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Alzheimer's Research & Therapy Jun 2023Chemokines, which are chemotactic inflammatory mediators involved in controlling the migration and residence of all immune cells, are closely associated with brain... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Chemokines, which are chemotactic inflammatory mediators involved in controlling the migration and residence of all immune cells, are closely associated with brain inflammation, recognized as one of the potential processes/mechanisms associated with cognitive impairment. We aim to determine the chemokines which are significantly altered in Alzheimer's disease (AD) and mild cognitive impairment (MCI), as well as the respective effect sizes, by performing a meta-analysis of chemokines in cerebrospinal fluid (CSF) and blood (plasma or serum).
METHODS
We searched three databases (Pubmed, EMBASE and Cochrane library) for studies regarding chemokines. The three pairwise comparisons were as follows: AD vs HC, MCI vs healthy controls (HC), and AD vs MCI. The fold-change was calculated using the ratio of mean (RoM) chemokine concentration for every study. Subgroup analyses were performed for exploring the source of heterogeneity.
RESULTS
Of 2338 records identified from the databases, 61 articles comprising a total of 3937 patients with AD, 1459 with MCI, and 4434 healthy controls were included. The following chemokines were strongly associated with AD compared with HC: blood CXCL10 (RoM, 1.92, p = 0.039), blood CXCL9 (RoM, 1.78, p < 0.001), blood CCL27 (RoM, 1.34, p < 0.001), blood CCL15 (RoM, 1.29, p = 0.003), as well as CSF CCL2 (RoM, 1.19, p < 0.001). In the comparison of AD with MCI, there was significance for blood CXCL9 (RoM, 2.29, p < 0.001), blood CX3CL1 (RoM, 0.77, p = 0.017), and blood CCL1 (RoM, 1.37, p < 0.001). Of the chemokines tested, blood CX3CL1 (RoM, 2.02, p < 0.001) and CSF CCL2 (RoM, 1.16, p = 0.004) were significant for the comparison of MCI with healthy controls.
CONCLUSIONS
Chemokines CCL1, CCL2, CCL15, CCL27, CXCL9, CXCL10, and CX3CL1 might be most promising to serve as key molecular markers of cognitive impairment, although more cohort studies with larger populations are needed.
Topics: Humans; Alzheimer Disease; Cognitive Dysfunction; Encephalitis; Biomarkers
PubMed: 37291639
DOI: 10.1186/s13195-023-01254-1 -
Canadian Journal of Psychiatry. Revue... Jun 2020In 2016, the global number of individuals living with dementia was 43.8 million, representing a 117% increase from 1990-mainly due to increases in aging and population... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In 2016, the global number of individuals living with dementia was 43.8 million, representing a 117% increase from 1990-mainly due to increases in aging and population growth. Up to 90% of individuals with dementia experience neuropsychiatric symptoms (NPS). However, the limitations of current treatments for NPS have drivent he search for safer pharmacotherapies-including cannabinoids.
AIM
To assess the efficacy and acceptability of cannabinoids for the treatment of NPS in individuals with dementia.
DESIGN
Systematic review and meta-analysis of clinical trials.
SETTING AND PARTICIPANTS
Of 6,902 papers, 9 were eligible ( = 205, 44% female, 78 ± 7 years, 85% Alzheimer disease). Trials were in North America and Europe and explored tetrahydrocannabinol ( = 3), dronabinol ( = 5), or nabilone ( = 1).
MEASUREMENT
Titles/abstracts were independently screened by one reviewer and reviewed by a second. Full-text screening was by two reviewers with discrepancies resolved via a third reviewer. We extracted data on the standardized mean difference (SMD) for several NPS instruments, trial completion, and adverse events. Data were pooled using random-effects models.
FINDINGS
Cannabinoids led to significant improvements across NPS instruments, including the Cohen Mansfield Agitation Inventory (SMD = -0.80; 95% confidence interval [CI], -1.45 to -0.16), the Neuropsychiatric Inventory (SMD = -0.61; CI, -1.07 to -0.15), and nocturnal actigraphy (SMD = -1.05; CI, -1.56 to -0.54h). Cannabinoids were well-tolerated, with an overall trial completion rate of 93% (193/205) and no serious treatment-related adverse events. Treatment efficacy was associated with baseline dementia severity and dose, but not dementia subtype, age, or sex. The overall study quality was rated as low.
CONCLUSIONS
There is preliminary evidence for the efficacy and tolerability of cannabinoids as treatments for NPS. Population-based studies are needed to characterize their real-world effectiveness and acceptability.
Topics: Alzheimer Disease; Cannabinoids; Female; Humans; Male; North America; Treatment Outcome
PubMed: 31835954
DOI: 10.1177/0706743719892717 -
Neuroepidemiology 2022Previous studies have investigated the potential role of traumatic brain injury (TBI) in subsequent development of dementia and Alzheimer's disease (AD) but reported... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Previous studies have investigated the potential role of traumatic brain injury (TBI) in subsequent development of dementia and Alzheimer's disease (AD) but reported inconsistent results. We aimed to determine the association between TBI and subsequent occurrence of dementia and AD.
METHODS
We performed a systematic search in PubMed and Web of Science for studies that quantitatively investigated the association between TBI and risk of dementia and AD and were published on or before September 21, 2021. A random-effects model was used to combine the estimates.
RESULTS
Twenty-five eligible articles were included in this meta-analysis. The results suggested that TBI was associated with an increased risk of dementia (pooled odds ratio [OR] = 1.81, 95% confidence interval [CI] = 1.53-2.14). However, no association was observed between TBI and AD (pooled OR = 1.02, 95% CI = 0.91-1.15). In the subgroup analysis, TBI with loss of consciousness was not associated with risk of dementia (pooled OR = 0.96, 95% CI = 0.84-1.09). Besides, Asian ethnicity, male gender, and mean age of the participants less than 65 years were associated with a higher risk of dementia.
CONCLUSION
Our study suggests an increased risk of dementia among individuals with TBI, highlighting the need for more intensive medical monitoring and health education in individuals with TBI. Biological mechanisms linking TBI and the development of dementia are needed in future studies.
Topics: Aged; Alzheimer Disease; Brain Injuries, Traumatic; Humans; Male; Risk Factors
PubMed: 34818648
DOI: 10.1159/000520966 -
The European Journal of Neuroscience Nov 2022A biomarker associated with cognition in neurodegenerative dementias would aid in the early detection of disease progression, complement clinical staging and act as a...
A biomarker associated with cognition in neurodegenerative dementias would aid in the early detection of disease progression, complement clinical staging and act as a surrogate endpoint in clinical trials. The current systematic review evaluates the association between cerebrospinal fluid protein markers of synapse loss and neuronal injury and cognition. We performed a systematic search which revealed 67 studies reporting an association between cerebrospinal fluid markers of interest and neuropsychological performance. Despite the substantial heterogeneity between studies, we found some evidence for an association between neurofilament-light and worse cognition in Alzheimer's diseases, frontotemporal dementia and typical cognitive ageing. Moreover, there was an association between cerebrospinal fluid neurogranin and cognition in those with an Alzheimer's-like cerebrospinal fluid biomarker profile. Some evidence was found for cerebrospinal fluid neuronal pentraxin-2 as a correlate of cognition across dementia syndromes. Due to the substantial heterogeneity of the field, no firm conclusions can be drawn from this review. Future research should focus on improving standardization and reporting as well as establishing the importance of novel markers such as neuronal pentraxin-2 and whether such markers can predict longitudinal cognitive decline.
Topics: Humans; Amyloid beta-Peptides; tau Proteins; Alzheimer Disease; Cognitive Dysfunction; Cognition; Biomarkers; Aging
PubMed: 35338546
DOI: 10.1111/ejn.15656 -
CNS Neuroscience & Therapeutics Feb 2024Transcranial pulse stimulation (TPS) is a novel noninvasive ultrasonic brain stimulation that can increase cortical and corticospinal excitability, induce...
BACKGROUND
Transcranial pulse stimulation (TPS) is a novel noninvasive ultrasonic brain stimulation that can increase cortical and corticospinal excitability, induce neuroplasticity, and increase functional connectivity within the brain. Several trials have confirmed its potential in treating Alzheimer's disease (AD).
OBJECTIVE
To investigate the effect and safety of TPS on AD.
DESIGN
A systematic review.
METHODS
PubMed, Embase via Ovid, Web of Science, Cochrane Library, CNKI (China National Knowledge Infrastructure), VIP (China Science and Technology Journal Database), and WanFang were searched from inception to April 1, 2023. Study selection, data extraction, and quality evaluation of the studies were conducted by two reviewers independently, with any controversy resolved by consensus. The Methodological Index for Nonrandomized Studies was used to assess the risk of bias.
RESULTS
Five studies were included in this review, with a total of 99 patients with AD. For cognitive performance, TPS significantly improved the scores of the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) test battery, Alzheimer's Disease Assessment Scale (cognitive), Montreal Cognitive Assessment, and Mini-Mental Status Examination. For depressive symptoms, TPS significantly reduced the scores of the Alzheimer's Disease Assessment Scale (affective), Geriatric Depression Score, and Beck Depression Inventory. By functional magnetic resonance imaging, studies have shown that TPS improved cognitive performance in AD patients by increasing functional connectivity in the hippocampus, parahippocampal cortex, precuneus, and parietal cortex, and activating cortical activity in the bilateral hippocampus. TPS alleviated depressive symptoms in AD patients by decreasing functional connectivity between the ventromedial network (left frontal orbital cortex) and the salience network (right anterior insula). Adverse events in this review, including headache, worsening mood, jaw pain, nausea, and drowsiness, were reversible and lasted no longer than 1 day. No serious adverse events or complications were observed.
CONCLUSIONS
TPS is promising in improving cognitive performance and reducing depressive symptoms in patients with AD. TPS may be a safe adjunct therapy in the treatment of AD. However, these findings lacked a sham control and were limited by the small sample size of the included studies. Further research may be needed to better explore the potential of TPS.
PATIENT AND PUBLIC INVOLVEMENT
Patients and the public were not involved in this study.
Topics: Humans; Aged; Alzheimer Disease; Brain; Magnetic Resonance Imaging; Hippocampus; Mental Status and Dementia Tests; Transcranial Magnetic Stimulation
PubMed: 37469252
DOI: 10.1111/cns.14372 -
Dementia and Geriatric Cognitive... 2018Acetylcholinesterase inhibitors (AChEIs) and memantine are commonly used in the management of dementia. In routine clinical practice, dementia is often monitored via the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acetylcholinesterase inhibitors (AChEIs) and memantine are commonly used in the management of dementia. In routine clinical practice, dementia is often monitored via the Mini-Mental State Examination (MMSE). We conducted a systematic review and meta-analysis of the effects of these drugs on MMSE scores.
SUMMARY
Eighty trials were identified. Pooled effect estimates were in favour of both AChEIs and memantine at 6 months. Meta-regression indicated that dementia subtype was a moderator of AChEI treatment effect, with the effect of treatment versus control twice as high for patients with Parkinson disease dementia/ dementia with Lewy bodies (2.11 MMSE points at 6 months) as for patients with Alzheimer disease/vascular dementia (0.91 MMSE points at 6 months). Key Messages: AChEIs demonstrate a modest effect versus control on MMSE scores which is moderated by dementia subtype. For memantine the effect is smaller.
Topics: Alzheimer Disease; Cholinesterase Inhibitors; Cognition; Dementia, Vascular; Dopamine Agents; Humans; Memantine; Treatment Outcome
PubMed: 29734182
DOI: 10.1159/000486546 -
Journal of Alzheimer's Disease : JAD 2017Alzheimer's disease (AD) is a devastating disease mainly afflicting elderly people, characterized by decreased cognition, loss of memory, and eventually death. Although... (Review)
Review
Alzheimer's disease (AD) is a devastating disease mainly afflicting elderly people, characterized by decreased cognition, loss of memory, and eventually death. Although risk and deterministic genes are known, major genetics research programs are underway to gain further insights into the inheritance of AD. In the last years, in particular, new developments in genome-wide scanning methodologies have enabled the association of a number of previously uncharacterized copy number variants (CNVs, gain or loss of DNA) in AD. Because of the exceedingly large number of studies performed, it has become difficult for geneticists as well as clinicians to systematically follow, evaluate, and interpret the growing number of (sometime conflicting) CNVs implicated in AD. In this review, after a brief introduction of this type of structural variation, and a description of available databases, computational analyses, and technologies involved, we provide a systematic review of all published data showing statistical and scientific significance of pathogenic CNVs and discuss the role they might play in AD.
Topics: Alzheimer Disease; Animals; DNA Copy Number Variations; Humans
PubMed: 27662298
DOI: 10.3233/JAD-160469 -
Journal of Human Genetics May 2015Mutations in APP, PSEN1 and PSEN2 as the genetic causes of familial Alzheimer's disease (FAD) have been found in various ethnic populations. A substantial number of FAD... (Meta-Analysis)
Meta-Analysis Review
Mutations in APP, PSEN1 and PSEN2 as the genetic causes of familial Alzheimer's disease (FAD) have been found in various ethnic populations. A substantial number of FAD pedigrees with mutations have been reported in the Japanese population; however, it remains unclear whether the genetic and clinical features of FAD in the Japanese population differ from those in other populations. To address this issue, we conducted a systematic review and meta-analysis of Japanese FAD and frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) by literature search. Using this analysis, we identified 39 different PSEN1 mutations in 140 patients, 5 APP mutations in 35 patients and 16 MAPT mutations in 84 patients. There was no PSEN2 mutation among Japanese patients. The age at onset in Japanese FAD patients with PSEN1 mutations was significantly younger than that in patients with APP mutations. Kaplan-Meier analysis revealed that patients with MAPT mutations showed a shorter survival than patients with PSEN1 or APP mutations. Patients with mutations in different genes exhibit characteristic clinical presentations, suggesting that mutations in causative genes may modify the clinical presentations. By collecting and cataloging genetic and clinical information on Japanese FAD and FTDP-17, we developed an original database designated as Japanese Familial Alzheimer's Disease Database, which is accessible at http://alzdb.bri.niigata-u.ac.jp/.
Topics: Age of Onset; Alzheimer Disease; Chromosomes, Human, Pair 17; Frontotemporal Dementia; Genetic Predisposition to Disease; Humans; Mutation
PubMed: 25694106
DOI: 10.1038/jhg.2015.15 -
Neurobiology of Aging Sep 2014Cognitive disorders of later life are potentially devastating. To estimate the relationship between saturated and trans fat intake and risk of cognitive disorders.... (Meta-Analysis)
Meta-Analysis
Cognitive disorders of later life are potentially devastating. To estimate the relationship between saturated and trans fat intake and risk of cognitive disorders. PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for studies reporting saturated or trans fat intake and incident dementia, Alzheimer's disease (AD), or mild cognitive impairment (MCI) or cognitive decline. Only observational studies met the inclusion criteria: 4 for AD or other dementias, 4 for MCI, and 4 for cognitive decline. Saturated fat intake was positively associated with AD risk in 3 of 4 studies, whereas the fourth suggested an inverse relationship. Saturated fat intake was also positively associated with total dementia in 1 of 2 studies, with MCI in 1 of 4 studies, and with cognitive decline in 2 of 4 studies. Relationships between trans fat intake and dementia were examined in 3 reports with mixed results. Several, although not all, prospective studies indicate relationships between saturated and trans fat intake and risk of cognitive disorders.
Topics: Alzheimer Disease; Cognitive Dysfunction; Databases, Bibliographic; Dementia; Dietary Fats; Fatty Acids; Humans; Incidence; Risk; Trans Fatty Acids
PubMed: 24916582
DOI: 10.1016/j.neurobiolaging.2014.02.030 -
Ageing Research Reviews Jul 2023Alzheimer's disease (AD) is the most common cause of dementia, characterized by the aggregation of amyloid-beta (Aβ) proteins into plaques. Individuals with AD... (Meta-Analysis)
Meta-Analysis Review
The cross-sectional association between amyloid burden and white matter hyperintensities in older adults without cognitive impairment: A systematic review and meta-analysis.
Alzheimer's disease (AD) is the most common cause of dementia, characterized by the aggregation of amyloid-beta (Aβ) proteins into plaques. Individuals with AD frequently show mixed pathologies, often caused by cerebral small vessel disease (CSVD), resulting in lesions such as white matter hyperintensities (WMH). The current systematic review and meta-analysis investigated the cross-sectional relationship between amyloid burden and WMH in older adults without objective cognitive impairment. A systematic search performed in PubMed, Embase, and PsycINFO yielded 13 eligible studies. Aβ was assessed using PET, CSF, or plasma measurements. Two meta-analyses were performed: one on Cohen's d metrics and one on correlation coefficients. The meta-analyses revealed an overall weighted small-to-medium Cohen's d of 0.55 (95% CI: 0.31-0.78) in CSF, an overall correlation of 0.31 (0.09-0.50) in CSF, and a large Cohen's d of 0.96 (95% CI: 0.66-1.27) in PET. Only two studies assessed this relationship in plasma, with an effect size of - 0.20 (95% CI: -0.75 to 0.34). These findings indicate a relationship between both amyloid and vascular pathologies in cognitively normal adults in PET and CSF. Future studies should assess the possible relationship of blood amyloid-beta and WMH for broader identification of at risk individuals showing mixed pathology in preclinical stages.
Topics: Humans; Aged; White Matter; Alzheimer Disease; Cognitive Dysfunction; Amyloid beta-Peptides; Amyloid; Magnetic Resonance Imaging
PubMed: 37178806
DOI: 10.1016/j.arr.2023.101952