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Journal of Alzheimer's Disease Reports 2024Alzheimer's disease (AD) causes progressive decline of cognition and function. There is a lack of systematic literature reviews on prognostic and predictive factors in...
BACKGROUND
Alzheimer's disease (AD) causes progressive decline of cognition and function. There is a lack of systematic literature reviews on prognostic and predictive factors in its early clinical stages (eAD), i.e., mild cognitive impairment due to AD and mild AD dementia.
OBJECTIVE
To identify prognostic factors affecting eAD progression and predictive factors for treatment efficacy and safety of approved and/or under late-stage development disease-modifying treatments.
METHODS
Databases were searched (August 2022) for studies reporting prognostic factors associated with eAD progression and predictive factors for treatment response. The Quality in Prognostic Factor Studies tool or the Cochrane risk of bias tool were used to assess risk of bias. Two reviewers independently screened the records. A single reviewer performed data extraction and quality assessment. A second performed a 20% check. Content experts reviewed and interpreted the data collected.
RESULTS
Sixty-one studies were included. Self-reporting, diagnosis definition, and missing data led to high risk of bias. Population size ranged from 110 to 11,451. Analyses found data indicating that older age was and depression may be associated with progression. Greater baseline cognitive impairment was associated with progression. may be a prognostic factor, a predictive factor for treatment efficacy and predicts an adverse response (ARIA). Elevated biomarkers (CSF/plasma p-tau, CSF t-tau, and plasma neurofilament light) were associated with disease progression.
CONCLUSIONS
Age was the strongest risk factor for progression. Biomarkers were associated with progression, supporting their use in trial selection and aiding diagnosis. Baseline cognitive impairment was a prognostic factor. predicted ARIA, aligning with emerging evidence and relevant to treatment initiation/monitoring.
PubMed: 38405341
DOI: 10.3233/ADR-230045 -
Sleep Medicine Reviews Aug 2023Alzheimer's disease (AD) is the most common type of dementia and is characterized by the aggregation of extracellular amyloid-beta and intracellular hyperphosphorylation... (Meta-Analysis)
Meta-Analysis Review
Alzheimer's disease (AD) is the most common type of dementia and is characterized by the aggregation of extracellular amyloid-beta and intracellular hyperphosphorylation of tau proteins. Obstructive Sleep Apnea (OSA) is associated with increased AD risk. We hypothesize that OSA is associated with higher levels of AD biomarkers. The study aims to conduct a systematic review and meta-analysis of the association between OSA and levels of blood and cerebrospinal fluid biomarkers of AD. Two authors independently searched PubMed, Embase, and Cochrane Library for studies comparing blood and cerebrospinal fluid levels of dementia biomarkers between patients with OSA and healthy controls. Meta-analyses of the standardized mean difference were conducted using random-effects models. From 18 studies with 2804 patients, meta-analysis found that cerebrospinal fluid amyloid beta-40 (SMD:-1.13, 95%CI:-1.65 to -0.60), blood total amyloid beta (SMD:0.68, 95%CI: 0.40 to 0.96), blood amyloid beta-40 (SMD:0.60, 95%CI: 0.35 to 0.85), blood amyloid beta-42 (SMD:0.80, 95%CI: 0.38 to 1.23) and blood total-tau (SMD: 0.664, 95% CI: 0.257 to 1.072, I = 82, p<0.01, 7 studies) were significantly higher in OSA patients compared with healthy controls. These findings suggest that OSA is associated with an elevation of some biomarkers of AD.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; tau Proteins; Sleep Apnea, Obstructive; Biomarkers
PubMed: 37245474
DOI: 10.1016/j.smrv.2023.101790 -
Evidence-based Dentistry Sep 2023To summarize the data on association between periodontal diseases and cognitive impairment in adults this systematic review scrutinized various observational studies...
DESIGN
To summarize the data on association between periodontal diseases and cognitive impairment in adults this systematic review scrutinized various observational studies till September 2021. This review was carried out in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA 2020) guidelines. The authors used PECO framework question,: population-Adults (18 years or older), exposure-adults suffering from periodontitis, comparator-adult group without periodontitis, outcome-adults at high risk for cognitive impairment.
CASE/CONTROL SELECTION
Search for the literature was conducted on PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Search was limited to human studies with no limitation to year of publication prior to September 2021. Search terms used were related to gingiva, oral bacteria like Porphyromonas gingivalis, gum inflammation, periodontitis, dementia, neuroinflammation, cognitive impairment, Alzheimer's disease, Parkinson disease. Following research, all the studies providing association between periodontal diseases and neurodegenerative diseases with quantitative measures were included in the study. Non-human studies, studies on patients below 18 year old, studies related to influence of treatment and in subjects already suffering from neurological disease were excluded. After removing duplicates, eligible studies were identified and data extracted by two reviewers to make ensure inter examiner reliability and to prevent data entry errors. Data from the studies were tabulated as study design, sample characteristics, diagnosis, exposure biomarkers/measures, outcomes and results.
DATA ANALYSIS
Methodological quality of studies was assessed by adapted Newcastle-Ottawa scale. Selection of study groups, comparability and exposure/outcome were used as parameters. Case-control and cohort studies were considered as high-quality studies if six or more stars were awarded out of nine maximum stars and four or more stars for cross-sectional studies out of six stars. Comparability among the groups was studied by taking into account primary factors for Alzheimer's disease such as age and sex and secondary factors like hypertension, osteoarthritis, depression, diabetes mellitus, and cerebrovascular disease. For cohort studies, 10 year follow up and dropout of <10% was considered to be successful.
RESULTS
A total of 3693 studies were identified by two independent reviewers and finally 11 studies were included in the final analysis. Six cohort studies, three cross-sectional and two case-control studies were included after excluding remaining studies. Bias in studies was assessed by adapted Newcastle-Ottawa Scale. All included studies were of high methodological quality. Association between periodontitis and cognitive impairment was determined by using different criteria like International classification of disease, clinical measurement of periodontitis subjects, inflammatory biomarkers, microbes and antibodies. It was suggested that subjects with chronic periodontitis since 8 years or more, are at a higher risk of having dementia. Clinical measures of periodontal disease like probing depth, clinical attachment loss, alveolar bone loss were found to be positively associated with cognitive impairment. Inflammatory biomarkers and pre-existing elevated levels of serum IgG specific to periodontopathogens was reported to be associated with cognitive impairment. Within the limitations of the study, the authors concluded that though the patients with long-standing periodontitis are at greater risk for developing cognitive impairment by neurodegenerative diseases, the mechanism by which periodontitis can lead to cognitive impairment is still vague.
CONCLUSIONS
Evidence suggests a strong association between periodontitis and cognitive impairment. Still further studies should be done to explore the mechanism involved.
Topics: Adult; Humans; Alzheimer Disease; Cross-Sectional Studies; Reproducibility of Results; Chronic Periodontitis; Cognitive Dysfunction; Biomarkers
PubMed: 37433922
DOI: 10.1038/s41432-023-00915-2 -
International Journal of Molecular... Sep 2023Aging is a complex process influenced by genetics and the environment, leading to physiological decline and increased susceptibility to diseases. Cognitive decline is a... (Review)
Review
Aging is a complex process influenced by genetics and the environment, leading to physiological decline and increased susceptibility to diseases. Cognitive decline is a prominent feature of aging, with implications for different neurodegenerative disorders. The gut microbiome has gained attention for its potential impact on health and disease, including cognitive function. This systematic review and meta-analysis aimed to investigate the relationship between the gut microbiome and cognitive function in the context of aging. Following PRISMA guidelines, a comprehensive search strategy was employed in PubMed, Scopus, and Web of Science databases. Studies exploring the role of the microbiome in cognition and neurodegenerative disorders, published between 2013 and 2023, were included. Data extraction and quality assessment were performed. Quantitative synthesis using statistical analyses was performed to examine microbial diversity and relative abundance in various cognitive conditions. Sixteen studies involving a total of 1303 participants were included in the analysis. The gut microbiota's relative abundance was different in individuals with cognitive impairments such as Alzheimer's disease, Parkinson's disease, and dementia, compared to the healthy controls. The most prevalent phyla affected were Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria. Meta-analyses indicated substantial heterogeneity among studies focusing on Alzheimer's disease. The overall quality of evidence related to microbial analysis was moderate. The gut microbiome's role in cognitive decline and neurodegenerative disorders warrants investigation. Altered microbial abundance, particularly in specific phyla, is associated with cognitive impairments. However, variations in study findings and methodologies highlight the complexity of the relationship between the gut microbiome and cognitive function. Further studies are needed to better understand the mechanisms underlying this connection and its potential implications for aging and cognitive health.
PubMed: 37761988
DOI: 10.3390/ijms241813680 -
Journal of Alzheimer's Disease Reports 2023Traditional methods for diagnosing dementia are costly, time-consuming, and somewhat invasive. Since the retina shares significant anatomical similarities with the...
BACKGROUND
Traditional methods for diagnosing dementia are costly, time-consuming, and somewhat invasive. Since the retina shares significant anatomical similarities with the brain, retinal abnormalities detected via optical coherence tomography (OCT) and OCT angiography (OCTA) have been studied as a potential non-invasive diagnostic tool for neurodegenerative disorders; however, the most effective retinal changes remain a mystery to be unraveled in this review.
OBJECTIVE
This study aims to explore the relationship between retinal abnormalities in OCT/OCTA images and cognitive decline as well as evaluating biomarkers' effectiveness in detecting neurodegenerative diseases.
METHODS
A systematic search was conducted on PubMed, Web of Science, and Scopus until December 2022, resulted in 64 papers using agreed search keywords, and inclusion/exclusion criteria.
RESULTS
The superior peripapillary retinal nerve fiber layer (pRNFL) is a trustworthy biomarker to identify most Alzheimer's disease (AD) cases; however, it is inefficient when dealing with mild AD and mild cognitive impairment (MCI). The global pRNFL (pRNFL-G) is another reliable biomarker to discriminate frontotemporal dementia from mild AD and healthy controls (HCs), moderate AD and MCI from HCs, as well as identifing pathological Aβ/tau in cognitively healthy individuals. Conversely, pRNFL-G fails to realize mild AD and the progression of AD. The average pRNFL thickness variation is considered a viable biomarker to monitor the progression of AD. Finally, the superior and average pRNFL thicknesses are considered consistent for advanced AD but not for early/mild AD.
CONCLUSIONS
Retinal changes may indicate dementia, but further research is needed to confirm the most effective biomarkers for early and mild AD.
PubMed: 38025800
DOI: 10.3233/ADR-230042 -
Neuroscience and Biobehavioral Reviews Dec 2023Non-Alzheimer's dementia (NAD) accounts for 30% of all neurodegenerative conditions and is characterized by cognitive decline beyond mere memory dysfunction. Diagnosing... (Meta-Analysis)
Meta-Analysis Review
Non-Alzheimer's dementia (NAD) accounts for 30% of all neurodegenerative conditions and is characterized by cognitive decline beyond mere memory dysfunction. Diagnosing NAD remains challenging due to the lack of established biomarkers. Transcranial magnetic stimulation (TMS) is a non-invasive neurophysiological tool that enables the investigation of cortical excitability in the human brain. Paired-pulse TMS paradigms include short- and long-interval intracortical inhibition (SICI/LICI), intracortical facilitation (ICF), and short-latency afferent inhibition (SAI), which can assess neurophysiological functions of GABAergic, glutamatergic, and cholinergic neural circuits, respectively. We conducted the first systematic review and meta-analysis to compare these TMS indices among patients with NAD and healthy controls. Our meta-analyses indicated that TMS neurophysiological examinations revealed decreased glutamatergic function in patients with frontotemporal dementia (FTD) and decreased GABAergic function in patients with FTD, progressive supranuclear palsy, Huntington's disease, cortico-basal syndrome, and multiple system atrophy-parkinsonian type. In addition, decreased cholinergic function was found in dementia with Lewy body and vascular dementia. These results suggest the potential of TMS as an additional diagnostic tool to differentiate NAD.
Topics: Humans; Transcranial Magnetic Stimulation; Frontotemporal Dementia; Neurodegenerative Diseases; NAD; Alzheimer Disease; Cholinergic Agents; Neural Inhibition; Evoked Potentials, Motor
PubMed: 37926239
DOI: 10.1016/j.neubiorev.2023.105451 -
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 -
The Saudi Dental Journal Sep 2023The number of older people increases globally, so is the risk of cognitive impairment. Periodontal diseases are common among older adults with significant tooth loss and... (Review)
Review
BACKGROUND
The number of older people increases globally, so is the risk of cognitive impairment. Periodontal diseases are common among older adults with significant tooth loss and periodontal problems. Thus, this review explored the periodontal disease conditions among individuals with and without dementia.
METHODS
Available databases such as Medline/Pubmed, Web of Science, Scopus, Cochrane Library and Embase/OVID were used in the search. Case-control studies reporting on periodontal disease and dementia parameters were selected based on PICO (Population, Intervention, Comparison and Outcomes) framework. A Newcastle-Ottawa Scale (NOS) was used to assess the quality reporting of the studies and PRISMA guideline was used for screening.
RESULTS
A total of ten studies were identified for analysis. Most studies reported higher plaque index score (PI), bleeding on probing (BoP), pocket depth (PD) and clinical attachment loss (CAL) among individuals diagnosed with dementia or Alzheimer's disease compared with clinically healthy controls or individual diagnosed without dementia. A higher prevalence of subjects with severe periodontal disease was also observed in individuals diagnosed with dementia/Alzheimer's disease. The quality of the studies was found to be moderate with lower comparability and ascertainment criteria scores.
CONCLUSION
This qualitative analysis has shown poor periodontal health and increased inflammatory mediators in case groups compared to the control groups. Thus, more quality studies and novel intervention are warranted to reduce the impact of periodontal health on dementia globally.
PubMed: 37817782
DOI: 10.1016/j.sdentj.2023.06.004 -
Journal of Geriatric Psychiatry and... Feb 2024Patient involvement is a critical component of dementia research priority-setting exercises to ensure that research benefits are relevant and acceptable to those who... (Review)
Review
INTRODUCTION
Patient involvement is a critical component of dementia research priority-setting exercises to ensure that research benefits are relevant and acceptable to those who need the most. This systematic review synthesises research priorities and preferences identified by people living with dementia and their caregivers.
METHODS
Guided by Joanna Briggs Institute methodology, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework, we conducted a systematic search in five electronic databases: CINAHL, Medline, PsycINFO, Web of Science and Scopus. The reference lists of the included studies were also manually searched. We combined quantitative and qualitative data for synthesis and descriptive thematic analysis.
RESULTS
Eleven studies were included in this review. Findings are grouped into four main categories: Increase in knowledge, education, and awareness; Determining the cause; Sustainability of care; and Cure of dementia and related conditions.
CONCLUSION
There is a need to respond to the stigma associated with dementia, which limits access to care and the quality of life for both people living with dementia and their caregivers. We need to work on changing public, private and workplace attitudes about dementia and encourage supporting and participating in dementia research. Future research should involve people living with dementia and their primary caregivers from culturally and linguistically diverse communities in priority-setting exercises.
PubMed: 38337159
DOI: 10.1177/08919887241232647 -
PloS One 2023Atopic dermatitis (AD) is a common chronic inflammatory skin disease that affects adults worldwide. Recent evidence suggests that AD may be associated with cognitive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atopic dermatitis (AD) is a common chronic inflammatory skin disease that affects adults worldwide. Recent evidence suggests that AD may be associated with cognitive dysfunction, but the results of individual studies have been inconsistent. This systematic review and meta-analysis aimed to evaluate the association between AD and cognitive dysfunction in middle-aged and older adults.
METHODS
To find relevant research, a comprehensive search of electronic databases from the beginning to March 2023 was carried out. Data were taken from studies that were eligible, and a meta-analysis was done to determine the pooled hazard ratio (HR) and 95% confidence interval (CI).
RESULTS
We searched three databases and found a total of 15 studied arms included in 5 cohort studies with over 8.5 million participants were included in the analysis. The results showed that individuals with AD had a higher risk of developing dementia of all-cause dementia (pooled hazard ratio (HR) = 1.16; 95% CI, 1.10-1.23,P<0.001) and the Alzheimer type (pooled HR = 1.28; 95% CI, 1.01-1.63,P<0.001) but not vascular dementia (pooled HR = 1.42; 95% CI, 0.99-2.04,P<0.001). Subgroup analyses showed that the association between atopic dermatitis and all-cause dementia was significant in Europe (P = 0.004) but not in Asia (P = 0.173) and was significant in prospective cohort studies (P<0.001) but not in non-prospective cohort studies (P = 0.068). Sensitivity analysis and publication bias detection confirmed the reliability of the overall findings.
CONCLUSIONS
In conclusion, this study demonstrated that AD was associated with increased risk of cognitive dysfunction, particularly dementia of the Alzheimer type and all-cause dementia, in middle-aged and older participants. Further research is needed to understand the mechanisms behind this association and its potential implications for clinical practice.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier (CRD42023411627).
Topics: Middle Aged; Humans; Aged; Alzheimer Disease; Dermatitis, Atopic; Prospective Studies; Reproducibility of Results; Cognitive Dysfunction
PubMed: 37878635
DOI: 10.1371/journal.pone.0292987