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Lakartidningen Mar 2024The aging population makes the increase in cognitive disorders a challenge. One of the risk factors is old age, but also oral diseases, especially periodontitis, have...
The aging population makes the increase in cognitive disorders a challenge. One of the risk factors is old age, but also oral diseases, especially periodontitis, have been linked to an increased risk of dementia, especially Alzheimer's disease (AD), although research studies show varying correlations. Dental care utilization also decreases after a dementia diagnosis. The periodontal diseases are inflammatory disorders and common in the adult population. Periodontitis leads to loss of the supporting tissue of the tooth and, if untreated, to loss of teeth. Inflammation also plays a role in AD, the most common form of dementia. The reason for an association could be that periodontitis may lead to a spread of pro-inflammatory mediators and oral microorganisms to the brain. Another explanation suggests that chewing may stimulate nerve impulses and increase the blood flow to the brain. Fewer teeth could lead to less stimulation and reduced blood flow. In conclusion, oral diseases and dementia appear to be associated. Whether this connection constitutes a causal connection is more uncertain.
Topics: Adult; Humans; Aged; Brain; Aging; Alzheimer Disease; Cognition Disorders; Periodontitis
PubMed: 38470275
DOI: No ID Found -
Translational Neurodegeneration Jan 2024Ageing is a crucial risk factor for Alzheimer's disease (AD) and is characterised by systemic changes in both intracellular and extracellular microenvironments that... (Review)
Review
Ageing is a crucial risk factor for Alzheimer's disease (AD) and is characterised by systemic changes in both intracellular and extracellular microenvironments that affect the entire body instead of a single organ. Understanding the specific mechanisms underlying the role of ageing in disease development can facilitate the treatment of ageing-related diseases, such as AD. Signs of brain ageing have been observed in both AD patients and animal models. Alleviating the pathological changes caused by brain ageing can dramatically ameliorate the amyloid beta- and tau-induced neuropathological and memory impairments, indicating that ageing plays a crucial role in the pathophysiological process of AD. In this review, we summarize the impact of several age-related factors on AD and propose that preventing pathological changes caused by brain ageing is a promising strategy for improving cognitive health.
Topics: Animals; Humans; Alzheimer Disease; Amyloid beta-Peptides; Aging; Brain; Memory Disorders
PubMed: 38254235
DOI: 10.1186/s40035-024-00397-x -
Radiographics : a Review Publication of... Sep 2023Alzheimer disease (AD) is the most common form of dementia worldwide. Treatment of AD has mainly been focused on symptomatic treatment until recently with the advent and...
Alzheimer disease (AD) is the most common form of dementia worldwide. Treatment of AD has mainly been focused on symptomatic treatment until recently with the advent and approval of monoclonal antibody (MAB) immunotherapy. U.S. Food and Drug Administration-approved drugs such as aducanumab, as well as upcoming newer-generation drugs, have provided an exciting new therapy focused on reducing the amyloid plaque burden in AD. Although this new frontier has shown benefits for patients, it is not without complications, which are mainly neurologic. Increased use of MABs led to the discovery of amyloid-related imaging abnormalities (ARIA). ARIA has been further classified into two categories, ARIA-E and ARIA-H, representing edema and/or effusion and hemorrhage, respectively. ARIA is thought to be caused by increased vascular permeability following an inflammatory response, leading to the extravasation of blood products and proteinaceous fluid. Patients with ARIA may present with headaches, but they are usually asymptomatic and ARIA is only diagnosable at MRI; it is essential for the radiologist to recognize and monitor ARIA. Increased incidence and investigation into this concern have led to the creation of grading scales and monitoring guidelines to diagnose and guide treatment using MABs. Cerebral amyloid angiopathy has an identical pathogenesis to that of ARIA and is its closest differential diagnosis, with imaging findings being the same for both entities and only a history of MAB administration allowing differentiation. The authors discuss the use of MABs for treating AD, expand on ARIA and its consequences, and describe how to identify and grade ARIA to guide treatment properly. RSNA, 2023 Quiz questions for this article are available through the Online Learning Center See the invited commentary by Yu in this issue.
Topics: United States; Humans; Alzheimer Disease; Amyloid beta-Peptides; Diagnostic Imaging; Immunotherapy; Antibodies, Monoclonal
PubMed: 37651273
DOI: 10.1148/rg.230009 -
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 -
Translational Neurodegeneration Oct 2023Microglia, the resident immune cells of the brain, are increasingly implicated in the regulation of brain health and disease. Microglia perform multiple functions in the... (Review)
Review
Microglia, the resident immune cells of the brain, are increasingly implicated in the regulation of brain health and disease. Microglia perform multiple functions in the central nervous system, including surveillance, phagocytosis and release of a variety of soluble factors. Importantly, a majority of their functions are closely related to changes in their metabolism. This natural inter-dependency between core microglial properties and metabolism offers a unique opportunity to modulate microglial activities via nutritional or metabolic interventions. In this review, we examine the existing scientific literature to synthesize the hypothesis that microglial phagocytosis of amyloid beta (Aβ) aggregates in Alzheimer's disease (AD) can be selectively enhanced via metabolic interventions. We first review the basics of microglial metabolism and the effects of common metabolites, such as glucose, lipids, ketone bodies, glutamine, pyruvate and lactate, on microglial inflammatory and phagocytic properties. Next, we examine the evidence for dysregulation of microglial metabolism in AD. This is followed by a review of in vivo studies on metabolic manipulation of microglial functions to ascertain their therapeutic potential in AD. Finally, we discuss the effects of metabolic factors on microglial phagocytosis of healthy synapses, a pathological process that also contributes to the progression of AD. We conclude by enlisting the current challenges that need to be addressed before strategies to harness microglial phagocytosis to clear pathological protein deposits in AD and other neurodegenerative disorders can be widely adopted.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Microglia; Phagocytosis; Brain
PubMed: 37908010
DOI: 10.1186/s40035-023-00382-w -
Progress in Neurobiology May 2024Here, we provide an in-depth consideration of our current understanding of engrams, spanning from molecular to network levels, and hippocampal neurogenesis, in health... (Review)
Review
Here, we provide an in-depth consideration of our current understanding of engrams, spanning from molecular to network levels, and hippocampal neurogenesis, in health and Alzheimer's disease (AD). This review highlights novel findings in these emerging research fields and future research directions for novel therapeutic avenues for memory failure in dementia. Engrams, memory in AD, and hippocampal neurogenesis have each been extensively studied. The integration of these topics, however, has been relatively less deliberated, and is the focus of this review. We primarily focus on the dentate gyrus (DG) of the hippocampus, which is a key area of episodic memory formation. Episodic memory is significantly impaired in AD, and is also the site of adult hippocampal neurogenesis. Advancements in technology, especially opto- and chemogenetics, have made sophisticated manipulations of engram cells possible. Furthermore, innovative methods have emerged for monitoring neurons, even specific neuronal populations, in vivo while animals engage in tasks, such as calcium imaging. In vivo calcium imaging contributes to a more comprehensive understanding of engram cells. Critically, studies of the engram in the DG using these technologies have shown the important contribution of hippocampal neurogenesis for memory in both health and AD. Together, the discussion of these topics provides a holistic perspective that motivates questions for future research.
Topics: Neurogenesis; Humans; Alzheimer Disease; Animals; Hippocampus; Dementia; Memory
PubMed: 38570083
DOI: 10.1016/j.pneurobio.2024.102601 -
Communications Biology Nov 2023The proteasome plays key roles in synaptic plasticity and memory by regulating protein turnover, quality control, and elimination of oxidized/misfolded proteins. Here,...
The proteasome plays key roles in synaptic plasticity and memory by regulating protein turnover, quality control, and elimination of oxidized/misfolded proteins. Here, we investigate proteasome function and localization at synapses in Alzheimer's disease (AD) post-mortem brain tissue and in experimental models. We found a marked increase in ubiquitinylated proteins in post-mortem AD hippocampi compared to controls. Using several experimental models, we show that amyloid-β oligomers (AβOs) inhibit synaptic proteasome activity and trigger a reduction in synaptic proteasome content. We further show proteasome inhibition specifically in hippocampal synaptic fractions derived from APPswePS1ΔE9 mice. Reduced synaptic proteasome activity instigated by AβOs is corrected by treatment with rolipram, a phosphodiesterase-4 inhibitor, in mice. Results further show that dynein inhibition blocks AβO-induced reduction in dendritic proteasome content in hippocampal neurons. Finally, proteasome inhibition induces AD-like pathological features, including reactive oxygen species and dendritic spine loss in hippocampal neurons, inhibition of hippocampal mRNA translation, and memory impairment in mice. Results suggest that proteasome inhibition may contribute to synaptic and memory deficits in AD.
Topics: Mice; Animals; Alzheimer Disease; Amyloid beta-Peptides; Proteasome Endopeptidase Complex; Neuronal Plasticity; Memory Disorders
PubMed: 37935829
DOI: 10.1038/s42003-023-05511-9 -
Alzheimer's Research & Therapy Oct 2023Alterations in mitochondrial DNA (mtDNA) levels have been observed in Alzheimer's disease and are an area of research that shows promise as a useful biomarker. It is... (Review)
Review
BACKGROUND
Alterations in mitochondrial DNA (mtDNA) levels have been observed in Alzheimer's disease and are an area of research that shows promise as a useful biomarker. It is well known that not only are the mitochondria a key player in producing energy for the cell, but they also are known to interact in other important intracellular processes as well as extracellular signaling and communication. BODY: This mini review explores how cells use mtDNA as a stress signal, particularly in Alzheimer's disease. We investigate the measurement of these mtDNA alterations, the mechanisms of mtDNA release, and the immunological effects from the release of these stress signals.
CONCLUSION
Literature indicates a correlation between the release of mtDNA in Alzheimer's disease and increased immune responses, showing promise as a potential biomarker. However, several questions remain unanswered and there is great potential for future studies in this area.
Topics: Humans; DNA, Mitochondrial; Alzheimer Disease; Mitochondria; Signal Transduction; Biomarkers; Oxidative Stress
PubMed: 37821944
DOI: 10.1186/s13195-023-01322-6 -
Psychiatry Research Mar 2024The nature of the relationship between sleep problems and dementia remains unclear. This study investigated the relationship between sleep measures and dementia in older...
The nature of the relationship between sleep problems and dementia remains unclear. This study investigated the relationship between sleep measures and dementia in older adults (≥ 65) using data from the English Longitudinal Study of Ageing (ELSA) and further investigated the causal association in Mendelian randomization (MR) analysis. In total of 7,223 individuals, 5.7 % developed dementia (1.7 % Alzheimer's disease (AD)) within an average of 8 (± 2.9) years. Cox regression models and MR were employed. Long sleep duration (>8 h) was associated with 64 % increased risk of incident dementia and 2-fold high risk of AD compared to ideal sleep duration (7-8 h). This association was particularly evident in older-older adults (≥70 years) and those who consumed alcohol. Short sleep duration (<7 h) was associated with lower risk of incident dementia among older-older but higher risk among younger-older adults. Sleep disturbances and perceived sleep quality were not associated with dementia or AD. The MR study did not reveal causal associations between sleep duration and dementia. These findings suggest that self-reported short sleep in younger-older and long sleep in older-older adults and those with frequent alcohol consumption are associated with dementia. Early detection of these sleep patterns may help identify individuals at higher dementia risk.
Topics: Humans; Aged; Alzheimer Disease; Follow-Up Studies; Longitudinal Studies; Sleep Duration; Incidence; Sleep; Sleep Wake Disorders
PubMed: 38301285
DOI: 10.1016/j.psychres.2024.115760 -
Role of Exosomes in the Pathogenesis and Theranostic of Alzheimer's Disease and Parkinson's Disease.International Journal of Molecular... Jul 2023Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases (NDDs) threatening the lives of millions of people worldwide,... (Review)
Review
Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases (NDDs) threatening the lives of millions of people worldwide, including especially elderly people. Currently, due to the lack of a timely diagnosis and proper intervention strategy, AD and PD largely remain incurable. Innovative diagnosis and therapy are highly desired. Exosomes are small vesicles that are present in various bodily fluids, which contain proteins, nucleic acids, and active biomolecules, and which play a crucial role especially in intercellular communication. In recent years, the role of exosomes in the pathogenesis, early diagnosis, and treatment of diseases has attracted ascending attention. However, the exact role of exosomes in the pathogenesis and theragnostic of AD and PD has not been fully illustrated. In the present review, we first introduce the biogenesis, components, uptake, and function of exosomes. Then we elaborate on the involvement of exosomes in the pathogenesis of AD and PD. Moreover, the application of exosomes in the diagnosis and therapeutics of AD and PD is also summarized and discussed. Additionally, exosomes serving as drug carriers to deliver medications to the central nervous system are specifically addressed. The potential role of exosomes in AD and PD is explored, discussing their applications in diagnosis and treatment, as well as their current limitations. Given the limitation in the application of exosomes, we also propose future perspectives for better utilizing exosomes in NDDs. Hopefully, it would pave ways for expanding the biological applications of exosomes in fundamental research as well as theranostics of NDDs.
Topics: Humans; Aged; Alzheimer Disease; Exosomes; Parkinson Disease; Precision Medicine
PubMed: 37446231
DOI: 10.3390/ijms241311054