-
Neurologia May 2018Early-onset Alzheimer disease (EOAD), which presents in patients younger than 65 years, has frequently been described as having different features from those of... (Review)
Review
Early-onset Alzheimer disease (EOAD), which presents in patients younger than 65 years, has frequently been described as having different features from those of late-onset Alzheimer disease (LOAD). This review analyses the most recent studies comparing the clinical presentation and neuropsychological, neuropathological, genetic, and neuroimaging findings of both types in order to determine whether EOAD and LOAD are different entities or distinct forms of the same entity. We observed consistent differences between clinical findings in EOAD and in LOAD. Fundamentally, the onset of EOAD is more likely to be marked by atypical symptoms, and cognitive assessments point to poorer executive and visuospatial functioning and praxis with less marked memory impairment. Alzheimer-type features will be more dense and widespread in neuropathology studies, with structural and functional neuroimaging showing greater and more diffuse atrophy extending to neocortical areas (especially the precuneus). In conclusion, available evidence suggests that EOAD and LOAD are 2 different forms of a single entity. LOAD is likely to be influenced by ageing-related processes.
Topics: Age of Onset; Aging; Alzheimer Disease; Humans
PubMed: 26546285
DOI: 10.1016/j.nrl.2015.08.002 -
Der Radiologe May 2015Alzheimer's disease is a progressive neurodegenerative disorder with characteristic neuropathological changes. It is the most common form of dementia. As a definitive...
Alzheimer's disease is a progressive neurodegenerative disorder with characteristic neuropathological changes. It is the most common form of dementia. As a definitive diagnosis requires a neuropathological examination, clinical criteria have been established for the diagnostics of a probable Alzheimer's disease. In addition to the articles in this issue that focus on the imaging of dementia, this article provides a brief overview of clinically relevant aspects of Alzheimer's disease.
Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Brain; Cognitive Dysfunction; Cross-Sectional Studies; Diagnosis, Differential; Diagnostic Imaging; Disease Progression; Humans; Mental Status Schedule; Middle Aged; Neuropsychological Tests
PubMed: 25957008
DOI: 10.1007/s00117-014-2796-2 -
The Veterinary Clinics of North... May 2019Canine cognitive dysfunction (CCD) is the canine analog of human Alzheimer disease (AD). The pathophysiology of CCD/AD is multifaceted. CCD is common in aged (>8 years)... (Review)
Review
Canine cognitive dysfunction (CCD) is the canine analog of human Alzheimer disease (AD). The pathophysiology of CCD/AD is multifaceted. CCD is common in aged (>8 years) dogs, affecting between 14% and 35% of the pet dog population. Apparent confusion, anxiety, disturbance of the sleep/wake cycle, and decreased interaction with owners are all common clinical signs of CCD. Although there is no cure for CCD, several proven effective therapeutic approaches are available for improving cognitive ability and maintaining a good quality of life; instituting such therapies early in the disease course is likely to have the greatest positive clinical effect.
Topics: Alzheimer Disease; Animals; Dog Diseases; Dogs; Palliative Care; Veterinary Medicine
PubMed: 30846383
DOI: 10.1016/j.cvsm.2019.01.013 -
Expert Review of Molecular Diagnostics Mar 2015Alzheimer's disease (AD), the most common form of dementia in western societies, is a pathologically and clinically heterogeneous disease with a strong genetic... (Review)
Review
Alzheimer's disease (AD), the most common form of dementia in western societies, is a pathologically and clinically heterogeneous disease with a strong genetic component. The recent advances in high-throughput genome technologies allowing for the rapid analysis of millions of polymorphisms in thousands of subjects has significantly advanced our understanding of the genomic underpinnings of AD susceptibility. During the last 5 years, genome-wide association and whole-exome- and whole-genome sequencing studies have mapped more than 20 disease-associated loci, providing insights into the molecular pathways involved in AD pathogenesis and hinting at potential novel therapeutic targets. This review article summarizes the challenges and opportunities of when using genomic information for the diagnosis and prognosis of AD.
Topics: Alzheimer Disease; Biomarkers; Computational Biology; Genetic Predisposition to Disease; Genetic Testing; Genome-Wide Association Study; Genomics; Humans; Prognosis
PubMed: 25634383
DOI: 10.1586/14737159.2015.1002469 -
EBioMedicine Jul 2016
Topics: Alzheimer Disease; Animals; Biomarkers; Disease Management; Drug Discovery; Early Diagnosis; Humans
PubMed: 27412262
DOI: 10.1016/j.ebiom.2016.07.001 -
Current Alzheimer Research 2016Alzheimer's disease (AD) is a multifactorial disease with genetic (70%) and environmental (30%) causes. Among the genetic factors are genes associated with a family... (Review)
Review
Alzheimer's disease (AD) is a multifactorial disease with genetic (70%) and environmental (30%) causes. Among the genetic factors are genes associated with a family history of the disease (familial AD, FAD) and sporadic AD (SAD). The genes: APP (amyloid precursor protein), PSEN1 (Presenilin 1) and PSEN2 (Presenilin 2) are responsible for the presence of FAD. The APOE gene is responsible for the sporadic form of the disease. Other molecular factors related to the immunological cause (TREM2) of the disease are a disorder of the lipid (ABCA1, ABCA7) or biothiol (MTHFD1) metabolism and of the transport of metabolites (BIN1). Currently, it is believed that APOE is a risk factor for both SAD and late-onset FAD. The pathomechanism of AD is most commonly explained as based on the amyloid cascade theory. This theory is related to the FAD, although there are reports indicating the probability of its occurrence in the SAD. It seems that the excessive deposition of β-amyloid (Aβ) peptides and intracellular neurofibrillary tangles of tau protein hyperphosphorylated forms contribute to the damage of both DNA and RNA. Furthermore, it is believed that RNA-interference can affect both the level of pathological proteins (Aβ, tau protein) and the onset and progress of AD. It seems that a complete understanding of both FAD and SAD pathogenesis may contribute to the search for earlier clinical diagnosis and to an understanding of later occurrence of the disease, which may help modify its course and affect more effective therapy of this incurable neurological disease.
Topics: Alzheimer Disease; Animals; Humans
PubMed: 26971934
DOI: 10.2174/1567205013666160314150501 -
Nature Reviews. Neurology Nov 2021Dysregulation of the immune system is a cardinal feature of Alzheimer disease (AD), and a considerable body of evidence indicates pathological alterations in central and... (Review)
Review
Dysregulation of the immune system is a cardinal feature of Alzheimer disease (AD), and a considerable body of evidence indicates pathological alterations in central and peripheral immune responses that change over time. Considering AD as a systemic immune process raises important questions about how communication between the peripheral and central compartments occurs and whether this crosstalk represents a therapeutic target. We established a whitepaper workgroup to delineate the current status of the field and to outline a research prospectus for advancing our understanding of peripheral-central immune crosstalk in AD. To guide the prospectus, we begin with an overview of seminal clinical observations that suggest a role for peripheral immune dysregulation and peripheral-central immune communication in AD, followed by formative animal data that provide insights into possible mechanisms for these clinical findings. We then present a roadmap that defines important next steps needed to overcome conceptual and methodological challenges, opportunities for future interdisciplinary research, and suggestions for translating promising mechanistic studies into therapeutic interventions.
Topics: Alzheimer Disease; Animals; Humans; Immune System; Research
PubMed: 34522039
DOI: 10.1038/s41582-021-00549-x -
Alzheimer's Research & Therapy Aug 2017Basic research advances in recent years have furthered our understanding of the natural history of Alzheimer's disease (AD). It is now recognized that pathophysiological... (Review)
Review
Basic research advances in recent years have furthered our understanding of the natural history of Alzheimer's disease (AD). It is now recognized that pathophysiological changes begin many years prior to clinical manifestations of disease and the spectrum of AD spans from clinically asymptomatic to severely impaired. Defining AD purely by its clinical presentation is thus artificial and efforts have been made to recognize the disease based on both clinical and biomarker findings. Advances with biomarkers have also prompted a shift in how the disease is considered as a clinico-pathophysiological entity, with an increasing appreciation that AD should not only be viewed with discrete and defined clinical stages, but as a multifaceted process moving along a seamless continuum. Acknowledging this concept is critical to understanding the development process for disease-modifying therapies, and for initiating effective diagnostic and disease management options. In this article, we discuss the concept of a disease continuum from pathophysiological, biomarker, and clinical perspectives, and highlight the importance of considering AD as a continuum rather than discrete stages. While the pathophysiology of AD has still not been elucidated completely, there is ample evidence to support researchers and clinicians embracing the view of a disease continuum in their study, diagnosis, and management of the disease.
Topics: Alzheimer Disease; Biomarkers; Disease Progression; Humans
PubMed: 28793924
DOI: 10.1186/s13195-017-0283-5 -
Journal of Internal Medicine Aug 2021The critical role of primary care clinicians (PCCs) in Alzheimer's disease (AD) prevention, diagnosis and management must evolve as new treatment paradigms and... (Review)
Review
The critical role of primary care clinicians (PCCs) in Alzheimer's disease (AD) prevention, diagnosis and management must evolve as new treatment paradigms and disease-modifying therapies (DMTs) emerge. Our understanding of AD has grown substantially: no longer conceptualized as a late-in-life syndrome of cognitive and functional impairments, we now recognize that AD pathology builds silently for decades before cognitive impairment is detectable. Clinically, AD first manifests subtly as mild cognitive impairment (MCI) due to AD before progressing to dementia. Emerging optimism for improved outcomes in AD stems from a focus on preventive interventions in midlife and timely, biomarker-confirmed diagnosis at early signs of cognitive deficits (i.e. MCI due to AD and mild AD dementia). A timely AD diagnosis is particularly important for optimizing patient care and enabling the appropriate use of anticipated DMTs. An accelerating challenge for PCCs and AD specialists will be to respond to innovations in diagnostics and therapy for AD in a system that is not currently well positioned to do so. To overcome these challenges, PCCs and AD specialists must collaborate closely to navigate and optimize dynamically evolving AD care in the face of new opportunities. In the spirit of this collaboration, we summarize here some prominent and influential models that inform our current understanding of AD. We also advocate for timely and accurate (i.e. biomarker-defined) diagnosis of early AD. In doing so, we consider evolving issues related to prevention, detecting emerging cognitive impairment and the role of biomarkers in the clinic.
Topics: Alzheimer Disease; Humans; Primary Health Care; Time Factors
PubMed: 33458891
DOI: 10.1111/joim.13244 -
Neurology Mar 2020To test the hypothesis that distinct subtypes of Alzheimer disease (AD) exist and underlie the heterogeneity within AD, we conducted a systematic review and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To test the hypothesis that distinct subtypes of Alzheimer disease (AD) exist and underlie the heterogeneity within AD, we conducted a systematic review and meta-analysis on AD subtype studies based on postmortem and neuroimaging data.
METHODS
EMBASE, PubMed, and Web of Science databases were consulted until July 2019.
RESULTS
Neuropathology and neuroimaging studies have consistently identified 3 subtypes of AD based on the distribution of tau-related pathology and regional brain atrophy: typical, limbic-predominant, and hippocampal-sparing AD. A fourth subtype, minimal atrophy AD, has been identified in several neuroimaging studies. Typical AD displays tau-related pathology and atrophy both in hippocampus and association cortex and has a pooled frequency of 55%. Limbic-predominant, hippocampal-sparing, and minimal atrophy AD had a pooled frequency of 21%, 17%, and 15%, respectively. Between-subtype differences were found in age at onset, age at assessment, sex distribution, years of education, global cognitive status, disease duration, APOE ε4 genotype, and CSF biomarker levels.
CONCLUSION
We identified 2 core dimensions of heterogeneity: typicality and severity. We propose that these 2 dimensions determine individuals' belonging to one of the AD subtypes based on the combination of protective factors, risk factors, and concomitant non-AD brain pathologies. This model is envisioned to aid with framing hypotheses, study design, interpretation of results, and understanding mechanisms in future subtype studies. Our model can be used along the A/T/N classification scheme for AD biomarkers. Unraveling the heterogeneity within AD is critical for implementing precision medicine approaches and for ultimately developing successful disease-modifying drugs for AD.
Topics: Alzheimer Disease; Humans
PubMed: 32047067
DOI: 10.1212/WNL.0000000000009058