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Cells May 2023Blood biomarkers have been considered tools for the diagnosis, prognosis, and monitoring of Alzheimer's disease (AD). Although amyloid-β peptide (Aβ) and tau are... (Meta-Analysis)
Meta-Analysis Review
Blood biomarkers have been considered tools for the diagnosis, prognosis, and monitoring of Alzheimer's disease (AD). Although amyloid-β peptide (Aβ) and tau are primarily blood biomarkers, recent studies have identified other reliable candidates that can serve as measurable indicators of pathological conditions. One such candidate is the glial fibrillary acidic protein (GFAP), an astrocytic cytoskeletal protein that can be detected in blood samples. Increasing evidence suggests that blood GFAP levels can be used to detect early-stage AD. In this systematic review and meta-analysis, we aimed to evaluate GFAP in peripheral blood as a biomarker for AD and provide an overview of the evidence regarding its utility. Our analysis revealed that the GFAP level in the blood was higher in the Aβ-positive group than in the negative groups, and in individuals with AD or mild cognitive impairment (MCI) compared to the healthy controls. Therefore, we believe that the clinical use of blood GFAP measurements has the potential to accelerate the diagnosis and improve the prognosis of AD.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Cognitive Dysfunction; Glial Fibrillary Acidic Protein
PubMed: 37174709
DOI: 10.3390/cells12091309 -
Atencion Primaria May 2020The objective of this review is to analyze through a the scientific evidence about the effects of physical activity in patients with Alzheimer's disease (AD) as a...
OBJECTIVE
The objective of this review is to analyze through a the scientific evidence about the effects of physical activity in patients with Alzheimer's disease (AD) as a preventive and non-pharmacological treatment.
DESIGN
Systematic review.
DATA SOURCES
We have identified articles from Pubmed, Science Direct, Medline and Scopus databases, with the keywords Alzheimer, Exercise, Neuroimaging, MRI, PET y Physical Activity. Selected articles: We included those studies that evaluated the effects of physical activity on Alzheimer's disease and those which also included magnetic resonance imaging or positron emission tomography with Pittsburg Compound B marker (PiB) analyzing brain atrophy or increase of the beta-amyloid deposit respectively. We excluded studies including other types of dementia, different of AD. We also excluded articles which not included neuroimaging tests, single cases or non-English language articles.
DATA EXTRACTION
The PRISMA quality scale was used for the critical lecture of the studies. The researchers independently assessed the articles and the discrepancies were resolved by consensus.
RESULTS
We identified 75 articles, of which 23 were finally included in the review.
CONCLUSIONS
Most of the studies included do not allow us to know the impact of physical exercise on cognition and the cerebral structural-functional changes in patients at risk of developing AD or in patients who already have the disease. Without being able to rule out a possible beneficial effect, more studies are needed with a better design and methodological rigor that allows a better known about this association.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Atrophy; Brain; Exercise; Humans; Magnetic Resonance Imaging; Neuroimaging; Positron-Emission Tomography
PubMed: 31153668
DOI: 10.1016/j.aprim.2018.09.010 -
Journal of Alzheimer's Disease : JAD 2017In the last decade, the association between diet and cognitive function or dementia has been largely investigated. In the present article, we systematically reviewed... (Meta-Analysis)
Meta-Analysis Review
In the last decade, the association between diet and cognitive function or dementia has been largely investigated. In the present article, we systematically reviewed observational studies published in the last three years (2014-2016) on the relationship among dietary factors and late-life cognitive disorders at different levels of investigation (i.e., dietary patterns, foods and food-groups, and dietary micro- and macronutrients), and possible underlying mechanisms of the proposed associations. From the reviewed evidence, the National Institute on Aging-Alzheimer's Association guidelines for Alzheimer's disease (AD) and cognitive decline due to AD pathology introduced some evidence suggesting a direct relation between diet and changes in the brain structure and activity. There was also accumulating evidence that combinations of foods and nutrients into certain patterns may act synergistically to provide stronger health effects than those conferred by their individual dietary components. In particular, higher adherence to a Mediterranean-type diet was associated with decreased cognitive decline. Moreover, also other emerging healthy dietary patterns such as the Dietary Approach to Stop Hypertension (DASH) and the Mediterranean-DASH diet Intervention for Neurodegenerative Delay (MIND) diets were associated with slower rates of cognitive decline and significant reduction of AD rate. Furthermore, some foods or food groups traditionally considered harmful such as eggs and red meat have been partially rehabilitated, while there is still a negative correlation of cognitive functions with saturated fatty acids and a protective effect against cognitive decline of elevated fish consumption, high intake of monounsaturated fatty acids and polyunsaturated fatty acids (PUFA), particularly n-3 PUFA.
Topics: Alzheimer Disease; Cognition Disorders; Databases, Bibliographic; Diet; Feeding Behavior; Humans; Nutritional Status; Risk Factors
PubMed: 28697569
DOI: 10.3233/JAD-170248 -
Journal of Neurochemistry Mar 2021Similar to dementia, the risk for developing type 2 diabetes mellitus (T2DM) increases with age, and T2DM also increases the risk for dementia, particularly Alzheimer's...
Similar to dementia, the risk for developing type 2 diabetes mellitus (T2DM) increases with age, and T2DM also increases the risk for dementia, particularly Alzheimer's disease (AD). Although T2DM is primarily a peripheral disorder and AD is a central nervous system disease, both share some common features as they are chronic and complex diseases, and both show involvement of oxidative stress and inflammation in their progression. These characteristics suggest that T2DM may be associated with AD, which gave rise to a new term, type 3 diabetes (T3DM). In this study, we searched for matching peripheral proteomic biomarkers of AD and T2DM based in a systematic review of the available literature. We identified 17 common biomarkers that were differentially expressed in both patients with AD or T2DM when compared with healthy controls. These biomarkers could provide a useful workflow for screening T2DM patients at risk to develop AD.
Topics: Alzheimer Disease; Animals; Biomarkers; Diabetes Mellitus, Type 2; Humans; Proteomics
PubMed: 32909269
DOI: 10.1111/jnc.15166 -
Translational Psychiatry Apr 2022Polysomnography (PSG) studies of sleep changes in Alzheimer's disease (AD) have reported but not fully established the relationship between sleep disturbances and AD. To... (Meta-Analysis)
Meta-Analysis
Polysomnography (PSG) studies of sleep changes in Alzheimer's disease (AD) have reported but not fully established the relationship between sleep disturbances and AD. To better detail this relationship, we conducted a systematic review and meta-analysis of reported PSG differences between AD patients and healthy controls. An electronic literature search was conducted in EMBASE, MEDLINE, All EBM databases, CINAHL, and PsycINFO inception to Mar 2021. Twenty-eight studies were identified for systematic review, 24 of which were used for meta-analysis. Meta-analyses revealed significant reductions in total sleep time, sleep efficiency, and percentage of slow-wave sleep (SWS) and rapid eye movement (REM) sleep, and increases in sleep latency, wake time after sleep onset, number of awakenings, and REM latency in AD compared to controls. Importantly, both decreased SWS and REM were significantly associated with the severity of cognitive impairment in AD patients. Alterations in electroencephalogram (EEG) frequency components and sleep spindles were also observed in AD, although the supporting evidence for these changes was limited. Sleep in AD is compromised with increased measures of wake and decreased TST, SWS, and REM sleep relative to controls. AD-related reductions in SWS and REM sleep correlate with the degree of cognitive impairment. Alterations in sleep EEG frequency components such as sleep spindles may be possible biomarkers with relevance for diagnosing AD although their sensitivity and specificity remain to be clearly delineated. AD-related sleep changes are potential targets for early therapeutic intervention aimed at improving sleep and slowing cognitive decline.
Topics: Alzheimer Disease; Humans; Polysomnography; Sleep; Sleep Wake Disorders; Sleep, REM
PubMed: 35365609
DOI: 10.1038/s41398-022-01897-y -
The Cochrane Database of Systematic... Jul 2021Dementia is a progressive syndrome of global cognitive impairment with significant health and social care costs. Global prevalence is projected to increase, particularly...
BACKGROUND
Dementia is a progressive syndrome of global cognitive impairment with significant health and social care costs. Global prevalence is projected to increase, particularly in resource-limited settings. Recent policy changes in Western countries to increase detection mandates a careful examination of the diagnostic accuracy of neuropsychological tests for dementia.
OBJECTIVES
To determine the accuracy of the Montreal Cognitive Assessment (MoCA) for the detection of dementia.
SEARCH METHODS
We searched MEDLINE, EMBASE, BIOSIS Previews, Science Citation Index, PsycINFO and LILACS databases to August 2012. In addition, we searched specialised sources containing diagnostic studies and reviews, including MEDION (Meta-analyses van Diagnostisch Onderzoek), DARE (Database of Abstracts of Reviews of Effects), HTA (Health Technology Assessment Database), ARIF (Aggressive Research Intelligence Facility) and C-EBLM (International Federation of Clinical Chemistry and Laboratory Medicine Committee for Evidence-based Laboratory Medicine) databases. We also searched ALOIS (Cochrane Dementia and Cognitive Improvement Group specialized register of diagnostic and intervention studies). We identified further relevant studies from the PubMed 'related articles' feature and by tracking key studies in Science Citation Index and Scopus. We also searched for relevant grey literature from the Web of Science Core Collection, including Science Citation Index and Conference Proceedings Citation Index (Thomson Reuters Web of Science), PhD theses and contacted researchers with potential relevant data.
SELECTION CRITERIA
Cross-sectional designs where all participants were recruited from the same sample were sought; case-control studies were excluded due to high chance of bias. We searched for studies from memory clinics, hospital clinics, primary care and community populations. We excluded studies of early onset dementia, dementia from a secondary cause, or studies where participants were selected on the basis of a specific disease type such as Parkinson's disease or specific settings such as nursing homes.
DATA COLLECTION AND ANALYSIS
We extracted dementia study prevalence and dichotomised test positive/test negative results with thresholds used to diagnose dementia. This allowed calculation of sensitivity and specificity if not already reported in the study. Study authors were contacted where there was insufficient information to complete the 2x2 tables. We performed quality assessment according to the QUADAS-2 criteria. Methodological variation in selected studies precluded quantitative meta-analysis, therefore results from individual studies were presented with a narrative synthesis.
MAIN RESULTS
Seven studies were selected: three in memory clinics, two in hospital clinics, none in primary care and two in population-derived samples. There were 9422 participants in total, but most of studies recruited only small samples, with only one having more than 350 participants. The prevalence of dementia was 22% to 54% in the clinic-based studies, and 5% to 10% in population samples. In the four studies that used the recommended threshold score of 26 or over indicating normal cognition, the MoCA had high sensitivity of 0.94 or more but low specificity of 0.60 or less.
AUTHORS' CONCLUSIONS
The overall quality and quantity of information is insufficient to make recommendations on the clinical utility of MoCA for detecting dementia in different settings. Further studies that do not recruit participants based on diagnoses already present (case-control design) but apply diagnostic tests and reference standards prospectively are required. Methodological clarity could be improved in subsequent DTA studies of MoCA by reporting findings using recommended guidelines (e.g. STARDdem). Thresholds lower than 26 are likely to be more useful for optimal diagnostic accuracy of MoCA in dementia, but this requires confirmation in further studies.
Topics: Aged; Alzheimer Disease; Cognitive Dysfunction; Cross-Sectional Studies; Dementia; Executive Function; Humans; Memory, Short-Term; Mental Status and Dementia Tests; Neuropsychological Tests; Orientation; Reference Standards; Sensitivity and Specificity
PubMed: 34255351
DOI: 10.1002/14651858.CD010775.pub3 -
Neurology Mar 2020To test the hypothesis that distinct subtypes of Alzheimer disease (AD) exist and underlie the heterogeneity within AD, we conducted a systematic review and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To test the hypothesis that distinct subtypes of Alzheimer disease (AD) exist and underlie the heterogeneity within AD, we conducted a systematic review and meta-analysis on AD subtype studies based on postmortem and neuroimaging data.
METHODS
EMBASE, PubMed, and Web of Science databases were consulted until July 2019.
RESULTS
Neuropathology and neuroimaging studies have consistently identified 3 subtypes of AD based on the distribution of tau-related pathology and regional brain atrophy: typical, limbic-predominant, and hippocampal-sparing AD. A fourth subtype, minimal atrophy AD, has been identified in several neuroimaging studies. Typical AD displays tau-related pathology and atrophy both in hippocampus and association cortex and has a pooled frequency of 55%. Limbic-predominant, hippocampal-sparing, and minimal atrophy AD had a pooled frequency of 21%, 17%, and 15%, respectively. Between-subtype differences were found in age at onset, age at assessment, sex distribution, years of education, global cognitive status, disease duration, APOE ε4 genotype, and CSF biomarker levels.
CONCLUSION
We identified 2 core dimensions of heterogeneity: typicality and severity. We propose that these 2 dimensions determine individuals' belonging to one of the AD subtypes based on the combination of protective factors, risk factors, and concomitant non-AD brain pathologies. This model is envisioned to aid with framing hypotheses, study design, interpretation of results, and understanding mechanisms in future subtype studies. Our model can be used along the A/T/N classification scheme for AD biomarkers. Unraveling the heterogeneity within AD is critical for implementing precision medicine approaches and for ultimately developing successful disease-modifying drugs for AD.
Topics: Alzheimer Disease; Humans
PubMed: 32047067
DOI: 10.1212/WNL.0000000000009058 -
Neurotoxicology Jul 2017A systematic review was conducted to identify risk factors associated with the onset and progression of Alzheimer's disease (AD). Moderate and high quality systematic... (Meta-Analysis)
Meta-Analysis Review
A systematic review was conducted to identify risk factors associated with the onset and progression of Alzheimer's disease (AD). Moderate and high quality systematic reviews were eligible for inclusion. Primary studies reporting on non-genetic risk factors associated with neuropathologically or clinically confirmed AD were considered. Eighty one systematic reviews reporting on AD onset and 12 reporting on progression satisfied the eligibility criteria. Four hundred and thirty-two relevant primary studies reporting on onset were identified; however, only those published between 2010 and 2012 (n=65) were included in the qualitative synthesis. Several factors including statins, light-to-moderate alcohol consumption, compliance with a Mediterranean diet, higher educational attainment, physically and cognitively stimulating activities, and APOE ε2 appeared to be associated with a decreased risk of AD onset. The evidence was suggestive of an increased risk of AD associated with head injury in males, age, diabetes mellitus, conjugated equine estrogen use with medroxyprogesterone acetate, current smoking, and lower social engagement. With respect to genetic factors, APOE ε4 remained the strongest predictor of AD. Physical and cognitive activities were associated with a beneficial effect on cognitive function and other indicators of dementia progression while higher educational attainment was associated with faster cognitive decline. Although suggestive of an association, the current evidence for a majority of the identified putative factors for AD onset and progression was weak, at best due to conflicting findings across studies or inadequate evidence. Further research is required to confirm the etiological or protective role of a number of risk factors.
Topics: Age of Onset; Alzheimer Disease; Apolipoprotein E4; Disease Progression; Humans; Risk Factors
PubMed: 28363508
DOI: 10.1016/j.neuro.2017.03.006 -
Journal of Alzheimer's Disease : JAD 2017Depression is common in people with Alzheimer's disease (AD) affecting overall outcomes and decreasing quality of life. Although depression in AD is primarily treated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Depression is common in people with Alzheimer's disease (AD) affecting overall outcomes and decreasing quality of life. Although depression in AD is primarily treated with antidepressants, there are few randomized controlled trials (RCTs) assessing efficacy and results have been conflicting.
OBJECTIVES
To systematically review evidence on efficacy of antidepressant treatments for depression in AD.
METHODS
Systematic review and meta-analysis of double blind RCTs comparing antidepressants versus placebo for depression in AD. We searched MEDLINE, CINAHL, EMBASE, PsycINFO, the Cochrane Controlled Trials Register and on line national and international registers. Primary outcomes were treatment response and depressive symptoms. Secondary outcomes were cognition, acceptability, and tolerability. Risk of bias was also assessed.
RESULTS
Seven studies met inclusion criteria. Three compared sertraline with placebo; one compared both sertraline and mirtazapine to placebo; imipramine, fluoxetine, and clomipramine were evaluated in one study each. In terms of response to treatment (6 studies, 297 patients treated with antidepressants and 223 with placebo), no statistically significant difference between antidepressants and placebo was found (odds ratio (OR) 1.95, 95% CI 0.97-3.92). We found no significant drug-placebo difference for depressive symptoms (5 studies, 311 patients, SMD -0.13; 95% CI -0.49 to 0.24). Overall quality of the evidence was moderate because of methodological limitations in studies and the small number of trials.
CONCLUSION
Despite the importance of depression in people with AD, few RCTs are available on efficacy of antidepressants, limiting clear conclusions of their potential role. There is a need for further high quality RCTs.
Topics: Alzheimer Disease; Antidepressive Agents; Depressive Disorder; Humans; Randomized Controlled Trials as Topic
PubMed: 28505970
DOI: 10.3233/JAD-161247 -
Journal of Affective Disorders Jan 2016Neuropsychiatric symptoms (NPS) are being increasingly recognized as common serious problems in Alzheimer's disease (AD). However, published data on the prevalence of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neuropsychiatric symptoms (NPS) are being increasingly recognized as common serious problems in Alzheimer's disease (AD). However, published data on the prevalence of NPS in persons with AD are conflicting. This meta-analysis aimed to estimate the prevalence of NPS in persons with AD.
METHODS
Studies published from 1964 to September 30, 2014, were identified from PubMed and Embase database, reference lists and conference abstracts. We calculated prevalence rates and conducted meta-regression analysis with random-effects model, according to study characteristics, population demographics or condition information.
RESULTS
We identified 48 eligible articles, which provided data for 12 NPS reported in Neuropsychiatric Inventory (NPI). The most frequent NPS was apathy, with an overall prevalence of 49% (95% CI 41-57%), followed by depression, aggression, anxiety and sleep disorder, the pooled prevalence estimates of which were 42% (95% CI 37-46%), 40% (95% CI 33-46%), 39% (95% CI 32-46%) and 39% (95% CI 30-47%), respectively. The less prevalent NPS were irritability (36%, 31-41%), appetite disorder (34%, 27-41%), aberrant motor behavior (32%, 25-38%), delusion (31%, 27-35%), disinhibition (17%, 12-21%) and hallucination (16%, 13-18%). Least common was euphoria, with an overall prevalence of 7% (95% CI 5-9%).
LIMITATIONS
Several aspects, such as the quality of included studies were not always optimal and there was significant heterogeneity of prevalence estimate across studies.
CONCLUSIONS
NPS were observed to be highly prevalent in AD patients. Disease duration, age, education level, population origin and the severity of cognitive impairment had influence on the prevalence of some NPS.
Topics: Aggression; Alzheimer Disease; Anxiety; Apathy; Comorbidity; Delusions; Depression; Euphoria; Feeding and Eating Disorders; Hallucinations; Humans; Irritable Mood; Prevalence; Sleep Wake Disorders
PubMed: 26540080
DOI: 10.1016/j.jad.2015.09.069