-
1.
Epidemiology of aging and associated cognitive disorders: Prevalence and incidence of Alzheimer's disease and other dementias.
Lopez, OL, Kuller, LH
Handbook of clinical neurology. 2019;:139-148
Abstract
The study of the incidence and prevalence of dementia is important to understand the distribution of dementing illness among age and sex groups, and for the detection of possible causes of these disorders. A variation in the incidence or prevalence of dementia, especially Alzheimer's disease (AD) by region or specific populations can be because of greater or lesser exposure to the causal agents of dementia. For example, in the past the striking differences in the incidence of coronary heart disease (CHD) led to the understanding of the relationship between dietary factors, such as saturated fat and dietary cholesterol, and the incidence of CHD. However, there is a high prevalence of dementia in elderly individuals around the world, and multiple studies conducted in industrialized and nonindustrialized countries have shown an age-standardized prevalence of dementia ranging from 5% to 7% in most countries. Dementia is not a specific disease but rather a constellation of cognitive changes and disability due to several "causes," i.e., AD, Lewy bodies, vascular disease, drugs, and alcohol. Whether there is a trend for reduced incidence of dementia has to be further evaluated. It is possible that the improvement in the treatments of risk factors, especially vascular disease, has resulted in decreased incidence. However, this could result in an increase in prevalence, since the improved therapies for risk factors will lead to increased longevity in patients with dementia.
-
2.
Molecular basis of vitamin D action in neurodegeneration: the story of a team perspective.
Gezen-Ak, D, Dursun, E
Hormones (Athens, Greece). 2019;(1):17-21
Abstract
Vitamin D, a secosteroid hormone, has, over the years, mainly been known for its classic role in the maintenance of calcium homeostasis of the human body. However, there is increasing understanding that vitamin D contributes to the regulation of Ca2+ homeostasis, especially via voltage-gated calcium channels, in another major organ that uses calcium, the brain. Almost 30 years ago, the role of dysregulation in the aging brain and in Alzheimer's disease (AD) gave rise to the Ca2+ hypothesis of brain aging and dementia. We thus made calcium homeostasis the starting point of our studies, proposing the notion that the consequences of long-term deficiency and/or inefficient utilization of vitamin D may cause the disruption of calcium homeostasis in neurons, this creating a vulnerability of neurons to aging and neurodegeneration. In this mini-review, we aim to describe the potential of vitamin D (cholecalciferol) as a neurosteroid based on our findings and conclusions.
-
3.
Current State of Saliva Biomarkers for Aging and Alzheimer's Disease.
François, M, Bull, CF, Fenech, MF, Leifert, WR
Current Alzheimer research. 2019;(1):56-66
Abstract
INTRODUCTION Aging is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular diseases, and neurodegenerative diseases such as Alzheimer's Disease (AD). AD is a progressive degenerative disorder of the brain and is the most common form of dementia. METHODS To-date no simple, inexpensive and minimally invasive procedure is available to confirm with certainty the early diagnosis of AD prior to the manifestations of symptoms characteristic of the disease. Therefore, if population screening of individuals is to be performed, easily accessible tissues would need to be used for a diagnostic test that would identify those who exhibit altered or aberrant aging profiles that may be indicative of AD risk, so that they can be prioritized for primary prevention. This need for minimally invasive tests could be achieved by targeting saliva, since it is now well recognized that many aging diseases including AD are associated with peripheral biomarkers that are not only restricted to pathology and biomarkers within the brain. RESULTS Therefore, the aim of this review is to summarize some of the main findings of salivary biomarkers of aging and AD; including various proteins, metabolites, and alterations to DNA and miRNA. The future of healthy aging resides in innovative platforms, biosensors and point-of-care devices that can extract real time information on the health status of an individual. Those platforms may be achieved through the development and validation of novel biomarkers of health using saliva which, although being the least explored for biomedical purposes, has the distinct advantage that it can be self-collected in a non-invasive manner.
-
4.
Energy and Protein Intake of Alzheimer's Disease Patients Compared to Cognitively Normal Controls: Systematic Review.
Doorduijn, AS, van de Rest, O, van der Flier, WM, Visser, M, de van der Schueren, MAE
Journal of the American Medical Directors Association. 2019;(1):14-21
Abstract
OBJECTIVES Protein and energy malnutrition and unintended weight loss are frequently reported in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Possible underlying mechanisms include increased energy expenditure, altered uptake of nutrients, a reduced nutritional intake, or a combination of these 3. We aimed at systematically reviewing the literature to examine potential differences in energy and protein intake in patients with MCI and AD compared to controls as a possible mechanism for unintended weight loss. DESIGN Systematic review and meta-analysis. SETTING PubMed and Cochrane Electronic databases were searched from inception to September 2017 for case control studies. PARTICIPANTS Patients with MCI or AD compared to cognitive healthy controls, all adhering to a Western dietary pattern. MEASUREMENTS Energy and protein intake. RESULTS The search resulted in 7 articles on patients with AD versus controls, and none on patients with MCI. Four articles found no differences in energy and protein intakes, 1 found higher intakes in patients with AD, and 1 article found lower intakes in patients with AD compared to controls. One article reported on intakes, but did not test differences. A meta-analysis of the results indicated no difference between patients with AD and controls in energy [-8 kcal/d, 95% confidence interval (CI): -97, 81; P = .85], or protein intake (2 g/d, 95% CI: -4, 9; P = .47). However, heterogeneity was high (I2 > 70%), and study methodology was generally poor or moderate. CONCLUSION Contrary to frequently reported unintended weight loss, our systematic review does not provide evidence for a lower energy or protein intake in patients with AD compared to controls. High heterogeneity of the results as well as of participant characteristics, setting, and study methods was observed. High-quality studies are needed to study energy and protein intake as a possible mechanism for unintended weight loss and malnutrition in both patients with MCI and AD.
-
5.
Alzheimer's Disease: Physical Activities as an Effective Intervention Tool - A Mini-Review.
Klimova, B, Maresova, P, Kuca, K
Current Alzheimer research. 2019;(2):166-171
Abstract
BACKGROUND There are a few risk factors which definitely have an impact on the development of Alzheimer's disease (AD). Those include genetics, gender, age, diabetes, head injuries, and lifestyle. Physical activity together with a healthy diet is part of people's lifestyle. At present, there exist several research studies showing that the physical activities can be a good intervention tool in the delay of cognitive decline in AD. OBJECTIVE The aim of this study is to discuss a relationship between the physical activities and the delay and/or maintenance of cognitive decline in AD and the types of physical activities which are especially suitable for this delay. METHODS The method of this review study consists of a method of literature review analysing the data contained in the world's prestigious scientific databases: PubMed, Springer, Web of Science and Scopus in the period of 2010 - 2015. In addition, a method of comparison of different research studies discussing various aspects and factors of the correlation of physical activities and AD is used. RESULTS The findings of this review confirm that in most cases, physical activities have a positive effect on the improvement of cognitive decline in AD. CONCLUSION Although physical activities seem to be beneficial for people with AD, more convincing results, particularly in the area of specific types of exercises and their impact on slowing down the cognitive decline, respectively AD, are needed.
-
6.
INTREPAD: A randomized trial of naproxen to slow progress of presymptomatic Alzheimer disease.
Meyer, PF, Tremblay-Mercier, J, Leoutsakos, J, Madjar, C, Lafaille-Magnan, ME, Savard, M, Rosa-Neto, P, Poirier, J, Etienne, P, Breitner, J, et al
Neurology. 2019;(18):e2070-e2080
-
-
Free full text
-
Abstract
OBJECTIVE To evaluate the safety and efficacy of low-dose naproxen for prevention of progression in presymptomatic Alzheimer disease (AD) among cognitively intact persons at risk. METHODS Investigation of Naproxen Treatment Effects in Pre-symptomatic Alzheimer's Disease (INTREPAD), a 2-year double-masked pharmaco-prevention trial, enrolled 195 AD family history-positive elderly (mean age 63 years) participants screened carefully to exclude cognitive disorder (NCT-02702817). These were randomized 1:1 to naproxen sodium 220 mg twice daily or placebo. Multimodal imaging, neurosensory, cognitive, and (in ∼50%) CSF biomarker evaluations were performed at baseline, 3, 12, and 24 months. A modified intent-to-treat analysis considered 160 participants who remained on-treatment through their first follow-up examination. The primary outcome was rate of change in a multimodal composite presymptomatic Alzheimer Progression Score (APS). RESULTS Naproxen-treated individuals showed a clear excess of adverse events. Among treatment groups combined, the APS increased by 0.102 points/year (SE 0.014; p < 10-12), but rate of change showed little difference by treatment assignment (0.019 points/year). The treatment-related rate ratio of 1.16 (95% confidence interval 0.64-1.96) suggested that naproxen does not reduce the rate of APS progression by more than 36%. Secondary analyses revealed no notable treatment effects on individual CSF, cognitive, or neurosensory biomarker indicators of progressive presymptomatic AD. CONCLUSIONS In cognitively intact individuals at risk, sustained treatment with naproxen sodium 220 mg twice daily increases frequency of adverse health effects but does not reduce apparent progression of presymptomatic AD. CLASSIFICATION OF EVIDENCE This study provides Class I evidence that, for people who are cognitively intact, low-dose naproxen does not significantly reduce progression of a composite indicator of presymptomatic AD.
-
7.
Effect of Caffeine and Other Methylxanthines on Aβ-Homeostasis in SH-SY5Y Cells.
Janitschke, D, Nelke, C, Lauer, AA, Regner, L, Winkler, J, Thiel, A, Grimm, HS, Hartmann, T, Grimm, MOW
Biomolecules. 2019;(11)
Abstract
Methylxanthines (MTX) are alkaloids derived from the purine-base xanthine. Whereas especially caffeine, the most prominent known MTX, has been formerly assessed to be detrimental, this point of view has changed substantially. MTXs are discussed to have beneficial properties in neurodegenerative diseases, however, the mechanisms of action are not completely understood. Here we investigate the effect of the naturally occurring caffeine, theobromine and theophylline and the synthetic propentofylline and pentoxifylline on processes involved in Alzheimer's disease (AD). All MTXs decreased amyloid-β (Aβ) level by shifting the amyloid precursor protein (APP) processing from the Aβ-producing amyloidogenic to the non-amyloidogenic pathway. The α-secretase activity was elevated whereas β-secretase activity was decreased. Breaking down the molecular mechanism, caffeine increased protein stability of the major α-secretase ADAM10, downregulated BACE1 expression and directly decreased β-secretase activity. Additionally, APP expression was reduced. In line with literature, MTXs reduced oxidative stress, decreased cholesterol and a decreased in Aβ1-42 aggregation. In conclusion, all MTXs act via the pleiotropic mechanism resulting in decreased Aβ and show beneficial properties with respect to AD in neuroblastoma cells. However, the observed effect strength was moderate, suggesting that MTXs should be integrated in a healthy diet rather than be used exclusively to treat or prevent AD.
-
8.
Factors Associated with Alzheimer's Disease: An Overview of Reviews.
Rochoy, M, Rivas, V, Chazard, E, Decarpentry, E, Saudemont, G, Hazard, PA, Puisieux, F, Gautier, S, Bordet, R
The journal of prevention of Alzheimer's disease. 2019;(2):121-134
Abstract
Alzheimer's disease (AD) is a frequent pathology, with a poor prognosis, for which no curative treatment is available in 2018. AD prevention is an important issue, and is an important research topic. In this manuscript, we have synthesized the literature reviews and meta-analyses relating to modifiable risk factors associated with AD. Smoking, diabetes, high blood pressure, obesity, hypercholesterolemia, physical inactivity, depression, head trauma, heart failure, bleeding and ischemic strokes, sleep apnea syndrome appeared to be associated with an increased risk of AD. In addition to these well-known associations, we highlight here the existence of associated factors less described: hyperhomocysteinemia, hearing loss, essential tremor, occupational exposure to magnetic fields. On the contrary, some oral antidiabetic drugs, education and intellectual activity, a Mediterranean-type diet or using Healthy Diet Indicator, consumption of unsaturated fatty acids seemed to have a protective effect. Better knowledge of risk factors for AD allows for better identification of patients at risk. This may contribute to the emergence of prevention policies to delay or prevent the onset of AD.
-
9.
Natural Compounds with Anti-BACE1 Activity as Promising Therapeutic Drugs for Treating Alzheimer's Disease.
Naushad, M, Durairajan, SSK, Bera, AK, Senapati, S, Li, M
Planta medica. 2019;(17):1316-1325
Abstract
Alzheimer's disease is a neurodegenerative disease that leads to irreversible neuronal damage. Senile plaques, composed of amyloid beta peptide, is the principal abnormal characteristic of the disease. Among the factors involved, the secretase enzymes, namely, α secretase, beta-site amyloid precursor protein-cleaving enzyme, β secretase, and γ secretase, hold consequential importance. Beta-site amyloid precursor protein-cleaving enzyme 1 is considered to be the rate-limiting factor in the production of amyloid beta peptide. Research supporting the concept of inhibition of beta-site amyloid precursor protein-cleaving enzyme activity as one of the effective therapeutic targets in the mitigation of Alzheimer's disease is well accepted. The identification of natural compounds, such as β-amyloid precursor protein-selective beta-site amyloid precursor protein-cleaving enzyme inhibitors, and the idea of compartmentalisation of the beta-site amyloid precursor protein-cleaving enzyme 1 action have caused a dire need to closely examine the natural compounds and their effectiveness in the disease mitigation. Many natural compounds have been reported to effectively modulate beta-site amyloid precursor protein-cleaving enzyme 1. At lower doses, compounds like 2,2',4'-trihydroxychalcone acid, quercetin, and myricetin have been shown to effectively reduce beta-site amyloid precursor protein-cleaving enzyme 1 activity. The currently used five drugs that are marketed and used for the management of Alzheimer's disease have an increased risk of toxicity and restricted therapeutic efficiency, hence, the search for new anti-Alzheimer's disease drugs is of primary concern. A variety of natural compounds having pure pharmacological moieties showing multitargeting activity and others exhibiting specific beta-site amyloid precursor protein-cleaving enzyme 1 inhibition as discussed below have superior biosafety. Many of these compounds, which are isolated from medicinal herbs and marine flora, have been long used for the treatment of various ailments since ancient times in the Chinese and Ayurvedic medical systems. The aim of this article is to review the available data on the selected natural compounds, giving emphasis to the inhibition of beta-site amyloid precursor protein-cleaving enzyme 1 activity as a mode of Alzheimer's disease treatment.
-
10.
MIND not Mediterranean diet related to 12-year incidence of cognitive impairment in an Australian longitudinal cohort study.
Hosking, DE, Eramudugolla, R, Cherbuin, N, Anstey, KJ
Alzheimer's & dementia : the journal of the Alzheimer's Association. 2019;(4):581-589
Abstract
INTRODUCTION Associations between the Mediterranean-DASH diet Intervention for Neurological Delay (MIND) diet and incidence of cognitive impairment have not been evaluated outside the United States. METHODS We investigated MIND and Mediterranean diet relations with 12-year incidence of Alzheimer's disease/Vascular dementia (National Institute of Neurological Disorders criteria) and mild cognitive impairment (Winbald criteria) in the Personality and Total Health (PATH) Through Life cohort (n = 1220) set in Canberra, Australia: wave-1 2001-2002; wave-2 2005-2006; wave-3 2009-2010; and wave-4 2013-2014. MIND diet and two alternate Mediterranean diet scores were calculated from the baseline food frequency questionnaire responses. Higher dietary scores signified greater adherence. RESULTS In adjusted logistic regression models, MIND diet (OR = 0.47, 95% CI 0.24, 0.91), but not Mediterranean diet, was associated with reduced odds of 12-year cognitive impairment. DISCUSSION Preliminary evidence suggests that protective effects of the MIND diet are geographically generalizable. Additional prospective studies are needed in diverse samples to determine the relative effects of the MIND and the Mediterranean diets against cognitive decline.