The oldest-old and dementia at the end of life

2020 ◽  
pp. 171-180
Author(s):  
María M Corrada ◽  
Claudia H Kawas
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
End Of Life ◽  
Hippocampal Sclerosis ◽  
Oldest Old ◽  
Vascular Lesions ◽  
Age Group ◽  
Elderly Individuals ◽  
The World

The oldest-old and dementia at the end of life describes what is known about the prevalence, incidence, and risk factors for dementia in people aged 90 and older, the fastest growing segment of the population in much of the world. It reviews the main neuropathological abnormalities found during autopsy, including Alzheimer’s disease (AD), vascular lesions, and hippocampal sclerosis and discusses how these abnormalities are related to dementia in very elderly individuals. The chapter highlights differences in risk and protective factors, and underlying neuropathologies associated with dementia compared to younger elderly. Taking into consideration the rapid increase in the number of oldest-old by the middle of the century, it reviews the potential impact of interventions to reduce Alzheimer’s disease pathology on the prevalence of dementia in this age group. Finally, it presents methodological challenges in studying this age group and offers potential strategies to address some of these challenges.

scholarly journals Role of the oral microbiota in the development of Alzheimer’s disease

2020 ◽  
Vol 15 (4) ◽  
pp. 231-238
Author(s):  
Natalia Gavrilova ◽  
◽  
Nikita Gladyshev ◽  
Anna Kotrova ◽  
Anastasiia Morozova ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Oral Microbiota ◽  
Practical Application ◽  
Pathophysiological Role ◽  
The World ◽  
Important Practical Application

Dementia and, in particular, Alzheimer’s disease (AD), affects millions of people around the world and its prevalence is steadily rising annually. Some risk factors for AD, such as age, cannot be modified, while others could possibly be corrected. In recent years, many studies are tackling the problem of the oral and gut microbiota as a provoking factor for AD and other neurodegenerative diseases, but their relationship and specific pathophysiological mechanisms remain understudied. The microbiota of the oral cavity can be of particular importance due to the specificity of microorganisms and their localization, as well as the possibility of provoking neuroinflammation, which requires further study. This review covers the specific features of the oral microbiota, current views on the pathophysiological role of the oral microbiota in the development of AD, as well as the beneficial role of probiotics. The study of this issue can have an important practical application both for the early diagnosis of AD, and for its further treatment.

Elucidating the risk factors for progression from amyloid-negative amnestic mild cognitive impairment to dementia

2020 ◽  
Vol 17 ◽  
Author(s):  
Hyung-Ji Kim ◽  
Jae-Hong Lee ◽  
E-nae Cheong ◽  
Sung-Eun Chung ◽  
Sungyang Jo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amnestic Mild Cognitive Impairment ◽  
Amyloid Pet ◽  
Clinical Progression ◽  
Amnestic Mci

Background: Amyloid PET allows for the assessment of amyloid β status in the brain, distinguishing true Alzheimer’s disease from Alzheimer’s disease-mimicking conditions. Around 15–20% of patients with clinically probable Alzheimer’s disease have been found to have no significant Alzheimer’s pathology on amyloid PET. However, a limited number of studies had been conducted this subpopulation in terms of clinical progression. Objective: We investigated the risk factors that could affect the progression to dementia in patients with amyloid-negative amnestic mild cognitive impairment (MCI). Methods: This study was a single-institutional, retrospective cohort study of patients over the age of 50 with amyloidnegative amnestic MCI who visited the memory clinic of Asan Medical Center with a follow-up period of more than 36 months. All participants underwent brain magnetic resonance imaging (MRI), detailed neuropsychological testing, and fluorine-18[F18]-florbetaben amyloid PET. Results: During the follow-up period, 39 of 107 patients progressed to dementia from amnestic MCI. In comparison with the stationary group, the progressed group had a more severe impairment in verbal and visual episodic memory function and hippocampal atrophy, which showed an Alzheimer’s disease-like pattern despite the lack of evidence for significant Alzheimer’s disease pathology. Voxel-based morphometric MRI analysis revealed that the progressed group had a reduced gray matter volume in the bilateral cerebellar cortices, right temporal cortex, and bilateral insular cortices. Conclusion: Considering the lack of evidence of amyloid pathology, clinical progression of these subpopulation may be caused by other neuropathologies such as TDP-43, abnormal tau or alpha synuclein that lead to neurodegeneration independent of amyloid-driven pathway. Further prospective studies incorporating biomarkers of Alzheimer’s diseasemimicking dementia are warranted.

scholarly journals Tau and TDP-43 synergy: a novel therapeutic target for sporadic late-onset Alzheimer’s disease

GeroScience ◽  
2021 ◽  
Author(s):  
Caitlin S. Latimer ◽  
Nicole F. Liachko
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Hippocampal Sclerosis ◽  
Model Organism ◽  
Amyloid Β ◽  
Underlying Disease ◽  
Therapeutic Interventions ◽  
Disease Biology ◽  
Rapid Cognitive Decline

AbstractAlzheimer’s disease (AD) is traditionally defined by the presence of two types of protein aggregates in the brain: amyloid plaques comprised of the protein amyloid-β (Aβ) and neurofibrillary tangles containing the protein tau. However, a large proportion (up to 57%) of AD patients also have TDP-43 aggregates present as an additional comorbid pathology. The presence of TDP-43 aggregates in AD correlates with hippocampal sclerosis, worse brain atrophy, more severe cognitive impairment, and more rapid cognitive decline. In patients with mixed Aβ, tau, and TDP-43 pathology, TDP-43 may interact with neurodegenerative processes in AD, worsening outcomes. While considerable progress has been made to characterize TDP-43 pathology in AD and late-onset dementia, there remains a critical need for mechanistic studies to understand underlying disease biology and develop therapeutic interventions. This perspectives article reviews the current understanding of these processes from autopsy cohort studies and model organism-based research, and proposes targeting neurotoxic synergies between tau and TDP-43 as a new therapeutic strategy for AD with comorbid TDP-43 pathology.

scholarly journals Examining the possible causal relationship between lung function, COPD and Alzheimer’s disease: a Mendelian randomisation study

2021 ◽  
Vol 8 (1) ◽  
pp. e000759
Author(s):  
Daniel Higbee ◽  
Raquel Granell ◽  
Esther Walton ◽  
Roxanna Korologou-Linden ◽  
George Davey Smith ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lung Function ◽  
Causal Relationship ◽  
Mendelian Randomisation ◽  
P Value ◽  
Unmeasured Confounding ◽  
Increased Risk ◽  
Shared Risk

RationaleLarge retrospective case-control studies have reported an association between chronic obstructive pulmonary disease (COPD), reduced lung function and an increased risk of Alzheimer’s disease. However, it remains unclear if these diseases are causally linked, or due to shared risk factors. Conventional observational epidemiology suffers from unmeasured confounding and reverse causation. Additional analyses addressing causality are required.ObjectivesTo examine a causal relationship between COPD, lung function and Alzheimer’s disease.MethodsUsing two-sample Mendelian randomisation, we used single nucleotide polymorphisms (SNPs) identified in a genome wide association study (GWAS) for lung function as instrumental variables (exposure). Additionally, we used SNPs discovered in a GWAS for COPD in those with moderate to very severe obstruction. The effect of these SNPs on Alzheimer’s disease (outcome) was taken from a GWAS based on a sample of 24 807 patients and 55 058 controls.ResultsWe found minimal evidence for an effect of either lung function (OR: 1.02 per SD; 95% CI 0.91 to 1.13; p value 0.68) or liability for COPD on Alzheimer’s disease (OR: 0.97 per SD; 95% CI 0.92 to 1.03; p value 0.40).ConclusionNeither reduced lung function nor liability COPD are likely to be causally associated with an increased risk of Alzheimer’s, any observed association is likely due to unmeasured confounding. Scientific attention and health prevention policy may be better focused on overlapping risk factors, rather than attempts to reduce risk of Alzheimer’s disease by targeting impaired lung function or COPD directly.

Practical Geriatrics: End-of-Life Care for Persons With Alzheimer's Disease

2005 ◽  
Vol 56 (2) ◽  
pp. 139-141 ◽  
Author(s):  
Kye Y. Kim ◽  
Paul A. Yeaman ◽  
Reba L. Keene
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
End Of Life ◽  
End Of Life Care ◽  
Life Care
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