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International Journal of Molecular... Feb 2023Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accounts for more than half of all dementia cases in the elderly. Interestingly, the clinical... (Review)
Review
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accounts for more than half of all dementia cases in the elderly. Interestingly, the clinical manifestations of AD disproportionately affect women, comprising two thirds of all AD cases. Although the underlying mechanisms for these sex differences are not fully elucidated, evidence suggests a link between menopause and a higher risk of developing AD, highlighting the critical role of decreased estrogen levels in AD pathogenesis. The focus of this review is to evaluate clinical and observational studies in women, which have investigated the impact of estrogens on cognition or attempted to answer the prevailing question regarding the use of hormone replacement therapy (HRT) as a preventive or therapeutic option for AD. The articles were retrieved through a systematic review of the databases: OVID, SCOPUS, and PubMed (keywords "memory", "dementia," "cognition," "Alzheimer's disease", "estrogen", "estradiol", "hormone therapy" and "hormone replacement therapy" and by searching reference sections from identified studies and review articles). This review presents the relevant literature available on the topic and discusses the mechanisms, effects, and hypotheses that contribute to the conflicting findings of HRT in the prevention and treatment of age-related cognitive deficits and AD. The literature suggests that estrogens have a clear role in modulating dementia risk, with reliable evidence showing that HRT can have both a beneficial and a deleterious effect. Importantly, recommendation for the use of HRT should consider the age of initiation and baseline characteristics, such as genotype and cardiovascular health, as well as the dosage, formulation, and duration of treatment until the risk factors that modulate the effects of HRT can be more thoroughly investigated or progress in the development of alternative treatments can be made.
Topics: Female; Humans; Male; Aged; Alzheimer Disease; Estrogen Replacement Therapy; Hormone Replacement Therapy; Estrogens; Estradiol; Risk Factors
PubMed: 36834617
DOI: 10.3390/ijms24043205 -
Alzheimer's & Dementia : the Journal of... Jan 2022Reported prevalence estimates of sporadic cerebral amyloid angiopathy (CAA) vary widely. CAA is associated with cognitive dysfunction and intracerebral hemorrhage, and... (Meta-Analysis)
Meta-Analysis
Reported prevalence estimates of sporadic cerebral amyloid angiopathy (CAA) vary widely. CAA is associated with cognitive dysfunction and intracerebral hemorrhage, and linked to immunotherapy-related side-effects in Alzheimer's disease (AD). Given ongoing efforts to develop AD immunotherapy, accurate estimates of CAA prevalence are important. CAA can be diagnosed neuropathologically or during life using MRI markers including strictly lobar microbleeds. In this meta-analysis of 170 studies including over 73,000 subjects, we show that in patients with AD, CAA prevalence based on pathology (48%) is twice that based on presence of strictly lobar cerebral microbleeds (22%); in the general population this difference is three-fold (23% vs 7%). Both methods yield similar estimated prevalences of CAA in cognitively normal elderly (5% to 7%), in patients with intracerebral hemorrhage (19% to 24%), and in patients with lobar intracerebral hemorrhage (50% to 57%). However, we observed large heterogeneity among neuropathology and MRI protocols, which calls for standardized assessment and reporting of CAA.
Topics: Alzheimer Disease; Cerebral Amyloid Angiopathy; Cerebral Hemorrhage; Cognitive Dysfunction; Humans; Immunotherapy; Magnetic Resonance Imaging; Neuropathology; Prevalence
PubMed: 34057813
DOI: 10.1002/alz.12366 -
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 -
European Journal of Neurology Oct 2020Dementia is one of the most common disorders and is associated with increased morbidity, mortality and decreased quality of life. The present guideline addresses... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
Dementia is one of the most common disorders and is associated with increased morbidity, mortality and decreased quality of life. The present guideline addresses important medical management issues including systematic medical follow-up, vascular risk factors in dementia, pain in dementia, use of antipsychotics in dementia and epilepsy in dementia.
METHODS
A systematic review of the literature was carried out. Based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework, we developed a guideline. Where recommendations based on GRADE were not possible, a good practice statement was formulated.
RESULTS
Systematic management of vascular risk factors should be performed in patients with mild to moderate dementia as prevention of cerebrovascular pathology may impact on the progression of dementia (Good Practice statement). Individuals with dementia (without previous stroke) and atrial fibrillation should be treated with anticoagulants (weak recommendation). Discontinuation of opioids should be considered in certain individuals with dementia (e.g. for whom there are no signs or symptoms of pain or no clear indication, or suspicion of side effects; Good Practice statement). Behavioral symptoms in persons with dementia should not be treated with mild analgesics (weak recommendation). In all patients with dementia treated with opioids, assessment of the individual risk-benefit ratio should be performed at regular intervals. Regular, preplanned medical follow-up should be offered to all patients with dementia. The setting will depend on the organization of local health services and should, as a minimum, include general practitioners with easy access to dementia specialists (Good Practice statement). Individuals with dementia and agitation and/or aggression should be treated with atypical antipsychotics only after all non-pharmacological measures have been proven to be without benefit or in the case of severe self-harm or harm to others (weak recommendation). Antipsychotics should be discontinued after cessation of behavioral disturbances and in patients in whom there are side effects (Good Practice statement). For treatment of epilepsy in individuals with dementia, newer anticonvulsants should be considered as first-line therapy (Good Practice statement).
CONCLUSION
This GRADE-based guideline offers recommendations on several important medical issues in patients with dementia, and thus adds important guidance for clinicians. For some issues, very little or no evidence was identified, highlighting the importance of further studies within these areas.
Topics: Academies and Institutes; Aged; Alzheimer Disease; Analgesics; Dementia; Humans; Neurology; Randomized Controlled Trials as Topic
PubMed: 32713125
DOI: 10.1111/ene.14412 -
Geriatric Nursing (New York, N.Y.) 2021Persons with dementia are at risk of malnutrition, evidenced by low dietary intake, which has consequences for nutritional status, activity of daily living and disease...
OBJECTIVE
Persons with dementia are at risk of malnutrition, evidenced by low dietary intake, which has consequences for nutritional status, activity of daily living and disease progression. The effects of oral nutrition supplements (ONS) on nutritional intake, nutritional status, and cognitive and physical outcomes in older persons with dementia were evaluated.
METHODS
PubMed, Medline, Embase, CINAHL and the Cochrane Central Register of Controlled Trials were searched in December 2017, and this was repeated in May 2019. The Preferred Reporting Items for Systematic Reviews and Analysis (PRISMA) checklist was used. Papers were considered if they presented experimental clinical trials using oral nutritional supplements to persons diagnosed with dementia, including Alzheimer's disease and mild cognitive impairment, and conducted in hospitals, nursing homes or homes.
RESULTS
We included ten articles reporting nine clinical trials. A total of 407 persons with dementia were included, of whom 228 used ONS for 7 to 180 days. Nutritional intake improved by 201 to 600 kcal/day. Energy intake from ordinary foods was not affected, thus ONS improved the persons daily intake of energy and protein. Body weight, muscle mass, and nutritional biomarkers in blood improved in the intervention groups compared with the control groups. No effects on cognition or physical outcomes were observed.
CONCLUSION
ONS increases the intake of energy and protein and improves nutritional status in persons with dementia; however, RCTs with longer intervention periods are needed to investigate the impact on cognitive and functional outcomes.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Dietary Supplements; Energy Intake; Humans; Malnutrition; Nutritional Status
PubMed: 33383439
DOI: 10.1016/j.gerinurse.2020.12.005 -
Neuroscience and Biobehavioral Reviews Aug 2021Endogenous melatonin levels are inversely associated with age and cognitive deficits. Although melatonin can improve psychopathological behavior disturbances in clinical... (Meta-Analysis)
Meta-Analysis Review
Neurocognitive effects of melatonin treatment in healthy adults and individuals with Alzheimer's disease and insomnia: A systematic review and meta-analysis of randomized controlled trials.
Endogenous melatonin levels are inversely associated with age and cognitive deficits. Although melatonin can improve psychopathological behavior disturbances in clinical trials, whether melatonin may also enhance cognitive function remains elusive. This study examined cognitive outcomes from randomized trials of melatonin treatment for Alzheimer's disease (AD), insomnia, and healthy-subjects. Twenty-two studies met the inclusion criteria (AD = 9, insomnia = 2, healthy-subjects = 11). AD patients receiving >12 weeks of melatonin treatment improved mini-mental state examination (MMSE) score [MD: 1.82 (1.01; 2.63) p < 0.0001]. Importantly, melatonin significantly improved MMSE score in mild stage of AD [MD: 1.89 (0.96; 2.82) p < 0.0001]. In healthy-subjects, although daytime melatonin treatment notably decreased in accuracy by correct responses [SMD: -0.74 (-1.03; -0.45) p < 0.00001], the reaction-time score on different stimuli (p = 0.37) did not increased. Additionally, by pooling of short-term, spatial, and visual memory scores, melatonin did not reduce memory function (p = 0.08). Meta-analysis of MMSE score suggested that melatonin is effective in treatment for mild stage of AD. Additionally, we propose that melatonin may be preferable to traditional hypnotics in management of insomnia.
Topics: Adult; Alzheimer Disease; Cognition Disorders; Humans; Melatonin; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders
PubMed: 33957167
DOI: 10.1016/j.neubiorev.2021.04.034 -
Brain and Behavior Jan 2023In recent years, longitudinal studies of Alzheimer's disease (AD) have been successively concluded. Our aim is to determine the efficacy of amyloid-β (Aβ) PET in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In recent years, longitudinal studies of Alzheimer's disease (AD) have been successively concluded. Our aim is to determine the efficacy of amyloid-β (Aβ) PET in diagnosing AD and early prediction of mild cognitive impairment (MCI) converting to AD. By pooling studies from different centers to explore in-depth whether diagnostic performance varies by population type, radiotracer type, and diagnostic approach, thus providing a more comprehensive theoretical basis for the subsequent widespread application of Aβ PET in the clinical setting.
METHODS
Relevant studies were searched through PubMed. The pooled sensitivities, specificities, DOR, and the summary ROC curve were obtained based on a Bayesian random-effects model.
RESULTS
Forty-eight studies, including 5967 patients, were included. Overall, the pooled sensitivity, specificity, DOR, and AUC of Aβ PET for diagnosing AD were 0.90, 0.80, 35.68, and 0.91, respectively. Subgroup analysis showed that Aβ PET had high sensitivity (0.91) and specificity (0.81) for differentiating AD from normal controls but very poor specificity (0.49) for determining AD from MCI. The pooled sensitivity and specificity were 0.84 and 0.62, respectively, for predicting the conversion of MCI to AD. The differences in diagnostic efficacy between visual assessment and quantitative analysis and between C-PIB PET and F-florbetapir PET were insignificant.
CONCLUSIONS
The overall performance of Aβ PET in diagnosing AD is favorable, but the differentiation between MCI and AD patients should consider that some MCI may be at risk of conversion to AD and may be misdiagnosed. A multimodal diagnostic approach and machine learning analysis may be effective in improving diagnostic accuracy.
Topics: Humans; Alzheimer Disease; Bayes Theorem; Amyloid beta-Peptides; Cognitive Dysfunction; Sensitivity and Specificity; Positron-Emission Tomography
PubMed: 36573329
DOI: 10.1002/brb3.2850 -
International Journal of Environmental... Jan 2022The purpose of this meta-analysis was to examine the effects of physical activity (PA) on cognition and activities of daily living in adults with Alzheimer's Disease... (Meta-Analysis)
Meta-Analysis Review
Physical Activity Improves Cognition and Activities of Daily Living in Adults with Alzheimer's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
OBJECTIVE
The purpose of this meta-analysis was to examine the effects of physical activity (PA) on cognition and activities of daily living in adults with Alzheimer's Disease (AD).
METHODS
Six electronic databases (MEDLINE, CINAHL, PsycArticles, SPORTDiscus, EMBASE and CNKI) were used to search for potential studies from inception until October 2021. Randomized controlled trials (RCTs) investigating the effect of physical activity (PA) on cognition and activities of daily living in AD patients compared to a control condition were included. The effect sizes were synthesized using a random effects model with a 95% confidence interval (CI).
RESULTS
Sixteen articles including 945 participants (aged 70 to 88 years, 34.6% male) met the inclusion criteria. The pooled effect sizes demonstrated that PA intervention was associated with significant improvements in global cognition (Standard Mean Difference (SMD) = 0.41, 95% CI [0.24, 0.58], < 0.01) and activities of daily living (SMD = 0.56, 95% CI [0.32, 0.79], < 0.01) in AD patients. Subgroup analyses suggested that PA for 3-4 times per week for 30-45 min for more than 12 weeks had a relatively strong effect on improving global cognition in AD patients. The sensitivity analysis showed robust results.
CONCLUSIONS
The findings from the current meta-analysis suggested that AD patients can improve their global cognition and Activities of Daily Living (ADL) through engaging in aerobic and mixed exercise (aerobic and anaerobic exercise).
Topics: Activities of Daily Living; Adult; Aged; Aged, 80 and over; Alzheimer Disease; Cognition; Exercise; Female; Humans; Male; Randomized Controlled Trials as Topic
PubMed: 35162238
DOI: 10.3390/ijerph19031216 -
Dementia and Geriatric Cognitive... 2021In the absence of a cure, dementia is often managed by minimizing risk factors contributing to quality of life (QOL). Attitudes to dementia in older adults may differ...
INTRODUCTION
In the absence of a cure, dementia is often managed by minimizing risk factors contributing to quality of life (QOL). Attitudes to dementia in older adults may differ from those in relatively younger adults. The aim was to conduct a systematic review of the literature to determine how QOL was assessed in adults, 65 years and older with dementia, and identify factors that influence the reported scores.
METHODS
A systematic review of full-text articles addressing QOL in older adults with dementia, published in English from January 1995 to September 2020, was conducted using PubMed and PsycINFO. We included studies that assessed QOL and involved participants 65 years and older. Studies were evaluated for inclusion by 2 independent pairs of reviewers. We assessed the quality of the studies using the Joanna Briggs Institute's Critical Appraisal Checklist. Study characteristics and findings were summarized. Analysis was by narrative synthesis. We identified social and clinical factors influencing QOL scores.
RESULTS
Of the 1,010 articles identified, 19 met the inclusion criteria. These 19 studies involved 6,279 persons with dementia, with sample sizes from 32 to 1,366. Mean age of participants ranged from 77.1 to 86.6 years. Five measurement tools were identified; Quality of Life in Alzheimer Disease (QOL-AD), Alzheimer Disease-Related Quality of Life (ADRQL), Quality of Life in Late-Stage Dementia (QUALID), QUALIDEM (a dementia-specific QOL tool), and DEMQOL (health-related QOL for people with dementia). Self-ratings of QOL were higher than proxy ratings. Factors commonly influencing self-ratings of QOL included depression, functional impairment, and polypharmacy. Common factors that influenced proxy ratings included functional impairment, presence of neuropsychiatric symptoms, cognitive impairment, and caregiver burden.
CONCLUSION
In evaluating QOL in dementia, self- and proxy reports may complement each other to ensure that all perspectives are addressed.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Caregivers; Dementia; Humans; Proxy; Quality of Life
PubMed: 34167127
DOI: 10.1159/000515317 -
The Journal of Clinical Psychiatry Oct 2022To summarize the breadth of data exploring the relationship between major depressive disorder (MDD) and both the incidence and the disease course of a range of...
To summarize the breadth of data exploring the relationship between major depressive disorder (MDD) and both the incidence and the disease course of a range of comorbidities. The authors searched MEDLINE, Embase, PsycINFO, Cochrane Database of Systematic Reviews, and several prespecified congresses. Searches included terms related to MDD and several comorbidity categories, restricted to those published in the English language from 2005 onward. Eligibility criteria included observational studies within North America and Europe that examined the covariate-adjusted impact of MDD on the risk and/or severity of comorbidities. A total of 6,811 articles were initially identified for screening. : Two investigators extracted data and assessed study quality. In total, 199 articles were included. Depression was significantly ( < .05) associated with an increased incidence of dementia and Alzheimer's disease as well as cognitive decline in individuals with existing disease; increased incidence and worsening of cardiovascular disease/events (although mixed results were found for stroke); worsening of metabolic syndrome; increased incidence of diabetes, particularly among men, and worsening of existing diabetes; increased incidence of obesity, particularly among women; increased incidence and worsening of certain autoimmune diseases; increased incidence and severity of HIV/AIDS; and increased incidence of drug abuse and severity of both alcohol and drug abuse. The presence of MDD was identified as a risk factor for both the development and the worsening of a range of comorbidities. These results highlight the importance of addressing depression early in its course and the need for integrating mental and general health care.
Topics: Female; Humans; Male; Alzheimer Disease; Cognitive Dysfunction; Comorbidity; Depressive Disorder, Major
PubMed: 36264099
DOI: 10.4088/JCP.21r14328