COMMENTARY: TREATING ALZHEIMER’S DISEASE : COMBINE OR FAIL ?

2019 ◽  
pp. 1-3
Author(s):  
S. Bakchine
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Life Expectancy ◽  
Neurodegenerative Disease ◽  
Elderly People

Alzheimer’s disease (AD) is the most frequent neurodegenerative disease and accounts for more than 75% of cases of dementia in elderly people. Based on increasing life expectancy, it is predicted that the number of subjects suffering from AD and other dementias will reach the number of 131.5 millions worldwide in 2050 (1).

scholarly journals Recent Progress on Biological Activity of Amaryllidaceae and Further Isoquinoline Alkaloids in Connection with Alzheimer’s Disease

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5240
Author(s):  
Lucie Cahlíková ◽  
Rudolf Vrabec ◽  
Filip Pidaný ◽  
Rozálie Peřinová ◽  
Negar Maafi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Biological Activity ◽  
Life Expectancy ◽  
Neurodegenerative Disease ◽  
Elderly People ◽  
Recent Progress ◽  
Isoquinoline Alkaloids ◽  
Amaryllidaceae Alkaloids ◽  
Age Related

Alzheimer’s disease (AD) is a progressive age-related neurodegenerative disease recognized as the most common form of dementia among elderly people. Due to the fact that the exact pathogenesis of AD still remains to be fully elucidated, the treatment is only symptomatic and available drugs are not able to modify AD progression. Considering the increase in life expectancy worldwide, AD rates are predicted to increase enormously, and thus the search for new AD drugs is urgently needed. Due to their complex nitrogen-containing structures, alkaloids are considered to be promising candidates for use in the treatment of AD. Since the introduction of galanthamine as an antidementia drug in 2001, Amaryllidaceae alkaloids (AAs) and further isoquinoline alkaloids (IAs) have been one of the most studied groups of alkaloids. In the last few years, several compounds of new structure types have been isolated and evaluated for their biological activity connected with AD. The present review aims to comprehensively summarize recent progress on AAs and IAs since 2010 up to June 2021 as potential drugs for the treatment of AD.

Lighting and Alzheimer’s disease and related dementias: Spotlight on sleep and depression

2021 ◽  
Vol 53 (5) ◽  
pp. 405-422
Author(s):  
MG Figueiro ◽  
HC Kales
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disease ◽  
Sleep Disturbances ◽  
Well Being ◽  
Pharmacological Intervention ◽  
Negative Effects ◽  
Health And Well Being ◽  
Positive Results

Alzheimer’s disease and related dementias is the collective term for a progressive neurodegenerative disease for which there is presently no cure. This paper focuses on two symptoms of the disease, sleep disturbances and depression, and discusses how light can be used as a non-pharmacological intervention to mitigate their negative effects. Bright days and dark nights are needed for health and well-being, but the present components of the built environment, especially those places where older adults spend most of their days, are too dimly illuminated during the day and too bright at night. To be effective light needs to be correctly specified, implemented and measured. Yet, without the appropriate specification and measurement of the stimulus, researchers will not be able to successfully demonstrate positive results in the field, nor will lighting designers and specifiers have the confidence to implement lighting solutions for promoting better sleep and mood in this population.

scholarly journals The health of elderly people bearing Alzheimer’s disease: an integrative review / Saúde do idoso com doença de Alzheimer: revisão integrativa

2018 ◽  
Vol 10 (4) ◽  
pp. 941
Author(s):  
Hemmily Nóbrega Ventura ◽  
Leila De Cássia Tavares da Fonseca ◽  
Bruno César Fernandes Borges ◽  
Jéssica Yasmine Lacerda Nóbrega ◽  
Herbert Nóbrega Ventura ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Elderly People ◽  
Integrative Review

Objetivo: Verificar o conhecimento produzido pelos pesquisadores a respeito da saúde do idoso com Doença de Alzheimer (DA). Métodos: Revisão integrativa da literatura com levantamento bibliográfico realizado na Biblioteca Virtual em Saúde (BVS), MEDLINE e nos bancos de dados do Portal de Periódicos Capes.  Resultados: Observou-se a incipiência de artigos científicos publicados sobre a Doença de Alzheimer com enfoque na saúde da pessoa idosa. Conclusão: Verificou-se a necessidade de pesquisas para investigar a saúde do idoso em face à doença de Alzheimer que possibilitem aporte teórico na elaboração de políticas públicas de saúde mais abrangentes para os cuidados aos idosos. Descritores: Envelhecimento, Doença de Alzheimer, Autonomia pessoal, Saúde do idoso.

scholarly journals Heparan sulphate compounds regulate cholesterol metabolism in neurodegenerative disease models

2021 ◽  
Author(s):  
◽  
Rosemary Heathcott
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disease ◽  
Cell Line ◽  
Cholesterol Metabolism ◽  
Neurodegenerative Disorder ◽  
Heparan Sulphate ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Lysosomal Storage

<p>Heparan sulphate proteoglycans (HSPG) are central to numerous processes of the mammalian cell. The highly charged negative side chains of the heparan sulphate (HS) oligosaccharides are essential for the regulatory and structural functions of the proteoglycan. Synthetic HS compounds have potential therapeutic value due to their ability to mimic naturally occurring HS. Niemann-Pick disease type C (NPC) is a fatal childhood neurodegenerative disease with characteristic cholesterol and sphingolipid accumulation in the late endosome or lysosome. Alzheimer’s disease, another neurodegenerative disorder, shares alterations of cholesterol and amyloid β metabolism with NPC. In this study,a set of novel heparan sulphate compounds with a range of structures and oligosaccharide side groups with a variety of degrees of sulphation was investigated with regards to their effects on cholesterol and amyloid β metabolism in cell line models of these two diseases. Fluorescent staining of cholesterol and confocal microscopy showed highly sulphated compounds reduce the accumulation of cholesterol in the perinuclear lysosomal storage organelles in patient fibroblast cell lines. The compounds had no effect on secreted amyloid β levels or amyloid precursor protein levels in a neuronal cell line model of early onset Alzheimer’s disease. The mechanism of cholesterol reduction is unclear but may be related to a reduction in HSPG-associated endocytosis of LDL/cholesterol.</p>

Predictors of Life Expectancy in Autopsy-Confirmed Alzheimer’s Disease

2022 ◽  
pp. 1-11
Author(s):  
Jeff Schaffert ◽  
Christian LoBue ◽  
Linda S. Hynan ◽  
John Hart ◽  
Heidi Rossetti ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Life Expectancy ◽  
Functional Impairment ◽  
Neuropsychiatric Symptoms ◽  
Primary Objective ◽  
Cognitive Predictors ◽  
Clinical Diagnoses ◽  
Neurological Exam ◽  
Univariate Analyses

Background: Life expectancy (LE) following Alzheimer’s disease (AD) is highly variable. The literature to date is limited by smaller sample sizes and clinical diagnoses. Objective: No study to date has evaluated predictors of AD LE in a retrospective large autopsy-confirmed sample, which was the primary objective of this study. Methods: Participants (≥50 years old) clinically and neuropathologically diagnosed with AD were evaluated using National Alzheimer’s Coordinating Center (N = 1,401) data. Analyses focused on 21 demographic, medical, neuropsychiatric, neurological, functional, and global cognitive predictors of LE at AD dementia diagnosis. These 21 predictors were evaluated in univariate analyses. Variables found to be significant were then entered into a forward multiple regression. LE was defined as months between AD diagnosis and death. Results: Fourteen predictors were significant in univariate analyses and entered into the regression. Seven predictors explained 27% of LE variance in 764 total participants. Mini-Mental State Examination (MMSE) score was the strongest predictor of LE, followed by sex, age, race/ethnicity, neuropsychiatric symptoms, abnormal neurological exam results, and functional impairment ratings. Post-hoc analyses revealed correlations of LE were strongest with MMSE ≤12. Conclusion: Global cognitive functioning was the strongest predictor of LE following diagnosis, and AD patients with severe impairment had the shortest LE. AD patients who are older, male, white, and have more motor symptoms, functional impairment, and neuropsychiatric symptoms were also more likely have shorter LE. While this model cannot provide individual prognoses, additional studies may focus on these variables to enhance predictions of LE in patients with AD.

The Early Diagnosis of Alzheimer's Disease

2016 ◽  
pp. 1-16
Author(s):  
Yanna Ren ◽  
Weiping Yang ◽  
Xiaoyu Tang ◽  
Fengxia Wu ◽  
Satoshi Takahashi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Life Expectancy ◽  
Early Stage ◽  
Memory Loss ◽  
Cerebral Atrophy ◽  
Future Research ◽  
Research Perspectives ◽  
Genetic Examination ◽  
Imaging Detection

Alzheimer's disease, a common form of dementia, is a type of neurodegenerative disease that affects more than 30% of the population older than 85. Clinically, it is characterized as memory loss and cognitive decline. Pathologically, its symptoms include cerebral atrophy, amyloid plaques and NFTs. Generally, the life expectancy is no more than nine years after the definite diagnosis, and life expectancy exceeds 14 years in only 3% of patients. Presently, there is no effective treatment to stop the process; the only measures we can take are to ease or improve symptoms temporarily. Therefore, it is necessary to diagnosis the disease in the early stage, such as through imaging detection via CT, MRI, PET and MSR, or prediction before the disease (genetic examination). However, literature data have supported the notion that Alzheimer's disease patients show cognitive reserve abilities to some degree. In the future, research perspectives may focus on the cognitive training paradigms in compensatory and restorative strategies.

Unraveling the Role of Mitochondria in Alzheimer’s Disease

2020 ◽  
pp. 407-430
Author(s):  
Sónia C. Correia ◽  
Paula I. Moreira ◽  
George Perry
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disease ◽  
Scientific Community ◽  
Future Research ◽  
Mitochondrial Bioenergetics ◽  
Limited Knowledge ◽  
Comprehensive Picture ◽  
Mitochondrial Defects

Alzheimer’s disease (AD) is an intriguing and still unsolved puzzle that has attracted, over the last decades, the interest of the scientific community. Despite the limited knowledge regarding the initial cause(s) of AD, mitochondrial abnormalities have been pinpointed as one of the earliest and strongest events related with the pathological course of this complex neurodegenerative disease. In this sense, the present chapter addresses three distinct but connected pieces of the AD puzzle: (a) how could defects of mitochondrial bioenergetics and dynamics contribute to AD pathology? (b) Could mitochondrial defects promote the disease-defining amyloid-β‎ and tau pathologies, and vice versa? and (c) Are mitochondria feasible therapeutic targets to postpone AD symptomatology and neuropathology, and, if so, how and when? The understanding and connection of these puzzle pieces provide a more comprehensive picture about the fundamental role of mitochondrial (mal)function in the neurodegenerative processes that occur in AD and propels future research interventions aimed to forestall AD-related pathological phenotype by bolstering mitochondrial “health.”

scholarly journals P38α MAPK Signaling—A Robust Therapeutic Target for Rab5-Mediated Neurodegenerative Disease

2020 ◽  
Vol 21 (15) ◽  
pp. 5485
Author(s):  
Ursula A. Germann ◽  
John J. Alam
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Therapeutic Target ◽  
Kinase Inhibitors ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Therapeutic Effects ◽  
P38α Kinase

Multifactorial pathologies, involving one or more aggregated protein(s) and neuroinflammation are common in major neurodegenerative diseases, such as Alzheimer’s disease and dementia with Lewy bodies. This complexity of multiple pathogenic drivers is one potential explanation for the lack of success or, at best, the partial therapeutic effects, respectively, with approaches that have targeted one specific driver, e.g., amyloid-beta, in Alzheimer’s disease. Since the endosome-associated protein Rab5 appears to be a convergence point for many, if not all the most prominent pathogenic drivers, it has emerged as a major therapeutic target for neurodegenerative disease. Further, since the alpha isoform of p38 mitogen-activated protein kinase (p38α) is a major regulator of Rab5 activity and its effectors, a biology that is distinct from the classical nuclear targets of p38 signaling, brain-penetrant selective p38α kinase inhibitors provide the opportunity for significant therapeutic advances in neurogenerative disease through normalizing dysregulated Rab5 activity. In this review, we provide a brief summary of the role of Rab5 in the cell and its association with neurodegenerative disease pathogenesis. We then discuss the connection between Rab5 and p38α and summarize the evidence that through modulating Rab5 activity there are therapeutic opportunities in neurodegenerative diseases for p38α kinase inhibitors.

scholarly journals Omega-3 Fatty Acids in Early Prevention of Inflammatory Neurodegenerative Disease: A Focus on Alzheimer’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
J. Thomas ◽  
C. J. Thomas ◽  
J. Radcliffe ◽  
C. Itsiopoulos
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fatty Acids ◽  
Neurodegenerative Disease ◽  
Dietary Intervention ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Early Prevention ◽  
Markers Of Inflammation ◽  
Long Chain

Alzheimer’s disease (AD) is the leading cause of dementia and the most common neurodegenerative disease in the elderly. Furthermore, AD has provided the most positive indication to support the fact that inflammation contributes to neurodegenerative disease. The exact etiology of AD is unknown, but environmental and genetic factors are thought to contribute, such as advancing age, family history, presence of chronic diseases such as cardiovascular disease (CVD) and diabetes, and poor diet and lifestyle. It is hypothesised that early prevention or management of inflammation could delay the onset or reduce the symptoms of AD. Normal physiological changes to the brain with ageing include depletion of long chain omega-3 fatty acids and brains of AD patients have lower docosahexaenoic acid (DHA) levels. DHA supplementation can reduce markers of inflammation. This review specifically focusses on the evidence in humans from epidemiological, dietary intervention, and supplementation studies, which supports the role of long chain omega-3 fatty acids in the prevention or delay of cognitive decline in AD in its early stages. Longer term trials with long chain omega-3 supplementation in early stage AD are warranted. We also highlight the importance of overall quality and composition of the diet to protect against AD and dementia.

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