Validation of AD8-Philippines (AD8-P): A Brief Informant-Based Questionnaire for Dementia Screening in the Philippines

Aim. This study was aimed at validating the Filipino version of AD8 (AD8-P). Methods. Community-dwelling Filipino older persons aged ≥60 years, together with their informants, participated in this study. Psychologists independently interviewed the informants with AD8-P and administered the Filipino-validated Mini-Mental State Examination (MMSE-P) and Montreal Cognitive Assessment (MoCA-P) to the older persons. Neurologists and geriatrician conducted physical and neurological examination and Clinical Dementia Rating™ (CDR™) to determine cognitive diagnosis and were blinded with the results of AD8-P. Dementia was diagnosed based on DSM-IV-TR criteria. AD8-P discriminatory ability to screen for dementia was evaluated according to DSM-IV-TR diagnostic criteria for dementia. Results. A total of 366 community-dwelling Filipino older persons aged ≥60 years, 213 with normal cognition and 153 with dementia, and their informants were included in this study. Majority (90%) were at the mildest stage of dementia. Area under the receiver-operating-characteristic curve (AUROC) for AD8-P was 0.94 (95% CI 0.92 to 0.96), demonstrating excellent overall predictive power to screen for dementia. The optimal AD8-P cut-off score with best balance sensitivity (91.5%) and specificity (77.9%) was ≥3. Conclusion. AD8-P demonstrated good psychometric properties to screen for dementia, even at the earliest stage of cognitive decline.

The Genetic Research in Alzheimer Disease (GERALD) Initiative Finds rs9320913 as a Neural eQTL of lincRNA AL589740.1

Alzheimer’s disease is the most common cause of dementia worldwide, and longitudinal studies are crucial to find the factors affecting disease development. Here, we describe a novel initiative from southern Spain designed to contribute in the identification of the genetic component of the cognitive decline of Alzheimer’s disease patients. The germline variant rs9320913 is a C>A substitution mapping within a gene desert. Although it has been previously associated to a higher educational achievement and increased fluid intelligence, its role on Alzheimer’s disease risk and progression remains elusive. A total of 407 subjects were included in the study, comprising 153 Alzheimer disease patients and 254 healthy controls. We have explored the rs9320913 contribution to both Alzheimer disease risk and progression according to the Mini-Mental State Exams. We found that rs9320913 maps within a central nervous system lincRNA AL589740.1. eQTL results show that rs9320913 correlated with the brain-frontal cortex ( beta = − 0.15 , p value = 0.057) and brain-spinal cord (beta of -0.23, p value = 0.037). We did not find rs9320913 to be associated to AD risk, although AA patients seemed to exhibit a less pronounced Mini-Mental State Exam score decline.

Modifying the Mini-Cog to Screen for Cognitive Impairment in Nonliterate Individuals

Objectives. The Mini-Cog, a rapid, valid, and reliable screening tool for cognitive impairment, consists of 3-word recall and an executive clock drawing test (CDT). However, CDT requires at least basic literacy and cultural exposure to analog clocks, conditions not met in many population groups around the world. We developed a modification of the Mini-Cog (MMC) for use with nonliterate and literate individuals. Methods. Participants were adults (≥60 years) with no neurological diagnosis, with known cognitive impairment due to stroke, Parkinsonism, traumatic brain injury, or Alzheimer’s disease, and whose family members were able to read and write. We replaced the CDT with two tasks of everyday life: a serial subtraction task or a multistep performance task. Family members rated the acceptability and feasibility of the Mini-Cog versions using a 6-point scale and completed a proxy-rated cognitive staging tool, the Dementia Severity Rating Scale (DSRS). Spearman’s rho, Mann-Whitney U , and chi-square tests were used to evaluate group differences and associations between measures. Results. Data were collected from 63 participants ( 75 % ≥ 60 years , 67% nonliterate). Literacy was associated with CDT (chi-square strength 0.9, p < 0.001 ). Both MMC versions correlated with DSRS in healthy adults and patients (rho 0.6-0.7, p < 0.05 ). In literate individuals, the acceptability and feasibility of CDT and both alternate distractors were similarly high (5/6). Conclusions. Two alternate distractor tasks may successfully replace CDT in the Mini-Cog. The MMC versions are promising and deserve further study as screening tools for cognitive impairment in larger and more fully characterized samples.

Improving the Quality of Life of Family Caregivers of People with Alzheimer’s Disease through Virtual Communities of Practice: A Quasiexperimental Study

Caring for a person with dementia burdens family caregivers, and there is a close negative relationship between this burden and their quality of life (QoL). Research suggests that caregivers’ main needs are information and training about the disease and support from others experiencing the same situation, and Internet interventions hold considerable promise for meeting these needs. Virtual communities of practice (VCoPs) are Internet frameworks to share knowledge where members collaborate and achieve a sense of trust in the community. This paper seeks to evaluate the impact of participating in a VCoP (developed through an App) on the QoL of caregivers to people with Alzheimer’s. Results show QoL before and after the intervention changed significantly. The impact of VCoP on caregivers’ overall QoL is moderated by age and relation with the person with Alzheimer’s, specifically those over 65, and spouses. VCoPs allow interaction and knowledge sharing among caregivers which provide them mainly with information and support from peers helping them to meet their needs. Furthermore, caregivers’ QoL did not decrease when their relative deteriorated functionally, which could be due to the participation in VCoP. Although we found significant pre- and post differences in caregivers’ health literacy, we must report the ambiguous result that this variable only impacts on QoL’s physical domain. Participants also reported that they had a positive experience because the App was perceived to be a useful tool, because they could manage their own participation and they met peers and felt less lonely. Results suggest that participation in a VCoP impacts positively on caregivers’ QoL.

Current State of Non-wearable Sensor Technologies for Monitoring Activity Patterns to Detect Symptoms of Mild Cognitive Impairment to Alzheimer’s Disease

Mild cognitive impairment (MCI) could be a transitory stage to Alzheimer’s disease (AD) and underlines the importance of early detection of this stage. In MCI stage, though the older adults are not completely dependent on others for day-to-day tasks, mild impairments are seen in memory, attention, etc., subtly affecting their daily activities/routines. Smart sensing technologies, such as wearable and non-wearable sensors, coupled with advanced predictive modeling techniques enable daily activities/routines based early detection of MCI symptoms. Non-wearable sensors are less intrusive and can monitor activities at naturalistic environment with no interference to an individual’s daily routines. This review seeks to answer the following questions: (1) What is the evidence for use of non-wearable sensor technologies in early detection of MCI/AD utilizing daily activity data in an unobtrusive manner? (2) How are the machine learning methods being employed in analyzing activity data in this early detection approach? A systematic search was conducted in databases such as IEEE Explorer, PubMed, Science Direct, and Google Scholar for the papers published from inception till March 2019. All studies that fulfilled the following criteria were examined: a research goal of detecting/predicting MCI/AD, daily activities data to detect MCI/AD, noninvasive/non-wearable sensors for monitoring activity patterns, and machine learning techniques to create the prediction models. Out of 2165 papers retrieved, 12 papers were eligible for inclusion in this review. This review found a diverse selection of aspects such as sensors, activity domains/features, activity recognition methods, and abnormality detection methods. There is no conclusive evidence on superiority of one or more of these aspects over the others, especially on the activity feature that would be the best indicator of cognitive decline. Though all these studies demonstrate technological developments in this field, they all suggest it is far in the future it becomes an effective diagnostic tool in real-life clinical practice.

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 2.55±0.10 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 (p<0.05). 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.