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Ageing Research Reviews Sep 2021Alterations in olfactory functions are proposed to be early biomarkers for neurodegeneration. Many neurodegenerative diseases are age-related, including two of the most... (Review)
Review
Alterations in olfactory functions are proposed to be early biomarkers for neurodegeneration. Many neurodegenerative diseases are age-related, including two of the most common, Parkinson's disease (PD) and Alzheimer's disease (AD). The establishment of biomarkers that promote early risk identification is critical for the implementation of early treatment to postpone or avert pathological development. Olfactory dysfunction (OD) is seen in 90% of early-stage PD patients and 85% of patients with early-stage AD, which makes it an attractive biomarker for early diagnosis of these diseases. Here, we systematically review widely applied smelling tests available for humans as well as olfaction assessments performed in some animal models and the relationships between OD and normal aging, PD, AD, and other conditions. The utility of OD as a biomarker for neurodegenerative disease diagnosis and future research directions are also discussed.
Topics: Aging; Alzheimer Disease; Animals; Humans; Neurodegenerative Diseases; Olfaction Disorders; Parkinson Disease; Smell
PubMed: 34325072
DOI: 10.1016/j.arr.2021.101416 -
Journal of the Neurological Sciences Mar 2022Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most prevalent neurodegenerative diseases, both without prevention or cure. The Mediterranean diet... (Review)
Review
Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most prevalent neurodegenerative diseases, both without prevention or cure. The Mediterranean diet (MeDi) may be neuroprotective by modulating gut microbiota. We aimed to assess the effects of adherence to MeDi on the gut microbiota in relation to AD or PD risk. A search from inception to November 2020 was conducted in PubMed, CINAHL, EMBASE, Web of Science, Global Health, Biological Abstracts, and Grey Literature Report databases. Two searches were conducted: 1) (MeDi or Microbiota) and (PD or AD) and 2) MeDi and microbiota. Inclusion criteria for papers were specified prior to review. Of 4672 studies identified, 64 were eligible for inclusion. These studies were divided into five groups: MeDi and AD risk (n = 4), MeDi and PD risk (n = 2), MeDi and microbial composition or metabolomics (n = 21), AD and microbial composition or metabolomics (n = 7), and PD and microbial composition or metabolomics (n = 30). Adherence to the MeDi was associated with a lower risk of AD and PD development. Eight genera and two species of bacteria had an inverse relationship with MeDi and AD, and one family, eight genera and three species of bacteria had an inverse relationship with MeDi and PD. More studies are needed to investigate if MeDi, gut microbiota, and neurodegeneration are causally related.
Topics: Alzheimer Disease; Diet, Mediterranean; Gastrointestinal Microbiome; Humans; Parkinson Disease; Risk
PubMed: 35144237
DOI: 10.1016/j.jns.2022.120166 -
Journal of Neurology Feb 2023During the last decade, physical activity (PA) (or "exercise") has been identified as one of the main modifiable factors that influence the development of Alzheimer's... (Review)
Review
INTRODUCTION
During the last decade, physical activity (PA) (or "exercise") has been identified as one of the main modifiable factors that influence the development of Alzheimer's disease (AD) pathophysiology. We performed an umbrella review to summarize the evidence on the association between PA/exercise and the risk of developing AD risk, and the effect of exercise interventions on the progression of AD.
METHODS
A systematic search was performed in PubMed, SportDiscus, Cochrane Library and Web of Science (March 2022) to identify meta-analyses assessing the association between PA and the incidence of AD, and assessing the effect of exercise interventions on patients with AD.
RESULTS
Twenty-one studies were included. The results with strongest evidence revealed the positive effects of PA on AD risk. Specifically, meeting the WHO recommendations for PA was associated with a lower risk of AD. They also revealed positive effects of exercise on cognitive function, physical performance, and functional independence.
CONCLUSIONS
There is strong evidence of a protective effect of regular PA against AD risk; however, the dose-response association remains unclear. Physical exercise seems to improve several dimensions in patients with AD, although research is warranted to elucidate the exercise characteristics that promote the greatest benefits.
Topics: Humans; Alzheimer Disease; Cognition; Exercise; Exercise Therapy; Meta-Analysis as Topic
PubMed: 36342524
DOI: 10.1007/s00415-022-11454-8 -
Neurobiology of Aging Feb 2020Repetitive transcranial magnetic stimulation (rTMS), a noninvasive brain stimulation technique, has emerged as a promising treatment for mild cognitive impairment (MCI)... (Meta-Analysis)
Meta-Analysis
Repetitive transcranial magnetic stimulation (rTMS), a noninvasive brain stimulation technique, has emerged as a promising treatment for mild cognitive impairment (MCI) and Alzheimer's disease (AD). Currently, however, the effectiveness of this therapy is unclear because of the low statistical power and heterogeneity of previous trials. The purpose of the meta-analysis was to systematically characterize the effectiveness of various combinations of rTMS parameters on different cognitive domains in patients with MCI and AD. Thirteen studies comprising 293 patients with MCI or AD were included in this analysis. Random-effects analysis revealed an overall medium-to-large effect size (0.77) favoring active rTMS over sham rTMS in the improvement of cognitive functions. Subgroup analyses revealed that (1) high-frequency rTMS over the left dorsolateral prefrontal cortex and low-frequency rTMS at the right dorsolateral prefrontal cortex significantly improved memory functions; (2) high-frequency rTMS targeting the right inferior frontal gyrus significantly enhanced executive performance; and (3) the effects of 5-30 consecutive rTMS sessions could last for 4-12 weeks. Potential mechanisms of rTMS effects on cognitive functions are discussed.
Topics: Alzheimer Disease; Cognition; Cognitive Dysfunction; Humans; Memory; Prefrontal Cortex; Transcranial Magnetic Stimulation
PubMed: 31783330
DOI: 10.1016/j.neurobiolaging.2019.08.020 -
Molecular Neurodegeneration Mar 2022Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive cognitive impairment and neurodegeneration. Extensive clinical and genomic... (Review)
Review
Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive cognitive impairment and neurodegeneration. Extensive clinical and genomic studies have revealed biomarkers, risk factors, pathways, and targets of AD in the past decade. However, the exact molecular basis of AD development and progression remains elusive. The emerging single-cell sequencing technology can potentially provide cell-level insights into the disease. Here we systematically review the state-of-the-art bioinformatics approaches to analyze single-cell sequencing data and their applications to AD in 14 major directions, including 1) quality control and normalization, 2) dimension reduction and feature extraction, 3) cell clustering analysis, 4) cell type inference and annotation, 5) differential expression, 6) trajectory inference, 7) copy number variation analysis, 8) integration of single-cell multi-omics, 9) epigenomic analysis, 10) gene network inference, 11) prioritization of cell subpopulations, 12) integrative analysis of human and mouse sc-RNA-seq data, 13) spatial transcriptomics, and 14) comparison of single cell AD mouse model studies and single cell human AD studies. We also address challenges in using human postmortem and mouse tissues and outline future developments in single cell sequencing data analysis. Importantly, we have implemented our recommended workflow for each major analytic direction and applied them to a large single nucleus RNA-sequencing (snRNA-seq) dataset in AD. Key analytic results are reported while the scripts and the data are shared with the research community through GitHub. In summary, this comprehensive review provides insights into various approaches to analyze single cell sequencing data and offers specific guidelines for study design and a variety of analytic directions. The review and the accompanied software tools will serve as a valuable resource for studying cellular and molecular mechanisms of AD, other diseases, or biological systems at the single cell level.
Topics: Alzheimer Disease; Animals; Computational Biology; DNA Copy Number Variations; Data Analysis; Mice; Single-Cell Analysis
PubMed: 35236372
DOI: 10.1186/s13024-022-00517-z -
Journal of Alzheimer's Disease : JAD 2015Many studies reported that physiotherapy interventions are available to treat Alzheimer's disease (AD), but the efficacy remains uncertain. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many studies reported that physiotherapy interventions are available to treat Alzheimer's disease (AD), but the efficacy remains uncertain.
OBJECTIVE
To evaluate the effectiveness of physiotherapy intervention on AD.
METHODS
The data sources were searched from literature databases, journals, and reference lists from 1 January 1990 to the end of 1 April 2014. Randomized and non-randomized controlled trials with physiotherapy intervention were included in our meta-analysis. Jadad score and Newcastle-Ottawa scale were used to assess the quality of included trials. Outcome measures were cognition function, physical function, activity of daily life (ADL) and neuropsychiatric inventory (NPI).
RESULTS
23 trials met the inclusion standard finally. Significant changes were seen in cognitive function: Mini-Mental State Examination score (weighted mean difference (WMD): 1.84, 95% confidence interval (CI): [0.76, to, 2.93], p < 0.0001), and verbal fluency (standard mean difference (SMD): 0.34, 95% CI: [0.01 to 0.66], p = 0.04). Other outcomes are also significant, they were timed up and go test (SMD: 0.56, 95% CI: [0.30 to 0.83], p < 0.0001), berg functional balance scale (SMD: 1.11, 95% CI: [0.37 to 1.84], p = 0.003), 6-min walk distance test (SMD: 141.45, 95% CI: [11.72 to 271.18], p = 0.03), ADL (SMD: 0.78, 95% CI: [0.33 to 1.23], p = 0.0007) and NPI (SMD: -0.69, 95% CI: [-1.31 to -0.07], p = 0.03).
CONCLUSION
The available data indicate that physiotherapy intervention may have benefits in AD. However, current data are not definitive; more carefully designed and conducted observational studies are needed to definitively establish that whether physiotherapy intervention can effectively alleviate symptoms of AD.
Topics: Activities of Daily Living; Alzheimer Disease; Cognition; Humans; Motor Activity; Physical Therapy Modalities; Quality of Life
PubMed: 25201787
DOI: 10.3233/JAD-141377 -
The American Journal of Psychiatry Apr 2017Previous meta-analyses indicate that computerized cognitive training (CCT) is a safe and efficacious intervention for cognition in older adults. However, efficacy varies... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Previous meta-analyses indicate that computerized cognitive training (CCT) is a safe and efficacious intervention for cognition in older adults. However, efficacy varies across populations and cognitive domains, and little is known about the efficacy of CCT in people with mild cognitive impairment or dementia.
METHOD
The authors searched Medline, Embase, PsychINFO, CINAHL, and CENTRAL through July 1, 2016, for randomized controlled trials of CCT in older adults with mild cognitive impairment or dementia. Overall cognition, individual cognitive domains, psychosocial function, and activities of daily living were pooled separately for mild cognitive impairment and dementia trials.
RESULTS
The overall effect on cognition in mild cognitive impairment across 17 trials was moderate (Hedges' g=0.35, 95% CI=0.20-0.51). There was no evidence of publication bias or difference between active- and passive-controlled trials. Small to moderate effects were found for global cognition, attention, working memory, learning, and memory, with the exception of nonverbal memory, and for psychosocial functioning, including depressive symptoms. In dementia, statistically significant effects were found on overall cognition (k=11, g=0.26, 95% CI=0.01-0.52) and visuospatial skills, but these were driven by three trials of virtual reality or Nintendo Wii.
CONCLUSIONS
CCT is efficacious on global cognition, select cognitive domains, and psychosocial functioning in people with mild cognitive impairment. This intervention therefore warrants longer-term and larger-scale trials to examine effects on conversion to dementia. Conversely, evidence for efficacy in people with dementia is weak and limited to trials of immersive technologies.
Topics: Aged; Alzheimer Disease; Cognitive Dysfunction; Computer-Assisted Instruction; Humans; Middle Aged; Neuropsychological Tests; Treatment Outcome
PubMed: 27838936
DOI: 10.1176/appi.ajp.2016.16030360 -
International Journal of Molecular... Mar 2021Alzheimer's disease (AD) is a complex and severe neurodegenerative disease that still lacks effective methods of diagnosis. The current diagnostic methods of AD rely on...
BACKGROUND
Alzheimer's disease (AD) is a complex and severe neurodegenerative disease that still lacks effective methods of diagnosis. The current diagnostic methods of AD rely on cognitive tests, imaging techniques and cerebrospinal fluid (CSF) levels of amyloid-β1-42 (Aβ42), total tau protein and hyperphosphorylated tau (p-tau). However, the available methods are expensive and relatively invasive. Artificial intelligence techniques like machine learning tools have being increasingly used in precision diagnosis.
METHODS
We conducted a meta-analysis to investigate the machine learning and novel biomarkers for the diagnosis of AD.
METHODS
We searched PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews for reviews and trials that investigated the machine learning and novel biomarkers in diagnosis of AD.
RESULTS
In additional to Aβ and tau-related biomarkers, biomarkers according to other mechanisms of AD pathology have been investigated. Neuronal injury biomarker includes neurofiliament light (NFL). Biomarkers about synaptic dysfunction and/or loss includes neurogranin, BACE1, synaptotagmin, SNAP-25, GAP-43, synaptophysin. Biomarkers about neuroinflammation includes sTREM2, and YKL-40. Besides, d-glutamate is one of coagonists at the NMDARs. Several machine learning algorithms including support vector machine, logistic regression, random forest, and naïve Bayes) to build an optimal predictive model to distinguish patients with AD from healthy controls.
CONCLUSIONS
Our results revealed machine learning with novel biomarkers and multiple variables may increase the sensitivity and specificity in diagnosis of AD. Rapid and cost-effective HPLC for biomarkers and machine learning algorithms may assist physicians in diagnosing AD in outpatient clinics.
Topics: Aged; Alzheimer Disease; Biomarkers; Chromatography, High Pressure Liquid; Diagnosis, Computer-Assisted; Female; Humans; Machine Learning; Middle Aged
PubMed: 33803217
DOI: 10.3390/ijms22052761 -
Ageing Research Reviews Dec 2021Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in ageing, affecting around 46 million people worldwide but few treatments are currently... (Review)
Review
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in ageing, affecting around 46 million people worldwide but few treatments are currently available. The etiology of AD is still puzzling, and new drugs development and clinical trials have high failure rates. Urgent outline of an integral (multi-target) and effective treatment of AD is needed. Accumulation of amyloid-β (Aβ) peptides is considered one of the fundamental neuropathological pillars of the disease, and its dyshomeostasis has shown a crucial role in AD onset. Therefore, many amyloid-targeted therapies have been investigated. Here, we will systematically review recent (from 2014) investigational, follow-up and review studies focused on anti-amyloid strategies to summarize and analyze their current clinical potential. Combination of anti-Aβ therapies with new developing early detection biomarkers and other therapeutic agents acting on early functional AD changes will be highlighted in this review. Near-term approval seems likely for several drugs acting against Aβ, with recent FDA approval of a monoclonal anti-Aβ oligomers antibody -aducanumab- raising hopes and controversies. We conclude that, development of oligomer-epitope specific Aβ treatment and implementation of multiple improved biomarkers and risk prediction methods allowing early detection, together with therapies acting on other factors such as hyperexcitability in early AD, could be the key to slowing this global pandemic.
Topics: Alzheimer Disease; Amyloid; Amyloid beta-Peptides; Biomarkers; Humans; Neurodegenerative Diseases
PubMed: 34687956
DOI: 10.1016/j.arr.2021.101496 -
CNS Drugs Jun 2016Pain in patients with Alzheimer's disease is a complex issue; these patients suffer from the common causes of acute and chronic pain, and some also have neuropathic or... (Review)
Review
BACKGROUND AND OBJECTIVE
Pain in patients with Alzheimer's disease is a complex issue; these patients suffer from the common causes of acute and chronic pain, and some also have neuropathic or nociceptive pain. Whatever the mechanism of pain in these patients, their pain will require careful assessment and management, to insure the correct type and level of analgesia is given. The objective of this systematic review was the identification of studies that have investigated the efficacy of different analgesics on pain intensity or pain-related behavior during nursing home stay and at the end of life.
METHODS
A search using pain, pain treatment, and dementia MESH terms and keywords was conducted (October 15, 2015) in MEDLINE, EMBASE, PsychINFO, CINAHL, and Cochrane libraries.
RESULTS
Our search yielded 3138 unique hits, published between 1990 and October 2015. We read titles and abstracts, identified 124 papers for full-text evaluation, and included 12 papers to reflect and synthesize the following questions: (1) Which pain assessment tools for people with dementia are responsive to change in pain intensity scores? (2) Which analgesics are efficacy-tested by controlled trials including people with dementia living in nursing homes, including at the end of life? (3) Which outcome measures have been used to identify pain, pain behavior, and/or treatment efficacy in people with dementia?
CONCLUSION
Despite increased use of analgesics, pain is still prevalent in people with dementia. Validated pain tools are available but not implemented and not fully tested on responsiveness to treatment. Official guidelines for pain assessment and treatment addressing people with dementia living in a nursing home are lacking. The efficacy of analgesic drug use on pain or neuropsychiatric behavior related to dementia has been hardly investigated.
Topics: Alzheimer Disease; Analgesics; Chronic Pain; Dementia; Humans; Pain Management; Psychomotor Agitation
PubMed: 27240869
DOI: 10.1007/s40263-016-0342-7