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BMC Geriatrics Dec 2023Both osteoporosis and cognitive impairment affect overall health in elderly individuals. This study aimed to investigate the association between cognitive impairment and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Both osteoporosis and cognitive impairment affect overall health in elderly individuals. This study aimed to investigate the association between cognitive impairment and the risk of osteoporosis.
METHODS
PubMed, Web of Science, and the Cochrane Library were searched for studies on the association between osteoporosis and cognitive impairment from their inception until August 2023. The random-effects model was used to calculate the pooled risk ratio (RR) of osteoporosis in patients with cognitive impairment. Subgroup analysis was used to detect the sources of heterogeneity. Sensitivity analysis was used to test the robustness of the pooled results. Funnel plots, Egger's test, and Begg's test were used to test publication bias.
RESULTS
Ten studies involving 9,872 patients were included in this meta-analysis. The pooled results showed that patients with cognitive impairment had an increased risk of osteoporosis (RR = 1.56, 95% confidence interval [CI]: 1.30-1.87, p < 0.001). Subgroup analysis showed that patients with Alzheimer's disease (AD) are at 1.7-fold risk of osteoporosis compared with the control group (RR = 1.70, 95% CI: 1.23-2.37, p = 0.001), and sex, cognitive classification, study region, study design, and study quality might be the sources of heterogeneity. Sensitivity analysis showed robustness of the pooled results. No significant publication bias was found (Begg's test, p = 0.474; Egger's test, p = 0.065).
CONCLUSION
Current evidence suggests that patients with cognitive impairment are at increased risk of osteoporosis, especially patients with AD.
Topics: Humans; Aged; Cognitive Dysfunction; Osteoporosis; Alzheimer Disease; Odds Ratio
PubMed: 38049723
DOI: 10.1186/s12877-023-04548-z -
Cureus Aug 2023Being one of the most prevalent progressive neurodegenerative disorders (falling second only to Alzheimer's disease) with a clinical pattern affecting millions of lives... (Review)
Review
Being one of the most prevalent progressive neurodegenerative disorders (falling second only to Alzheimer's disease) with a clinical pattern affecting millions of lives all over the world, Parkinson's disease (PD) has never failed to attract a formidable interest from the vast majority of neurologists and researchers worldwide. This review article will analyze the pathophysiology, etiology, genetics, and pathological stages of Parkinson's disease with their corresponding clinical sequels. A review article was conducted using research databases including PubMed, PubMed Central, Springer, and Elsevier. The research articles reviewed using databases were written in English, German, Japanese, and Chinese and published within the preceding 50 years. Based on the article's findings, we concluded that Parkinson's disease is a progressive disorder with a variety of motor and non-motor symptoms that are influenced by a cascade of pathological neuronal abnormalities such as Lewy neurites and Lewy bodies that gradually build up with an eventual consequence of neurodegeneration of dopamine-secreting neurons. Multiple genetic mutations, pathophysiological events, and environmental factors act as the foundation to initiate that cascade.
PubMed: 37664277
DOI: 10.7759/cureus.44353 -
Frontiers in Neurology 2023Transcranial magnetic stimulation (TMS) is a non-invasive intervention that holds promise for improving cognitive function in individuals with Alzheimer's disease (AD)....
INTRODUCTION
Transcranial magnetic stimulation (TMS) is a non-invasive intervention that holds promise for improving cognitive function in individuals with Alzheimer's disease (AD). However, the effectiveness of this therapy and the optimal TMS parameters has not reached a consensus. The purpose of the meta-analysis was to systematically discern the effectiveness of different components of TMS protocols on cognitive improvement in patients with mild cognitive impairment (MCI) and AD.
METHODS
The meta-analysis was preregistered on Prospero (registration number: CRD42022345482). PubMed, Web of Science, Science Direct, and Cochrane Library databases were used to search, screen and identify eligible studies with the following keywords: Transcranial Magnetic Stimulation OR TMS OR theta burst stimulation AND Alzheimer OR Alzheimers OR Alzheimer's OR mild cognitive impairment OR MCI. Randomized controlled trials (RCTs) of participants with accepted standardized diagnostic criteria were searched by two authors independently. The risk of bias was assessed using an adapted Cochrane Risk of Bias tool. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated using the random-effects models. Subgroup analyses were performed to investigate the influential factors.
RESULTS
A total of 21 studies and 25 trials were included in this meta-analysis. The findings revealed a significant overall cognition improvement of real stimulation compared with sham stimulation (short-term effects: SMD, 0.91; 95% CI 0.44-1.38; < 0.01; long-lasting effects: SMD, 0.91; 95% CI 0.27-1.55; < 0.01). Subgroup analysis demonstrated that stimulation of the left dorsolateral prefrontal cortex and bilateral cerebellums, as well as moderate frequency stimulation (5 Hz and 10 Hz) on mild and moderate cognitive impairment patients, were more effective than other TMS protocols. However, the additional application of cognitive training showed no significant improvement.
CONCLUSION
Cognitive improvement effect of TMS was demonstrated in MCI and AD patients in both short-term assessment and long-lasting outcomes, and the efficiency of TMS is affected by the stimulation frequency, stimulation site, and participant characteristics. Further RCTs are needed to validate the findings of our subgroup analysis.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022345482, identifier: CRD42022345482.
PubMed: 37528850
DOI: 10.3389/fneur.2023.1209205 -
Neuropsychology Review Mar 2024Despite the numerous pharmacological interventions targeting dementia, no disease-modifying therapy is available, and the prognosis remains unfavorable. A promising...
Despite the numerous pharmacological interventions targeting dementia, no disease-modifying therapy is available, and the prognosis remains unfavorable. A promising perspective involves tackling high-frequency gamma-band (> 30 Hz) oscillations involved in hippocampal-mediated memory processes, which are impaired from the early stages of typical Alzheimer's Disease (AD). Particularly, the positive effects of gamma-band entrainment on mouse models of AD have prompted researchers to translate such findings into humans using transcranial alternating current stimulation (tACS), a methodology that allows the entrainment of endogenous cortical oscillations in a frequency-specific manner. This systematic review examines the state-of-the-art on the use of gamma-tACS in Mild Cognitive Impairment (MCI) and dementia patients to shed light on its feasibility, therapeutic impact, and clinical effectiveness. A systematic search from two databases yielded 499 records resulting in 10 included studies and a total of 273 patients. The results were arranged in single-session and multi-session protocols. Most of the studies demonstrated cognitive improvement following gamma-tACS, and some studies showed promising effects of gamma-tACS on neuropathological markers, suggesting the feasibility of gamma-tACS in these patients anyhow far from the strong evidence available for mouse models. Nonetheless, the small number of studies and their wide variability in terms of aims, parameters, and measures, make it difficult to draw firm conclusions. We discuss results and methodological limitations of the studies, proposing possible solutions and future avenues to improve research on the effects of gamma-tACS on dementia.
Topics: Humans; Cognition; Cognitive Dysfunction; Dementia; Memory; Transcranial Direct Current Stimulation
PubMed: 36877327
DOI: 10.1007/s11065-023-09589-0 -
Frontiers in Psychology 2023Mild cognitive impairment (MCI), representing the 'transitional zone' between normal cognition and dementia, has become a novel topic in clinical research. Although... (Review)
Review
Mild cognitive impairment (MCI), representing the 'transitional zone' between normal cognition and dementia, has become a novel topic in clinical research. Although early detection is crucial, it remains logistically challenging at the same time. While traditional pen-and-paper tests require in-depth training to ensure standardized administration and accurate interpretation of findings, significant technological advancements are leading to the development of procedures for the early detection of Alzheimer's disease (AD) and facilitating the diagnostic process. Some of the diagnostic protocols, however, show significant limitations that hamper their widespread adoption. Concerns about the social and economic implications of the increasing incidence of AD underline the need for reliable, non-invasive, cost-effective, and timely cognitive scoring methodologies. For instance, modern clinical studies report significant oculomotor impairments among patients with MCI, who perform poorly in visual paired-comparison tasks by ascribing less attentional resources to novel stimuli. To accelerate the Global Action Plan on the Public Health Response to Dementia 2017-2025, this work provides an overview of research on saccadic and exploratory eye-movement deficits among older adults with MCI. The review protocol was drafted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic databases were systematically searched to identify peer-reviewed articles published between 2017 and 2022 that examined visual processing in older adults with MCI and reported gaze parameters as potential biomarkers. Moreover, following the contemporary trend for remote healthcare technologies, we reviewed studies that implemented non-commercial eye-tracking instrumentation in order to detect information processing impairments among the MCI population. Based on the gathered literature, eye-tracking-based paradigms may ameliorate the screening limitations of traditional cognitive assessments and contribute to early AD detection. However, in order to translate the findings pertaining to abnormal gaze behavior into clinical applications, it is imperative to conduct longitudinal investigations in both laboratory-based and ecologically valid settings.
PubMed: 37546488
DOI: 10.3389/fpsyg.2023.1197567 -
International Journal of Molecular... Jan 2024Alzheimer's Disease (AD) is the most common neurodegenerative disease which manifests with progressive cognitive impairment, leading to dementia. Considering the... (Meta-Analysis)
Meta-Analysis Review
Alzheimer's Disease (AD) is the most common neurodegenerative disease which manifests with progressive cognitive impairment, leading to dementia. Considering the noninvasive collection of saliva, we designed the systematic review to answer the question "Are salivary biomarkers reliable for the diagnosis of Alzheimer's Disease?" Following the inclusion and exclusion criteria, 30 studies were included in this systematic review (according to the PRISMA statement guidelines). Potential biomarkers include mainly proteins, metabolites and even miRNAs. Based on meta-analysis, in AD patients, salivary levels of beta-amyloid42 and p-tau levels were significantly increased, and t-tau and lactoferrin were decreased at borderline statistical significance. However, according to pooled AUC, lactoferrin and beta-amyloid42 showed a significant predictive value for salivary-based AD diagnosis. In conclusion, potential markers such as beta-amyloid42, tau and lactoferrin can be detected in the saliva of AD patients, which could reliably support the early diagnosis of this neurodegenerative disease.
Topics: Humans; Alzheimer Disease; Neurodegenerative Diseases; Lactoferrin; MicroRNAs; Biomarkers
PubMed: 38256241
DOI: 10.3390/ijms25021168 -
Genes Apr 2024Neurofilament proteins have been implicated to be altered in amyotrophic lateral sclerosis (ALS). The objectives of this study were to assess the diagnostic and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neurofilament proteins have been implicated to be altered in amyotrophic lateral sclerosis (ALS). The objectives of this study were to assess the diagnostic and prognostic utility of neurofilaments in ALS.
METHODS
Studies were conducted in electronic databases (PubMed/MEDLINE, Embase, Web of Science, and Cochrane CENTRAL) from inception to 17 August 2023, and investigated neurofilament light (NfL) or phosphorylated neurofilament heavy chain (pNfH) in ALS. The study design, enrolment criteria, neurofilament concentrations, test accuracy, relationship between neurofilaments in cerebrospinal fluid (CSF) and blood, and clinical outcome were recorded. The protocol was registered with PROSPERO, CRD42022376939.
RESULTS
Sixty studies with 8801 participants were included. Both NfL and pNfH measured in CSF showed high sensitivity and specificity in distinguishing ALS from disease mimics. Both NfL and pNfH measured in CSF correlated with their corresponding levels in blood (plasma or serum); however, there were stronger correlations between CSF NfL and blood NfL. NfL measured in blood exhibited high sensitivity and specificity in distinguishing ALS from controls. Both higher levels of NfL and pNfH either measured in blood or CSF were correlated with more severe symptoms as assessed by the ALS Functional Rating Scale Revised score and with a faster disease progression rate; however, only blood NfL levels were associated with shorter survival.
DISCUSSION
Both NfL and pNfH measured in CSF or blood show high diagnostic utility and association with ALS functional scores and disease progression, while CSF NfL correlates strongly with blood (either plasma or serum) and is also associated with survival, supporting its use in clinical diagnostics and prognosis. Future work must be conducted in a prospective manner with standardized bio-specimen collection methods and analytical platforms, further improvement in immunoassays for quantification of pNfH in blood, and the identification of cut-offs across the ALS spectrum and controls.
Topics: Amyotrophic Lateral Sclerosis; Humans; Neurofilament Proteins; Biomarkers; Intermediate Filaments; Prognosis
PubMed: 38674431
DOI: 10.3390/genes15040496 -
Dementia (London, England) Nov 2023People with dementia from culturally and linguistically diverse backgrounds often face poor health and social outcomes such as stigma, depression, and reduced help...
People with dementia from culturally and linguistically diverse backgrounds often face poor health and social outcomes such as stigma, depression, and reduced help seeking behaviours. Dementia friendly communities have been shown to reduce stigma, and the gap in health and social outcomes for people impacted by dementia. Despite the large presence of established dementia friendly communities, their functioning in multicultural communities remains underexplored. The aim of this review was to identify the barriers and facilitators of cultural inclusivity to inform the development of a multicultural dementia friendly community. We systematically searched for academic and grey literature regarding existing and prospective age or dementia-friendly communities that engaged with culturally and linguistically diverse communities. Using the matrix method, data on the barriers and facilitators to engagement were extracted. Papers were analysed for common themes and findings were integrated in a narrative format. A total of 3,164 papers were identified, 11 of which met inclusion criteria. There were 6 dementia friendly communities in North America, 3 in Europe, 1 in Australia and 1 in Asia. Analyses revealed that barriers to cultural inclusivity were centered around the accessibility of services, sociocultural factors, and the environment, including issues such as low awareness of dementia and stigma, language barriers, isolation, and the inaccessibility of transport and buildings. Leveraging existing cultural leaders and social structures to target culturally and linguistically diverse populations and develop tailored dementia friendly initiatives were key facilitators. To foster cultural inclusivity in dementia friendly communities, a culturally specific lens that addresses these barriers and utilises facilitators must be applied from the design stage through to implementation and evaluation.
Topics: Humans; Prospective Studies; Dementia; Language; Cultural Diversity; Australia
PubMed: 37871120
DOI: 10.1177/14713012231206292 -
Frontiers in Neuroscience 2023Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are aging related diseases with high incidence. Because of the correlation of incidence rate and some... (Review)
Review
BACKGROUND
Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are aging related diseases with high incidence. Because of the correlation of incidence rate and some possible mechanisms of comorbidity, the two diseases have been studied in combination by many researchers, and even some scholars call AD type 3 diabetes. But the relationship between the two is still controversial.
METHODS
This study used seed-based d mapping software to conduct a meta-analysis of the whole brain resting state functional magnetic resonance imaging (rs-fMRI) study, exploring the differences in amplitude low-frequency fluctuation (ALFF) and cerebral blood flow (CBF) between patients (AD or T2DM) and healthy controls (HCs), and searching for neuroimaging evidence that can explain the relationship between the two diseases.
RESULTS
The final study included 22 datasets of ALFF and 22 datasets of CBF. The results of T2DM group showed that ALFF increased in both cerebellum and left inferior temporal gyrus regions, but decreased in left middle occipital gyrus, right inferior occipital gyrus, and left anterior central gyrus regions. In the T2DM group, CBF increased in the right supplementary motor area, while decreased in the middle occipital gyrus and inferior parietal gyrus. The results of the AD group showed that the ALFF increased in the right cerebellum, right hippocampus, and right striatum, while decreased in the precuneus gyrus and right superior temporal gyrus. In the AD group, CBF in the anterior precuneus gyrus and inferior parietal gyrus decreased. Multimodal analysis within a disease showed that ALFF and CBF both decreased in the occipital lobe of the T2DM group and in the precuneus and parietal lobe of the AD group. In addition, there was a common decrease of CBF in the right middle occipital gyrus in both groups.
CONCLUSION
Based on neuroimaging evidence, we believe that T2DM and AD are two diseases with their respective characteristics of central nervous activity and cerebral perfusion. The changes in CBF between the two diseases partially overlap, which is consistent with their respective clinical characteristics and also indicates a close relationship between them.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO [CRD42022370014].
PubMed: 38125399
DOI: 10.3389/fnins.2023.1301778 -
Advances in Clinical and Experimental... Oct 2023Psychosis is a very common feature of Alzheimer's disease (AD) that can emerge as the neurodegenerative disease progresses. The 5-hydroxytryptamine (5-HT2A) receptors... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of negative allosteric modulators of 5-hydroxytryptamine 2A receptors in the treatment of Alzheimer's disease psychosis: A systematic review and meta-analysis.
BACKGROUND
Psychosis is a very common feature of Alzheimer's disease (AD) that can emerge as the neurodegenerative disease progresses. The 5-hydroxytryptamine (5-HT2A) receptors are located postsynaptically to serotonergic neurons in the frontal cortex and mediate both excitatory and inhibitory neurotransmissions. However, the effectiveness and tolerance of negative modulators of 5-HT2A receptors in Alzheimer's disease psychosis (ADP) are uncertain.
OBJECTIVES
To detect the negative modulators of the 5-HT2A receptor as a cure for ADP.
MATERIAL AND METHODS
The primary outcome indicator was the total Neuropsychiatric Inventory (NPI) score. Other prognostic indicators included Mini-Mental State Examination (MMSE), the Katz Index of Independence in Activities of Daily Living (KATZ), the discontinuation rate, and adverse events.
RESULTS
Compared to placebo, 5-HT2A inverse agonists significantly reduced the NPI total score, the KATZ and the MMSE score. The pooled odds ratio (OR) was 1.64 (95% confidence interval (95% CI): 1.01-2.65) and the heterogeneity variance was estimated at Tau2 = 0.52 with an I2 value of 90%, a χ2 value of 111.31, p = 0.04, and z-value of 2.01. The risk difference (RD) between the 5-HT2A receptor negative modulators and placebo groups was 0.12 (95% CI: 0.00-0.24) and the heterogeneity was estimated at Tau2 = 0.03, χ2 value of 127.23, degrees of freedom (df) value of 9, I2 value of 93%, z-value of 1.92, and p-value of 0.01 (<0.05).
CONCLUSION
Our results suggest that negative modulators of 5-HT2A receptors are beneficial and well-tolerated in the treatment of ADP.
Topics: Humans; Alzheimer Disease; Serotonin; Neurodegenerative Diseases; Activities of Daily Living; Drug Inverse Agonism; Receptor, Serotonin, 5-HT2A; Psychotic Disorders
PubMed: 37166012
DOI: 10.17219/acem/161159