Journal of Alzheimer's Disease Reports - Volume 8, issue 1

Authors: Yeerlan, Jianishaya | He, Binhong | Hu, Xianliang | Zhang, LuShun

Article Type: Review Article

Abstract: Background: Alzheimer’s disease (AD) is a genetically intricate neurodegenerative disorder. Studies on “Ferroptosis in AD”, “Pyroptosis in AD”, and “Necroptosis in AD” are becoming more prevalent and there is increasing evidence that they are closely related to AD. However, there has not yet been a thorough bibliometrics-based investigation on this subject. Objective: This study uses a bibliometric approach to visualize and analyze the literature within the field of three distinct types of cell death in AD and explores the current research hotspots and prospective research directions. Methods: We collected relevant articles from the Web of Science …and used CiteSpace, VOS viewer, and Pajek to perform a visual analysis. Results: A total of 123, 95, and 84 articles were published in “Ferroptosis in AD”, “Pyroptosis in AD”, and “Necroptosis in AD”, respectively. Based on keywords analysis, we can observe that “oxidative stress” and “lipid peroxidation”, “cell death” and “activation”, and “Nlrp3 inflammasome” and “activation” were the three most prominent words in the field of “Ferroptosis in AD”, “Pyroptosis in AD”, and “Necroptosis in AD”, respectively. Focusing on the breakout words in the keyword analysis, we reviewed the mechanisms of ferroptosis, pyroptosis, and necroptosis in AD. By mapping the time zones of the keywords, we speculated on the evolutionary trends of ferroptosis, pyrotosis, and necroptosis in AD. Conclusions: Our findings can help researchers grasp the research status of three types of cell death in AD and determine new directions for future research as soon as possible. Show more

Keywords: Alzheimer’s disease, bibliometric analysis, ferroptosis, necroptosis, pyroptosis

DOI: 10.3233/ADR-230092

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 129-142, 2024

Authors: Sayadnasiri, Mohammad | Darvishskandari, Sahar | Latifian, Maryam | Shariful Islam, Sheikh Mohammed

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is one of the most debilitating diseases in old age, associated with cognitive decline and behavioral symptoms. Objective: This study aimed to investigate the effect of adding mirtazapine to quetiapine in reducing agitation among patients with AD. Methods: Thirty-seven elderly patients (18 cases and 19 controls) with AD, diagnosed according to National Institute on Aging and Alzheimer’s Association (NIA-AA) criteria, were enrolled at Nezam-Mafi Clinic. Inclusion criteria comprised a minimum of two years post-diagnosis, a Cohen-Mansfield Agitation and Aggression Questionnaire (CMAI) score above 45, and treatment with 100–150 mg of quetiapine. Patients were …randomly assigned to receive mirtazapine (15 mg at night, increased to 30 mg at night after two weeks) or a placebo. Cognitive changes were assessed at weeks 0 and 6 using the Mini-Mental State Examination instrument. Furthermore, symptoms of agitation and aggression were evaluated using the CMAI questionnaire at weeks 4 and 6. Results: In this study, the mean duration of AD in the control group was 4.68 years, and in the case group, it was 5.05 years. Although the total agitation score showed no significant change at the end of the study compared to the control group, the rate of physical non-aggressive behavior showed a significant decrease (p  <  0.05). Conclusions: According to this study, adding mirtazapine to the antipsychotic drug regimen may not be an effective treatment for agitation in AD patients. Show more

Keywords: Agitation, Alzheimer’s disease, mirtazapine, quetiapine

DOI: 10.3233/ADR-230123

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 143-150, 2024

Authors: Takechi, Hajime | Yoshino, Hiroshi | Suzuki, Megumi | Maeda, Akiko | Suzumura, Shota | Kamiya, Eiko

Article Type: Research Article

Abstract: Background: Because dementia is a long-term condition, the appropriate involvement of health-care professionals is considered important. However, little is known about the factors associated with changes in family caregiver burden. Objective: To clarify changes in family caregiver burden and associated factors during follow-up at a memory clinic. Methods: A retrospective cohort study was conducted, enrolling 495 pairs of patients with dementia or mild cognitive impairment and their family caregivers. A total of 120 pairs completed the second evaluation. The caregiver burden was assessed using the Zarit Burden Interview (ZBI). Data at the initial …visit and after an average follow-up of about 2 years were compared and analyzed. Results: At initial visit, the patients’ mean age, Mini-Mental State Examination (MMSE) and ZBI scores were 78.6±5.6 years, 23.3±3.5, and 22.6±16.7, respectively. At follow-up, MMSE scores decreased (21.4±4.5, p  < 0.001), but ZBI scores remained similar (22.5±13.6). When the difference in ZBI scores between the two time points was defined as Δ ZBI, and the related factors were analyzed by multiple regression analysis, ZBI scores at the initial visit, start of psychotropic drug, and decrease of neuropsychiatric symptoms were identified as significant factors (p  < 0.001, p  = 0.003, p  < 0.001, respectively). A significant negative correlation was found between ZBI scores at the initial visit and Δ ZBI (r  = –0.588, p  < 0.001). Conclusions: These findings suggest the importance of assessing changes in the burden experienced by family caregivers during the disease follow-up. Show more

Keywords: Alzheimer’s disease, caregiver burden, dementia, longitudinal, memory clinic, mild cognitive impairment

DOI: 10.3233/ADR-230069

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 151-162, 2024

Authors: Çınar, Nilgün | Aslan Kendirli, Sude | Florentina Ateş, Miruna | Yakupoğlu, Ezgi | Akbuğa, Ebru | Bolu, Naci Emre | Karalı, Fenise Selin | Okluoğlu, Tuğba | Bülbül, Nazlı Gamze | Bayindir, Elif | Atam, Kamil Tolga | Hisarlı, Enis | Akgönül, Sarp | Bagatır, Oğulcan | Sahiner, Emre | Orgen, Bora | Sahiner, Türker Ahmet Hasan

Article Type: Research Article

Abstract: Background: Detecting cognitive impairment such as Alzheimer’s disease early and tracking it over time is essential for individuals at risk of cognitive decline. Objective: This research aimed to validate the Beynex app’s gamified assessment tests and the Beynex Performance Index (BPI) score, which monitor cognitive performance across seven categories, considering age and education data. Methods: Beynex test cut-off scores of participants (n  = 91) were derived from the optimization function and compared to the Montreal Cognitive Assessment (MoCA) test. Validation and reliability analyses were carried out with data collected from an additional 214 participants. …Results: Beynex categorization scores showed a moderate agreement with MoCA ratings (weighted Cohen’s Kappa = 0.48; 95% CI: 0.38–0.60). Calculated Cronbach’s Alpha indicates good internal consistency. Test-retest reliability analysis using a linear regression line fitted to results yielded R∧ 2 of 0.65 with a 95% CI: 0.58, 0.71. Discussion: Beynex’s ability to reliably detect and track cognitive impairment could significantly impact public health, early intervention strategies and improve patient outcomes. Show more

Keywords: Alzheimer’s disease, Beynex, cognitive decline, cognitive impairment, cognitive screening test, computerized cognitive tracking, dementia, early detection, memory, Montreal Cognitive Assessment

DOI: 10.3233/ADR-230117

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 163-171, 2024

Authors: Holmbom Larsen, Axel | Londos, Elisabet

Article Type: Case Report

Abstract: Background: Creativity is a multifaceted, complex, activity, and as such is an overarching function of the brain rather than being confined to a specific structure or region. Alzheimer’s disease effects several cognitive domains involved in the creative process of producing art. Objective: We analyze the art of a well-known Swedish visual artist who suffered from Alzheimer’s disease to determine if, and in what way, his art and creative process might have been influenced by the disease. Methods: We compared his artistic process and artwork along with information from his spouse, medical r ecords, …and cognitive tests as well as reviews of exhibitions written by art critics. Results: We show that not only did the artist continue to produce artwork well into a major decline in cognitive function, according to commonly used tests, but he could continue to do so for even longer with some assistance from his spouse. However, the artwork changed considerably as the disease progressed. We hypothesize that there is a substantial lack of representation of creative ability and function in cognitive tests. Conclusions: Signs of the Alzheimer’s disease can be seen in the early artwork if viewed by critics and those with more specialized knowledge into the artist’s production. Further analysis of the complex interaction between complex neural activities, such as artistic creativity, and cognitive diseases is warranted and might provide insight in the field of neurological degenerative disease. Show more

Keywords: Alzheimer’s disease, art, creativity, cognitive dysfunction, esthetics

DOI: 10.3233/ADR-230134

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 173-187, 2024

Authors: Moore, Arelis | Davis, Nicole J. | Dolins, Madeline | Barkley, Ethan | Reese, Ann | Meggett, Kinsey | Bailey-Taylor, Melissa J.

Article Type: Research Article

Abstract: Background: Alzheimer’s disease and related dementias (ADRD) disproportionately impact Latinx and other communities of color in the United States. The challenges for patients with ADRD and their informal caretakers can be attributed, in part, to the gaps that exist within health care services and systems. Objective: To understand the perspectives of barriers, beliefs, knowledge, and needs for the Latinx informal caregivers that take care of relatives with ADRD in the Upstate of South Carolina, region of Appalachia. Methods: This study was approved by the GHS-Prisma Health and Clemson University IRB, Study #Pro00086707. In-depth …phone interviews were conducted with a sample of Latinx informal caregivers. A descriptive and interpretive phenomenological approach was used for analysis. Participants were recruited through community partnerships with local organizations. Results: Salient themes identified in this study included the relevance of caregiver’s degree of awareness about the disease and a perspective of Alzheimer’s disease as a progressive and degenerative disease. Critical moments identified encompassed challenges related to patient engagement with the outside world, their attitudes, and behaviors, as well as caregiver-related challenges with access to culturally and linguistically relevant resources needed to provide proper care. Caregivers identified several culturally relevant coping strategies used and motivators in providing care for their relatives with ADRD. Conclusions: Linguistically and culturally sensitive programs and resources that account for knowledge, assets, and needs of Latinx informal caregivers of ADRD patients are needed to improve the quality of care and decrease disparities in health outcomes for Latinx older adults. Show more

Keywords: KeywordsAlzheimer’s disease, Alzheimer’s disease and related dementias, assessment of healthcare needs, coping strategies, culturally appropriate services, family caregiver, informal caregiver, Latinx/Latino/Hispanic

DOI: 10.3233/ADR-230108

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 189-202, 2024

Authors: Garcia, Maria João | Leadley, Regina | Ross, Janine | Bozeat, Sasha | Redhead, Gabrielle | Hansson, Oskar | Iwatsubo, Takeshi | Villain, Nicolas | Cummings, Jeffrey

Article Type: Systematic Review

Abstract: Background: Alzheimer’s disease (AD) causes progressive decline of cognition and function. There is a lack of systematic literature reviews on prognostic and predictive factors in its early clinical stages (eAD), i.e., mild cognitive impairment due to AD and mild AD dementia. Objective: To identify prognostic factors affecting eAD progression and predictive factors for treatment efficacy and safety of approved and/or under late-stage development disease-modifying treatments. Methods: Databases were searched (August 2022) for studies reporting prognostic factors associated with eAD progression and predictive factors for treatment response. The Quality in Prognostic Factor Studies tool …or the Cochrane risk of bias tool were used to assess risk of bias. Two reviewers independently screened the records. A single reviewer performed data extraction and quality assessment. A second performed a 20% check. Content experts reviewed and interpreted the data collected. Results: Sixty-one studies were included. Self-reporting, diagnosis definition, and missing data led to high risk of bias. Population size ranged from 110 to 11,451. Analyses found data indicating that older age was and depression may be associated with progression. Greater baseline cognitive impairment was associated with progression. APOE4 may be a prognostic factor, a predictive factor for treatment efficacy and predicts an adverse response (ARIA). Elevated biomarkers (CSF/plasma p-tau, CSF t-tau, and plasma neurofilament light) were associated with disease progression. Conclusions: Age was the strongest risk factor for progression. Biomarkers were associated with progression, supporting their use in trial selection and aiding diagnosis. Baseline cognitive impairment was a prognostic factor. APOE4 predicted ARIA, aligning with emerging evidence and relevant to treatment initiation/monitoring. Show more

Keywords: Alzheimer’s disease, cognitive dysfunction, prognosis, review

DOI: 10.3233/ADR-230045

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 203-240, 2024

Authors: Sleem, Tamara | Decourt, Boris | Sabbagh, Marwan N.

Article Type: Review Article

Abstract:  Huge investments continue to be made in treatment for Alzheimer’s disease (AD), with more than one hundred drugs currently in development. Pharmacological approaches and drug development, particularly those targeting amyloid-β, have dominated the therapeutic landscape. At the same time, there is also a growing interest in devices for treating AD. This review aimed to identify and describe devices under development for AD treatment. In this review, we queried the devices that are in development for the treatment of AD. PubMed was searched through the end of 2021 using the terms “device,” “therapeutics,” and “Alzheimer’s” for articles that report on devices …to treat AD. Ten devices with 31 references were identified as actively being developed for the treatment of AD. Many of these devices are far along in development. Device-based therapies are often overlooked when evaluating treatment approaches to AD. However, many devices for treating AD are in development and some show promising results. Show more

Keywords: Alzheimer’s disease, clinical trials, devices, treatment

DOI: 10.3233/ADR-230115

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 241-255, 2024

Authors: Sun, Wenxian | Wei, Cuibai

Article Type: Research Article

Abstract: Background: Previous observational research has indicated a correlation between ferritin levels and neuropsychiatric disorders, although the causal relationship remains uncertain. Objective: The objective of this study was to investigate the potential causal link between plasma ferritin levels and neuropsychiatric disorders. Methods: A two-sample Mendelian randomization (MR) study was conducted, wherein genetic instruments associated with ferritin were obtained from a previously published genome-wide association study (GWAS). Summary statistics pertaining to neuropsychiatric disorders were derived from five distinct GWAS datasets. The primary MR analysis employed the inverse variance weighted (IVW) method and was corroborated by …additional methods including MR-Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses were employed to identify potential pleiotropy and heterogeneity in the results. Results: The fixed effects IVW method revealed a statistically significant causal relationship between plasma ferritin level and the occurrence of Alzheimer’s disease (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.00–1.12, p  = 0.037), as well as Parkinson’s disease (OR = 1.06, 95% CI: 1.00–1.13, p  = 0.041). Various sensitivity analyses were conducted, which demonstrated no substantial heterogeneity or pleiotropy. Conversely, no compelling evidence was found to support a causal association between ferritin and amyotrophic lateral sclerosis, schizophrenia, or major depressive disorder. Conclusions: This MR study provides evidence at the genetic level for a causal relationship between plasma ferritin and an increased risk of Alzheimer’s disease and Parkinson’s disease. The exact genetic mechanisms underlying this connection necessitate further investigation. Show more

Keywords: Alzheimer’s disease, ferritin, Mendelian randomization, neuropsychiatric disorders, Parkinson’s disease

DOI: 10.3233/ADR-230136

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 257-266, 2024

Authors: Evans, Sarah A. | Paitel, Elizabeth R. | Bhasin, Riya | Nielson, Kristy A.

Article Type: Research Article

Abstract: Background: Subjective cognitive complaints (SCC) may be an early indicator of future cognitive decline. However, findings comparing SCC and objective cognitive performance have varied, particularly in the memory domain. Even less well established is the relationship between subjective and objective complaints in non-amnestic domains, such as in executive functioning, despite evidence indicating very early changes in these domains. Moreover, particularly early changes in both amnestic and non-amnestic domains are apparent in those carrying the Apolipoprotein-E ɛ4 allele, a primary genetic risk for Alzheimer’s disease (AD). Objective: This study investigated the role of the ɛ4 allele in …the consistency between subjective and objective executive functioning in 54 healthy, cognitively intact, middle-aged and older adults. Methods: Participants (M age  = 64.07, SD  = 9.27, range = 48–84; ɛ4+ = 18) completed the Frontal Systems Behavior Scale (FrSBe) Executive Dysfunction Scale (EXECDYS) to measure subjective executive functioning (SEF) and multiple executive functioning tasks, which were condensed into a single factor. Results: After accounting for age, depression, and anxiety, objective executive functioning performance significantly predicted SEF. Importantly, ɛ4 moderated this effect. Specifically, those carrying the ɛ4 allele had significantly less accurate self-awareness of their executive functioning compared to ɛ4 non-carriers. Conclusions: Utilizing an approach that integrates self-evaluation of executive functioning with objective neurocognitive assessment may help identify the earliest signs of impending cognitive decline, particularly in those with genetic risk for AD. Such an approach could sensitively determine those most prone to future cognitive decline prior to symptom onset, when interventions could be most effective. Show more

Keywords: Aging, Alzheimer’s disease, APOE ɛ4, executive function, subjective cognitive complaints

DOI: 10.3233/ADR-230166

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 267-279, 2024