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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 -
Ageing Research Reviews Sep 2023Dementia is prevalent in aged populations and is associated with disability and distress for those affected. Therapeutic benefits of drugs targeting dementia are small.... (Review)
Review
BACKGROUND
Dementia is prevalent in aged populations and is associated with disability and distress for those affected. Therapeutic benefits of drugs targeting dementia are small. Impaired nutrient sensing pathways have been implicated in the pathogenesis of dementia and may offer a novel treatment target.
AIMS
This systematic review collated evidence for novel therapeutic compounds that modify nutrient sensing pathways, particularly the sirtuin pathway, in preventing cognitive decline or improving cognition in normal ageing, mild cognitive impairment (MCI), and dementia.
METHODS
PubMed, Embase and Web of Science databases were searched using key search terms. Articles were screened using Covidence systematic review software. The risk of bias was assessed using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE)'s risk of bias tool for animal studies and Cochrane Risk of Bias tool v 2.0 for human studies.
RESULTS
Out of 3841 articles, 68 were included describing 38 different novel therapeutic compounds that modulate the nutrient sensing pathway via the sirtuin pathway. In animal models (58 studies), all investigated novel therapeutic compounds showed cognitive benefits. Ten studies were human intervention trials targeting normal ageing (1 study) and dementia populations (9 studies). Direct sirtuin (silent mating type information regulation 2 homolog) 1 (SIRT1) activators Resveratrol and Nicotinamide derivatives improved cognitive outcomes among human subjects with normal cognition and MCI.
CONCLUSION
Animal studies support that modulation of the sirtuin pathway has the potential to improve cognitive outcomes. Overall, there is a clear lack of translation from animal models to human populations.
Topics: Humans; Aged; Alzheimer Disease; Sirtuins; Cognitive Dysfunction; Cognition; Nutrients
PubMed: 37549873
DOI: 10.1016/j.arr.2023.102029 -
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 -
Journal of Alzheimer's Disease : JAD 2023Perfusion imaging has the potential to identify neurodegenerative disorders in a preclinical stage. However, to correctly interpret perfusion-derived parameters, the...
BACKGROUND
Perfusion imaging has the potential to identify neurodegenerative disorders in a preclinical stage. However, to correctly interpret perfusion-derived parameters, the impact of perfusion modifiers should be evaluated.
OBJECTIVE
In this systematic review, the impact of acute and chronic intake of four acetylcholinesterase inhibitors (AChEIs) on cerebral perfusion in adults was investigated: physostigmine, donepezil, galantamine, and rivastigmine.
RESULTS
Chronic AChEI treatment results in an increase of cerebral perfusion in treatment-responsive patients with Alzheimer's disease, dementia with Lewy bodies, and Parkinson's disease dementia in the frontal, parietal, temporal, and occipital lobes, as well as the cingulate gyrus. These effects appear to be temporary, dose-related, and consistent across populations and different AChEI types. On the contrary, further perfusion decline was reported in patients not receiving AChEIs or not responding to the treatment.
CONCLUSION
AChEIs appear to be a potential perfusion modifier in neurodegenerative patients. More research focused on quantitative perfusion in both patients with and without a cholinergic deficit is needed to draw conclusions on whether AChEI intake should be considered when analyzing perfusion data.
Topics: Humans; Cholinesterase Inhibitors; Acetylcholinesterase; Dementia; Piperidines; Indans; Phenylcarbamates; Parkinson Disease; Rivastigmine; Alzheimer Disease; Galantamine; Cognition; Perfusion; Cerebrovascular Circulation
PubMed: 37182871
DOI: 10.3233/JAD-221125 -
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 -
Journal of the American Association of... Mar 2021Pain continues to be underrecognized and undertreated in Alzheimer's disease (AD) while existing guidance about pain assessment and management in dementia is not...
BACKGROUND
Pain continues to be underrecognized and undertreated in Alzheimer's disease (AD) while existing guidance about pain assessment and management in dementia is not widespread. Brain regions involved in pain processing and modulation are damaged during AD, and the pain experience in AD is not well understood. Experimental pain studies using psychophysics can further our understanding of the pain experience in AD, which may lead to improved assessment and management of pain in people living with AD.
OBJECTIVE
A systematic review was conducted to explicate the current understanding of experimentally evoked pain in AD from primary research using psychophysical methods.
DATA SOURCES
Peer-reviewed publications were found via PubMed, CINAHL, and PsycINFO. A total of 18 primary research, peer-reviewed full articles that met inclusion criteria were included, representing 929 total participants.
CONCLUSIONS
Experimentally evoked pain in people with AD demonstrates that despite cognitive impairment and a reduced ability to effectively communicate, individuals with AD experience pain similar to or more unpleasant than cognitively intact older adults. This may mean amplified pain unpleasantness in people with AD.
IMPLICATIONS FOR PRACTICE
Our current best practices need to be widely disseminated and put into clinical practice. Self-report of pain continues to be the gold standard, but it is ineffective for noncommunicative patients and those unable to understand pain scales or instructions because of memory/cognitive impairment. Instead, pain treatment should be ethically initiated based on patient reports and behaviors, caregiver/surrogate reports, review of the medical record for painful conditions, analgesic trials, and regular reassessments.
Topics: Aged; Alzheimer Disease; Brain; Cognitive Dysfunction; Humans; Pain; Pain Measurement
PubMed: 33731557
DOI: 10.1097/JXX.0000000000000580 -
The Cochrane Database of Systematic... Jul 2018Weight loss, malnutrition and dehydration are common problems for people with dementia. Environmental modifications such as, change of routine, context or ambience at... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Weight loss, malnutrition and dehydration are common problems for people with dementia. Environmental modifications such as, change of routine, context or ambience at mealtimes, or behavioural modifications, such as education or training of people with dementia or caregivers, may be considered to try to improve food and fluid intake and nutritional status of people with dementia.
OBJECTIVES
Primary: To assess the effects of environmental or behavioural modifications on food and fluid intake and nutritional status in people with dementia. Secondary: To assess the effects of environmental or behavioural modifications in connection with nutrition on mealtime behaviour, cognitive and functional outcomes and quality of life, in specific settings (i.e. home care, residential care and nursing home care) for different stages of dementia. To assess the adverse consequences or effects of the included interventions.
SEARCH METHODS
We searched the Specialized Register of Cochrane Dementia and Cognitive Improvement (ALOIS), MEDLINE, Eembase, PsycINFO, CINAHL, ClinicalTrials.gov and the World Health Organization (WHO) portal/ICTRP on 17 January 2018. We scanned reference lists of other reviews and of included articles.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) investigating interventions designed to modify the mealtime environment of people with dementia, to modify the mealtime behaviour of people with dementia or their caregivers, or both, with the intention of improving food and fluid intake. We included people with any common dementia subtype.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, extracted data and assessed the risk of bias of included trials. We assessed the quality of evidence for each outcome using the GRADE approach.
MAIN RESULTS
We included nine studies, investigating 1502 people. Three studies explicitly investigated participants with Alzheimer's disease; six did not specify the type of dementia. Five studies provided clear measures to identify the severity of dementia at baseline, and overall very mild to severe stages were covered. The interventions and outcome measures were diverse. The overall quality of evidence was mainly low to very low.One study implemented environmental as well as behavioural modifications by providing additional food items between meals and personal encouragement to consume them. The control group received no intervention. Differences between groups were very small and the quality of the evidence from this study was very low, so we are very uncertain of any effect of this intervention.The remaining eight studies implemented behavioural modifications.Three studies provided nutritional education and nutrition promotion programmes. Control groups did not receive these programmes. After 12 months, the intervention group showed slightly higher protein intake per day (mean difference (MD) 0.11 g/kg, 95% confidence interval (CI) -0.01 to 0.23; n = 78, 1 study; low-quality evidence), but there was no clear evidence of a difference in nutritional status assessed with body mass index (BMI) (MD -0.26 kg/m² favouring control, 95% CI -0.70 to 0.19; n = 734, 2 studies; moderate-quality evidence), body weight (MD -1.60 kg favouring control, 95% CI -3.47 to 0.27; n = 656, 1 study; moderate-quality evidence), or score on Mini Nutritional Assessment (MNA) (MD -0.10 favouring control, 95% CI -0.67 to 0.47; n = 656, 1 study; low-quality evidence). After six months, the intervention group in one study had slightly lower BMI (MD -1.79 kg/m² favouring control, 95% CI -1.28 to -2.30; n = 52, 1 study; moderate-quality evidence) and body weight (MD -8.11 kg favouring control, 95% CI -2.06 to -12.56; n = 52, 1 study; moderate-quality evidence). This type of intervention may have a small positive effect on food intake, but little or no effect, or a negative effect, on nutritional status.Two studies compared self-feeding skills training programmes. In one study, the control group received no training and in the other study the control group received a different self-feeding skills training programme. For both comparisons the quality of the evidence was very low and we are very uncertain whether these interventions have any effect.One study investigated general training of nurses to impart knowledge on how to feed people with dementia and improve attitudes towards people with dementia. Again, the quality of the evidence was very low so that we cannot be certain of any effect.Two studies investigated vocal or tactile positive feedback provided by caregivers while feeding participants. After three weeks, the intervention group showed an increase in calories consumed per meal (MD 200 kcal, 95% CI 119.81 to 280.19; n = 42, 1 study; low-quality evidence) and protein consumed per meal (MD 15g, 95% CI 7.74 to 22.26; n = 42, 1 study; low-quality evidence). This intervention may increase the intake of food and liquids slightly; nutritional status was not assessed.
AUTHORS' CONCLUSIONS
Due to the quantity and quality of the evidence currently available, we cannot identify any specific environmental or behavioural modifications for improving food and fluid intake in people with dementia.
Topics: Alzheimer Disease; Dementia; Dietary Proteins; Energy Intake; Humans; Meals; Nutrition Disorders; Nutritional Status; Patient Education as Topic; Randomized Controlled Trials as Topic; Time Factors
PubMed: 30021248
DOI: 10.1002/14651858.CD011542.pub2 -
Dementia and Geriatric Cognitive... 2018Cognitive therapy is a well-established intervention for treating elderly suffering from dementia. In particular, reality orientation and skills training seem to be... (Comparative Study)
Comparative Study Review
BACKGROUND
Cognitive therapy is a well-established intervention for treating elderly suffering from dementia. In particular, reality orientation and skills training seem to be effective interventions for reversing cognitive impairment among elderly, although findings are inconclusive. Therefore, a systematic update of the existing evidence of cognitive therapy for people suffering from dementia is needed.
AIM
To review existing scientific evidence regarding the efficacy of cognitive therapies for elderly suffering from dementia.
METHODS
Studies were retrieved from several bibliographic databases (January 2009 to December 2017) with prespecified selection criteria, data extraction, and methodological quality assessment.
RESULTS
In total, 10 reality orientation, 25 skills training, and 12 mixed trials were identified as meeting the inclusion criteria and were systematically reviewed. Results from reality orientation trials showed minor effects for cognitive assessments, while skills training trials and mixed trials showed contradicting effects on cognition. Effects on other outcomes (e.g., daily functioning, depression, language) were limited or not found.
CONCLUSIONS
Skills training trials and mixed trials seem to affect cognitive impairment in a positive way, although the results are inconclusive. Comparison between studies was difficult due to differences in form of intervention. Because findings are inconclusive, more structuralized and comparable randomized controlled trials are needed.
Topics: Adaptation, Psychological; Aged; Alzheimer Disease; Cognition; Cognition Disorders; Cognitive Behavioral Therapy; Depressive Disorder; Female; Humans; Language; Male; Randomized Controlled Trials as Topic; Reality Testing; Treatment Outcome
PubMed: 30092585
DOI: 10.1159/000490851 -
PloS One 2023Bullous pemphigoid (BP) is a rare autoimmune skin condition that causes large fluid-filled blisters on the skin, especially in older adults. BP has been linked to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bullous pemphigoid (BP) is a rare autoimmune skin condition that causes large fluid-filled blisters on the skin, especially in older adults. BP has been linked to various diseases and medications, but its association with cognitive outcomes is unclear.
METHODS
We conducted a systematic review and meta-analysis of studies investigating the association between BP and cognitive outcomes, such as all-cause dementia, Alzheimer's disease, and vascular dementia in middle-aged and older adults. We searched PubMed, Embase, and Web of Science databases for relevant studies published up to March 2023. We included studies that reported odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between BP and cognitive outcomes. We pooled the ORs, or HRs using random-effects models and performed subgroup and sensitivity analyses to explore potential sources of heterogeneity.
RESULTS
The study selection process identified 13 studies for inclusion in the analysis, 11 studied arms of which used a case-control design and 7 studied arms of which used a cohort design. The studies were conducted primarily in Europe, with a few from Asia and the United States. The meta-analysis found that BP was associated with higher odds of all-cause dementia in middle-aged and older participants in both cohort studies(HR = 1.41,95% CI: 1.20-1.66, P = 0.000) and case-control (OR = 4.25, 95% CI, 2.73-6.61; P = 0.000). The study found no significant publication bias in the included studies. The meta-regression analyses identified some subgroups associated with significantly reported odds ratios in case-control association analysis, including Europe, BP diagnosed based on clinical, histology, immunofluorescence, and both adjustment status of NO and YES.
CONCLUSIONS
Our meta-analysis suggests that BP is associated with an increased risk of all-cause dementia in middle-aged and older adults. Further studies are needed to elucidate the underlying mechanisms and causal relationship between BP and cognitive outcomes.
Topics: Middle Aged; Humans; Aged; Pemphigoid, Bullous; Alzheimer Disease; Cohort Studies; Europe; Autoimmune Diseases; Cognition; Cognitive Dysfunction
PubMed: 38033098
DOI: 10.1371/journal.pone.0295135 -
European Journal of Clinical... Jul 2021People with dementia may have indications for aspirin prescription and clinicians are asked to balance the potential risks against benefits. This review examines the...
PURPOSE
People with dementia may have indications for aspirin prescription and clinicians are asked to balance the potential risks against benefits. This review examines the evidence for the risk and benefit of long-term aspirin use in people with dementia aged over 65 years, including randomised controlled trials and observational studies.
METHODS
We searched three databases for research published between 2007 and 2020. Each eligible article was assessed for risk of bias, and confidence in findings was rated using Grading of Recommendations Assessment, Development and Evaluation (GRADE).
RESULTS
Four papers met inclusion criteria: one randomised controlled trial, two cohort studies, and one with pooled data. All looked only at dementia of Alzheimer's type, and none addressed myocardial or cerebral infarction as outcomes. Dementia progression was reported by two studies, with conflicting results. The trial found no significant effect of aspirin on mortality (odds ratio aspirin vs. no aspirin 1.07, 95% confidence interval 0.58-1.97) but found more events of severe bleeding with aspirin (OR aspirin vs. no aspirin 6.9, 1.5-31.2). An excess in intracranial haemorrhage in the aspirin group was judged plausible based on two non-randomised studies.
CONCLUSIONS
The review findings are limited because studies include only people with Alzheimer's-type dementia and lack confirmatory studies, although an increased risk of bleeding events is recognised. Further research that addresses the benefits and risks of aspirin in more representative groups of people with dementia is needed to guide prescribing decisions.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cardiovascular Diseases; Disease Progression; Hemorrhage; Humans; Observational Studies as Topic; Randomized Controlled Trials as Topic
PubMed: 33483830
DOI: 10.1007/s00228-021-03089-x