A Novel Study and Meta-Analysis of the Genetic Variation of the Serotonin Transporter Promoter in the Italian Population Do Not Support a Large Effect on Alzheimer's Disease Risk

Alzheimer’s disease (AD) is a neurodegenerative disorder whose clinical onset is mainly characterized by memory loss. During AD progression, behavioral and psychological symptoms of dementia (BPSD) frequently occur. In this paper we evaluated the association between AD and the short/long (S/L) functional polymorphism of the promoter region of the 5-hydroxytryptamine (5-HT) transporter gene (SLC6A4). The S-allele shows a 2-fold reduced transcriptional rate, causing an imbalance in 5-HT intracellular availability that might in turn trigger behavioral and cognitive alterations. We also genotyped theSLC6A4promoter functional variantrs25531(A→G). By comparing the genotypic and allelic frequencies in an Italian population of 235 AD and 207 controls, we found an association between5-HTTLPRand AD (odds ratio for the L-allele versus the S-allele: 0.74, associatedPvalue = .03), while no difference was found for thers25531. A meta-analysis of studies in Italy assessing5-HTTLPRand AD risk gave an estimation of odds ratio for the L-allele versus the S-allele of 0.85 (associatedPvalue = .08). Overall, our findings are not supportive of a large genetic effect of the explored polymorphisms on AD risk.

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Spiritual Fitness: A New Dimension in Alzheimer’s Disease Prevention

Journal of Alzheimer s Disease ◽

10.3233/jad-201433 ◽

2021 ◽

Vol 80 (2) ◽

pp. 505-519

Author(s):

Dharma Singh Khalsa ◽

Andrew B. Newberg

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Disease Prevention ◽

Chronic Stress ◽

Disease Risk ◽

Memory Loss ◽

Well Being ◽

Cognitive Disability ◽

Spiritual Wellbeing ◽

Spiritual Fitness

Background: Religious and spiritual interventions may have an effect on Alzheimer’s disease prevention. Kirtan Kriya meditation has been shown to mitigate the deleterious effects of chronic stress on cognition, reverse memory loss, and create psychological and spiritual wellbeing, which may reduce multiple drivers of Alzheimer’s disease risk. Objective: To detail a new concept in medicine called Spiritual Fitness, a merging of stress reduction, basic wellbeing, and psycho/spiritual wellbeing to prevent Alzheimer’s disease. Methods: The literature on the topics mentioned above is described, including an in-depth discussion on why and how each are critical to advancing the future of Alzheimer’s disease prevention. The many negative effects of chronic stress, and the benefits of Kirtan Kriya, are reviewed. The four pillars of basic wellbeing, six practical aspects of psychological wellbeing, and the four new non-sectarian features of spiritual fitness are then disclosed. Moreover, instructions on practicing Kirtan Kriya are offered in the Supplementary Material. Conclusion: Religious and spiritual practices, including Kirtan Kriya, are crucial components in the development of enhanced cognition and well-being, which may help prevent and, in some cases, reverse cognitive decline. The key point of this review is that making a commitment to live a brain longevity lifestyle including spiritual fitness is a critically important way for aging Alzheimer’s disease free. We hope that this article will inspire scientists, clinicians, and patients to embrace this new concept of spiritual fitness and make it a part of every multidomain program for the prevention of cognitive disability.

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Meta-Analysis of Alzheimer's Disease Risk with Obesity, Diabetes, and Related Disorders

Biological Psychiatry ◽

10.1016/j.biopsych.2009.02.013 ◽

2010 ◽

Vol 67 (6) ◽

pp. 505-512 ◽

Cited By ~ 318

Author(s):

Louis A. Profenno ◽

Anton P. Porsteinsson ◽

Stephen V. Faraone

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Disease Risk ◽

Meta Analysis

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Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk

Nature Genetics ◽

10.1038/s41588-018-0311-9 ◽

2019 ◽

Vol 51 (3) ◽

pp. 404-413 ◽

Cited By ~ 398

Author(s):

Iris E. Jansen ◽

Jeanne E. Savage ◽

Kyoko Watanabe ◽

Julien Bryois ◽

Dylan M. Williams ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Disease Risk ◽

Meta Analysis ◽

Genome Wide ◽

Functional Pathways

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Impact of Physical Activity on Cognitive Decline, Dementia, and Its Subtypes: Meta-Analysis of Prospective Studies

BioMed Research International ◽

10.1155/2017/9016924 ◽

2017 ◽

Vol 2017 ◽

pp. 1-13 ◽

Cited By ~ 59

Author(s):

Chris B. Guure ◽

Noor A. Ibrahim ◽

Mohd B. Adam ◽

Salmiah Md Said

Keyword(s):

Physical Activity ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Protective Effect ◽

Cognitive Decline ◽

Vascular Dementia ◽

Prospective Studies ◽

Odds Ratio ◽

Meta Analysis ◽

Nonparametric Models

The association of physical activity with dementia and its subtypes has remained controversial in the literature and has continued to be a subject of debate among researchers. A systematic review and meta-analysis of longitudinal studies on the relationship between physical activity and the risk of cognitive decline, all-cause dementia, Alzheimer’s disease, and vascular dementia among nondemented subjects are considered. A comprehensive literature search in all available databases was conducted up until April 2016. Well-defined inclusion and exclusion criteria were developed with focus on prospective studies ≥ 12 months. The overall sample from all studies is 117410 with the highest follow-up of 28 years. The analyses are performed with both Bayesian parametric and nonparametric models. Our analysis reveals a protective effect for high physical activity on all-cause dementia, odds ratio of 0.79, 95% CI (0.69, 0.88), a higher and better protective effect for Alzheimer’s disease, odds ratio of 0.62, 95% CI (0.49, 0.75), cognitive decline odds ratio of 0.67, 95% CI (0.55, 0.78), and a nonprotective effect for vascular dementia of 0.92, 95% CI (0.62, 1.30). Our findings suggest that physical activity is more protective against Alzheimer’s disease than it is for all-cause dementia, vascular dementia, and cognitive decline.

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Clinical course of Alzheimer’s disease

10.1093/med/9780199569854.003.0002 ◽

2011 ◽

Author(s):

Alberto Lleo ◽

Rafael Blesa

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Daily Living ◽

Clinical Course ◽

Neurodegenerative Disorder ◽

Memory Loss ◽

Remote Memory ◽

Initial Symptom ◽

Delayed Recall ◽

Age Related

• Alzheimer’s disease is an age-related neurodegenerative disorder, with onset usually in late life, characterized by cognitive impairment, a variety of behavioural symptoms, and restrictions in the activities of daily living• The initial symptom is episodic memory loss, in particular in delayed recall of visual and/or verbal material. Immediate and remote memory is usually preserved in early stages...

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WWOX is a Risk Factor for Alzheimer’s Disease: How and Why?

Proceedings of the Singapore National Academy of Science ◽

10.1142/s2591722620400037 ◽

2020 ◽

Vol 14 (01) ◽

pp. 31-45

Author(s):

Chun-I Sze ◽

Kuang-Yu Wen ◽

Nan-Shan Chang

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Middle Ages ◽

Meta Analysis ◽

Memory Loss ◽

Early Death ◽

Cancer Cell Growth ◽

Functional Antagonism ◽

Wwox Gene

A recent large genome-wide association meta-analysis revealed that the human WWOX gene is regarded as one of the five newly identified risk factors for Alzheimer’s disease (AD). However, this study did not functionally characterize how WWOX protein deficiency affects AD initiation, progression and neurodegeneration. In this review, evidence and perspectives are provided regarding how WWOX works in limiting neurodegeneration. Firstly, loss of WWOX/Wwox gene leads to severe neural diseases with degeneration, metabolic disorder and early death in the newborns. Downregulation of pY33-WWOX may start at middle ages, and this leads to slow aggregation of a cascade of proteins, namely TRAPPC6A[Formula: see text], TIAF1 and SH3GLB2, that leads to amyloid-beta (A[Formula: see text]) formation and tau tangle formation in old-aged AD patients. Secondly, functional antagonism between tumor suppressors p53 and WWOX may occur in vivo, in which p53-mediated inflammation is blocked by WWOX. Loss of balance in the functional antagonism leads to aggregation of pathogenic proteins for AD such as tau and A[Formula: see text] in the brain cortex and hippocampus. Thirdly, downregulation of pY33-WWOX is accompanied by upregulation of pS14-WWOX. The event frequently correlates with enhanced AD progression and cancer cell growth in vivo. A small peptide Zfra4-10 dramatically suppresses pS14-WWOX and restores memory loss in triple transgenic (3xTg) mice, and inhibits cancer growth in mice as well. Finally, a supporting scenario is that WWOX deficiency induces enhanced cell migration and loss of cell-to-cell recognition. This allows the generation of neuronal heterotopia and associated epileptic seizure in WWOX-deficient newborn patients.

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The Three Nociceptive Responses of the Orbicularis Oculi Reflex in Alzheimer’s Disease: State of the Evidence and Meta-analysis

Clinical EEG and Neuroscience ◽

10.1177/1550059418825169 ◽

2019 ◽

Vol 50 (5) ◽

pp. 354-360

Author(s):

Juan S. Leon-Ariza ◽

Diddier G. Prada ◽

Daniel S. Leon-Ariza ◽

Camilo Castillo ◽

Fidias E. Leon-Sarmiento

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Odds Ratio ◽

Meta Analysis ◽

Blink Reflex ◽

Review Of The Literature ◽

Number Of Patients ◽

Nociceptive Responses ◽

Regression Test ◽

Orbicularis Oculi Reflex

There is an emerging belief that electrically elicited blink reflexes (BR) may distinguish Alzheimer’s disease (AD) from other disorders characterized by memory dysfunction. To qualitatively and quantitatively distinguish the effects that electrical stimulation has over the blink reflex (eBR) recorded from patients with AD and healthy controls (HCs), we did a systematic review of the literature, and conducted a meta-analysis. Following our selected criteria, 94 AD patients and 97 HCs were identified from articles published in English between 1950 and 2017. Although the 3 responses (R1, R2 and R3) of the eBR were studied in a number of patients, only the R2 response was quantified in all studies. Thresholds and stimulation intensities parameters were found to be used in a miscellaneous form, and the majority of times, such parameters deviated from validated guidelines. The stimulation frequencies used to elicit the BR responses ranged between 0.14 and 0.2 Hz. These frequencies favored HCs compared with AD patients (odds ratio = 1.08; 95% CI = 0.30-1.85), I2 = 0% [ P = .99]; Q = 271.89 [ df = 7, P < .000]). Egger’s regression test suggested publication bias (intercept = 32.38; 95% CI = −8.98 to −3.2; P = .001). Our results unveiled key shortcomings in the data reported; such shortcomings need to be corrected in future AD research looking for obtaining more reliable and reproducible eBR studies; otherwise, interventions may be misleading.

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Blood circulating miRNAs as biomarkers of Alzheimer’s disease: a systematic review and meta-analysis

Biomarkers in Medicine ◽

10.2217/bmm-2018-0341 ◽

2019 ◽

Vol 13 (12) ◽

pp. 1045-1054

Author(s):

Ya-Heng Zhang ◽

Shu-Feng Bai ◽

Jun-Qiang Yan

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Odds Ratio ◽

Diagnostic Performance ◽

Meta Analysis ◽

Diagnostic Odds Ratio ◽

Circulating Mirnas ◽

Cognitively Normal ◽

Specificity And Sensitivity ◽

Normal Controls

Aim: It is already known that miRNAs can be differentially expressed in Alzheimer’s disease (AD). We aimed to evaluate the performance of miRNAs from blood as potential biomarkers for AD. Materials & methods: MEDLINE, PubMed and Embase were searched for studies about peripheral blood miRNAs that could discriminate patients with AD from cognitively normal controls. The data regarding the specificity and sensitivity were extracted. STATA 14.0 was used to analyze the data. Results: Ten studies containing 770 AD and 664 normal controls. The analysis showed that miRNAs presented excellent diagnostic performance and the overall sensitivity was 0.80 (95% CI: 0.75–0.83), specificity was 0.83 (95% CI: 0.78–0.87) and diagnostic odds ratio was 14 (95% CI: 11–19). Subgroup analysis suggested that the Caucasian group and blood group showed a better performance in AD diagnosis and the diagnostic odds ratio was 42 and 34, respectively. Conclusion: This meta-analysis showed that miRNAs may be a promising biomarkers for AD.

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