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Alzheimer's disease.
Literature Information
| PMID | 26921134 |
|---|---|
| Journal | Lancet (London, England) |
| Publication Year | 2016 |
| Times Cited | 1416 |
| Keywords | Alzheimer's disease, biomarkers, imaging techniques, preclinical stage, lifestyle interventions |
| Literature Type | Journal Article, Review |
| ISSN | 0140-6736 |
| Pages | 505-17 |
| Issue | 388(10043) |
| Authors | Philip Scheltens, Kaj Blennow, Monique M B Breteler, Bart de Strooper, Giovanni B Frisoni, Stephen Salloway, Wiesje Maria Van der Flier |
TL;DR
This research highlights the evolving understanding of Alzheimer's disease, emphasizing that while traditional biomarkers like amyloid and tau remain critical, the interaction of various age-related factors complicates the disease's pathology. It suggests a promising future for combining specific anti-Alzheimer's therapies with lifestyle interventions aimed at enhancing brain health, particularly in preclinical stages of the disease.
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Alzheimer's disease · biomarkers · imaging techniques · preclinical stage · lifestyle interventions
Abstract
Although the prevalence of dementia continues to increase worldwide, incidence in the western world might have decreased as a result of better vascular care and improved brain health. Alzheimer's disease, the most prevalent cause of dementia, is still defined by the combined presence of amyloid and tau, but researchers are gradually moving away from the simple assumption of linear causality as proposed in the original amyloid hypothesis. Age-related, protective, and disease-promoting factors probably interact with the core mechanisms of the disease. Amyloid β42, and tau proteins are established core cerebrospinal biomarkers; novel candidate biomarkers include amyloid β oligomers and synaptic markers. MRI and fluorodeoxyglucose PET are established imaging techniques for diagnosis of Alzheimer's disease. Amyloid PET is gaining traction in the clinical arena, but validity and cost-effectiveness remain to be established. Tau PET might offer new insights and be of great help in differential diagnosis and selection of patients for trials. In the search for understanding the disease mechanism and keys to treatment, research is moving increasingly into the earliest phase of disease. Preclinical Alzheimer's disease is defined as biomarker evidence of Alzheimer's pathological changes in cognitively healthy individuals. Patients with subjective cognitive decline have been identified as a useful population in whom to look for preclinical Alzheimer's disease. Moderately positive results for interventions targeting several lifestyle factors in non-demented elderly patients and moderately positive interim results for lowering amyloid in pre-dementia Alzheimer's disease suggest that, ultimately, there will be a future in which specific anti-Alzheimer's therapy will be combined with lifestyle interventions targeting general brain health to jointly combat the disease. In this Seminar, we discuss the main developments in Alzheimer's research.
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Primary Questions Addressed
- What are the latest findings on the interaction between lifestyle factors and Alzheimer's disease progression?
- How do emerging biomarkers like amyloid β oligomers and synaptic markers compare to traditional biomarkers in terms of diagnostic accuracy?
- What role does tau PET imaging play in the early diagnosis and differentiation of Alzheimer's disease from other types of dementia?
- How might the concept of preclinical Alzheimer's disease change the approach to early intervention and treatment strategies?
- What are the implications of combining anti-Alzheimer's therapies with lifestyle interventions for long-term patient outcomes?
Key Findings
Research Background and Objectives
The study addresses the growing global prevalence of dementia, particularly Alzheimer's disease (AD), which remains the leading cause of dementia. While the incidence of dementia appears to be decreasing in the Western world due to advancements in vascular care and enhanced brain health, the complexity of Alzheimer's pathophysiology necessitates a deeper understanding beyond the classic amyloid hypothesis. The objective of this research is to explore the evolving understanding of Alzheimer's disease mechanisms, diagnostic approaches, and potential therapeutic strategies, particularly focusing on preclinical stages and lifestyle interventions.
Main Methods and Findings
The research utilizes established cerebrospinal fluid (CSF) biomarkers, specifically amyloid β42 and tau proteins, to characterize Alzheimer's disease. It highlights the emergence of novel candidate biomarkers like amyloid β oligomers and synaptic markers, which could enhance diagnostic accuracy. Imaging techniques such as MRI and fluorodeoxyglucose PET are reaffirmed as vital diagnostic tools, while amyloid PET is recognized for its growing clinical relevance, despite unresolved questions regarding its validity and cost-effectiveness. Tau PET is also proposed as a promising method for differential diagnosis and patient selection for clinical trials.
The study emphasizes the importance of investigating the preclinical phase of Alzheimer's disease, characterized by biomarker evidence in cognitively healthy individuals. It identifies patients with subjective cognitive decline as a critical demographic for this research. Furthermore, the study reports moderately positive outcomes from interventions focusing on lifestyle factors in non-demented elderly patients, alongside interim results indicating the potential for amyloid-lowering therapies in pre-dementia stages.
Core Conclusions
The research concludes that Alzheimer's disease pathophysiology is influenced by a complex interplay of age-related, protective, and disease-promoting factors, challenging the linear causality suggested by earlier models. It posits that future strategies for combating Alzheimer's should integrate specific anti-Alzheimer's therapies with lifestyle interventions aimed at promoting overall brain health. This dual approach could enhance outcomes for individuals at various risk levels for Alzheimer's disease.
Research Significance and Impact
The significance of this research lies in its comprehensive approach to understanding Alzheimer's disease, emphasizing the need for multifaceted diagnostic and therapeutic strategies. By shifting focus to preclinical stages, it opens avenues for early intervention, potentially altering the disease trajectory. The integration of lifestyle modifications with pharmacological treatments represents a paradigm shift in managing Alzheimer's disease, highlighting the importance of holistic health in combating neurodegenerative diseases. The findings could influence future research agendas, guide clinical practices, and ultimately contribute to improved patient outcomes in Alzheimer's care.
Literatures Citing This Work
- CB2 Cannabinoid Receptor As Potential Target against Alzheimer's Disease. - Ester Aso;Isidro Ferrer - Frontiers in neuroscience (2016)
- DNA-PK Deficiency in Alzheimer's Disease. - Jyotshna Kanungo - Journal of neurology & neuromedicine (2016)
- Identification of learning-induced changes in protein networks in the hippocampi of a mouse model of Alzheimer's disease. - E Ferreira;D M Shaw;S Oddo - Translational psychiatry (2016)
- Treatment for Rheumatoid Arthritis and Risk of Alzheimer's Disease: A Nested Case-Control Analysis. - Richard C Chou;Michael Kane;Sanjay Ghimire;Shiva Gautam;Jiang Gui - CNS drugs (2016)
- Effect of mouse strain as a background for Alzheimer's disease models on the clearance of amyloid-β. - Hisham Qosa;Amal Kaddoumi - Journal of systems and integrative neuroscience (2016)
- Cystatin C Shifts APP Processing from Amyloid-β Production towards Non-Amyloidgenic Pathway in Brain Endothelial Cells. - Xia-Fei Wang;Dong-Xin Liu;Yue Liang;Li-Li Xing;Wen-Hui Zhao;Xiao-Xue Qin;De-Shu Shang;Bo Li;Wen-Gang Fang;Liu Cao;Wei-Dong Zhao;Yu-Hua Chen - PloS one (2016)
- Therapies for Prevention and Treatment of Alzheimer's Disease. - J Mendiola-Precoma;L C Berumen;K Padilla;G Garcia-Alcocer - BioMed research international (2016)
- Putative Role of Red Wine Polyphenols against Brain Pathology in Alzheimer's and Parkinson's Disease. - Mario Caruana;Ruben Cauchi;Neville Vassallo - Frontiers in nutrition (2016)
- Characterization of FRM-36143 as a new γ-secretase modulator for the potential treatment of familial Alzheimer's disease. - Jean-François Blain;Matthew G Bursavich;Emily A Freeman;Lori A Hrdlicka;Hilliary E Hodgdon;Ting Chen;Don E Costa;Bryce A Harrison;Sudarshan Kapadnis;Deirdre A Murphy;Scott Nolan;Zhiming Tu;Cuyue Tang;Duane A Burnett;Holger Patzke;Gerhard Koenig - Alzheimer's research & therapy (2016)
- The mismatch negativity as an index of cognitive decline for the early detection of Alzheimer's disease. - Manuela Ruzzoli;Cornelia Pirulli;Veronica Mazza;Carlo Miniussi;Debora Brignani - Scientific reports (2016)
... (1406 more literatures)
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