scholarly journals Immunological Aspects and Anti-Amyloid Strategy for Alzheimer’s Dementia

2013 ◽  
Vol 64 (4) ◽  
pp. 603-608 ◽  
Author(s):  
Rajka M. Liščić
Keyword(s):  
The Elderly ◽  
Alzheimer’S Dementia ◽  
Paper Briefly ◽  
Complement Components ◽  
Synaptic Loss ◽  
Alzheimer's Dementia ◽  
Amyloid Deposits ◽  
Presymptomatic Stage ◽  
The Brain

Abstract Alzheimer’s dementia (AD) is the most common form of dementia among the elderly, accounting for at least two-thirds of all dementia cases. It represents a costly burden, since its global prevalence is estimated at 24 million cases. Amyloid beta or Aβ plaques and neurofibrillary tangles define AD pathologically but do not fully explain it, because dementia may also be caused by inflammation resulting in neuronal, axonal synaptic loss and dysfunction. An important component of AD pathophysiology are amyloid plaques surrounded by activated microglia, cytokines, and complement components, suggesting inflammation. In the diagnosis of AD, cerebrospinal fluid markers, especially in vivo amyloid measurements, contribute to an accurate assessment of AD pathology and differential diagnosis. Aβ levels are a very good marker for the presence of amyloid deposits in the brain, while total tau and phosphorylated tau are useful for the detection of neurodegeneration. The implementation of anti-amyloid therapy and other disease-modifying interventions may have immense clinical impact if initiated at an early or presymptomatic stage of AD, before significant brain damage occurs. This paper briefly reviews the abovementioned topics and provides recommendations for future studies.

Metabolomic Alterations in the Blood and Brain in Association with Alzheimer’s Disease: Evidence from in vivo to Clinical Studies

2021 ◽  
pp. 1-28
Author(s):  
Sirawit Sriwichaiin ◽  
Nipon Chattipakorn ◽  
Siriporn C. Chattipakorn
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Studies ◽  
Elderly Population ◽  
The Elderly ◽  
Pathological Findings ◽  
Major Health Problem ◽  
Major Health ◽  
The Brain

Alzheimer’s disease (AD) has become a major health problem among the elderly population. Some evidence suggests that metabolic disturbance possibly plays a role in the pathophysiology of AD. Currently, the study of metabolomics has been used to explore changes in multiple metabolites in several diseases, including AD. Thus, the metabolomics research in AD might provide some information regarding metabolic dysregulations, and their possible associated pathophysiology. This review summarizes the information discovered regarding the metabolites in the brain and the blood from the metabolomics research of AD from both animal and clinical studies. Additionally, the correlation between the changes in metabolites and outcomes, such as pathological findings in the brain and cognitive impairment are discussed. We also deliberate on the findings of cohort studies, demonstrating the alterations in metabolites before changes of cognitive function. All of these findings can be used to inform the potential identity of specific metabolites as possible biomarkers for AD.

scholarly journals The impact of bilingualism on brain reserve and metabolic connectivity in Alzheimer's dementia

2017 ◽  
Vol 114 (7) ◽  
pp. 1690-1695 ◽  
Author(s):  
Daniela Perani ◽  
Mohsen Farsad ◽  
Tommaso Ballarini ◽  
Francesca Lubian ◽  
Maura Malpetti ◽  
...  
Keyword(s):  
Neuroprotective Effect ◽  
Alzheimer’S Dementia ◽  
Synaptic Function ◽  
Compensatory Mechanisms ◽  
Neuroprotective Effects ◽  
Alzheimer's Dementia ◽  
Bilingual Speakers ◽  
Metabolic Connectivity ◽  
The Impact

Cognitive reserve (CR) prevents cognitive decline and delays neurodegeneration. Recent epidemiological evidence suggests that lifelong bilingualism may act as CR delaying the onset of dementia by ∼4.5 y. Much controversy surrounds the issue of bilingualism and its putative neuroprotective effects. We studied brain metabolism, a direct index of synaptic function and density, and neural connectivity to shed light on the effects of bilingualism in vivo in Alzheimer’s dementia (AD). Eighty-five patients with probable AD and matched for disease duration (45 German-Italian bilingual speakers and 40 monolingual speakers) were included. Notably, bilingual individuals were on average 5 y older than their monolingual peers. In agreement with our predictions and with models of CR, cerebral hypometabolism was more severe in the group of bilingual individuals with AD. The metabolic connectivity analyses crucially supported the neuroprotective effect of bilingualism by showing an increased connectivity in the executive control and the default mode networks in the bilingual, compared with the monolingual, AD patients. Furthermore, the degree of lifelong bilingualism (i.e., high, moderate, or low use) was significantly correlated to functional modulations in crucial neural networks, suggesting both neural reserve and compensatory mechanisms. These findings indicate that lifelong bilingualism acts as a powerful CR proxy in dementia and exerts neuroprotective effects against neurodegeneration. Delaying the onset of dementia is a top priority of modern societies, and the present in vivo neurobiological evidence should stimulate social programs and interventions to support bilingual or multilingual education and the maintenance of the second language among senior citizens.

scholarly journals 3D Mapping of Neurofibrillary Tangle Burden in the Human Medial Temporal Lobe

2021 ◽  
Author(s):  
Paul A Yushkevich ◽  
Mónica Muñoz López ◽  
Maria Mercedes Iñiguez de Onzoño Martin ◽  
Ranjit Ittyerah ◽  
Sydney Lim ◽  
...  
Keyword(s):  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Ex Vivo ◽  
Neurofibrillary Tangle ◽  
Imaging Biomarkers ◽  
Synaptic Loss ◽  
The Brain ◽  
Transentorhinal Region ◽  
Anterior Posterior

Abstract Tau protein neurofibrillary tangles (NFT) are closely linked to neuronal/synaptic loss and cognitive decline in Alzheimer's disease (AD) and related dementias. Our knowledge of the pattern of NFT progression in the human brain, critical to the development of imaging biomarkers and interpretation of in vivo imaging studies in AD, is based on conventional 2D histology studies that only sample the brain sparsely. To address this limitation, ex vivo MRI and dense serial histological imaging in 18 human medial temporal lobe (MTL) specimens were used to construct 3D quantitative maps of NFT burden in the MTL at individual and group levels. These maps reveal significant variation in NFT burden along the anterior-posterior axis. While early NFT pathology is thought to be confined to the transentorhinal region, we find similar levels of NFT burden in this region and other MTL subregions, including amygdala, temporopolar cortex, and subiculum/CA1.

scholarly journals EK100 and Antrodin C Improve Brain Amyloid Pathology in APP/PS1 Transgenic Mice by Promoting Microglial and Perivascular Clearance Pathways

2021 ◽  
Vol 22 (19) ◽  
pp. 10413
Author(s):  
Huey-Jen Tsay ◽  
Hui-Kang Liu ◽  
Yueh-Hsiung Kuo ◽  
Chuan-Sheng Chiu ◽  
Chih-Chiang Liang ◽  
...  
Keyword(s):  
Hippocampal Neurogenesis ◽  
Amyloid Peptide ◽  
Oxidative Enzymes ◽  
Nesting Behavior ◽  
Amyloid Deposits ◽  
Bv2 Cells ◽  
Β Amyloid Peptide ◽  
The Brain ◽  
Microglia Morphology

Alzheimer’s disease (AD) is characterized by the deposition of β-amyloid peptide (Aβ). There are currently no drugs that can successfully treat this disease. This study first explored the anti-inflammatory activity of seven components isolated from Antrodia cinnamonmea in BV2 cells and selected EK100 and antrodin C for in vivo research. APPswe/PS1dE9 mice were treated with EK100 and antrodin C for one month to evaluate the effect of these reagents on AD-like pathology by nesting behavior, immunohistochemistry, and immunoblotting. Ergosterol and ibuprofen were used as control. EK100 and antrodin C improved the nesting behavior of mice, reduced the number and burden of amyloid plaques, reduced the activation of glial cells, and promoted the perivascular deposition of Aβ in the brain of mice. EK100 and antrodin C are significantly different in activating astrocytes, regulating microglia morphology, and promoting plaque-associated microglia to express oxidative enzymes. In contrast, the effects of ibuprofen and ergosterol are relatively small. In addition, EK100 significantly improved hippocampal neurogenesis in APPswe/PS1dE9 mice. Our data indicate that EK100 and antrodin C reduce the pathology of AD by reducing amyloid deposits and promoting nesting behavior in APPswe/PS1dE9 mice through microglia and perivascular clearance, indicating that EK100 and antrodin C have the potential to be used in AD treatment.

Amyloidosis

2010 ◽  
pp. 1766-1779
Author(s):  
M.B. Pepys ◽  
P.N. Hawkins
Keyword(s):  
Clinical Benefit ◽  
Clinical Condition ◽  
Amyloid Fibrils ◽  
Structure And Function ◽  
Seminal Vesicles ◽  
Amyloid Deposits ◽  
Precursor Proteins ◽  
And Function ◽  
The Brain

Amyloidosis is the clinical condition caused by extracellular deposition of amyloid in the tissues. Amyloid deposits are composed of amyloid fibrils, abnormal insoluble protein fibres formed by misfolding of their normally soluble precursors. About 30 different proteins can form clinically or pathologically significant amyloid fibrils in vivo as a result of either acquired or hereditary abnormalities. Small, focal, clinically silent amyloid deposits in the brain, heart, seminal vesicles, and joints are a universal accompaniment of ageing. However, clinically important amyloid deposits usually accumulate progressively, disrupting the structure and function of affected tissues and lead inexorably to organ failure and death. No treatment yet exists which can specifically clear amyloid deposits, but intervention which reduces the availability of the amyloid fibril precursor proteins may lead to amyloid regression with clinical benefit....

Music Cognition in Frontotemporal Dementia and Non-Alzheimer’s Dementias

2019 ◽  
pp. 88-102
Author(s):  
Rohani Omar
Keyword(s):  
Frontotemporal Dementia ◽  
Social Role ◽  
Music Cognition ◽  
Alzheimer’S Dementia ◽  
Healthy Individuals ◽  
Alzheimer's Dementia ◽  
The Social ◽  
The Brain ◽  
Alzheimer's Dementias

This chapter examines how music knowledge is affected in non-Alzheimer’s dementias, with a focus on frontotemporal dementia syndromes. It discusses the clinical and neurobiological rationale for studying music knowledge in non-Alzheimer’s dementia. It describes some of the ways in which music knowledge has been investigated in these patients, what musical abilities are lost or preserved in non-Alzheimer’s dementia, and how this information helps us improve our knowledge of how the brain processes music. The social role of music in evolution is briefly discussed. The chapter examines how emotions generated by and recognized in music are processed differently in frontotemporal dementia compared to healthy individuals and Alzheimer’s disease patients, including the phenomenon of musicophilia, the abnormally enhanced craving for music. Finally it explains how the differences in emotion processing between dementia diseases highlight the need for some selectivity in designing music-based therapies.

scholarly journals Mixed dementia: A review of the evidence

2017 ◽  
Vol 11 (4) ◽  
pp. 364-370 ◽  
Author(s):  
Nilton Custodio ◽  
Rosa Montesinos ◽  
David Lira ◽  
Eder Herrera-Pérez ◽  
Yadira Bardales ◽  
...  
Keyword(s):  
Pathological Finding ◽  
The Elderly ◽  
Alzheimer’S Dementia ◽  
Healthy Diet ◽  
Diagnosis And Treatment ◽  
Pharmacologic Therapy ◽  
Mixed Dementia ◽  
Alzheimer's Dementia ◽  
Alzheimer Dementia ◽  
Clinical Benefits

ABSTRACT. Mixed dementia is the coexistence of Alzheimer's disease and cerebrovascular disease (CVD) in the same demented patient. Currently, its diagnosis and treatment remains a challenge for practitioners. To provide an overview of the epidemiology, pathogenesis, natural history, diagnosis, and therapy of Mixed Vascular-Alzheimer Dementia (MVAD). The literature was reviewed for articles published between 1990-2016 by using the keywords linked to MVAD. Neuropathological studies indicate that MVAD is a very common pathological finding in the elderly with a prevalence about of 22%. The distinction between Alzheimer's dementia and vascular dementia (VD) is complex because their clinical presentation can overlap. There are international criteria for the MVAD diagnosis. The pharmacologic therapy shows modest clinical benefits that are similar among all drugs used in patients with Alzheimer's dementia and VD. The non-pharmacologic therapy includes the rigorous management of cardiovascular risk factors (especially hypertension) and the promotion of a healthy diet. The diagnosis and treatment of MVAD cannot be improved without further studies. Currently available medications provide only modest clinical benefits once a patient has developed MVAD. In subjects at risk, the antihypertensive therapy and healthy diet should be recommend for preventing or slowing the progression of MVAD.

Temperature and Cognition in Alzheimer's Dementia

CNS Spectrums ◽  
1997 ◽  
Vol 2 (2) ◽  
pp. 55-55
Keyword(s):  
The Elderly ◽  
Epidemiological Studies ◽  
Alzheimer’S Dementia ◽  
Cognitively Impaired ◽  
Alzheimer's Dementia ◽  
Temperature Oscillations ◽  
Statistical Analysis System ◽  
And Performance ◽  
Analysis System ◽  
Figure Copying

Epidemiological studies have identified thermotaxic decline in the elderly, with lower temperatures than the general population by 0.36-0.54°F. Researchers consider the lower temperatures to be due to a diminished thermoregulatory discrimination sensitivity to environmental temperature oscillations. Every 1.8°F reduction in temperature from 98.6° Fahrenheit is known to effect a decrease in laminar cerebral blood flow (CBF) by approximately 6%-7%. This reduction in CBF, however, is not without significant central nervous system effects. Correlations between CBF and performance on tests of language, memory, attention, figure copying, judgment, and similarity discrimination have been described.We have recently attempted to identify thermoregulatory changes occurring in a cognitively impaired population. We examined 39 subjects randomly selected from a clinical database (Statistical Analysis System) based upon NINCDS criteria for Alzheimer's dementia, probable and possible subtypes. Exclusion criteria included indications of abnormal endocrine or immune indices, histories of head trauma, cerebrovascular accidents, substance abuse, or current use of medications known to affect thermoregulation.

scholarly journals 1135 Longer And More Frequent Naps Predict Incident Alzheimer’s Dementia In Community-based Older Adults

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A432-A432
Author(s):  
P Li ◽  
L Gao ◽  
A Gaba ◽  
L Yu ◽  
A S Buchman ◽  
...  
Keyword(s):  
Older Adults ◽  
Proportional Hazards ◽  
The Elderly ◽  
Sleep Time ◽  
Cox Proportional Hazards ◽  
Alzheimer’S Dementia ◽  
Alzheimer's Dementia ◽  
Cox Proportional Hazards Models ◽  
Motor Activities ◽  
Underlying Mechanisms

Abstract Introduction Excessive napping duration has been associated with cognitive decline. The effect of napping frequency is less understood, and little is known about the development of Alzheimer’s dementia associated with napping. We tested whether longer or more frequent naps in the elderly are linked to the development of incident Alzheimer’s dementia. Methods We studied 1,180 older adults (age: 81.0±7.3 [SD]) in the Rush Memory and Aging Project who have been followed for up to 14 years. Motor activities of up to 10 days were recorded at baseline to assess napping characteristics objectively. We defined daytime napping episodes as motor activity segments between 10AM and 7PM with continuous zero-activity for ≥10min but <1h (to avoid off-wrist periods). Segments that were <5min apart were merged. Alzheimer’s dementia diagnosis was determined using the criteria of the National Institute of Neurological and Communicative Disorders and Strone and the Alzheimer’s Disease and Related Disorders Association. Cox proportional hazards models were performed to examine the associations of daily napping duration and frequency with incident AD. Results Of 1,180 non-demented participants at baseline (including 264 with mild cognitive impairment), 277 developed Alzheimer’s dementia within 5.74±3.36 years. On average, participants napped for 38.3±1.0 (SE) min and1.56±0.04 (SE) times per day at baseline. After adjustment for age, sex, and education, every 30-min increase in daily napping duration was associated with a 20% increase in the risk of incident AD (95% confidence interval [CI]: 9%-31%; p=0.0002). One more nap per day was associated with a 19% increase in the risk of AD (95% CI: 8%-30%; p=0.0003). These associations remained after further adjustment for total sleep time. Conclusion Longer and more frequent daytime naps predict a higher risk of incident Alzheimer’s dementia. Future studies are needed to examine specific underlying mechanisms. Support This work was supported by NIH grants RF1AG064312, RF1AG059867, R01AG017917, and R01AG56352.

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