriorates. Advanced age and sex, two of the most prominent risk factors for dementia, are not modifiable. Lifestyle factors such as smoking, excessive alcohol use, and poor diet modulate susceptibility to dementia in both males and females. The degree to which the resulting health conditions (eg, obesity, type 2 diabetes, and cardiovascular disease) impact dementia risk varies by sex. Depending on the subtype of dementia, the ratio of male to female prevalence differs. For example, females are at greater risk of developing Alzheimer disease dementia, whereas males are at greater risk of developing vascular dementia. This review examines sex and gender differences in the development of dementia with the goal of highlighting factors that require further investigation. Considering sex as a biological variable in dementia research promises to advance our understanding of the pathophysiology and treatment of these conditions.
Topics: Alzheimer Disease; Dementia; Female; Gender Identity; Humans; Male; Risk Factors; Sex Characteristics; Sex Factors
PubMed: 28179815
DOI: 10.31887/DCNS.2016.18.4/cepperson