Journal of Alzheimer's Disease - Volume 94, issue 2

Authors: Oliveira, Fabricio Ferreira de

Article Type: Article Commentary

Abstract: Amyloid-PET studies of neurodegenerative diseases may yield inconclusive findings due to lacking stratification according to genetic or demographic variants. APOE ɛ 4 alleles are the major variants to increase disease susceptibility and cause earlier onset and more behavioral features in patients with late-onset Alzheimer’s disease, but have no linear effects on cognitive or functional decline; thus, sample stratification according to APOE ɛ 4 carrier status may be the best option. Interactions among APOE ɛ 4 alleles, sex, and age on amyloid-β deposition may reveal even more innovative findings with sufficiently large samples, suggesting variable genomic effects of …cognitive reserve, sex differences, and cerebrovascular risk on neurodegeneration. Show more

Keywords: Age groups, Alzheimer’s disease, amyloidosis, APOE, genetics, mild cognitive impairment, sex

DOI: 10.3233/JAD-230561

Citation: Journal of Alzheimer's Disease, vol. 94, no. 2, pp. 777-780, 2023

Authors: Curran, Eleanor | Palmer, Victoria J. | Ellis, Kathryn A. | Chong, Terence W.H. | Rego, Thomas | Cox, Kay L. | Anstey, Kaarin J. | Westphal, Alissa | Moorhead, Rebecca | Southam, Jenny | Lai, Rhoda | You, Emily | Lautenschlager, Nicola T.

Article Type: Research Article

Abstract: Background: People experiencing cognitive concerns and symptoms of depression or anxiety are at risk for Alzheimer’s disease and dementia. We know physical activity can benefit cognition but understanding how to best support engagement is an ongoing challenge. Evidence-based conceptual models of factors underpinning physical activity engagement in target populations can inform intervention tailoring to address this challenge. Objective: This study (part of a pragmatic physical activity implementation trial) aimed to develop a specified model of physical activity engagement in people experiencing depressive or anxiety symptoms and cognitive concerns, to enable optimized dementia risk reduction intervention tailoring. …Methods: We employed a qualitative design, triangulating data from three sources: semi-structured individual interviews with people experiencing cognitive concerns and mild to moderate depressive or anxiety symptoms; review of published evidence; and the Capability, Opportunity and Motivation system of behavior, an existing behavioral science model. Findings were integrated to develop a contextualized model of mechanisms of action for optimizing engagement. Results: Twenty-one participants were interviewed, and 24 relevant papers included. Convergent and complementary themes extended understanding of intervention needs. Findings highlighted emotional regulation, capacities to enact intentions despite barriers, and confidence in existing skills as areas of population-specific need that have not previously been emphasized. The final model provides specificity, directionality, and linked approaches for intervention tailoring. Conclusion: This study demonstrated that people experiencing cognitive concerns and symptoms of depression or anxiety require different interventions to improve physical activity engagement. This novel model can enable more precise intervention tailoring, and, ultimately, benefits for a key at-risk population. Show more

Keywords: Alzheimer’s disease, anxiety, dementia, depression, exercise, intervention, mild cognitive impairment, physical activity, prevention, subjective cognitive decline

DOI: 10.3233/JAD-221216

Citation: Journal of Alzheimer's Disease, vol. 94, no. 2, pp. 781-799, 2023

Authors: Chong, Terence W.H. | Rego, Thomas | Lai, Rhoda | Westphal, Alissa | Pond, Constance Dimity | Curran, Eleanor | Kootar, Scherazad | Peters, Ruth | Anstey, Kaarin J. | Lautenschlager, Nicola T.

Article Type: Research Article

Abstract: Background: Dementia risk reduction is a public health priority and general practitioners (GPs) play a pivotal role in preventative healthcare. Therefore, risk assessment tools should be designed with GPs’ preferences and perspectives in mind. Objective: The LEAD! GP project aimed to investigate Australian GPs’ preferences and perspectives relating to design, use and implementation of a new risk assessment tool that simultaneously calculates risk for four outcomes— dementia, diabetes mellitus, myocardial infarct, and stroke. Methods: A mixed methods study using semi-structured interviews of a diverse group of 30 Australian GPs was conducted. Interview transcripts were analyzed thematically. …Demographics and questions that elicited categorical answers were analyzed descriptively. Results: Overall, GPs felt that preventative healthcare was important with some finding it rewarding, and others finding it difficult. GPs currently use many risk assessment tools. GPs’ perception of the usefulness and negatives/barriers of tools related to clinical practice applicability, patient engagement, and practical aspects. The largest barrier was lack of time. GPs responded positively to the concept of a four-in-one tool and preferred it to be relatively short, supported by practice nurses and some patient involvement, linked to education resources, available in different formats, and integrated into practice software. Conclusion: GPs recognize the importance of preventative healthcare and the potential benefit of a new tool that simultaneously predicts risk for those four outcomes. Findings provide important guidance to inform the final development and piloting of this tool with potential to improve efficiency and practical integration of preventative healthcare for dementia risk reduction. Show more

Keywords: Alzheimer’s disease, dementia, diabetes, heart disease, general practice, primary care, risk, stroke

DOI: 10.3233/JAD-230287

Citation: Journal of Alzheimer's Disease, vol. 94, no. 2, pp. 801-814, 2023

Authors: Jiang, Wan-Rong | Wu, Wei | Yang, Li-Jie | Yang, Wanzhexi | Tian, Qing | Yao, Zhao-Hui

Article Type: Research Article

Abstract: Background: Both Alzheimer’s disease (AD) and aging have aging-related cognitive dysfunction with a high incidence. These neurological diseases cause serious cognitive problems in patients’ daily life. But the cognitive dysfunction mechanism in-depth of aging is far less known than that of AD. Objective: To reveal the different mechanisms of AD and aging-related cognitive dysfunction, we compared the mechanisms of aging and AD through analysis of differentially expressed genes. Methods: Mice were divided into four groups (3-month C57BL, 16-month C57BL, 3-month 3xTg AD mice, and 16-month 3xTg AD mice) according to genotype and age. The Morris water …maze was employed to investigate the spatial cognition of mice. Differential expressions of genes of AD and aging were analyzed through RNA sequencing and GO, KEGG, Reactome analysis, and the dynamic change trend analysis. Microglia was stained with immunofluorescence and its numbers were counted for analysis. Results: The cognitive function of elderly mice were worse through testing with the Morris water maze. The cognitive function of 16-month 3xTg AD mice were worse than 16-month C57BL mice. The alteration tendencies of DE genes were uncovered, and microglia numbers increased during aging and AD progression through immunofluorescence. Conclusion: These results suggest that immune-related pathways might play a critical role in aging and AD-related cognitive dysfunction. Our research will help to provide some new potential targets for treating cognitive dysfunction in aging and AD. Show more

Keywords: Aging; Alzheimer’s disease, cognitive function, microglia, neuroimmune

DOI: 10.3233/JAD-230292

Citation: Journal of Alzheimer's Disease, vol. 94, no. 2, pp. 815-839, 2023

Authors: Treacy, Ciara | Levenstein, Jacob M. | Jefferies, Annelise | Metse, Alexandra P. | Schaumberg, Mia A. | Villani, Anthony | Boucas, Ana P. | Hermens, Daniel F. | Lagopoulos, Jim | Andrews, Sophie C.

Article Type: Research Article

Abstract: Dementia is understood to arise from a mixed etiology, enveloping chronic inflammatory and vascular impacts on the brain, driven by a constellation of modifiable risk factors which are largely mediated by lifestyle-related behaviors. These risk factors manifest over a prolonged preclinical period and account for up to 40% of the population attributable risk for dementia, representing viable targets for early interventions aimed at abating disease onset and progression. Here we outline the protocol for a 12-week randomized control trial (RCT) of a multimodal Lifestyle Intervention Study for Dementia Risk Reduction (LEISURE), with longitudinal follow-up at 6-months and 24-months post-intervention. This …trial integrates exercise, diet, sleep, and mindfulness to simultaneously target multiple different etiopathogenetic mechanisms and their interplay in a healthy older adult population (aged 50–85 years), and assesses dementia risk reduction as the primary endpoint. The LEISURE study is located in the Sunshine Coast region of Australia, which has one of the nation’s highest proportions of adults aged over 50 years (36.4%), and corresponding dementia prevalence. This trial is novel in its inclusion of mindfulness and sleep as multidomain lifestyle targets, and in its comprehensive suite of secondary outcomes (based on psychological, physical health, sleep activity, and cognitive data) as well as exploratory neuroimaging (magnetic resonance imaging and electroencephalography) and molecular biology measures. These measures will provide greater insights into the brain-behavioral underpinnings of dementia prevention, as well as the predictors and impacts of the proposed lifestyle intervention. The LEISURE study was prospectively registered (ACTRN12620000054910) on 19 January 2020. Show more

Keywords: Aging, Alzheimer’s disease, biomarkers, individualized medicine, neurobiology, prevention

DOI: 10.3233/JAD-230193

Citation: Journal of Alzheimer's Disease, vol. 94, no. 2, pp. 841-856, 2023

Authors: Jiang, Chunyan | Wang, Yongxiang | Dong, Yi | Song, Lin | Wang, Shanshan | Xu, Zhe | Ren, Yifei | Han, Xiaodong | Zhao, Mingqing | Wang, Jiafeng | Cong, Lin | Hou, Tingting | Zhang, Qinghua | Du, Yifeng | Qiu, Chengxuan

Article Type: Correction

DOI: 10.3233/JAD-239004

Citation: Journal of Alzheimer's Disease, vol. 94, no. 2, pp. 857-857, 2023