Current State of Non-wearable Sensor Technologies for Monitoring Activity Patterns to Detect Symptoms of Mild Cognitive Impairment to Alzheimer’s DiseaseRead the full article
International Journal of Alzheimer’s Disease publishes original research articles, review articles, and clinical studies in all areas of Alzheimer's disease.
International Journal of Alzheimer’s Disease maintains an Editorial Board of practicing researchers from around the world, to ensure manuscripts are handled by editors who are experts in the field of study.
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Structural Brain Imaging Phenotypes of Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD) Found by Hierarchical Clustering
A hierarchical clustering algorithm was applied to magnetic resonance images (MRI) of a cohort of 751 subjects having a mild cognitive impairment (MCI), 282 subjects having received Alzheimer’s disease (AD) diagnosis, and 428 normal controls (NC). MRIs were preprocessed to gray matter density maps and registered to a stereotactic space. By first rendering the gray matter density maps comparable by regressing out age, gender, and years of education, and then performing the hierarchical clustering, we found clusters displaying structural features of typical AD, cortically-driven atypical AD, limbic-predominant AD, and early-onset AD (EOAD). Among these clusters, EOAD subjects displayed marked cortical gray matter atrophy and atrophy of the precuneus. Furthermore, EOAD subjects had the highest progression rates as measured with ADAS slopes during the longitudinal follow-up of 36 months. Striking heterogeneities in brain atrophy patterns were observed with MCI subjects. We found clusters of stable MCI, clusters of diffuse brain atrophy with fast progression, and MCI subjects displaying similar atrophy patterns as the typical or atypical AD subjects. Bidirectional differences in structural phenotypes were found with MCI subjects involving the anterior cerebellum and the frontal cortex. The diversity of the MCI subjects suggests that the structural phenotypes of MCI subjects would deserve a more detailed investigation with a significantly larger cohort. Our results demonstrate that the hierarchical agglomerative clustering method is an efficient tool in dividing a cohort of subjects with gray matter atrophy into coherent clusters manifesting different structural phenotypes.
Scopolamine-Induced Memory Impairment in Mice: Neuroprotective Effects of Carissa edulis (Forssk.) Valh (Apocynaceae) Aqueous Extract
Alzheimer’s disease is first characterised by memory loss related to the central cholinergic system alteration. Available drugs provide symptomatic treatment with known side effects. The present study is aimed to evaluate the properties of Carissa edulis aqueous extract on a Scopolamine mouse model as an attempt to search for new compounds against Alzheimer’s disease-related memory impairment. Memory impairment was induced by administration of 1 mg/kg (i.p.) of Scopolamine for 7 days, and mice were treated with Carissa edulis aqueous extract. Behavioural studies were performed using T-maze and novel object recognition task for assessing learning and memory and open field test for locomotion. Brain acetylcholinesterase enzyme (AChE) activity was measured to evaluate the central cholinergic system. The level of MDA, glutathione, and catalase activity were measured to evaluate the oxidative stress level. Administration of Scopolamine shows a decrease in learning and memory enhancement during behavioural studies. A significant decrease in the time spent in the preferred arm of T-maze, in the time spent in the exploration of the novel object, and in the discrimination index of the familiar object was also observed. The significant impairment of the central cholinergic system was characterised in mice by an increase of AChE activity to mol/min/g with an increase in oxidative stress. Treatment with the different doses of Carissa edulis (62.8, 157, 314, and 628 mg/kg orally administrated) significantly increased the memory of mice in T-maze and novel object recognition tests and also ameliorated locomotion of mice in the open field. Carissa edulis aqueous extract treatment also decreases the AChE activity and brain oxidative stress. It is concluded that administration of Carissa edulis aqueous extract enhances memory of mice by reducing AChE activity and demonstrating antioxidant properties. This could be developed into a novel therapy against memory impairment related to Alzheimer’s disease.
Taxonomic Distribution of Medicinal Plants for Alzheimer’s Disease: A Cue to Novel Drugs
Alzheimer’s disease (AD) is a neurodegenerative disorder manifested by decline in memory and mild cognitive impairment leading to dementia. Despite global occurrence of AD, the severity and hence onset of dementia vary among different regions, which was correlated with the customary use of medicinal herbs and exposure level to the causatives. In spite of execution of versatile therapeutic strategies to combat AD and other neurodegenerative diseases, success is only limited to symptomatic treatment. The role of natural remedies remained primitive and irreplaceable in all ages. In some examples, the extracted drugs failed to show comparable results due to lack of micro ingredients. Micro ingredients impart a peerless value to natural remedies which are difficult to isolate and/or determine their precise role during treatment. A variety of plants have been used for memory enhancement and other dementia-related complications since ages. Acetyl choline esterase inhibition, antioxidant potential, neuroprotection, mitochondrial energy restoration, and/or precipitated protein clearance put a vast taxonomic variety into a single group of anti-AD plants. Secondary metabolites derived from these medicinal plants have the potential to treat AD and other brain diseases of common pathology. This review summarizes the potential of taxonomically diverse medicinal plants in the treatment of AD serving as a guide to further exploration.
Clinical Trials in Alzheimer’s Disease: A Hurdle in the Path of Remedy
Human clinical trials seek to ameliorate the disease states and symptomatic progression of illnesses that, as of yet, are largely untreatable according to clinical standards. Ideally, clinical trials test “disease-modifying drugs,” i.e., therapeutic agents that specifically modify pathological features or molecular bases of the disease and would presumably have a large impact on disease progression. In the case of Alzheimer’s disease (AD), however, this approach appears to have stalled progress in the successful development of clinically useful therapies. For the last 25 years, clinical trials involving AD have centered on beta-amyloid (Aβ) and the Aβ hypothesis of AD progression and pathology. According to this hypothesis, the progression of AD begins following an accumulation of Aβ peptide, leading to eventual synapse loss and neuronal cell death: the true overriding pathological feature of AD. Clinical trials arising from the Aβ hypothesis target causal steps in the pathway in order to reduce the formation of Aβ or enhance clearance, and though agents have been successful in this aim, they remain unsuccessful in rescuing cognitive function or slowing cognitive decline. As such, further use of resources in the development of treatment options for AD that target Aβ, its precursors, or its products should be reevaluated. The purpose of this review was to give an overview of how human clinical trials are conducted in the USA and to assess the results of recent failed trials involving AD, the majority of which were based on the Aβ hypothesis. Based on these current findings, it is suggested that lowering Aβ is an unproven strategy, and it may be time to refocus on other targets for the treatment of this disease including pathological forms of tau.
In Vivo Cognitive-Enhancing, Ex Vivo Malondialdehyde-Lowering Activities and Phytochemical Profiles of Aqueous and Methanolic Stem Bark Extracts of Piliostigma thonningii (Schum.)
Cognitive impairment (CI) is among the leading causes of disability in humans. It is estimated that over 35.6 million people are suffering from Alzheimer’s disease- (AD-) associated cognitive deficits globally with these statistics projected to rise over 115.4 million by the year 2050. There is no specific etiology for this cognitive impairment; however, various contributing factors including advancing age (>60 years old), oxidative stress, cerebral injuries, infections, neurologic disorders, and cancer have been implicated. Despite various attempts to manage CI, no curative medicines are yet available. The current drugs used to manage symptoms of AD-associated CI including Donepezil and Rivastigmine among others are only palliative rather than therapeutic. Furthermore, these agents have been associated with undesirable side effects. This calls for alternative and complementary approaches aimed at either preventing or reverting AD-related CI in a curative way without causing adverse events. It is estimated that over 80% of the world’s population utilize herbal medicines for basic healthcare as it is considered safe, affordable, and easily accessible as opposed to conventional healthcare. Various parts of P. thonningii are used in traditional medicine to manage various conditions including CI. However, empirical and scientific data to validate these uses is lacking. In this study, the Morris water maze (MWM) experiment was adopted to evaluate the cognitive-enhancing effects of the studied plant extracts. The malondialdehyde (MDA) profiles in the brains of experimental mice were determined using the thiobarbituric acid reactive substances (TBARS) test. Moreover, qualitative phytochemical profiling of the studied plant extracts was performed using standard procedures. The results showed remarkable cognitive-enhancing activities which were reflected in significantly shorter transfer latencies, navigation distances, longer time spent in platform quadrant, and lower MDA levels compared with those recorded for the negative control mice (). Phytochemical screening of the studied plant extracts revealed the presence of antioxidant phytocompounds, which may have played key roles in the extracts’ potency. Based on the findings herein, P. thonningii extracts, especially the aqueous ones have a promising potential for the management of AD-associated CI. Further studies aimed at isolating and characterizing specific active compounds for CI from P. thonningii are recommended. Additionally, specific mode(s) of action of active principles should be elucidated. Moreover, toxicity studies should be done on the studied plant extracts to ascertain their safety.
The Development and Psychometric Validation of a Comprehensive Measure Assessing Fear of Incompetence among Adults Who Have a Family Member with Dementia
Because the interpersonal skills of individuals with dementia often decline, family members may question their own ability to interact meaningfully. These family members may experience fear of incompetence (i.e., fear of being unable to relate in a meaningful way or take care of a close family member with dementia). Thus, the goal of this research was to develop, refine, and psychometrically validate a scale (Fear of Incompetence—Dementia Scale; FOI-D) assessing fear of incompetence in the context of relationships with a close family member diagnosed with dementia. Three online studies were conducted to accomplish the primary objective. In Study One, the factor structure of the FOI-D was assessed by conducting an exploratory factor analysis using data from 710 adults who indicated having a close living family member who had been diagnosed with dementia. In Study Two, the factor structure was validated via a confirmatory factor analysis and the psychometric properties were established using data from 636 adults who had a family member with dementia. Finally, Study Three determined the temporal consistency of the scale by retesting 58 participants from Study Two. The results from Study One indicated that the FOI-D Scale accounted for 51.75% of the variance and was comprised of three subscales: the Interaction Concerns subscale, the Caregiving Concerns subscale, and the Knowledge Concerns subscale. In Study Two, the three-factor structure was supported, resulting in a 58-item scale. Investigation of the psychometric properties demonstrated the FOI-D to be reliable and valid. In Study Three, the FOI-D Scale demonstrated excellent temporal consistency. This research provides future investigators, educators, and practitioners with an adaptable comprehensive tool assessing fear of incompetence in a variety of settings.