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

Authors: Nguyen, Michelle | Wood, Colby | Rios, Andres | Salter, Zach | Reddy, P. Hemachandra

Article Type: Review Article

Abstract: Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is characterized by memory loss and multiple cognitive impairments. AD is pathologically characterized by age-dependent accumulation of amyloid-β protein and the phosphorylation of tau protein in the brains of patients with AD. Clinically, manifestations of AD include cognitive decline, dementia, alterations of high-order brain functions, and movement disorders. Double-stranded DNA breaks are a lethal form of DNA damage and are typically repaired via non-homologous end joining and homologous recombination. However, in AD brain, repair mechanism is disrupted, leading to a cascade of events, cognitive dysfunction, organ failure and reduced lifespan. Increased …circulating cell-free DNA in the blood, cerebrospinal fluid, and urine in patients with AD, can be used as early detectable biomarkers for AD. The purpose of our article is to explore the potential uses of cell-free DNA and double-stranded DNA breaks as prognostic markers for AD and examine the recent research on the application of these markers in studies. Show more

Keywords: Alzheimer’s disease, cell-free DNA, dementia, double-stranded DNA breaks

DOI: 10.3233/ADR-240012

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 627-635, 2024

Authors: Besser, Lilah M. | Edwards, Kyle | Lobban, Nina-Simone | Tolea, Magdalena I. | Galvin, James E.

Article Type: Research Article

Abstract: Background: Few studies have investigated associations between perceived social determinants of health (SDOH) and Alzheimer’s disease and related dementia (ADRD) biomarkers or between SDOH and resilience against ADRD. Objective: To examine associations between perceived and objective SDOH and ADRD-related outcomes. Methods: We used cross-sectional data on≥50-year-olds without dementia in the Healthy Brain Initiative (n = 162). Questionnaires captured trust in neighbors and indices of perceived neighborhood greenspace access, time spent in neighborhood greenspaces, and interpersonal discrimination. Residential addresses were linked to 2021 Area Deprivation Index scores. The Vulnerability Index (VI) is based on 12 dementia risk factors (e.g., …age, race/ethnicity, diabetes) and Resilience Index (RI) is based on 6 protective factors (e.g., diet, mindfulness, physical activity). Cognitive measured included number symbol coding task and Montreal Cognitive Assessment. Biomarkers included Aβ42/40 and pTau-217/npTau-217, hippocampal and white matter hyperintensity volume, lipoprotein A, and high-sensitivity c-reactive protein. Results: Perceived greater access to greenspaces (estimate = 2.83, 95% CI = 1.40–4.26) and greater time in neighborhood greenspaces were associated with greater RI scores (estimate = 2.30, 95% CI = 1.24–3.35). Reporting greater discrimination (estimate = 0.10, 95% CI = 0.04–0.16) and living in higher deprivation neighborhoods were associated with greater VI scores (estimate = 0.017, 95% CI = 0.003–0.032). Greater discrimination was associated with greater white matter hyperintensity volume (estimate = 0.27, 95% CI = 0.04–0.51). Conclusions: Perceived greenspace access and time spent in greenspaces were associated with resilience against ADRD, and interpersonal discrimination was associated with vulnerability to ADRD. Future work needs to validate perceived SDOH measures, examine associations in racially/ethnic diverse populations, and investigate longitudinal associations between SDOH and ADRD-related biomarkers. Show more

Keywords: Alzheimer’s disease, biomarkers, built environment, dementia, green space, neighborhood resilience, social determinants of health, socioeconomic status, structural determinants of health

DOI: 10.3233/ADR-230155

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 637-646, 2024

Authors: Wang, Weiye | Cui, Ruxin | Leng, Luming | Wang, Gang | Peng, Guoping

Article Type: Review Article

Abstract: Cognitive impairment is a primary manifestation of neurological symptoms associated with COVID-19 and may occur after disease resolution. Although cognitive impairment has been extensively reported in the literature, its duration and rate of remission remain controversial. This study discusses the various factors that influence cognitive impairment, including demographic characteristics, genetics, as well as disease course and severity. Furthermore, imaging and laboratory data have suggested various associations with cognitive impairment, most notably changes in EEG patterns, PET imaging, and serum markers. Some findings suggest similarities and potential links between COVID-related cognitive impairment and Alzheimer’s disease. Moreover, this study reviews the various …mechanisms proposed to explain the development of cognitive impairment in COVID-19, including cytokine storm, damage to the blood-brain barrier, compromise of small vessel integrity, hypoxic conditions, and immune dysregulation. Show more

Keywords: Alzheimer’s disease, cognitive impairment, COVID-19, mechanism, nervous system, SARS-CoV-2

DOI: 10.3233/ADR-230172

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 647-658, 2024

Authors: Czerwinski-Alley, Natasha C. | Chithiramohan, Tamara | Subramaniam, Hari | Beishon, Lucy | Mukaetova-Ladinska, Elizabeta B.

Article Type: Systematic Review

Abstract: Background: The current cognitive tests have been developed based on and standardized against Western constructs and normative data. With older people of minority ethnic background increasing across Western countries, there is a need for cognitive screening tests to address factors which influence performance bias and timely diagnostic dementia accuracy. The diagnostic accuracy in translated and culturally adapted cognitive screening tests and their impact on test performance in diverse populations have not been well addressed to date. Objective: This review aims to highlight considerations relating to the adaptation processes, language, cultural influences, impact of immigration, and level of education …to assess for dementia in non-Western and/or non-English speaking populations. Methods: We conducted a systematic search for studies addressing the effects of translation and cultural adaptations of cognitive screening tests (developed in a Western context) upon their diagnostic accuracy and test performance across diverse populations. Four electronic databases and manual searches were conducted, using a predefined search strategy. A narrative synthesis of findings was conducted. Results: Search strategy yielded 2,890 articles, and seventeen studies (4,463 participants) met the inclusion criteria. There was variability in the sensitivity and specificity of cognitive tests, irrespective of whether they were translated only, culturally adapted only, or both. Cognitive test performance was affected by education, linguistic ability, and aspects of acculturation. Conclusions: We highlight the importance of translating and culturally adapting tests that have been developed in the Western context. However, these findings should be interpreted with caution as results varied due to the broad selection of included cognitive tests. Show more

Keywords: Alzheimer’s disease, cognitive test, dementia, ethnic minority, mild cognitive impairment, translation

DOI: 10.3233/ADR-230198

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 659-675, 2024

Authors: Jamshidi-Naeini, Yasaman | Escobar Velasquez, Nicolas | Golzarri-Arroyo, Lilian | Ali, Sumayyah | Howard, Luke R. | Dickinson, Stephanie | Allison, David B.

Article Type: Article Commentary

DOI: 10.3233/ADR-240006

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 677-679, 2024

Authors: Hedayatjoo, Mohammad | Tehrani-Doost, Mehdi | Vahabi, Zahra | Akbarfahimi, Malahat | Khosrowabadi, Reza

Article Type: Research Article

Abstract: Background: Some pathological changes occur in patients with Alzheimer’s disease (AD) prior to the onset of clinical symptoms. Objective: In the present study, we aimed to investigate the potential of event-related potential (ERP) components in error processing performance as a neuromarker of mild cognitive impairment (MCI) and transition to AD and their relation with cognitive functions. Methods: We conducted an evaluation of 16 patients diagnosed with AD, 16 patients with MCI, and 15 normal controls using three subtests from the Cambridge Neuropsychological Testing Automated Battery (CANTAB). The ERP components of error processing were extracted and compared …among the three groups using a modified version of the Eriksen flanker task. Additionally, we assessed the correlation between the cognitive results and the ERP components. Results: Significant differences were observed among the three groups in terms of providing correct responses following errors and the amplitude of error-related negativity (ERN). These differences were also significant between all paired groups. Regarding other ERP components of error processing and the peak latency of ERN, no significant differences were observed among the three groups. The findings revealed that the spatial working memory and new learning were correlated with the amplitude of ERN. Conclusions: In the context of error processing performance, both the accuracy of responses following an error and the amplitude of ERN can be considered as indicators of MCI and its progression to AD. The present findings do not support the use of other error processing components as differential markers in the three groups. Show more

Keywords: Alzheimer’s disease, brain mapping, error processing, event-related potential, mild cognitive impairment

DOI: 10.3233/ADR-230104

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 681-696, 2024

Authors: Amos, Jessica G. | Zheng, Lidan | Eramudugolla, Ranmalee | Andrews, Sophie C. | Anstey, Kaarin J.

Article Type: Research Article

Abstract: Background: Digital dementia risk reduction interventions are cost-effective and scalable. However, it is unknown how they are perceived by people already experiencing cognitive concerns or decline. Objective: To understand the current use, interest, and preferences for online learning courses and interest in learning about factors influencing brain health and dementia risk among adults ≥45. To explore potential differences between individuals experiencing cognitive concerns and those without. Methods: Adults aged 45 and older completed a survey on technology use and healthy ageing (n  = 249, Mean age = 65.6, 76.3% female). The Memory Assessment Clinic-Questionnaire was used to assess subjective …memory decline, and 153 participants met the study criteria for cognitive concerns (≥25). Results: Almost all participants (98.4%) reported using two or more digital devices, and 51.8% reported increasing device usage following COVID-19. Most (92.1%) were interested in learning about healthy living and memory within an online course, and over 80% indicated a high interest in learning about dementia risk factors. People with cognitive concerns were more likely to report using a ‘routine or system’ to aid memory than people without (82.4% versus 62.9%, p  = 0.001). However, no significant difference was found in technology use, course preferences, or interest in learning about different risk factors. Conclusions: We conclude that adults 45 years and over are interested in online methods for learning about brain health and offer unique insights into adapting dementia prevention programs for cognitive concerns. Show more

Keywords: Alzheimer’s disease, cognition, dementia, prevention and control, technology

DOI: 10.3233/ADR-230160

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 697-708, 2024

Authors: García-Roldán, Ernesto | Tsai, Richard | Berger, Amy | Franco-Macías, Emilio

Article Type: Case Report

Abstract: A 60-year-old man presented to a Neurology Clinic specialized in cognitive disorders to evaluate memory complaints. A comprehensive neuropsychological examination detected an isolated and severe hippocampal memory deficit. Laboratory tests, brain magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) tests, including Alzheimer’s disease (AD) biomarkers, did not show remarkable results. Due to family history of cognitive impairment, we extended the study to non-Alzheimer monogenic mutations (Next Generation Sequencing) detecting a pathogenic variant of the progranulin (PGRN) gene (c.1414-1 G > T) which has been previously associated with the same phenotype. These results should be considered in patients with an Alzheimer-like presentation, negative AD …biomarkers’ results, and family history of dementia. Show more

Keywords: Alzheimer’s disease, dementia, human GRN protein, limbic-predominant age-related TDP-43 encephalopathy, neurocognitive disorder

DOI: 10.3233/ADR-240014

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 709-713, 2024

Authors: Lehrer, Steven | Rheinstein, Peter H.

Article Type: Research Article

Abstract: Background: In comparison to persons who did not have viral encephalitis, people with viral encephalitis had a later-life risk of Alzheimer’s disease (AD) that was 31 times higher. In a previous study, we were able to confirm the association of viral encephalitis with AD and suggest that West Nile Virus infection is a significant AD risk factor. A genome wide association study (GWAS) with UK Biobank data revealed that the gene RAR Related Orphan Receptor B (RORB) is significantly associated with viral encephalitis. Objective: To use data from the 8 PheWeb datasets to try to identify genes other …than RORB that might be involved in both infectious encephalitis and AD. Methods: PheWeb includes data from UKBB and 5 other databanks. We used UK Biobank data to examine gene expression and phenotypic expression. Results: PheWeb identified additional genes associated with both infectious encephalitis and AD. RPTOR, a gene associated with the mTOR pathway, emerges as significant. Analyses of UK Biobank data reveal the impact of RPTOR on AD risk, with carriers of the minor allele A exhibiting decreased prevalence in subjects under age 55. Further analysis demonstrates that RPTOR genotypes influence body mass index (BMI) in subjects of all ages, with carriers of the minor allele A having lower BMI. Logistic regression analyses confirm the association between reduced BMI and increased AD risk, along with the established factor of age. Conclusions: RPTOR may represent an AD gene, though mTOR’s role in AD and BMI is complex. Nevertheless, RPTOR and mTOR could represent potential therapeutic targets for AD. Show more

Keywords: Alzheimer’s disease, body mass index, encephalitis, mTOR, neurodegeneration

DOI: 10.3233/ADR-230185

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 715-721, 2024

Authors: Makri, Marina | Despoti, Akyllina | Teichmann, Birgit | Gkioka, Mara | Moraitou, Despina | Fidani, Liana | Tegos, Thomas | Tsolaki, Magdalini

Article Type: Research Article

Abstract: Background: In recent years, studies have examined the acceptability and attitudes that influence the intention to early screen for Alzheimer’s disease (AD) in the general population, older people, carers, and asymptomatic individuals who report a family history of AD. However, it remains unclear what specific factors promote or reduce the acceptability of pre-symptomatic screening. Objective: The aim of this study is to explore the attitudes of family and non-family members as well as caregivers and non-caregivers toward the pre-symptomatic screening of AD. Methods: A total of 213 participants completed the Perceptions regarding pRE-symptomatic Alzheimer’s Disease Screening …(PRE-ADS) Questionnaire. Group comparisons using t-test and one-way ANOVA were used to examine differences in attitudes toward pre-symptomatic screening regarding age, family history, knowing someone with AD, influence of depression, and feelings of anxiety. The subscale “Acceptability of Screening” was developed to investigate the willingness to undergo pre-symptomatic screening. Results: Participants with a family history showed greater acceptance of pre-symptomatic screening while both caregivers and non-caregivers had similar attitudes. People with a family history as well as those with personal connections to dementia indicate a greater need for knowledge. The findings suggest that younger adults appear to perceive less harm from testing, whereas those who experience higher levels of anxiety and depression seem to perceive more testing harms. Conclusions: Comparing the attitudes of people with and without a family history as well as caregivers and non-caregivers toward pre-symptomatic screening of AD is critical to understand the differences between these groups and develop comprehensive screening programs. Show more

Keywords: Acceptance, Alzheimer’s disease, attitudes, caregivers, family history, screening

DOI: 10.3233/ADR-230145

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 723-735, 2024