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Alzheimer's Research & Therapy Feb 2019The objective of this systematic review was (1) to give an overview of the available short screening instruments for the early detection of Alzheimer's disease (AD) and...
OBJECTIVES
The objective of this systematic review was (1) to give an overview of the available short screening instruments for the early detection of Alzheimer's disease (AD) and (2) to review the psychometric properties of these instruments.
METHODS
First, a systematic search of titles and abstracts of PubMed and Web of Science was conducted between February and July 2015 and updated in April 2016 and May 2018. Only papers written in English or Dutch were considered. All full-text papers about cognitive screening instruments for the early detection of AD were included, resulting in the identification of 38 pencil and paper tests and 12 computer tests. In a second step, the psychometric quality of these instruments was evaluated. Therefore, the same databases were searched again to identify papers that described the psychometric properties of the instruments meanwhile applying diagnostic criteria for the diagnostic groups included.
RESULTS
Out of 1454 papers, 96 clearly discussed the psychometric properties of the instruments. Eighty-nine papers discussed pencil and paper tests of which 80 were validated in a memory clinic setting. Based on the number of studies (31 articles) and the sensitivity (84%) and specificity (74%) values, the Montreal Cognitive Assessment (MoCA) seems to be a promising (pencil and paper) screening test for memory clinic testing as well as for population screening. Regarding computer tests, validation studies were only available for 7 out of 12 tests.
CONCLUSIONS
A large number of screening tests for AD are available. However, most tests are only validated in a memory clinic setting and description of the psychometric properties of the instruments is limited. Especially, computer tests require further research. The MoCA is a promising instrument, but the specificity to detect early AD is rather low.
Topics: Alzheimer Disease; Brief Psychiatric Rating Scale; Cognition; Cognitive Dysfunction; Early Diagnosis; Humans; Mental Status and Dementia Tests
PubMed: 30819244
DOI: 10.1186/s13195-019-0474-3 -
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 Alzheimer's Disease : JAD 2022An infectious etiology of Alzheimer's disease has been postulated for decades. It remains unknown whether SARS-CoV-2 viral infection is associated with increased risk...
An infectious etiology of Alzheimer's disease has been postulated for decades. It remains unknown whether SARS-CoV-2 viral infection is associated with increased risk for Alzheimer's disease. In this retrospective cohort study of 6,245,282 older adults (age ≥65 years) who had medical encounters between 2/2020-5/2021, we show that people with COVID-19 were at significantly increased risk for new diagnosis of Alzheimer's disease within 360 days after the initial COVID-19 diagnosis (hazard ratio or HR:1.69, 95% CI: 1.53-1.72), especially in people age ≥85 years and in women. Our findings call for research to understand the underlying mechanisms and for continuous surveillance of long-term impacts of COVID-19 on Alzheimer's disease.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; COVID-19; COVID-19 Testing; Female; Humans; Retrospective Studies; SARS-CoV-2
PubMed: 35912749
DOI: 10.3233/JAD-220717 -
Alzheimer's Research & Therapy Oct 2023Development of in vivo biomarkers has shifted the diagnosis of Alzheimer's disease (AD) from the later dementia stages of disease towards the earlier stages and has... (Review)
Review
BACKGROUND
Development of in vivo biomarkers has shifted the diagnosis of Alzheimer's disease (AD) from the later dementia stages of disease towards the earlier stages and has introduced the potential for pre-symptomatic diagnosis. The International Working Group recommends that AD diagnosis is restricted in the clinical setting to people with specific AD phenotypes and supportive biomarker findings.
MAIN BODY
In this review, we discuss the phenotypic presentation and use of biomarkers for the early diagnosis of typical and atypical AD and describe how this can support clinical decision making, benefit patient communication, and improve the patient journey. Early diagnosis is essential to optimize the benefits of available and emerging treatments. As atypical presentations of AD often mimic other dementias, differential diagnosis can be challenging and can be facilitated using AD biomarkers. However, AD biomarkers alone are not sufficient to confidently diagnose AD or predict disease progression and should be supplementary to clinical assessment to help inform the diagnosis of AD.
CONCLUSIONS
Use of AD biomarkers with incorporation of atypical AD phenotypes into diagnostic criteria will allow earlier diagnosis of patients with atypical clinical presentations that otherwise would have been misdiagnosed and treated inappropriately. Early diagnosis is essential to guide informed discussion, appropriate care and support, and individualized treatment. It is hoped that disease-modifying treatments will impact the underlying AD pathology; thus, determining the patient's AD phenotype will be a critical factor in guiding the therapeutic approach and the assessment of the effects of interventions.
Topics: Humans; Alzheimer Disease; Diagnosis, Differential; Biomarkers; Recognition, Psychology; Disease Progression
PubMed: 37833762
DOI: 10.1186/s13195-023-01314-6 -
Alzheimer's & Dementia : the Journal of... Nov 2020Development of disease-modifying treatments for Alzheimer's disease (AD) has been challenging, with no drugs approved to date. The failures of several amyloid-targeted... (Review)
Review
Development of disease-modifying treatments for Alzheimer's disease (AD) has been challenging, with no drugs approved to date. The failures of several amyloid-targeted programs have led many to dismiss the amyloid beta (Aβ) hypothesis of AD. An antiamyloid antibody aducanumab recently showed modest but significant efficacy in a phase 3 trial, providing important validation of amyloid as a therapeutic target. However, the inconsistent results observed with aducanumab may be explained by the limited brain penetration and lack of selectivity for the soluble Aβ oligomers, which are implicated as upstream drivers of neurodegeneration by multiple studies. Development of agents that can effectively inhibit Aβ oligomer formation or block their toxicity is therefore warranted. An ideal drug would cross the blood-brain barrier efficiently and achieve sustained brain levels that can continuously prevent oligomer formation or inhibit their toxicity. A late-stage candidate with these attributes is ALZ-801, an oral drug with a favorable safety profile and high brain penetration that can robustly inhibit Aβ oligomer formation. An upcoming phase 3 trial with ALZ-801 in APOE4/4 homozygous patients with early AD will effectively test this amyloid oligomer hypothesis.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Antibodies, Monoclonal, Humanized; Drug Discovery; Humans; Taurine; Valine
PubMed: 31706733
DOI: 10.1016/j.jalz.2019.09.075 -
Journal of Internal Medicine Aug 2021The critical role of primary care clinicians (PCCs) in Alzheimer's disease (AD) prevention, diagnosis and management must evolve as new treatment paradigms and... (Review)
Review
The critical role of primary care clinicians (PCCs) in Alzheimer's disease (AD) prevention, diagnosis and management must evolve as new treatment paradigms and disease-modifying therapies (DMTs) emerge. Our understanding of AD has grown substantially: no longer conceptualized as a late-in-life syndrome of cognitive and functional impairments, we now recognize that AD pathology builds silently for decades before cognitive impairment is detectable. Clinically, AD first manifests subtly as mild cognitive impairment (MCI) due to AD before progressing to dementia. Emerging optimism for improved outcomes in AD stems from a focus on preventive interventions in midlife and timely, biomarker-confirmed diagnosis at early signs of cognitive deficits (i.e. MCI due to AD and mild AD dementia). A timely AD diagnosis is particularly important for optimizing patient care and enabling the appropriate use of anticipated DMTs. An accelerating challenge for PCCs and AD specialists will be to respond to innovations in diagnostics and therapy for AD in a system that is not currently well positioned to do so. To overcome these challenges, PCCs and AD specialists must collaborate closely to navigate and optimize dynamically evolving AD care in the face of new opportunities. In the spirit of this collaboration, we summarize here some prominent and influential models that inform our current understanding of AD. We also advocate for timely and accurate (i.e. biomarker-defined) diagnosis of early AD. In doing so, we consider evolving issues related to prevention, detecting emerging cognitive impairment and the role of biomarkers in the clinic.
Topics: Alzheimer Disease; Humans; Primary Health Care; Time Factors
PubMed: 33458891
DOI: 10.1111/joim.13244 -
Alzheimer's & Dementia : the Journal of... Jan 2019Alzheimer's disease and related dementias (ADRD) cause a high burden of morbidity and mortality in the United States. Age, race, and ethnicity are important risk factors...
INTRODUCTION
Alzheimer's disease and related dementias (ADRD) cause a high burden of morbidity and mortality in the United States. Age, race, and ethnicity are important risk factors for ADRD.
METHODS
We estimated the future US burden of ADRD by age, sex, and race and ethnicity by applying subgroup-specific prevalence among Medicare Fee-for-Service beneficiaries aged ≥65 years in 2014 to subgroup-specific population estimates for 2014 and population projection data from the United States Census Bureau for 2015 to 2060.
RESULTS
The burden of ADRD in 2014 was an estimated 5.0 million adults aged ≥65 years or 1.6% of the population, and there are significant disparities in ADRD prevalence among population subgroups defined by race and ethnicity. ADRD burden will double to 3.3% by 2060 when 13.9 million Americans are projected to have the disease.
DISCUSSION
These estimates can be used to guide planning and interventions related to caring for the ADRD population and supporting caregivers.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Fee-for-Service Plans; Female; Humans; Male; Medicare; Prevalence; Racial Groups; Risk Factors; United States
PubMed: 30243772
DOI: 10.1016/j.jalz.2018.06.3063 -
Alzheimer's & Dementia : the Journal of... Jan 2021The LipiDiDiet trial investigates the effects of the specific multinutrient combination Fortasyn Connect on cognition and related measures in prodromal Alzheimer's... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The LipiDiDiet trial investigates the effects of the specific multinutrient combination Fortasyn Connect on cognition and related measures in prodromal Alzheimer's disease (AD). Based on previous results we hypothesized that benefits increase with long-term intervention.
METHODS
In this randomized, double-blind, placebo-controlled trial, 311 people with prodromal AD were recruited using the International Working Group-1 criteria and assigned to active product (125 mL once-a-day drink) or an isocaloric, same tasting, placebo control drink. Main outcome was change in cognition (Neuropsychological Test Battery [NTB] 5-item composite). Analyses were by modified intention-to-treat, excluding (ie, censoring) data collected after the start of open-label active product and/or AD medication.
RESULTS
Of the 382 assessed for eligibility, 311 were randomized, of those 162 participants completed the 36-month study, including 81 with 36-month data eligible for efficacy analysis. Over 36 months, significant reductions in decline were observed for the NTB 5-item composite (-60%; between-group difference 0.212 [95% confidence interval: 0.044 to 0.380]; P = 0.014), Clinical Dementia Rating-Sum of Boxes (-45%; P = 0.014), memory (-76%; P = 0.008), and brain atrophy measures; small to medium Cohen's d effect size (0.25-0.31) similar to established clinically relevant AD treatment.
DISCUSSION
This multinutrient intervention slowed decline on clinical and other measures related to cognition, function, brain atrophy, and disease progression. These results indicate that intervention benefits increased with long-term use.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Atrophy; Cognition; Cognitive Dysfunction; Double-Blind Method; Female; Humans; Magnetic Resonance Imaging; Male; Mental Status and Dementia Tests; Middle Aged; Neuropsychological Tests; Nutrition Therapy; Prodromal Symptoms; Risk Factors
PubMed: 32920957
DOI: 10.1002/alz.12172 -
Alzheimer's & Dementia : the Journal of... Nov 2019Several microRNAs (miRNAs) have been implicated in Alzheimer's disease pathogenesis, but the evidence from individual case-control studies remains inconclusive. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Several microRNAs (miRNAs) have been implicated in Alzheimer's disease pathogenesis, but the evidence from individual case-control studies remains inconclusive.
METHODS
A systematic literature review was performed, followed by standardized multistage data extraction, quality control, and meta-analyses on eligible data for brain, blood, and cerebrospinal fluid specimens. Results were compared with miRNAs reported in the abstracts of eligible studies or recent qualitative reviews to assess novelty.
RESULTS
Data from 147 independent data sets across 107 publications were quantitatively assessed in 461 meta-analyses. Twenty-five, five, and 32 miRNAs showed studywide significant differential expression (α < 1·08 × 10) in brain, cerebrospinal fluid, and blood-derived specimens, respectively, with 5 miRNAs showing differential expression in both brain and blood. Of these 57 miRNAs, 13 had not been reported in the abstracts of previous original or review articles.
DISCUSSION
Our systematic assessment of differential miRNA expression is the first of its kind in Alzheimer's disease and highlights several miRNAs of potential relevance.
Topics: Alzheimer Disease; Biomarkers; Brain; Case-Control Studies; Epigenomics; Humans; MicroRNAs
PubMed: 31495604
DOI: 10.1016/j.jalz.2019.06.4952 -
Ugeskrift For Laeger Mar 2017Alzheimer's disease is a neurodegenerative disorder with insidious onset and slow progression. Prevalence is increasing, although not as fast as previously believed. The... (Review)
Review
Alzheimer's disease is a neurodegenerative disorder with insidious onset and slow progression. Prevalence is increasing, although not as fast as previously believed. The clinical diagnosis may be difficult, but diagnostic methods have been introduced and proven to be accurate in supporting the clinical diagnosis. Application of these methods increases, partly due to improved awareness of cognitive symptoms and the relevance of early detection and diagnosis, in particular when more efficient disease-modifying drugs become available. Currently, only symptomatic treatment can be prescribed, and focus should be on potential prophylactic strategies.
Topics: Aged; Alzheimer Disease; Cholinesterase Inhibitors; Excitatory Amino Acid Antagonists; Humans; Memantine; Risk Factors
PubMed: 28330540
DOI: No ID Found