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Journal of Alzheimer's Disease : JAD 2018The Alzheimer center of the VU University Medical Center opened in 2000 and was initiated to combine both patient care and research. Together, to date, all patients... (Review)
Review
The Alzheimer center of the VU University Medical Center opened in 2000 and was initiated to combine both patient care and research. Together, to date, all patients forming the Amsterdam Dementia Cohort number almost 6,000 individuals. In this cohort profile, we provide an overview of the results produced based on the Amsterdam Dementia Cohort. We describe the main results over the years in each of these research lines: 1) early diagnosis, 2) heterogeneity, and 3) vascular factors. Among the most important research efforts that have also impacted patients' lives and/or the research field, we count the development of novel, easy to use diagnostic measures such as visual rating scales for MRI and the Amsterdam IADL Questionnaire, insight in different subgroups of AD, and findings on incidence and clinical sequelae of microbleeds. Finally, we describe in the outlook how our research endeavors have improved the lives of our patients.
Topics: Alzheimer Disease; Biomarkers; Brain; Cohort Studies; Early Diagnosis; Humans; Magnetic Resonance Imaging; Netherlands; Quality Improvement; Surveys and Questionnaires
PubMed: 29562540
DOI: 10.3233/JAD-170850 -
Journal of Alzheimer's Disease : JAD 2019An estimated 47 million people live with Alzheimer's disease (AD) and other forms of dementia worldwide. Although no disease-modifying treatments are currently available... (Review)
Review
An estimated 47 million people live with Alzheimer's disease (AD) and other forms of dementia worldwide. Although no disease-modifying treatments are currently available for AD, earlier diagnosis and proper management of the disease could have considerable impact on patient and caregiver quality of life and functioning. Drugs currently approved for AD treat the cognitive, behavioral, and functional symptoms of the disease and consist of three cholinesterase inhibitors (ChEIs) and the N-methyl-D-aspartate receptor antagonist memantine. Treatment of patients with mild to moderate AD is generally initiated with a ChEI. Patients who show progression of symptoms while on ChEI monotherapy may be switched to another ChEI and/or memantine can be added to the treatment regimen. In recent years, putative disease-modifying therapies have emerged that aim to slow the progression of AD instead of only addressing its symptoms. However, many therapies have failed in clinical trials in patients with established AD, suggesting that, once developed, disease-modifying agents may need to be deployed earlier in the course of illness. The goal of this narrative literature review is to discuss present treatment algorithms and potential future therapies in AD.
Topics: Algorithms; Alzheimer Disease; Early Diagnosis; Early Medical Intervention; Humans; Nootropic Agents
PubMed: 30741683
DOI: 10.3233/JAD-180903 -
Neurotherapeutics : the Journal of the... Jan 2022The clinical presentation and the pathological processes underlying Alzheimer's disease (AD) can be very heterogeneous in severity, location, and composition including... (Review)
Review
The clinical presentation and the pathological processes underlying Alzheimer's disease (AD) can be very heterogeneous in severity, location, and composition including the amount and distribution of AB deposition and spread of neurofibrillary tangles in different brain regions resulting in atypical clinical patterns and the existence of distinct AD variants. Heterogeneity in AD may be related to demographic factors (such as age, sex, educational and socioeconomic level) and genetic factors, which influence underlying pathology, the cognitive and behavioral phenotype, rate of progression, the occurrence of neuropsychiatric features, and the presence of comorbidities (e.g., vascular disease, neuroinflammation). Heterogeneity is also manifest in the individual resilience to the development of neuropathology (brain reserve) and the ability to compensate for its cognitive and functional impact (cognitive and functional reserve). The variability in specific cognitive profiles and types of functional impairment may be associated with different progression rates, and standard measures assessing progression may not be equivalent for individual cognitive and functional profiles. Other factors, which may govern the presence, rate, and type of progression of AD, include the individuals' general medical health, the presence of specific systemic conditions, and lifestyle factors, including physical exercise, cognitive and social stimulation, amount of leisure activities, environmental stressors, such as toxins and pollution, and the effects of medications used to treat medical and behavioral conditions. These factors that affect progression are important to consider while designing a clinical trial to ensure, as far as possible, well-balanced treatment and control groups.
Topics: Alzheimer Disease; Brain; Disease Progression; Humans
PubMed: 35084721
DOI: 10.1007/s13311-022-01185-z -
Journal of Advanced Research Dec 2023Synaptic dysfunction is a major contributor to Alzheimeŕs disease (AD) pathogenesis in addition to the formation of neuritic β-amyloid plaques and neurofibrillary... (Review)
Review
BACKGROUND
Synaptic dysfunction is a major contributor to Alzheimeŕs disease (AD) pathogenesis in addition to the formation of neuritic β-amyloid plaques and neurofibrillary tangles of hyperphosphorylated Tau protein. However, how these features contribute to synaptic dysfunction and axonal loss remains unclear. While years of considerable effort have been devoted to gaining an improved understanding of this devastating disease, the unavailability of patient-derived tissues, considerable genetic heterogeneity, and lack of animal models that faithfully recapitulate human AD have hampered the development of effective treatment options. Ongoing progress in human induced pluripotent stem cell (hiPSC) technology has permitted the derivation of patient- and disease-specific stem cells with unlimited self-renewal capacity. These cells can differentiate into AD-affected cell types, which support studies of disease mechanisms, drug discovery, and the development of cell replacement therapies in traditional and advanced cell culture models.
AIM OF REVIEW
To summarize current hiPSC-based AD models, highlighting the associated achievements and challenges with a primary focus on neuron and synapse loss.
KEY SCIENTIFIC CONCEPTS OF REVIEW
We aim to identify how hiPSC models can contribute to understanding AD-associated synaptic dysfunction and axonal loss. hiPSC-derived neural cells, astrocytes, and microglia, as well as more sophisticated cellular organoids, may represent reliable models to investigate AD and identify early markers of AD-associated neural degeneration.
Topics: Animals; Humans; Alzheimer Disease; Induced Pluripotent Stem Cells; Amyloid beta-Peptides; Neurons; Synapses
PubMed: 36646419
DOI: 10.1016/j.jare.2023.01.006 -
International Journal of Biological... Jun 2024The prevalence of Alzheimer's disease (AD) and its associated economic and societal burdens are on the rise, but there are no curative treatments for AD. Interestingly,... (Review)
Review
The prevalence of Alzheimer's disease (AD) and its associated economic and societal burdens are on the rise, but there are no curative treatments for AD. Interestingly, this neurodegenerative disease shares several biological and pathophysiological features with cancer, including cell-cycle dysregulation, angiogenesis, mitochondrial dysfunction, protein misfolding, and DNA damage. However, the genetic factors contributing to the overlap in biological processes between cancer and AD have not been actively studied. In this review, we discuss the shared biological features of cancer and AD, the molecular targets of anticancer drugs, and therapeutic approaches. First, we outline the common biological features of cancer and AD. Second, we describe several anticancer drugs, their molecular targets, and their effects on AD pathology. Finally, we discuss how protein-protein interactions (PPIs), receptor inhibition, immunotherapy, and gene therapy can be exploited for the cure and management of both cancer and AD. Collectively, this review provides insights for the development of AD theragnostics based on cancer drugs and molecular targets.
Topics: Humans; Alzheimer Disease; Neoplasms; Antineoplastic Agents; Immunotherapy; Animals; Molecular Targeted Therapy; Genetic Therapy
PubMed: 38685540
DOI: 10.1016/j.ijbiomac.2024.131925 -
Journal of Alzheimer's Disease : JAD 2022Impaired awareness of ability is common in dementia and has important clinical implications. Evidence from different clinical groups has shown that awareness can vary...
BACKGROUND
Impaired awareness of ability is common in dementia and has important clinical implications. Evidence from different clinical groups has shown that awareness can vary according to whether evaluation refers to self or other performance.
OBJECTIVE
The present study aimed to investigate awareness for self- and other-performance in Alzheimer's disease (AD) patients, exploring if results vary according to cognitive domain of the tasks. It was hypothesized that, particularly for memory tasks, AD patients would be inaccurate in relation to self-but not other-performance.
METHODS
Twenty-two mild to moderate AD patients and twenty-two healthy older adults participated. Two tasks, with reaction time and working memory tasks, were carried out, and each had a success and a failure condition. Participants were asked to estimate their own performance, as well as the performance of another person they observed. Awareness of performance was measured comparing participant estimations of performance with actual performance.
RESULTS
For both the reaction time and working memory tasks, results indicate that participants from both groups overestimated the performance in the failure condition and underestimated the performance in the success condition. They tended to overestimate more the performance of the other person compared to themselves. Additionally, for the working memory task, AD patients tended to overestimate more performances compared to controls.
CONCLUSION
Findings suggest that the AD and control groups present the same pattern, with attribution of better performance to another person. For the AD group, the pattern of response was different for memory tasks, which may suggest domain-specific limited awareness.
Topics: Humans; Aged; Alzheimer Disease; Neuropsychological Tests; Awareness; Reaction Time
PubMed: 36093698
DOI: 10.3233/JAD-220453 -
Journal of Alzheimer's Disease : JAD 2020As the most common form of senile dementia, Alzheimer's disease (AD) is accompanied by a great deal of uncertainty which can lead to fear and stigma for those identified... (Review)
Review
As the most common form of senile dementia, Alzheimer's disease (AD) is accompanied by a great deal of uncertainty which can lead to fear and stigma for those identified with this devastating disease. As the AD definition evolves from a syndromal to a biological construct, and early diagnoses becomes more commonplace, more confusion and stigma may result. We conducted a narrative review of the literature on AD stigma to consolidate information on this body of research. From the perspective of several stigma theories, we identified relevant studies to inform our understanding of the way in which implementation of the new framework for a biological based AD diagnosis may have resulted in new and emerging stigma. Herein, we discuss the emergence of new AD stigma as our understanding of the definition of the disease changes. We further propose recommendations for future research to reduce the stigma associated with AD.
Topics: Alzheimer Disease; Caregiver Burden; Cost of Illness; Early Diagnosis; Humans; Social Stigma
PubMed: 33044185
DOI: 10.3233/JAD-200932 -
Cells Mar 2021Astrocytes perform a wide variety of essential functions defining normal operation of the nervous system and are active contributors to the pathogenesis of... (Review)
Review
Astrocytes perform a wide variety of essential functions defining normal operation of the nervous system and are active contributors to the pathogenesis of neurodegenerative disorders such as Alzheimer's among others. Recent data provide compelling evidence that distinct astrocyte states are associated with specific stages of Alzheimer´s disease. The advent of transcriptomics technologies enables rapid progress in the characterisation of such pathological astrocyte states. In this review, we provide an overview of the origin, main functions, molecular and morphological features of astrocytes in physiological as well as pathological conditions related to Alzheimer´s disease. We will also explore the main roles of astrocytes in the pathogenesis of Alzheimer´s disease and summarize main transcriptional changes and altered molecular pathways observed in astrocytes during the course of the disease.
Topics: Alzheimer Disease; Astrocytes; Humans; Transcriptome
PubMed: 33806259
DOI: 10.3390/cells10030540 -
Journal of Alzheimer's Disease : JAD 2015A growing body of literature has investigated changes in eye movements as a result of Alzheimer's disease (AD). When compared to healthy, age-matched controls, patients... (Review)
Review
A growing body of literature has investigated changes in eye movements as a result of Alzheimer's disease (AD). When compared to healthy, age-matched controls, patients display a number of remarkable alterations to oculomotor function and viewing behavior. In this article, we review AD-related changes to fundamental eye movements, such as saccades and smooth pursuit motion, in addition to changes to eye movement patterns during more complex tasks like visual search and scene exploration. We discuss the cognitive mechanisms that underlie these changes and consider the clinical significance of eye movement behavior, with a focus on eye movements in mild cognitive impairment. We conclude with directions for future research.
Topics: Alzheimer Disease; Attention Deficit Disorder with Hyperactivity; Cognition Disorders; Eye Movements; Humans; Photic Stimulation; Psychomotor Performance
PubMed: 25182738
DOI: 10.3233/JAD-141173 -
Alzheimer's Research & Therapy Aug 2022Patient stratification is the division of a patient population into distinct subgroups based on the presence or absence of particular disease characteristics. As patient... (Review)
Review
BACKGROUND
Patient stratification is the division of a patient population into distinct subgroups based on the presence or absence of particular disease characteristics. As patient stratification can be used to account for the underlying pathology of a disease, it can help physicians to tailor therapeutic interventions to individuals and optimize their care management and treatment regime. Alzheimer's disease, the most common form of dementia, is a heterogeneous disease and its management benefits from patient stratification in clinical trials, and the development of personalized care and treatment strategies for people living with the disease.
MAIN BODY
In this review, we discuss the importance of the stratification of people living with Alzheimer's disease, the challenges associated with early diagnosis and patient stratification, and the evolution of patient stratification once disease-modifying therapies become widely available.
CONCLUSION
Patient stratification plays an important role in drug development in clinical trials and may play an even larger role in clinical practice. A timely diagnosis and stratification of people living with Alzheimer's disease is paramount in determining people who are at risk of progressing from mild cognitive impairment to Alzheimer's dementia. There are key issues associated with stratifying patients which include the heterogeneity and complex neurobiology behind Alzheimer's disease, our inadequately prepared healthcare systems, and the cultural perceptions of Alzheimer's disease. Stratifying people living with Alzheimer's disease may be the key in establishing precision and personalized medicine in the field, optimizing disease prevention and pharmaceutical treatment to slow or stop cognitive decline, while minimizing adverse effects.
Topics: Alzheimer Disease; Cognitive Dysfunction; Humans
PubMed: 35964143
DOI: 10.1186/s13195-022-01055-y