International Journal of Alzheimer's Disease最新文献

Alzheimer's disease (AD) is one of the most serious neurodegenerative diseases in the globe. As a result, there is an acute need to discover indications that allow for early disease detection. There is growing scientific data showing the similarities between the eye and other central nervous system components, suggesting that information obtained in ophthalmic research might be valuable in the study and diagnosis of AD. Fifty male albino Wistar rats were separated into five groups: the first group served as control, and the other four groups of animals were administrated aluminium chloride (AlCl₃) in a dose of 100 mg/kg body weight (b.w.) for 2, 4, 6, and 8 weeks, respectively. Insights into the function of the retina by electroretinogram (ERG) and the changes thought to have occurred in the molecular structure of the retina and brain using Fourier transform infrared spectroscopy (FTIR) as a result of AD progression induced by AlCl₃ in rats were done. Moreover, the measurement of acetylcholinesterase (AchE) was done. After 6 and 8 weeks of AlCl₃ injection, there was a substantial reduction (p ≤ 0.05) in a- and b-wave amplitudes and a significant rise (p ≤ 0.05) in implicit time compared to controls. A significant elevation (p ≤ 0.05) of AchE content was observed after 4, 6, and 8 weeks. FTIR revealed a significant increase (p ≤ 0.05) of β-turn and β-sheet content associated with significant decrease (p ≤ 0.05) of α-helix content for all groups administrated with AlCl₃. Our findings suggest that retinal biomarkers such as ERG of the retina may be used as a screening tool for detection of AD. Secondary structural changes in the proteins of the retina and the brain were similar in AD rats' model and precede retinal dysfunction.

Background: Aducanumab, a new monoclonal antibody that targets β-amyloid aggregates, has been granted conditional approval by the U.S. FDA for treatment of mild Alzheimer's disease (AD). The approval of this drug without a confirmed significant clinical impact has resulted in several debates.

Objective: In this narrative review, aducanumab approval-related controversy, the drug's pharmacokinetics and pharmacodynamic characteristics, evidence from the efficacy and safety trials of aducanumab, implications of the drug approval, and the future directions in the management of patients with AD are summarized.

Methods: Using relevant keywords, Google Scholar, Web of Science, and MEDLINE databases and manufacturer's website were searched.

Results: Infusion of aducanumab at a higher dose resulted in a modest slowing of cognitive decline among patients with mild cognitive impairment or early-onset AD dementia. The drug however can cause amyloid-related imaging abnormalities. Due to modest impact on cognition, the use of this drug by patients with AD will most likely be limited. The manufacturer is required to run an extended phase IIIb trial to verify the benefit of this drug. Access to therapy requires a careful selection of patients and periodic monitoring to ensure the optimal use of the drug.

Conclusion: Despite the limitations, aducanumab is the first disease-modifying therapy approved for the treatment of AD. Aducanumab addresses a part of the pathogenesis of AD; therefore, drugs that can act on multiple targets are needed. In addition, the search for preventive strategies, validated plasma-based assays, and newer drugs for AD, which are effective, safe, convenient, and affordable, is vital.

A multigenerational household is no longer a rare phenomenon in contemporary society. However, relevant literature has focused on elderly parents receiving support from their adult child, thereby coresiding. This is potentially problematic, as both generations could benefit from living together, and little is known about the benefit of living with adult children from older adults' perspectives compared to the risk of this living situation. Previous research suggests a significant negative effect of living alone, e.g., low psychological well-being, and it becomes more salient among single parents, such as widowed or divorced. The current paper utilizes the National Health Measurement Study with a sample of age 55 and over. Their SF-36 Mental Health and Physical Health Component and self-acceptance scores were measured. Path analysis reveals that both physical and mental health and self-acceptance scores are lower among single older adults at the time of the survey (e.g., divorced and widowed) than among those who are nonsingle and living with their adult child. A complete mediation effect of living with an adult child on older adults' mental health and self-acceptance was observed in both White and non-White minority older adults. This suggests that living with an adult child possibly serves as a protective factor for the negative relationship between living alone and their well-being. The current study seeks to stimulate ideas that might generate the following answer to community-based care in our contemporary aging society.

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.

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.

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.

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.

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.

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.