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Clinical Neurophysiology : Official... Dec 2022Alzheimer's disease dementia (AD) and its preclinical stage, mild cognitive impairment (MCI), are critical issues confronting the aging society. Non-invasive brain... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Alzheimer's disease dementia (AD) and its preclinical stage, mild cognitive impairment (MCI), are critical issues confronting the aging society. Non-invasive brain stimulation (NIBS) techniques have the potential to be effective tools for enhancing cognitive functioning. The main objective of our meta-analysis was to quantify and update the status of the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) and Transcranial Direct Current Stimulation (tDCS) when applied in AD and MCI.
METHODS
The systematic literature search was conducted in PubMed and Web of Science according to PRISMA statement.
RESULTS
Pooled effect sizes (Hedges' g) from 32 studies were analyzed using random effect models. We found both, rTMS and tDCS to have significant immediate cognition-enhancing effect in AD with rTMS inducing also beneficial long-term effects. We found no evidence for synergistic effect of cognitive training with NIBS.
CONCLUSIONS
In AD a clinical recommendation can be made for NEURO-AD system and for high-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC) as probably effective protocols (B-level of evidence) and for anodal tDCS over the left DLPFC as a possibly effective.
SIGNIFICANCE
According to scientific literature, NIBS may be an effective method for improving cognition in AD and possibly in MCI.
Topics: Humans; Alzheimer Disease; Brain; Cognition; Cognitive Dysfunction; Transcranial Direct Current Stimulation; Transcranial Magnetic Stimulation
PubMed: 36215904
DOI: 10.1016/j.clinph.2022.09.010 -
The Lancet. Healthy Longevity Aug 2021People with dementia die prematurely. Identifying differences in mortality rates between different types of dementia might aid in the development of preventive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
People with dementia die prematurely. Identifying differences in mortality rates between different types of dementia might aid in the development of preventive interventions for the most vulnerable populations. The aim of this study was to compare the difference in mortality rates between individuals without dementia and individuals with various types of dementia.
METHODS
For this systematic review and meta-analysis, we did a systematic search of MEDLINE, PubMed, Embase, and Cochrane Library from inception to July 11, 2020, for cross-sectional or cohort studies that assessed mortality and survival-related outcomes among people with different types of dementia compared with people without dementia. Single-arm studies without comparison groups and autopsy studies or family studies that used a selected sample were excluded. The Newcastle-Ottawa Scale was used by two authors (D-JL and C-SC) independently to measure the methodological quality of included studies, and two authors (F-CY and P-TT) independently extracted data. We assessed differences in all-cause mortality rate and survival time from dementia diagnosis between individuals without dementia, individuals with Alzheimer's disease, and individuals with non-Alzheimer's disease dementias. The secondary outcomes were age at death and survival time from disease onset. Random-effects meta-analyses were done. Effect sizes included hazard ratios (HRs) and mean differences (MDs) with 95% CIs. Potential moderators, including age-associated moderators, were identified through meta-regression and subgroup analyses. This study is registered with PROSPERO, CRD42020198786.
FINDINGS
Our database search identified 11 973 records, and we included 78 eligible studies in our analyses, encompassing 63 125 individuals with dementia and 152 353 controls. Individuals with any type of dementia had a higher mortality rate than individuals without dementia (HR 5·90, 95% CI 3·53 to 9·86), and the HR for all-cause mortality was highest for Lewy body dementia (17·88, 5·87 to 54·46). After diagnosis, the mean survival time for people with Alzheimer's disease was 5·8 years (SD 2·0). Compared with people with Alzheimer's disease, a diagnosis of any non-Alzheimer's disease dementia was associated with a higher risk of all-cause mortality (HR 1·33, 1·21 to 1·46), a shorter survival time from diagnosis (MD -1·12 years, 95% CI -1·52 to -0·72), and a younger age at death (-1·76 years, -2·66 to -0·85). Survival time from disease onset was also shorter in people with non-Alzheimer's dementia, across types, compared with people with Alzheimer's disease, but the subgroup analysis revealed that this difference was only significant for vascular dementia (MD -1·27 years, -1·90 to -0·65) and dementia with Lewy bodies (MD -1·06 years, -1·68 to -0·44). The interactions between age and several survival-related outcomes were significant. 39 (50%) of the 78 included studies were rated as good quality, and large heterogeneity (I>75%) was observed for most of the study outcomes.
INTERPRETATION
Alzheimer's disease is the most common type of dementia and one of the major causes of mortality worldwide. However, the findings from the current study suggest that non-Alzheimer's disease dementias were associated with higher morality rates and shorter life expectancy than Alzheimer's disease. Developing tailored treatment and rehabilitation programmes for different types of dementia is important for mental health providers, patients, and their families.
FUNDING
None.
Topics: Alzheimer Disease; Cross-Sectional Studies; Dementia; Dementia, Vascular; Humans; Lewy Body Disease
PubMed: 36097997
DOI: 10.1016/S2666-7568(21)00140-9 -
Neuropsychology Review Jun 2024Most people with dementia experience neuropsychiatric symptoms (NPS), including anxiety, depression or disinhibition. There is growing interest in the relationship... (Meta-Analysis)
Meta-Analysis Review
Most people with dementia experience neuropsychiatric symptoms (NPS), including anxiety, depression or disinhibition. There is growing interest in the relationship between NPS and cognitive impairment, but data is still limited. This study aimed to investigate the specific associations between NPS and cognition in people with dementia. MEDLINE, EMBASE and PsycINFO were searched for published, peer-reviewed studies of associations between at least one NPS and one cognitive ability in people with dementia. The quality of the studies was assessed with the NIH National Heart, Lung and Blood Institute's quality assessment tools. A meta-analysis was conducted using Robumeta package for R. Ninety studies were included. We found significant associations between NPS, global cognition and cognitive domains, e.g. apathy was associated with global cognitive and memory impairment; dysphoria was associated with worse attention; delusions with executive dysfunction. Increased NPS in people with dementia are associated with worse cognitive performance. There were few studies looking at associations between some neuropsychiatric clusters and cognitive abilities, and there was little research on causal relationships. Our review was limited by the inclusion of studies that reported associations in specific formats, and most included people with a diagnosis of Alzheimer's disease (AD). However, given the large number of studies, this is unlikely to have biased results. More research is needed that includes diverse people with different dementia syndromes. Registration: PROSPERO 2020 CRD42020165565.
Topics: Humans; Dementia; Cognitive Dysfunction; Cognition; Alzheimer Disease
PubMed: 37477839
DOI: 10.1007/s11065-023-09608-0 -
Alzheimer's & Dementia : the Journal of... Nov 2022Hypertension is an important risk factor for Alzheimer's disease (AD) and all-cause dementia. The mechanisms underlying this association are unclear. Hypertension may be... (Review)
Review
Hypertension is an important risk factor for Alzheimer's disease (AD) and all-cause dementia. The mechanisms underlying this association are unclear. Hypertension may be associated with AD neuropathological changes (ADNC), but reports are sparse and inconsistent. This systematic review included 15 autopsy studies (n = 5879) from observational cohorts. Studies were highly heterogeneous regarding populations, follow-up duration, hypertension operationalization, neuropathological methods, and statistical analyses. Hypertension seems associated with higher plaque and tangle burden, but results are inconsistent. Four studies (n = 3993/5879; 68%), reported clear associations between hypertension and ADNC. Another four suggested that antihypertensive medication may protect against ADNC. Larger studies with longer follow-up reported the strongest relationships. Our findings suggest a positive association between hypertension and ADNC, but effects may be modest, and possibly attenuate with higher hypertension age and antihypertensive medication use. Investigating interactions among plaques, tangles, cerebrovascular pathology, and dementia may be key in better understanding hypertension's role in dementia development.
Topics: Humans; Alzheimer Disease; Neurofibrillary Tangles; Autopsy; Antihypertensive Agents; Plaque, Amyloid; Hypertension; Brain
PubMed: 35758526
DOI: 10.1002/alz.12707 -
Ageing Research Reviews Aug 2022Sensitive and specific antemortem biomarkers of neurodegenerative disease and dementia are crucial to the pursuit of effective treatments, required both to reliably... (Review)
Review
Sensitive and specific antemortem biomarkers of neurodegenerative disease and dementia are crucial to the pursuit of effective treatments, required both to reliably identify disease and to track its progression. Atrophy is the structural magnetic resonance imaging (MRI) hallmark of neurodegeneration. However in most cases it likely indicates a relatively advanced stage of disease less susceptible to treatment as some disease processes begin decades prior to clinical onset. Among emerging metrics that characterise brain shape rather than volume, fractal dimension (FD) quantifies shape complexity. FD has been applied in diverse fields of science to measure subtle changes in elaborate structures. We review its application thus far to structural MRI of the brain in neurodegenerative disease and dementia. We identified studies involving subjects who met criteria for mild cognitive impairment, Alzheimer's Disease, Vascular Dementia, Lewy Body Dementia, Frontotemporal Dementia, Amyotrophic Lateral Sclerosis, Parkinson's Disease, Huntington's Disease, Multiple Systems Atrophy, Spinocerebellar Ataxia and Multiple Sclerosis. The early literature suggests that neurodegenerative disease processes are usually associated with a decline in FD of the brain. The literature includes examples of disease-related change in FD occurring independently of atrophy, which if substantiated would represent a valuable advantage over other structural imaging metrics. However, it is likely to be non-specific and to exhibit complex spatial and temporal patterns. A more harmonious methodological approach across a larger number of studies as well as careful attention to technical factors associated with image processing and FD measurement will help to better elucidate the metric's utility.
Topics: Alzheimer Disease; Atrophy; Brain; Fractals; Humans; Magnetic Resonance Imaging; Neurodegenerative Diseases
PubMed: 35643264
DOI: 10.1016/j.arr.2022.101651 -
Dementia and Geriatric Cognitive... 2015Although it is generally accepted that deaths associated with pneumonia are more common in patients with dementia, no comprehensive reviews on the subject have... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Although it is generally accepted that deaths associated with pneumonia are more common in patients with dementia, no comprehensive reviews on the subject have previously been published.
SUMMARY
Relevant studies were identified through a literature search of the PubMed, EMBASE, Scopus, and ISI Web of Science databases for publications up to August 2013. Studies were included if (1) a group of adult subjects with dementia and a (comparison) group composed of subjects without dementia were included, (2) the cause(s) of death was/were reported, and (3) pneumonia was identified as one of the possible causes of death. The occurrence of death due to pneumonia associated with dementia was expressed as an odds ratio (OR) with 95% confidence interval (CI). Thirteen studies were included. The odds of death resulting from pneumonia were significantly increased for persons with any form of dementia compared with those without dementia (OR = 2.22, 95% CI 1.44-3.42, p < 0.001). In a subgroup analysis, using the results from 8 studies that restricted inclusion to persons with Alzheimer's disease, the odds of death resulting from pneumonia were also significantly higher (OR = 1.70, 95% CI 1.12-2.58, p = 0.013). Key Messages: The odds of pneumonia-associated mortality were increased more than 2-fold for patients with dementia.
Topics: Alzheimer Disease; Cause of Death; Humans; Pneumonia; Risk Factors
PubMed: 25342272
DOI: 10.1159/000367783 -
The Cochrane Database of Systematic... Apr 2009Following the discovery of an endogenous cannabinoid system and the identification of specific cannabinoid receptors in the central nervous system, much work has been... (Review)
Review
BACKGROUND
Following the discovery of an endogenous cannabinoid system and the identification of specific cannabinoid receptors in the central nervous system, much work has been done to investigate the main effects of these compounds. There is increasing evidence that the cannabinoid system may regulate neurodegenerative processes such as excessive glutamate production, oxidative stress and neuroinflammation. Neurodegeneration is a feature common to the various types of dementia and this has led to interest in whether cannabinoids may be clinically useful in the treatment of people with dementia. Recent studies have also shown that cannabinoids may have more specific effects in interrupting the pathological process in Alzheimer's disease.
OBJECTIVES
To determine from available research whether cannabinoids are clinically effective in the treatment of dementia.
SEARCH STRATEGY
The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS were searched on 11 April 2008 using the terms: cannabis or cannabinoid* or endocannabinoid* or cannabidiol or THC or CBD or dronabinol or delta-9-tetrahydrocannabinol or marijuana or marihuana or hashish. The CDCIG Specialized Register contains records from all major health care databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS) as well as from many clinical trials registries and grey literature sources.
SELECTION CRITERIA
All double-blind and single (rater)-blind randomized placebo controlled trials assessing the efficacy of cannabinoids at any dose in the treatment of people with dementia.
DATA COLLECTION AND ANALYSIS
Two reviewers independently examined the retrieved studies for inclusion according to the selection criteria. They then independently assessed the methodological quality of selected trials and extracted data where possible.
MAIN RESULTS
Only one study met the inclusion criteria. The data in the study report were presented in such a way that they could not be extracted for further analysis and there was insufficient quantitative data to validate the results.
AUTHORS' CONCLUSIONS
This review finds no evidence that cannabinoids are effective in the improvement of disturbed behaviour in dementia or in the treatment of other symptoms of dementia. More randomized double-blind placebo controlled trials are needed to determine whether cannabinoids are clinically effective in the treatment of dementia.
Topics: Alzheimer Disease; Cannabinoids; Dementia; Dronabinol; Humans; Psychotropic Drugs
PubMed: 19370677
DOI: 10.1002/14651858.CD007204.pub2 -
The Cochrane Database of Systematic... 2003Dementia is a common mental health problem affecting 5% of those over 65. Various pathological processes are linked to memory impairment in dementia, particularly those... (Review)
Review
BACKGROUND
Dementia is a common mental health problem affecting 5% of those over 65. Various pathological processes are linked to memory impairment in dementia, particularly those affecting the cholinergic neurotransmitter system. Acetyl-l-carnitine (ALC) is derived from carnitine and is described as having several properties which may be beneficial in dementia. This includes activity at cholinergic neurons, membrane stabilization and enhancing mitochondrial function. Work on the effects of ALC has been ongoing since the 1980s yet the efficacy of ALC in cognitive decline remains unclear. Early studies suggested a beneficial effect of ALC on cognition and behaviour in aging subjects. However, later, larger studies have not supported these findings. Some of the difficulties lie in the early and later studies differing widely in methodology and assessment tools used, and are therefore difficult to compare. ALC is not currently in routine clinical use.
OBJECTIVES
The objective of this review is to establish whether Acetyl-l-carnitine is clinically effective in the treatment of people with dementia.
SEARCH STRATEGY
The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 8 January 2003 using the terms acetyl-l-carnitine, l-carnitine acetyl ester, acetylcarnitine.
SELECTION CRITERIA
All double-blind, randomized, trials involving people with dementia in which treatment with ALC was compared with a placebo group
DATA COLLECTION AND ANALYSIS
Data were extracted by a reviewer (SH) and entered into Revman 4.1 software. Where possible intention-to-treat data were used, but most of the analyses were of completers (people who completed the study).
MAIN RESULTS
There are 11 included trials, all of which had restricted the participants to people with Alzheimer's disease. All trials assessed the cognitive effects of ALC and in addition six considered severity of dementia, six considered functional ability and six considered clinical global impression. There were statistically significant treatment effects in favour of ALC at 12 and 24 weeks for the numbers showing improvement as determined by Clinical Global Impression, [OR 2.33, 95% CI 1.25 to 4.35, P<0.01] and [OR 3.91, 95% CI 1.32 to 11.54, P=0.01] but not as determined by the CIGIC at 52 weeks. There was no evidence of benefit for ALC in the areas of cognition, severity of dementia, functional ability or Clinical Global Impression as a continuous measure. Various adverse events were reported, but from the meta-analyses there were no statistically significant differences between treated and placebo groups.
REVIEWER'S CONCLUSIONS
There is evidence for benefit of ALC on clinical global impression, but there was no evidence using objective assessments in any other area of outcome. Given the large number of comparisons made, the statistically significant result may be due to chance. At present there is no evidence to recommend its routine use in clinical practice. Although the intention of the review was to access ALC for the treatment of all dementias, the included trials had confined themselves to participants with Alzheimer's disease. Individual patient data may add to the findings, as would trials including other types of dementia and other outcomes (e.g. mood and caregiver quality of life). However, the evidence does not suggest that ALC is likely to prove an important therapeutic agent. More work on the pharmacokinetics of ALC in humans is also required.
Topics: Acetylcarnitine; Aged; Alzheimer Disease; Dementia; Humans; Nootropic Agents; Randomized Controlled Trials as Topic
PubMed: 12804452
DOI: 10.1002/14651858.CD003158 -
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 -
International Journal of Geriatric... Apr 2023Alzheimer's disease and related dementias (ADRD) are common among nursing home residents. Yet, conclusive evidence regarding best care practices among this population is... (Review)
Review
BACKGROUND
Alzheimer's disease and related dementias (ADRD) are common among nursing home residents. Yet, conclusive evidence regarding best care practices among this population is lacking. Objectives of this systematic review were to explore features of dementia specialty care units (DSCUs) in long-term care settings and examine benefits for residents, staff, families, and facilities.
METHODS
PubMed, CINAHL, and PsychINFO were searched to identify articles involving DSCUs in long-term care settings published in English with full text available between 01.01.2008 and 06.03.2022. Articles containing empirical data about ADRD special care in long-term care settings were included in the review. Articles focused on clinic-based or out-patient dementia care programs (e.g., adult day care) were excluded. Articles were categorized based on geography (U.S. vs. international) and study design: interventions, descriptive studies, or comparison studies (traditional vs. specialty ADRD care).
RESULTS
Our review included 38 U.S. articles and 54 articles from 15 international countries. In the U.S., 12 intervention, 13 descriptive, and 13 comparison studies met the inclusion criteria. Articles from international countries included 22 intervention, 20 descriptive, and 12 comparison studies. Results were mixed in terms of the efficacy of DSCUs. Promising DSCU features include small-scale settings, dementia-educated staff, and multidisciplinary approaches to care.
CONCLUSION
Overall, our review did not find conclusive evidence regarding the benefits of DSCUs in long-term care settings. No rigorous study designs were found examining 'special' features of DSCUs and associations with outcomes among residents, family, staff, and the facility. Randomized clinical trials are needed to disentangle the 'special' features of DSCUs.
Topics: Humans; Long-Term Care; Dementia; Alzheimer Disease; Ambulatory Care Facilities
PubMed: 36971436
DOI: 10.1002/gps.5907