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BMC Geriatrics Sep 2023To systematically review the association between traumatic life events (TLE) and dementia risk. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To systematically review the association between traumatic life events (TLE) and dementia risk.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
APA, PsychINFO, Embase and MEDLINE from their inception to 29.05.21 and updated on 20.04.22.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Original research articles published in peer reviewed journals examining the association between TLE and all cause dementia in individuals aged 60 and over. Two researchers independently assessed the risk of bias using the Newcastle-Ottawa Scale. We conducted a generic inverse variance random effects meta-analysis to provide an overall estimate of TLE impact on dementia risk.
MAIN OUTCOME MEASURES
Risk, odds and hazards ratios relating to dementia risk.
RESULTS
Initially, 3,487 studies were retrieved in the search and seven studies were included in the meta-analysis with data being used from 276,570 participants. TLE were associated with increased dementia risk. Trauma in general had a pooled HR of 1.21, (95% CI 1.03, 1.43, P = 0.0001). War/ Holocaust trauma and childhood trauma were also associated with increased dementia risk (HR = 1.28 (95% CI 1.01-1.63, P = 0.02) and HR = 1.76 (95% CI 1.17-2.64, P = 0.007) respectively).
CONCLUSIONS
We have found an association between TLE and dementia risk. Future research exploring the dimensions of TLE and individual level factors are needed to better understand the relationship between TLE and dementia.
TRIAL REGISTRATION
PROSPERO CRD42021253090.
Topics: Humans; Middle Aged; Aged; Analysis of Variance; Dementia
PubMed: 37740188
DOI: 10.1186/s12877-023-04287-1 -
Stroke Apr 2024Vascular cognitive impairment is common after stroke, in memory clinics, medicine for the elderly services, and undiagnosed in the community. Vascular disease is said to... (Review)
Review
Vascular cognitive impairment is common after stroke, in memory clinics, medicine for the elderly services, and undiagnosed in the community. Vascular disease is said to be the second most common cause of dementia after Alzheimer disease, yet vascular dysfunction is now known to predate cognitive decline in Alzheimer disease, and most dementias at older ages are mixed. Neuroimaging has a major role in identifying the proportion of vascular versus other likely pathologies in patients with cognitive impairment. Here, we aim to provide a pragmatic but evidence-based summary of the current state of potential imaging biomarkers, focusing on magnetic resonance imaging and computed tomography, which are relevant to diagnosing, estimating prognosis, monitoring vascular cognitive impairment, and incorporating our own experiences. We focus on markers that are well-established, with a known profile of association with cognitive measures, but also consider more recently described, including quantitative tissue markers of vascular injury. We highlight the gaps in accessibility and translation to more routine clinical practice.
Topics: Humans; Aged; Alzheimer Disease; Dementia, Vascular; Cognitive Dysfunction; Stroke; Biomarkers
PubMed: 38445496
DOI: 10.1161/STROKEAHA.123.044171 -
The Medical Journal of Australia Jul 2023
Topics: Humans; Dementia; Age of Onset
PubMed: 37270187
DOI: 10.5694/mja2.51996 -
Ageing Research Reviews Aug 2023The associations between lipocalin-2 (LCN2) with mild cognitive impairment (MCI) and dementia have gained growing interest. However, population-based studies have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The associations between lipocalin-2 (LCN2) with mild cognitive impairment (MCI) and dementia have gained growing interest. However, population-based studies have yielded inconsistent findings. Therefore, we conducted this essential systematic review and meta-analysis to analyze and summarize the existing population-based evidence.
METHODS
PubMed, EMBASE, and Web of Science were systematically searched until Mar 18, 2022. Meta-analysis was performed to generate the standard mean difference (SMD) of peripheral blood and cerebrospinal fluid (CSF) LCN2. A qualitative review was performed to summarize the evidence from postmortem brain tissue studies.
RESULTS
In peripheral blood, the overall pooled results showed no significant difference in LCN2 across Alzheimer's disease (AD), MCI and control groups. Further subgroup analysis revealed higher serum LCN2 levels in AD compared to controls (SMD =1.28 [0.44;2.13], p = 0.003), while the difference remained insignificant in plasma (SMD =0.04 [-0.82;0.90], p = 0.931). Besides, peripheral blood LCN2 were higher in AD when age difference between AD and controls ≥ 4 years (SMD =1.21 [0.37;2.06], p = 0.005). In CSF, no differences were found in LCN2 across groups of AD, MCI and controls. However, CSF LCN2 was higher in vascular dementia (VaD) compared to controls (SMD =1.02 [0.17;1.87], p = 0.018), as well as compared to AD (SMD =1.19 [0.58;1.80], p < 0.001). Qualitative analysis supported that LCN2 was increased in the brain tissue of AD-related areas, especially in astrocytes and microglia; while LCN2 increased in infarct-related brain areas and over-expressed in astrocytes and macrophages in mixed dementia (MD).
CONCLUSION
The difference in peripheral blood LCN2 between AD and controls may be affected by the type of biofluid and age. No differences were found in CSF LCN2 across AD, MCI and controls groups. In contrast, CSF LCN2 was elevated in VaD patients. Moreover, LCN2 was increased in AD-related brain areas and cells in AD, while in infarcts-related brain areas and cells in MD.
Topics: Humans; Alzheimer Disease; Biomarkers; Cognitive Dysfunction; Dementia, Vascular; Lipocalin-2; Mixed Dementias
PubMed: 37330019
DOI: 10.1016/j.arr.2023.101984 -
Alzheimer's & Dementia : the Journal of... Sep 2023Angiotensin-converting enzyme (ACE) has been implicated in the metabolism of amyloid beta; however, the causal effect of ACE inhibition on risk of Alzheimer's disease...
INTRODUCTION
Angiotensin-converting enzyme (ACE) has been implicated in the metabolism of amyloid beta; however, the causal effect of ACE inhibition on risk of Alzheimer's disease (AD) dementia and other common dementias is largely unknown.
METHODS
We examined the causal association of genetically proxied ACE inhibition with four types of dementias using a two-sample Mendelian randomization (MR) approach.
RESULTS
Genetically proxied ACE inhibition was associated with increased risk of AD dementia (odds ratio per one standard deviation reduction in serum ACE [95% confidence interval]; 1.07 [1.04-1.10], P = 5 × 10 ) and frontotemporal dementia (1.16 [1.04-1.29], P = 0.01) but not with Lewy body dementia or vascular dementia (P > 0.05). These findings were independently replicated and remained consistent in sensitivity analyses.
DISCUSSION
This comprehensive MR study provided genetic evidence for an association between ACE inhibition and the risk for AD and frontotemporal dementias. These results should encourage further studies of the neurocognitive effects of ACE inhibition.
HIGHLIGHTS
This study evaluated genetically proxied angiotensin-converting enzyme (ACE) inhibition association with dementias. The results suggest an association between ACE inhibition and Alzheimer's disease. The results suggest an association between ACE inhibition and frontotemporal dementia. Those associations can be interpreted as potentially causal.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Frontotemporal Dementia; Dementia, Vascular; Angiotensins
PubMed: 37023267
DOI: 10.1002/alz.13062 -
Journal of Neural Transmission (Vienna,... Oct 2023Depression with an estimated prevalence of 35% is a frequent manifestation of dementia with Lewy bodies (DLB), having negative effects on cognitive performance and life... (Review)
Review
Depression with an estimated prevalence of 35% is a frequent manifestation of dementia with Lewy bodies (DLB), having negative effects on cognitive performance and life expectancy, yet the underlying neurobiology is poorly understood and most likely heterogeneous. Depressive symptoms in DLB can occur during the clinical course and, together with apathy, is a common prodromal neuropsychiatric symptom of this neurocognitive disorder in the group of Lewy body synucleinopathies. There are no essential differences in the frequency of depression in DLB and Parkinson disease-dementia (PDD), while its severity is up to twice as high as in Alzheimer disease (AD). Depression in DLB that is frequently underdiagnosed and undertreated, has been related to a variety of pathogenic mechanisms associated with the basic neurodegenerative process, in particular dysfunctions of neurotransmitter systems (decreased monoaminergic/serotonergic, noradrenergic and dopaminergic metabolism), α-synuclein pathology, synaptic zinc dysregulation, proteasome inhibition, gray matter volume loss in prefrontal and temporal areas as well as dysfunction of neuronal circuits with decreased functional connectivity of specific brain networks. Pharmacotherapy should avoid tricyclic antidepressants (anticholinergic adverse effects), second-generation antidepressants being a better choice, while modified electroconvulsive therapy, transcranial magnetic stimulation therapy and deep brain stimulation may be effective for pharmacotherapy-resistant cases. Since compared to depression in other dementias like Alzheimer disease and other parkinsonian syndromes, our knowledge of its molecular basis is limited, and further studies to elucidate the heterogeneous pathogenesis of depression in DLB are warranted.
Topics: Humans; Lewy Body Disease; Alzheimer Disease; Depression; Parkinson Disease; Parkinsonian Disorders; Brain
PubMed: 37418037
DOI: 10.1007/s00702-023-02669-8 -
JAMA Neurology Aug 2023
Topics: Humans; Dementia
PubMed: 37213130
DOI: 10.1001/jamaneurol.2023.1252 -
The Medical Journal of Australia Jul 2023
Topics: Humans; Dementia; Age of Onset
PubMed: 37270204
DOI: 10.5694/mja2.51995 -
Ageing Research Reviews Dec 2023Behavioral and psychological symptoms of dementia (BPSD) have been extensively studied in dementia than its prodromal stage, known as mild cognitive impairment (MCI). A... (Review)
Review
Behavioral and psychological symptoms of dementia (BPSD) have been extensively studied in dementia than its prodromal stage, known as mild cognitive impairment (MCI). A scientometric study on BPSD in MCI would be valuable in synthesizing the existing body of research and providing insights into the trends, networks, and influencers within this area. We searched for related literature in the Web of Science database and extracted complete text and citation records of each publication. The primary objective was to map the research evolution of BPSD in MCI and highlight dominant research themes. The secondary objective was to identify research network characteristics (authors, journals, countries, and institutions) and abundances. A total of 12,369 studies published between 1980 and 2022 were included in the analysis. We found 51 distinct clusters from the co-cited reference network that were highly credible with significant modularity (Q = 0.856) and silhouette scores (S = 0.932). Five major research domains were identified: symptoms, diagnosis, brain substrates, biochemical pathways, and interventions. In recent years, the research focus in this area has been on gut microbiota, e-health, COVID-19, cognition, and delirium. Collectively, findings from this scientometric analysis can help clarify the scope and direction of future research and clinical practices.
Topics: Humans; Cognitive Dysfunction; Cognition; Brain; Dementia
PubMed: 37981054
DOI: 10.1016/j.arr.2023.102129 -
Alzheimer's & Dementia : the Journal of... Mar 2024A 2013 systematic review and Delphi consensus study identified 12 modifiable risk and protective factors for dementia, which were subsequently merged into the "LIfestyle... (Review)
Review
A 2013 systematic review and Delphi consensus study identified 12 modifiable risk and protective factors for dementia, which were subsequently merged into the "LIfestyle for BRAin health" (LIBRA) score. We systematically evaluated whether LIBRA requires revision based on new evidence. To identify modifiable risk and protective factors suitable for dementia risk reduction, we combined an umbrella review of systematic reviews and meta-analyses with a two-round Delphi consensus study. The review of 608 unique primary studies and opinions of 18 experts prioritized six modifiable factors: hearing impairment, social contact, sleep, life course inequalities, atrial fibrillation, and psychological stress. Based on expert ranking, hearing impairment, social contact, and sleep were considered the most suitable candidates for inclusion in updated dementia risk scores. As such, the current study shows that dementia risk scores need systematic updates based on emerging evidence. Future studies will validate the updated LIBRA score in different cohorts. HIGHLIGHTS: An umbrella review was combined with opinions of 18 dementia experts. Various candidate targets for dementia risk reduction were identified. Experts prioritized hearing impairment, social contact, and sleep. Re-assessment of dementia risk scores is encouraged. Future work should evaluate the predictive validity of updated risk scores.
Topics: Humans; Dementia; Cognitive Dysfunction; Delphi Technique; Systematic Reviews as Topic; Risk Factors; Risk Reduction Behavior; Hearing Loss
PubMed: 38159267
DOI: 10.1002/alz.13577