New Frontiers in the Prevention, Diagnosis, and Treatment of Alzheimer’s Disease

2021 ◽  
pp. 1-13
Author(s):  
Leonardo Guzman-Martinez ◽  
Camila Calfío ◽  
Gonzalo A. Farias ◽  
Cristian Vilches ◽  
Raul Prieto ◽  
...  

One of the major puzzles in medical research and public health systems worldwide is Alzheimer’s disease (AD), reaching nowadays a prevalence near 50 million people. This is a multifactorial brain disorder characterized by progressive cognitive impairment, apathy, and mood and neuropsychiatric disorders. The main risk of AD is aging; a normal biological process associated with a continuum dynamic involving a gradual loss of people’s physical capacities, but with a sound experienced view of life. Studies suggest that AD is a break from normal aging with changes in the powerful functional capacities of neurons as well as in the mechanisms of neuronal protection. In this context, an important path has been opened toward AD prevention considering that there are elements of nutrition, daily exercise, avoidance of toxic substances and drugs, an active social life, meditation, and control of stress, to achieve healthy aging. Here, we analyze the involvement of such factors and how to control environmental risk factors for a better quality of life. Prevention as well as innovative screening programs for early detection of the disease using reliable biomarkers are becoming critical to control the disease. In addition, the failure of traditional pharmacological treatments and search for new drugs has stimulated the emergence of nutraceutical compounds in the context of a “multitarget” therapy, as well as mindfulness approaches shown to be effective in the aging, and applied to the control of AD. An integrated approach involving all these preventive factors combined with novel pharmacological approaches should pave the way for the future control of the disease.

2020 ◽  
Vol 27 ◽  
Author(s):  
Reyaz Hassan Mir ◽  
Abdul Jalil Shah ◽  
Roohi Mohi-ud-din ◽  
Faheem Hyder Potoo ◽  
Mohd. Akbar Dar ◽  
...  

: Alzheimer's disease (AD) is a chronic neurodegenerative brain disorder characterized by memory impairment, dementia, oxidative stress in elderly people. Currently, only a few drugs are available in the market with various adverse effects. So to develop new drugs with protective action against the disease, research is turning to the identification of plant products as a remedy. Natural compounds with anti-inflammatory activity could be good candidates for developing effective therapeutic strategies. Phytochemicals including Curcumin, Resveratrol, Quercetin, Huperzine-A, Rosmarinic acid, genistein, obovatol, and Oxyresvertarol were reported molecules for the treatment of AD. Several alkaloids such as galantamine, oridonin, glaucocalyxin B, tetrandrine, berberine, anatabine have been shown anti-inflammatory effects in AD models in vitro as well as in-vivo. In conclusion, natural products from plants represent interesting candidates for the treatment of AD. This review highlights the potential of specific compounds from natural products along with their synthetic derivatives to counteract AD in the CNS.


Open Biology ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 200286
Author(s):  
Niraj Kumar Jha ◽  
Ankur Sharma ◽  
Saurabh Kumar Jha ◽  
Shreesh Ojha ◽  
Dinesh Kumar Chellappan ◽  
...  

Excessive exposure to toxic substances or chemicals in the environment and various pathogens, including viruses and bacteria, is associated with the onset of numerous brain abnormalities. Among them, pathogens, specifically viruses, elicit persistent inflammation that plays a major role in Alzheimer's disease (AD) as well as dementia. AD is the most common brain disorder that affects thought, speech, memory and ability to execute daily routines. It is also manifested by progressive synaptic impairment and neurodegeneration, which eventually leads to dementia following the accumulation of Aβ and hyperphosphorylated Tau. Numerous factors contribute to the pathogenesis of AD, including neuroinflammation associated with pathogens, and specifically viruses. The human immunodeficiency virus (HIV) is often linked with HIV-associated neurocognitive disorders (HAND) following permeation through the blood–brain barrier (BBB) and induction of persistent neuroinflammation. Further, HIV infections also exhibited the ability to modulate numerous AD-associated factors such as BBB regulators, members of stress-related pathways as well as the amyloid and Tau pathways that lead to the formation of amyloid plaques or neurofibrillary tangles accumulation. Studies regarding the role of HIV in HAND and AD are still in infancy, and potential link or mechanism between both is not yet established. Thus, in the present article, we attempt to discuss various molecular mechanisms that contribute to the basic understanding of the role of HIV-associated neuroinflammation in AD and HAND. Further, using numerous growth factors and drugs, we also present possible therapeutic strategies to curb the neuroinflammatory changes and its associated sequels.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 149-149
Author(s):  
Zara Sajwani

Abstract The purpose of this presentation is to identify burden and problems experienced by caregivers of patients with Alzheimer’s Disease (AD). AD results in gradual deterioration of cognition, language, and memory that can impact an individual’s ability to independently perform daily functional activities (CDC, 2019). The role of caregivers is significant in providing assistance to the patients with chronic AD which can be a source of strain for caregiver population. About 16.3 million informal AD caregivers have spent 18.5 billion hours, which is equal to value of $234 billion, to assist patients with other dementia types and AD in 2018 (Alzheimer’s Association, 2019). In-depth literature synthesis was carried out using multiple databases. Recent and relevant articles were selected to be added in the review. Due to responsibility of constant vigilance of AD patients, the caregivers may overlook their self-care needs and detach themselves from social life. Literature analysis revealed common challenges and needs of AD care partners including limited social engagement, concerns of sexuality, and sleep problems. Understanding caregiver problems will help nurses and other health care professionals to support families by planning preventive measures. Resources can be invested to improve physical and mental well-being of caregivers. Researches can be planned to bridge the knowledge gap identified through literature review on this topic. References Alzheimer’s Association. (2019). Alzheimer’s disease caregivers. http://act.alz.org/site/DocServer/caregivers_fact_sheet.pdf?docID=3022 Centers for Disease Control and Prevention. (2019). Alzheimer’s disease and healthy aging. https://www.cdc.gov/aging/aginginfo/alzheimers.htm


GeroPsych ◽  
2012 ◽  
Vol 25 (4) ◽  
pp. 235-245 ◽  
Author(s):  
Katja Franke ◽  
Christian Gaser

We recently proposed a novel method that aggregates the multidimensional aging pattern across the brain to a single value. This method proved to provide stable and reliable estimates of brain aging – even across different scanners. While investigating longitudinal changes in BrainAGE in about 400 elderly subjects, we discovered that patients with Alzheimer’s disease and subjects who had converted to AD within 3 years showed accelerated brain atrophy by +6 years at baseline. An additional increase in BrainAGE accumulated to a score of about +9 years during follow-up. Accelerated brain aging was related to prospective cognitive decline and disease severity. In conclusion, the BrainAGE framework indicates discrepancies in brain aging and could thus serve as an indicator for cognitive functioning in the future.


2020 ◽  
Vol 21 (12) ◽  
pp. 1164-1173
Author(s):  
Siju Ellickal Narayanan ◽  
Nikhila Sekhar ◽  
Rajalakshmi Ganesan Rajamma ◽  
Akash Marathakam ◽  
Abdullah Al Mamun ◽  
...  

: Alzheimer’s disease (AD) is a progressive brain disorder and one of the most common causes of dementia and death. AD can be of two types; early-onset and late-onset, where late-onset AD occurs sporadically while early-onset AD results from a mutation in any of the three genes that include amyloid precursor protein (APP), presenilin 1 (PSEN 1) and presenilin 2 (PSEN 2). Biologically, AD is defined by the presence of the distinct neuropathological profile that consists of the extracellular β-amyloid (Aβ) deposition in the form of diffuse neuritic plaques, intraneuronal neurofibrillary tangles (NFTs) and neuropil threads; in dystrophic neuritis, consisting of aggregated hyperphosphorylated tau protein. Elevated levels of (Aβ), total tau (t-tau) and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) have become an important biomarker for the identification of this neurodegenerative disease. The aggregation of Aβ peptide derived from amyloid precursor protein initiates a series of events that involve inflammation, tau hyperphosphorylation and its deposition, in addition to synaptic dysfunction and neurodegeneration, ultimately resulting in dementia. The current review focuses on the role of proteomes in the pathogenesis of AD.


2018 ◽  
Vol 16 (1) ◽  
pp. 49-55 ◽  
Author(s):  
J. Stenzel ◽  
C. Rühlmann ◽  
T. Lindner ◽  
S. Polei ◽  
S. Teipel ◽  
...  

Background: Positron-emission-tomography (PET) using 18F labeled florbetaben allows noninvasive in vivo-assessment of amyloid-beta (Aβ), a pathological hallmark of Alzheimer’s disease (AD). In preclinical research, [<sup>18</sup>F]-florbetaben-PET has already been used to test the amyloid-lowering potential of new drugs, both in humans and in transgenic models of cerebral amyloidosis. The aim of this study was to characterize the spatial pattern of cerebral uptake of [<sup>18</sup>F]-florbetaben in the APPswe/ PS1dE9 mouse model of AD in comparison to histologically determined number and size of cerebral Aβ plaques. Methods: Both, APPswe/PS1dE9 and wild type mice at an age of 12 months were investigated by smallanimal PET/CT after intravenous injection of [<sup>18</sup>F]-florbetaben. High-resolution magnetic resonance imaging data were used for quantification of the PET data by volume of interest analysis. The standardized uptake values (SUVs) of [<sup>18</sup>F]-florbetaben in vivo as well as post mortem cerebral Aβ plaque load in cortex, hippocampus and cerebellum were analyzed. Results: Visual inspection and SUVs revealed an increased cerebral uptake of [<sup>18</sup>F]-florbetaben in APPswe/ PS1dE9 mice compared with wild type mice especially in the cortex, the hippocampus and the cerebellum. However, SUV ratios (SUVRs) relative to cerebellum revealed only significant differences in the hippocampus between the APPswe/PS1dE9 and wild type mice but not in cortex; this differential effect may reflect the lower plaque area in the cortex than in the hippocampus as found in the histological analysis. Conclusion: The findings suggest that histopathological characteristics of Aβ plaque size and spatial distribution can be depicted in vivo using [<sup>18</sup>F]-florbetaben in the APPswe/PS1dE9 mouse model.


Marine Drugs ◽  
2021 ◽  
Vol 19 (8) ◽  
pp. 410
Author(s):  
Salar Hafez Ghoran ◽  
Anake Kijjoa

Alzheimer’s disease (AD) is an irreversible and progressive brain disorder that slowly destroys memory and thinking skills, and, eventually, the ability to perform simple tasks. As the aging population continues to increase exponentially, AD has become a big concern for society. Therefore, neuroprotective compounds are in the spotlight, as a means to tackle this problem. On the other hand, since it is believed—in many cultures—that marine organisms in an individual diet cannot only improve brain functioning, but also slow down its dysfunction, many researchers have focused on identifying neuroprotective compounds from marine resources. The fact that the marine environment is a rich source of structurally unique and biologically and pharmacologically active compounds, with unprecedented mechanisms of action, marine macroorganisms, such as tunicates, corals, sponges, algae, as well as microorganisms, such as marine-derived bacteria, actinomycetes, and fungi, have been the target sources of these compounds. Therefore, this literature review summarizes and categorizes various classes of marine-derived compounds that are able to inhibit key enzymes involved in AD, including acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), β-secretase (BACE-1), and different kinases, together with the related pathways involved in the pathogenesis of AD. The compounds discussed herein are emerging as promising anti-AD activities for further in-depth in vitro and in vivo investigations, to gain more insight of their mechanisms of action and for the development of potential anti-AD drug leads.


2019 ◽  
Author(s):  
FR Farina ◽  
DD Emek-Savaş ◽  
L Rueda-Delgado ◽  
R Boyle ◽  
H Kiiski ◽  
...  

AbstractAlzheimer’s disease (AD) is a neurodegenerative disorder characterised by severe cognitive decline and loss of autonomy. AD is the leading cause of dementia. AD is preceded by mild cognitive impairment (MCI). By 2050, 68% of new dementia cases will occur in low- and middle-income countries. In the absence of objective biomarkers, psychological assessments are typically used to diagnose MCI and AD. However, these require specialist training and rely on subjective judgements. The need for low-cost, accessible and objective tools to aid AD and MCI diagnosis is therefore crucial. Electroencephalography (EEG) has potential as one such tool: it is relatively inexpensive (cf. magnetic resonance imaging; MRI) and is portable. In this study, we collected resting state EEG, structural MRI and rich neuropsychological data from older adults (55+ years) with AD, with MCI and from healthy controls (n~60 per group). Our goal was to evaluate the utility of EEG, relative to MRI, for the classification of MCI and AD. We also assessed the performance of combined EEG and behavioural (Mini-Mental State Examination; MMSE) and structural MRI classification models. Resting state EEG classified AD and HC participants with moderate accuracy (AROC=0.76), with lower accuracy when distinguishing MCI from HC participants (AROC=0.67). The addition of EEG data to MMSE scores had no additional value compared to MMSE alone. Structural MRI out-performed EEG (AD vs HC, AD vs MCI: AROCs=1.00; HC vs MCI: AROC=0.73). Resting state EEG does not appear to be a suitable tool for classifying AD. However, EEG classification accuracy was comparable to structural MRI when distinguishing MCI from healthy aging, although neither were sufficiently accurate to have clinical utility. This is the first direct comparison of EEG and MRI as classification tools in AD and MCI participants.


SURG Journal ◽  
2010 ◽  
Vol 4 (1) ◽  
pp. 57-64 ◽  
Author(s):  
Nila Ilhamto ◽  
Lisa M Duizer

Problems of inadequate nutrition and energy intake are common in the aging population. Smell and taste deficits associated with Late-Onset Alzheimer’s Disease (LOAD) may accentuate the decline in nutritional status of elderly individuals and indirectly enhance progression of cognitive problems in LOAD. The objective of this study was to explore and characterize smell and taste recognition abilities in early stages of LOAD, beyond that of normal healthy aging. A total of 29 healthy-younger subjects aged 18-40 (HY), 13 healthy-elderly (HA) and six elderly adults diagnosed with LOAD (AD) aged 60-85, were recruited from the Guelph community. The Sniffin’ Sticks Screening Test (SSST) and Taste Strips were used to test olfactory and gustatory functions, respectively. Participants also completed the mini-mental state examination (MMSE), clock test and word recall tests to assess cognitive/memory skills. Compared to HA individuals, people with AD had significant odour recognition impairment. Correlation analysis also revealed an age-associated decline in overall taste ability. When specific tastes were examined, impairments in sour and bitter identification were observed with increasing age. However, no significant differences in specific taste abilities were found between HA and AD individuals. In predicting health status (ie. presence or absence of LOAD), an assessment of all variables in this study was conducted using Generalized Linear Model (GLM). Results showed that sweet recognition and clock test scores were the best predictive variables of health status. However, this is a preliminary model that needs refinement through further research using more individuals.


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