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The Cochrane Database of Systematic... Jul 2021Dementia is a progressive global cognitive impairment syndrome. In 2010, more than 35 million people worldwide were estimated to be living with dementia. Some people... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dementia is a progressive global cognitive impairment syndrome. In 2010, more than 35 million people worldwide were estimated to be living with dementia. Some people with mild cognitive impairment (MCI) will progress to dementia but others remain stable or recover full function. There is great interest in finding good predictors of dementia in people with MCI. The Mini-Mental State Examination (MMSE) is the best-known and the most often used short screening tool for providing an overall measure of cognitive impairment in clinical, research and community settings.
OBJECTIVES
To determine the accuracy of the Mini Mental State Examination for the early detection of dementia in people with mild cognitive impairment SEARCH METHODS: We searched ALOIS (Cochrane Dementia and Cognitive Improvement Specialized Register of diagnostic and intervention studies (inception to May 2014); MEDLINE (OvidSP) (1946 to May 2014); EMBASE (OvidSP) (1980 to May 2014); BIOSIS (Web of Science) (inception to May 2014); Web of Science Core Collection, including the Conference Proceedings Citation Index (ISI Web of Science) (inception to May 2014); PsycINFO (OvidSP) (inception to May 2014), and LILACS (BIREME) (1982 to May 2014). We also searched specialized sources of diagnostic test accuracy studies and reviews, most recently in May 2014: MEDION (Universities of Maastricht and Leuven, www.mediondatabase.nl), DARE (Database of Abstracts of Reviews of Effects, via the Cochrane Library), HTA Database (Health Technology Assessment Database, via the Cochrane Library), and ARIF (University of Birmingham, UK, www.arif.bham.ac.uk). No language or date restrictions were applied to the electronic searches and methodological filters were not used as a method to restrict the search overall so as to maximize sensitivity. We also checked reference lists of relevant studies and reviews, tracked citations in Scopus and Science Citation Index, used searches of known relevant studies in PubMed to track related articles, and contacted research groups conducting work on MMSE for dementia diagnosis to try to locate possibly relevant but unpublished data.
SELECTION CRITERIA
We considered longitudinal studies in which results of the MMSE administered to MCI participants at baseline were obtained and the reference standard was obtained by follow-up over time. We included participants recruited and clinically classified as individuals with MCI under Petersen and revised Petersen criteria, Matthews criteria, or a Clinical Dementia Rating = 0.5. We used acceptable and commonly used reference standards for dementia in general, Alzheimer's dementia, Lewy body dementia, vascular dementia and frontotemporal dementia.
DATA COLLECTION AND ANALYSIS
We screened all titles generated by the electronic database searches. Two review authors independently assessed the abstracts of all potentially relevant studies. We assessed the identified full papers for eligibility and extracted data to create two by two tables for dementia in general and other dementias. Two authors independently performed quality assessment using the QUADAS-2 tool. Due to high heterogeneity and scarcity of data, we derived estimates of sensitivity at fixed values of specificity from the model we fitted to produce the summary receiver operating characteristic curve.
MAIN RESULTS
In this review, we included 11 heterogeneous studies with a total number of 1569 MCI patients followed for conversion to dementia. Four studies assessed the role of baseline scores of the MMSE in conversion from MCI to all-cause dementia and eight studies assessed this test in conversion from MCI to Alzheimer´s disease dementia. Only one study provided information about the MMSE and conversion from MCI to vascular dementia. For conversion from MCI to dementia in general, the accuracy of baseline MMSE scores ranged from sensitivities of 23% to 76% and specificities from 40% to 94%. In relationship to conversion from MCI to Alzheimer's disease dementia, the accuracy of baseline MMSE scores ranged from sensitivities of 27% to 89% and specificities from 32% to 90%. Only one study provided information about conversion from MCI to vascular dementia, presenting a sensitivity of 36% and a specificity of 80% with an incidence of vascular dementia of 6.2%. Although we had planned to explore possible sources of heterogeneity, this was not undertaken due to the scarcity of studies included in our analysis.
AUTHORS' CONCLUSIONS
Our review did not find evidence supporting a substantial role of MMSE as a stand-alone single-administration test in the identification of MCI patients who could develop dementia. Clinicians could prefer to request additional and extensive tests to be sure about the management of these patients. An important aspect to assess in future updates is if conversion to dementia from MCI stages could be predicted better by MMSE changes over time instead of single measurements. It is also important to assess if a set of tests, rather than an isolated one, may be more successful in predicting conversion from MCI to dementia.
Topics: Alzheimer Disease; Cognitive Dysfunction; Dementia; Dementia, Vascular; Disease Progression; Early Diagnosis; Frontotemporal Dementia; Humans; Lewy Body Disease; Mental Status and Dementia Tests; Neuropsychological Tests; Sensitivity and Specificity
PubMed: 34313331
DOI: 10.1002/14651858.CD010783.pub3 -
International Journal of Geriatric... Oct 2022Lewy body dementia (LBD) refers to both dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD). Sleep disturbances are common in LBD, and can... (Review)
Review
BACKGROUND
Lewy body dementia (LBD) refers to both dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD). Sleep disturbances are common in LBD, and can include poor sleep quality, excessive daytime sleepiness (EDS), and rapid eye movement behaviour disorder (RBD). Despite the high clinical prevalence of sleep disturbances in LBD, they are under-studied relative to other dementias. The aim of the present systematic review was to examine the nature of sleep disturbances in LBD, summarise the effect of treatment studies upon sleep, and highlight specific and necessary directions for future research.
METHODS
Published studies in English were located by searching PubMED and PSYCArticles databases (until 10 June 2022). The search protocol was pre-registered in PROSPERO (CRD42021293490) and performed in accordance with PRISMA guidelines.
RESULTS
Following full-text review, a final total of 70 articles were included. These included 20 studies focussing on subjective sleep, 14 on RBD, 8 on EDS, 7 on objective sleep, and 1 on circadian rhythms. The majority of the 18 treatment studies used pharmacological interventions (n = 12), had an open-label design (n = 8), and were of low-to-moderate quality. Most studies (n = 55) included only patients with DLB. Due to the heterogeneity of the studies, we reported a narrative synthesis without meta-analysis.
CONCLUSIONS
At least one form of sleep disturbance may be present in as many as 90% of people with LBD. Subjectively poor sleep quality, excessive daytime sleepiness, and RBD are more common and severe in LBD relative to other dementias.
Topics: Alzheimer Disease; Disorders of Excessive Somnolence; Humans; Lewy Body Disease; Sleep; Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders
PubMed: 36168299
DOI: 10.1002/gps.5814 -
Journal of Alzheimer's Disease : JAD 2020Alzheimer's disease and related dementias lack effective treatment or cures and are major public health challenges. Risk for Alzheimer's disease and related dementias is... (Review)
Review
Alzheimer's disease and related dementias lack effective treatment or cures and are major public health challenges. Risk for Alzheimer's disease and related dementias is partially attributable to environmental factors. The heavy metals lead, cadmium, and manganese are widespread and persistent in our environments. Once persons are exposed to these metals, they are adept at entering cells and reaching the brain. Lead and cadmium are associated with numerous health outcomes even at low levels of exposure. Although manganese is an essential metal, deficiency or environmental exposure or high levels of the metal can be toxic. In cell and animal model systems, lead, cadmium, and manganese are well documented neurotoxicants that contribute to canonical Alzheimer's disease pathologies. Adult human epidemiologic studies have consistently shown lead, cadmium, and manganese are associated with impaired cognitive function and cognitive decline. No longitudinal human epidemiology study has assessed lead or manganese exposure on Alzheimer's disease specifically though two studies have reported a link between cadmium and Alzheimer's disease mortality. More longitudinal epidemiologic studies with high-quality time course exposure data and incident cases of Alzheimer's disease and related dementias are warranted to confirm and estimate the proportion of risk attributable to these exposures. Given the widespread and global exposure to lead, cadmium, and manganese, even small increases in the risks of Alzheimer's disease and related dementias would have a major population impact on the burden on disease. This article reviews the experimental and epidemiologic literature of the associations between lead, cadmium, and manganese on Alzheimer's disease and related dementias and makes recommendations of critical areas of future investment.
Topics: Alzheimer Disease; Animals; Cadmium; Dementia; Environmental Exposure; Humans; Manganese; Metals, Heavy
PubMed: 32651318
DOI: 10.3233/JAD-200282 -
Molecular Psychiatry Oct 2023Dementia is a leading cause of disability and death worldwide. At present there is no disease modifying treatment for any of the most common types of dementia such as... (Review)
Review
Dementia is a leading cause of disability and death worldwide. At present there is no disease modifying treatment for any of the most common types of dementia such as Alzheimer's disease (AD), Vascular dementia, Lewy Body Dementia (LBD) and Frontotemporal dementia (FTD). Early and accurate diagnosis of dementia subtype is critical to improving clinical care and developing better treatments. Structural and molecular imaging has contributed to a better understanding of the pathophysiology of neurodegenerative dementias and is increasingly being adopted into clinical practice for early and accurate diagnosis. In this review we summarise the contribution imaging has made with particular focus on multimodal magnetic resonance imaging (MRI) and positron emission tomography imaging (PET). Structural MRI is widely used in clinical practice and can help exclude reversible causes of memory problems but has relatively low sensitivity for the early and differential diagnosis of dementia subtypes. F-fluorodeoxyglucose PET has high sensitivity and specificity for AD and FTD, while PET with ligands for amyloid and tau can improve the differential diagnosis of AD and non-AD dementias, including recognition at prodromal stages. Dopaminergic imaging can assist with the diagnosis of LBD. The lack of a validated tracer for α-synuclein or TAR DNA-binding protein 43 (TDP-43) imaging remain notable gaps, though work is ongoing. Emerging PET tracers such as C-UCB-J for synaptic imaging may be sensitive early markers but overall larger longitudinal multi-centre cross diagnostic imaging studies are needed.
Topics: Humans; Frontotemporal Dementia; Diagnosis, Differential; Alzheimer Disease; Lewy Body Disease; Neuroimaging; Positron-Emission Tomography
PubMed: 37608222
DOI: 10.1038/s41380-023-02215-8 -
The Journal of Clinical Psychiatry Mar 2019Disclosing the diagnosis of cognitive impairment or dementia due to Alzheimer's disease (AD) and Related Dementias (ADRD) can be one of the most challenging aspects of...
Disclosing the diagnosis of cognitive impairment or dementia due to Alzheimer's disease (AD) and Related Dementias (ADRD) can be one of the most challenging aspects of dementia care for clinicians. However difficult the diagnosis is to give or receive, evidence and evidence-based consensus support that disclosing a timely AD/ADRD diagnosis, accompanied by psychoeducation and care planning, is beneficial to patient-care partner dyads. Diagnosis, provided as early as possible, increases the likelihood for patients to be involved in decision-making and planning for their future and allows care options to be implemented sooner to provide greater clinical and quality-of-life benefits, reduce potential for harm, and mitigate symptoms and decline. Using patient-centered communication and following a structured process, clinicians can provide a successful disclosure of diagnosis as a component of the necessary foundation to implement impactful management and care planning for patients and caregivers going through a life-changing process.
Topics: Alzheimer Disease; Caregivers; Communication; Decision Making; Dementia; Disclosure; Humans
PubMed: 30900850
DOI: 10.4088/JCP.MS18002BR1C -
CNS Neuroscience & Therapeutics Feb 2019The Ginkgo biloba special extract, EGb 761 has been widely used in the treatment of neuropsychiatric disorders, including Alzheimer's disease (AD). (Review)
Review
BACKGROUND
The Ginkgo biloba special extract, EGb 761 has been widely used in the treatment of neuropsychiatric disorders, including Alzheimer's disease (AD).
METHODS
To guide clinical practice in the Asian region, the Asian Clinical Expert Group on Neurocognitive Disorders compiled evidence-based consensus recommendations regarding the use of EGb 761 in neurocognitive disorders with/without cerebrovascular disease.
RESULTS
Key randomized trials and robust meta-analyses have demonstrated significant improvement in cognitive function, neuropsychiatric symptoms, activities of daily living (ADL) and quality of life with EGb 761 versus placebo in patients with mild-to-moderate dementia. In those with mild cognitive impairment (MCI), EGb 761 has also demonstrated significant symptomatic improvement versus placebo. World Federation of Societies of Biological Psychiatry guidelines list EGb 761 with the same strength of evidence as acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) antagonists e.g. memantine (Grade 3 recommendation; Level B evidence). Only EGb 761 had Level B evidence in improving cognition, behaviour, and ADL in both AD and vascular dementia patients. Safety analyses show EGb 761 to have a positive risk-benefit profile. While concerns have been raised regarding a possible increased bleeding risk, several randomized trials and two meta-analyses have not supported this association.
CONCLUSIONS
The Expert Group foresee an important role for EGb 761 , used alone or as an add-on therapy, in the treatment of MCI and dementias, particularly when patients do not derive benefit from acetylcholinesterase inhibitors or NMDA antagonists. EGb 761 should be used in alignment with local clinical practice guidelines.
Topics: Cerebrovascular Disorders; Cognitive Dysfunction; Consensus; Dementia; Ginkgo biloba; Humans; Plant Extracts; Randomized Controlled Trials as Topic
PubMed: 30648358
DOI: 10.1111/cns.13095 -
Journal of Neurology, Neurosurgery, and... Jun 2022This longitudinal study compared emerging plasma biomarkers for neurodegenerative disease between controls, patients with Alzheimer's disease (AD), Lewy body dementia...
OBJECTIVES
This longitudinal study compared emerging plasma biomarkers for neurodegenerative disease between controls, patients with Alzheimer's disease (AD), Lewy body dementia (LBD), frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP).
METHODS
Plasma phosphorylated tau at threonine-181 (p-tau181), amyloid beta (Αβ)42, Aβ40, neurofilament light (NfL) and glial fibrillar acidic protein (GFAP) were measured using highly sensitive single molecule immunoassays (Simoa) in a multicentre cohort of 300 participants (controls=73, amyloid positive mild cognitive impairment (MCI+) and AD dementia=63, LBD=117, FTD=28, PSP=19). LBD participants had known positron emission tomography (PET)-Aβ status.
RESULTS
P-tau181 was elevated in MCI+AD compared with all other groups. Aβ42/40 was lower in MCI+AD compared with controls and FTD. NfL was elevated in all dementias compared with controls while GFAP was elevated in MCI+AD and LBD. Plasma biomarkers could classify between MCI+AD and controls, FTD and PSP with high accuracy but showed limited ability in differentiating MCI+AD from LBD. No differences were detected in the levels of plasma biomarkers when comparing PET-Aβ positive and negative LBD. P-tau181, NfL and GFAP were associated with baseline and longitudinal cognitive decline in a disease specific pattern.
CONCLUSION
This large study shows the role of plasma biomarkers in differentiating patients with different dementias, and at monitoring longitudinal change. We confirm that p-tau181 is elevated in MCI+AD, versus controls, FTD and PSP, but is less accurate in the classification between MCI+AD and LBD or detecting amyloid brain pathology in LBD. NfL was elevated in all dementia groups, while GFAP was elevated in MCI+AD and LBD.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Cognitive Dysfunction; Frontotemporal Dementia; Glial Fibrillary Acidic Protein; Humans; Lewy Body Disease; Longitudinal Studies; Neurodegenerative Diseases; Supranuclear Palsy, Progressive; tau Proteins
PubMed: 35078917
DOI: 10.1136/jnnp-2021-327788 -
Missouri Medicine 2017Neurocognitive and sleep problems are common, underdiagnosed, and frequently co-morbid. Sleep disruption, and fatigue, predict cognitive impairment. Cognitive... (Review)
Review
Neurocognitive and sleep problems are common, underdiagnosed, and frequently co-morbid. Sleep disruption, and fatigue, predict cognitive impairment. Cognitive impairment, in turn, can worsen sleep hygiene. In dementia patients, sleep disorders are common, and dementia medications affect sleep. Emerging insights on the brain's glymphatic system suggests that sleep may drive clearance of Aβ peptide to affect Alzheimer pathophysiology. Parkinsonian dementias are linked with REM behavior disorder, a highly treatable problem that predicts future conversion into dementia.
Topics: Amyloid beta-Peptides; Cognitive Dysfunction; Dementia; Humans; Neuropsychological Tests; Parkinsonian Disorders; Peptide Fragments; REM Sleep Behavior Disorder; Sleep Wake Disorders
PubMed: 30228618
DOI: No ID Found -
Journal of Neurology Nov 2016Hearing deficits associated with cognitive impairment have attracted much recent interest, motivated by emerging evidence that impaired hearing is a risk factor for... (Review)
Review
Hearing deficits associated with cognitive impairment have attracted much recent interest, motivated by emerging evidence that impaired hearing is a risk factor for cognitive decline. However, dementia and hearing impairment present immense challenges in their own right, and their intersection in the auditory brain remains poorly understood and difficult to assess. Here, we outline a clinically oriented, symptom-based approach to the assessment of hearing in dementias, informed by recent progress in the clinical auditory neuroscience of these diseases. We consider the significance and interpretation of hearing loss and symptoms that point to a disorder of auditory cognition in patients with dementia. We identify key auditory characteristics of some important dementias and conclude with a bedside approach to assessing and managing auditory dysfunction in dementia.
Topics: Dementia; Hearing Loss; Humans
PubMed: 27372450
DOI: 10.1007/s00415-016-8208-y -
Journal of Neurology, Neurosurgery, and... Nov 2019Traumatic brain injury (TBI) leads to increased rates of dementia, including Alzheimer's disease. The mechanisms by which trauma can trigger neurodegeneration are... (Review)
Review
Traumatic brain injury (TBI) leads to increased rates of dementia, including Alzheimer's disease. The mechanisms by which trauma can trigger neurodegeneration are increasingly understood. For example, diffuse axonal injury is implicated in disrupting microtubule function, providing the potential context for pathologies of tau and amyloid to develop. The neuropathology of post-traumatic dementias is increasingly well characterised, with recent work focusing on chronic traumatic encephalopathy (CTE). However, clinical diagnosis of post-traumatic dementia is problematic. It is often difficult to disentangle the direct effects of TBI from those produced by progressive neurodegeneration or other post-traumatic sequelae such as psychiatric impairment. CTE can only be confidently identified at postmortem and patients are often confused and anxious about the most likely cause of their post-traumatic problems. A new approach to the assessment of the long-term effects of TBI is needed. Accurate methods are available for the investigation of other neurodegenerative conditions. These should be systematically employed in TBI. MRI and positron emission tomography neuroimaging provide biomarkers of neurodegeneration which may be of particular use in the postinjury setting. Brain atrophy is a key measure of disease progression and can be used to accurately quantify neuronal loss. Fluid biomarkers such as neurofilament light can complement neuroimaging, representing sensitive potential methods to track neurodegenerative processes that develop after TBI. These biomarkers could characterise endophenotypes associated with distinct types of post-traumatic neurodegeneration. In addition, they might profitably be used in clinical trials of neuroprotective and disease-modifying treatments, improving trial design by providing precise and sensitive measures of neuronal loss.
Topics: Biomarkers; Brain; Brain Injuries, Traumatic; Chronic Traumatic Encephalopathy; Clinical Trials as Topic; Dementia; Disease Progression; Humans; Nerve Degeneration
PubMed: 31542723
DOI: 10.1136/jnnp-2017-317557